AVAHO

Meaningful progress has been made in reducing deaths due to breast cancer over the last half century, with a 43% decrease in mortality rate (breast cancer deaths per 100,000 population).¹ Screening mammography (SM) has contributed greatly to that success, accounting for 30% to 70% of the reduced mortality rate, with the remainder due to advancements in breast cancer treatment.² Despite these improvements, invasive breast cancer remains the highest incident cancer in the United States and in the world, is the second leading cause of cancer death in the United States, and results in more years of life lost than any other cancer (TABLE 1).^1,3

While the benefits and harms of SM are reasonably well understood, different guidelines groups have approached the relative value of the risks and benefits differently, which has led to challenges in implementation of shared decision making, particularly around the age to initiate routine screening.^4-6 In this article, we will focus on the data behind the controversy, current gaps in knowledge, challenges related to breast density and screening in diverse groups, and emerging technologies to address these gaps and provide a construct for appropriate counseling of the patient across the risk spectrum.

Breast cancer risk

Variables that affect risk

While female sex and older age are the 2 greatest risks for the development of breast cancer, many other factors can either increase or decrease breast cancer risk in a person’s lifetime. The importance of identifying risk factors is 3-fold:

1. to perform risk assessment to determine if individuals would benefit from average-risk versus high-risk breast cancer surveillance
2. to identify persons who might benefit from BRCA genetic counseling and screening, risk reduction medications or procedures, and
3. to allow patients to determine whether any modification in their lifestyle or reproductive choices would make sense to them to reduce their future breast cancer risk.

Most of these risk variables are largely inalterable (for example, family history of breast cancer, carriage of genetic pathogenic variants such as BRCA1 and BRCA2, age of menarche and menopause), but some are potentially modifiable, such as parity, age at first birth, lactation and duration, and dietary factors, among others. TABLE 2 lists common breast cancer risk factors.

Breast cancer risk assessment

Several validated tools have been developed to estimate a person’s breast cancer risk (TABLE 3). These tools combine known risk factors and, depending on the specific tool, can provide estimates of 5-year, 10-year, or lifetime risk of breast cancer. Patients at highest risk can benefit from earlier screening, supplemental screening with breast magnetic resonance imaging (MRI), or risk reduction (see the section, “High-risk screening”). Ideally, a risk assessment should be done by age 30 so that patients at high risk can be identified for earlier or more intensive screening and for possible genetic testing in those at risk for carriage of the BRCA or other breast cancer gene pathogenic variants.^5,7

Continue to: Breast cancer screening: Efficacy and harms...

Breast cancer screening: Efficacy and harms

The earliest studies of breast cancer screening with mammography were randomized controlled trials (RCTs) that compared screened and unscreened patients aged 40 to 74. Nearly all the RCTs and numerous well-designed incidence-based and case-control studies have demonstrated that SM results in a clinically and statistically significant reduction in breast cancer mortality (TABLE 4).^4,6,8 Since the mid-1980s and continuing to the current day, SM programs are routinely recommended in the United States. In addition to the mortality benefit outlined in TABLE 4, SM also is associated with a need for less invasive treatments if breast cancer is diagnosed.^9,10

With several decades of experience, SM programs have demonstrated that multiple harms are associated with SM, including callbacks, false-positive mammograms that result in a benign biopsy, and overdiagnosis of breast cancer (TABLE 4). Overdiagnosis is a mammographic detection of a breast cancer that would not have harmed that woman in her lifetime. Overdiagnosis leads to overtreatment of breast cancers with its attendant side effects, the emotional harms of a breast cancer diagnosis, and the substantial financial cost of cancer treatment. Estimates of overdiagnosis range from 0% to 50%, with the most likely estimate of invasive breast cancer overdiagnosis from SM between 5% and 15%.^11-13 Some of these overdiagnosed cancers are due to very slow growing cancers or breast cancers that may even regress. However, the higher rates of overdiagnosis occur in older persons who are screened and in whom competing causes of mortality become more prevalent. It is estimated that overdiagnosis of invasive breast cancer in patients younger than age 60 is less than 1%, but it exceeds 14% in those older than age 80 (TABLE 4).¹⁴

A structured approach is needed to counsel patients about SM so that they understand both the substantial benefit (earlier-stage diagnosis, reduced need for treatment, reduced breast cancer and all-cause mortality) and the potential harms (callback, false-positive results, and overdiagnosis). Moreover, the relative balance of the benefits and harms are influenced throughout their lifetime by both aging and changes in their personal and family medical history.

Counseling should consider factors beyond just the performance of mammography (sensitivity and specificity), such as the patient’s current health and age (competing causes of mortality), likelihood of developing breast cancer based on risk assessment (more benefit in higher-risk persons), and the individual patient’s values on the importance of the benefits and harms. The differing emphases on mammography performance and the relative value of the benefits and harms have led experts to produce disparate national guideline recommendations (TABLE 5).

Should SM start at age 40, 45, or 50 in average-risk persons?

There is not clear consensus about the age at which to begin to recommend routine SM in patients at average risk. The National Comprehensive Cancer Network (NCCN),⁷ American Cancer Society (ACS),⁴ and the US Preventive Services Task Force (USPSTF)⁵ recommend that those at average risk start SM at age 40, 45, and 50, respectively (TABLE 5). While the guideline groups listed in TABLE 5 agree that there is level 1 evidence that SM reduces breast cancer mortality in the general population for persons starting at age 40, because the incidence of breast cancer is lower in younger persons (TABLE 6),⁴ the net population-based screening benefit is lower in this group, and the number needed to invite to screening to save a single life due to breast cancer varies.

For patients in their 40s, it is estimated that 1,904 individuals need to be invited to SM to save 1 life, whereas for patients in their 50s, it is 1,339.¹⁵ However, for patients in their 40s, the number needed to screen to save 1 life due to breast cancer decreases from 1 in 1,904 if invited to be screened to 1 in 588 if they are actually screened.¹⁶ Furthermore, if a patient is diagnosed with breast cancer at age 40–50, the likelihood of dying is reduced at least 22% and perhaps as high as 48% if her cancer was diagnosed on SM compared with an unscreened individual with a symptomatic presentation (for example, palpable mass).^4,15,17,18 Another benefit of SM in the fifth decade of life (40s) is the decreased need for more extensive treatment, including a higher risk of need for chemotherapy (odds ratio [OR], 2.81; 95% confidence interval [CI], 1.16–6.84); need for mastectomy (OR, 3.41; 95% CI, 1.36–8.52); and need for axillary lymph node dissection (OR, 5.76; 95% CI, 2.40–13.82) in unscreened (compared with screened) patients diagnosed with breast cancer.¹⁰

The harms associated with SM are not inconsequential and include callbacks (approximately 1 in 10), false-positive biopsy (approximately 1 in 100), and overdiagnosis (likely <1% of all breast cancers in persons younger than age 50). Because most patients in their 40s will not develop breast cancer (TABLE 6), the benefit of reduced breast cancer mortality will not be experienced by most in this decade of life, but they are still just as likely to experience a callback, false-positive biopsy, or the possibility of overdiagnosis. Interpretation of this balance on a population level is the crux of the various guideline groups’ development of differing recommendations as to when screening should start. Despite this seeming disagreement, all the guideline groups listed in TABLE 5 concur that persons at average risk for breast cancer should be offered SM if they desire starting at age 40 after a shared decision-making conversation that incorporates the patient’s view on the relative value of the benefits and risks.

Continue to: High-risk screening...

 

 

High-risk screening

Unlike in screening average-risk patients, there is less disagreement about screening in high-risk groups. TABLE 7 outlines the various categories and recommended strategies that qualify for screening at younger ages or more intensive screening. Adding breast MRI to SM in high-risk individuals results in both higher cancer detection rates and less interval breast cancers (cancers diagnosed between screening rounds) diagnosed compared with SM alone.^19,20 Interval breast cancer tends to be more aggressive and is used as a surrogate marker for more recognized factors, such as breast cancer mortality. In addition to less interval breast cancers, high-risk patients are more likely to be diagnosed with node-negative disease if screening breast MRI is added to SM.

Long-term mortality benefit studies using MRI have not been conducted due to the prolonged follow-up times needed. Expense, lower specificity compared with mammography (that is, more false-positive results), and need for the use of gadolinium limit more widespread use of breast MRI screening in average-risk persons.

Screening in patients with dense breasts

Half of patients undergoing SM in the United States have dense breasts (heterogeneously dense breasts, 40%; extremely dense breasts, 10%). Importantly, increasing breast density is associated with a lower cancer detection rate with SM and is an independent risk factor for developing breast cancer. While most states already require patients to be notified if they have dense breasts identified on SM, the US Food and Drug Administration will soon make breast density patient notification a national standard (see: https://delauro.house.gov/media-center/press-releases/delauro-secures-timeline-fda-rollout-breast-density-notification-rule).

Most of the risk assessment tools listed in TABLE 3 incorporate breast density into their calculation of breast cancer risk. If that calculation places a patient into one of the highest-risk groups (based on additional factors like strong family history of breast cancer, reproductive risk factors, BRCA carriage, and so on), more intensive surveillance should be recommended (TABLE 7).⁷ However, once these risk calculations are done, most persons with dense breasts will remain in an average-risk category.

Because of the frequency and risks associated with dense breasts, different and alternative strategies have been recommended for screening persons who are at average risk with dense breasts. Supplemental screening with MRI, ultrasonography, contrast-enhanced mammography, and molecular breast imaging are all being considered but have not been studied sufficiently to demonstrate mortality benefit or cost-effectiveness.

Of all the supplemental modalities used to screen patients with dense breasts, MRI has been the best studied. A large RCT in the Netherlands evaluated supplemental MRI screening in persons with extremely dense breasts after a negative mammogram.²¹ Compared with no supplemental screening, the MRI group had 17 additional cancers detected per 1,000 screened and a 50% reduction in interval breast cancers; in addition, MRI was associated with a positive predictive value of 26% for biopsies. At present, high cost and limited access to standard breast MRI has not allowed its routine use for persons with dense breasts in the United States, but this may change with more experience and more widespread introduction and experience with abbreviated (or rapid) breast MRI in the future (TABLE 8).

Equitable screening

Black persons who are diagnosed with breast cancer have a 40% higher risk of dying than White patients due to multiple factors, including systemic racial factors (implicit and unconscious bias), reduced access to care, and a lower likelihood of receiving standard of care once diagnosed.^22-24 In addition, Black patients have twice the likelihood of being diagnosed with triple-negative breast cancers, a biologically more aggressive tumor.^22-24 Among Black, Asian, and Hispanic persons diagnosed with breast cancer, one-third are diagnosed younger than age 50, which is higher than for non-Hispanic White persons. Prior to the age of 50, Black, Asian, and Hispanic patients also have a 72% more likelihood of being diagnosed with invasive breast cancer, have a 58% greater risk of advanced-stage disease, and have a 127% higher risk of dying from breast cancer compared with White patients.^25,26 Based on all of these factors, delaying SM until age 50 may adversely affect the Black, Asian, and Hispanic populations.

Persons in the LGBTQ+ community do not present for SM as frequently as the general population, often because they feel threatened or unwelcome.²⁷ Clinicians and breast imaging units should review their inclusivity policies and training to provide a welcoming and respectful environment to all persons in an effort to reduce these barriers. While data are limited and largely depend on expert opinion, current recommendations for screening in the transgender patient depend on sex assigned at birth, the type and duration of hormone use, and surgical history. In patients assigned female sex at birth, average-risk and high-risk screening recommendations are similar to those for the general population unless bilateral mastectomy has been performed.²⁸ In transfeminine patients who have used hormones for longer than 5 years, some groups recommend annual screening starting at age 40, although well-designed studies are lacking.²⁹

Continue to: We have done well, can we do better?...

 

 

We have done well, can we do better?

Screening mammography clearly has been an important and effective tool in the effort to reduce breast cancer mortality, but there are clear limitations. These include moderate sensitivity of mammography, particularly in patients with dense breasts, and a specificity that results in either callbacks (10%), breast biopsies for benign disease (1%), or the reality of overdiagnosis, which becomes increasingly important in older patients.

With the introduction of mammography in the mid-1980s, a one-size-fits-all approach has proved challenging more recently due to an increased recognition of the harms of screening. As a result of this evolving understanding, different recommendations for average-risk screening have emerged. With the advent of breast MRI, risk-based screening is an important but underutilized tool to identify highest-risk individuals, which is associated with improved cancer detection rates, reduced node-positive disease, and fewer diagnosed interval breast cancers. Assuring that nearly all of this highest-risk group is identified through routine breast cancer risk assessment remains a challenge for clinicians.

But what SM recommendations should be offered to persons who fall into an intermediate-risk group (15%–20%), very low-risk groups (<5%), or patients with dense breasts? These are challenges that could be met through novel and individualized approaches (for example, polygenic risk scoring, further research on newer modalities of screening [TABLE 8]), improved screening algorithms for persons with dense breasts, and enhanced clinician engagement to achieve universal breast cancer and BRCA risk assessment of patients by age 25 to 30.

In 2023, best practice and consensus guidelines for intermediate- and low-risk breast cancer groups remain unclear, and one of the many ongoing challenges is to further reduce the impact of breast cancer on the lives of persons affected and the recognized harms of SM.

In the meantime, there is consensus in average-risk patients to provide counseling about SM by age 40. My approach has been to counsel all average-risk patients on the risks and benefits of mammography using the acronym TIP-V:

• Use a Tool to calculate breast cancer risk (TABLE 3). If they are at high risk, provide recommendations for high-risk management (TABLE 7).⁷
• For average-risk patients, counsel that their Incidence of developing breast cancer in the next decade is approximately 1 in 70 (TABLE 6).⁴
• Provide data and guidance on the benefits of SM for patients in their 40s (mortality improvement, decreased treatment) and the likelihood of harm from breast cancer screening (10% callback, 1% benign biopsy, and <1% likelihood of overdiagnosis [TABLE 4]).^4,14,15
• Engage the patient to better understand their relative Values of the benefits and harms and make a shared decision on screening starting at age 40, 45, or 50.

Looking forward

In summary, SM remains an important tool in the effort to decrease the risk of mortality due to breast cancer. Given the limitations of SM, however, newer tools and methods—abbreviated MRI, contrast-enhanced mammography, molecular breast imaging, customized screening intervals depending on individual risk/polygenic risk score, and customized counseling and screening based on risk factors (TABLES 2 and 7)—will play an increased role in recommendations for breast cancer screening in the future. ●

Meaningful progress has been made in reducing deaths due to breast cancer over the last half century, with a 43% decrease in mortality rate (breast cancer deaths per 100,000 population).¹ Screening mammography (SM) has contributed greatly to that success, accounting for 30% to 70% of the reduced mortality rate, with the remainder due to advancements in breast cancer treatment.² Despite these improvements, invasive breast cancer remains the highest incident cancer in the United States and in the world, is the second leading cause of cancer death in the United States, and results in more years of life lost than any other cancer (TABLE 1).^1,3

While the benefits and harms of SM are reasonably well understood, different guidelines groups have approached the relative value of the risks and benefits differently, which has led to challenges in implementation of shared decision making, particularly around the age to initiate routine screening.^4-6 In this article, we will focus on the data behind the controversy, current gaps in knowledge, challenges related to breast density and screening in diverse groups, and emerging technologies to address these gaps and provide a construct for appropriate counseling of the patient across the risk spectrum.

Breast cancer risk

Variables that affect risk

While female sex and older age are the 2 greatest risks for the development of breast cancer, many other factors can either increase or decrease breast cancer risk in a person’s lifetime. The importance of identifying risk factors is 3-fold:

1. to perform risk assessment to determine if individuals would benefit from average-risk versus high-risk breast cancer surveillance
2. to identify persons who might benefit from BRCA genetic counseling and screening, risk reduction medications or procedures, and
3. to allow patients to determine whether any modification in their lifestyle or reproductive choices would make sense to them to reduce their future breast cancer risk.

Most of these risk variables are largely inalterable (for example, family history of breast cancer, carriage of genetic pathogenic variants such as BRCA1 and BRCA2, age of menarche and menopause), but some are potentially modifiable, such as parity, age at first birth, lactation and duration, and dietary factors, among others. TABLE 2 lists common breast cancer risk factors.

Breast cancer risk assessment

Several validated tools have been developed to estimate a person’s breast cancer risk (TABLE 3). These tools combine known risk factors and, depending on the specific tool, can provide estimates of 5-year, 10-year, or lifetime risk of breast cancer. Patients at highest risk can benefit from earlier screening, supplemental screening with breast magnetic resonance imaging (MRI), or risk reduction (see the section, “High-risk screening”). Ideally, a risk assessment should be done by age 30 so that patients at high risk can be identified for earlier or more intensive screening and for possible genetic testing in those at risk for carriage of the BRCA or other breast cancer gene pathogenic variants.^5,7

Continue to: Breast cancer screening: Efficacy and harms...

Breast cancer screening: Efficacy and harms

The earliest studies of breast cancer screening with mammography were randomized controlled trials (RCTs) that compared screened and unscreened patients aged 40 to 74. Nearly all the RCTs and numerous well-designed incidence-based and case-control studies have demonstrated that SM results in a clinically and statistically significant reduction in breast cancer mortality (TABLE 4).^4,6,8 Since the mid-1980s and continuing to the current day, SM programs are routinely recommended in the United States. In addition to the mortality benefit outlined in TABLE 4, SM also is associated with a need for less invasive treatments if breast cancer is diagnosed.^9,10

With several decades of experience, SM programs have demonstrated that multiple harms are associated with SM, including callbacks, false-positive mammograms that result in a benign biopsy, and overdiagnosis of breast cancer (TABLE 4). Overdiagnosis is a mammographic detection of a breast cancer that would not have harmed that woman in her lifetime. Overdiagnosis leads to overtreatment of breast cancers with its attendant side effects, the emotional harms of a breast cancer diagnosis, and the substantial financial cost of cancer treatment. Estimates of overdiagnosis range from 0% to 50%, with the most likely estimate of invasive breast cancer overdiagnosis from SM between 5% and 15%.^11-13 Some of these overdiagnosed cancers are due to very slow growing cancers or breast cancers that may even regress. However, the higher rates of overdiagnosis occur in older persons who are screened and in whom competing causes of mortality become more prevalent. It is estimated that overdiagnosis of invasive breast cancer in patients younger than age 60 is less than 1%, but it exceeds 14% in those older than age 80 (TABLE 4).¹⁴

A structured approach is needed to counsel patients about SM so that they understand both the substantial benefit (earlier-stage diagnosis, reduced need for treatment, reduced breast cancer and all-cause mortality) and the potential harms (callback, false-positive results, and overdiagnosis). Moreover, the relative balance of the benefits and harms are influenced throughout their lifetime by both aging and changes in their personal and family medical history.

Counseling should consider factors beyond just the performance of mammography (sensitivity and specificity), such as the patient’s current health and age (competing causes of mortality), likelihood of developing breast cancer based on risk assessment (more benefit in higher-risk persons), and the individual patient’s values on the importance of the benefits and harms. The differing emphases on mammography performance and the relative value of the benefits and harms have led experts to produce disparate national guideline recommendations (TABLE 5).

Should SM start at age 40, 45, or 50 in average-risk persons?

There is not clear consensus about the age at which to begin to recommend routine SM in patients at average risk. The National Comprehensive Cancer Network (NCCN),⁷ American Cancer Society (ACS),⁴ and the US Preventive Services Task Force (USPSTF)⁵ recommend that those at average risk start SM at age 40, 45, and 50, respectively (TABLE 5). While the guideline groups listed in TABLE 5 agree that there is level 1 evidence that SM reduces breast cancer mortality in the general population for persons starting at age 40, because the incidence of breast cancer is lower in younger persons (TABLE 6),⁴ the net population-based screening benefit is lower in this group, and the number needed to invite to screening to save a single life due to breast cancer varies.

For patients in their 40s, it is estimated that 1,904 individuals need to be invited to SM to save 1 life, whereas for patients in their 50s, it is 1,339.¹⁵ However, for patients in their 40s, the number needed to screen to save 1 life due to breast cancer decreases from 1 in 1,904 if invited to be screened to 1 in 588 if they are actually screened.¹⁶ Furthermore, if a patient is diagnosed with breast cancer at age 40–50, the likelihood of dying is reduced at least 22% and perhaps as high as 48% if her cancer was diagnosed on SM compared with an unscreened individual with a symptomatic presentation (for example, palpable mass).^4,15,17,18 Another benefit of SM in the fifth decade of life (40s) is the decreased need for more extensive treatment, including a higher risk of need for chemotherapy (odds ratio [OR], 2.81; 95% confidence interval [CI], 1.16–6.84); need for mastectomy (OR, 3.41; 95% CI, 1.36–8.52); and need for axillary lymph node dissection (OR, 5.76; 95% CI, 2.40–13.82) in unscreened (compared with screened) patients diagnosed with breast cancer.¹⁰

The harms associated with SM are not inconsequential and include callbacks (approximately 1 in 10), false-positive biopsy (approximately 1 in 100), and overdiagnosis (likely <1% of all breast cancers in persons younger than age 50). Because most patients in their 40s will not develop breast cancer (TABLE 6), the benefit of reduced breast cancer mortality will not be experienced by most in this decade of life, but they are still just as likely to experience a callback, false-positive biopsy, or the possibility of overdiagnosis. Interpretation of this balance on a population level is the crux of the various guideline groups’ development of differing recommendations as to when screening should start. Despite this seeming disagreement, all the guideline groups listed in TABLE 5 concur that persons at average risk for breast cancer should be offered SM if they desire starting at age 40 after a shared decision-making conversation that incorporates the patient’s view on the relative value of the benefits and risks.

Continue to: High-risk screening...

 

 

High-risk screening

Unlike in screening average-risk patients, there is less disagreement about screening in high-risk groups. TABLE 7 outlines the various categories and recommended strategies that qualify for screening at younger ages or more intensive screening. Adding breast MRI to SM in high-risk individuals results in both higher cancer detection rates and less interval breast cancers (cancers diagnosed between screening rounds) diagnosed compared with SM alone.^19,20 Interval breast cancer tends to be more aggressive and is used as a surrogate marker for more recognized factors, such as breast cancer mortality. In addition to less interval breast cancers, high-risk patients are more likely to be diagnosed with node-negative disease if screening breast MRI is added to SM.

Long-term mortality benefit studies using MRI have not been conducted due to the prolonged follow-up times needed. Expense, lower specificity compared with mammography (that is, more false-positive results), and need for the use of gadolinium limit more widespread use of breast MRI screening in average-risk persons.

Screening in patients with dense breasts

Half of patients undergoing SM in the United States have dense breasts (heterogeneously dense breasts, 40%; extremely dense breasts, 10%). Importantly, increasing breast density is associated with a lower cancer detection rate with SM and is an independent risk factor for developing breast cancer. While most states already require patients to be notified if they have dense breasts identified on SM, the US Food and Drug Administration will soon make breast density patient notification a national standard (see: https://delauro.house.gov/media-center/press-releases/delauro-secures-timeline-fda-rollout-breast-density-notification-rule).

Most of the risk assessment tools listed in TABLE 3 incorporate breast density into their calculation of breast cancer risk. If that calculation places a patient into one of the highest-risk groups (based on additional factors like strong family history of breast cancer, reproductive risk factors, BRCA carriage, and so on), more intensive surveillance should be recommended (TABLE 7).⁷ However, once these risk calculations are done, most persons with dense breasts will remain in an average-risk category.

Because of the frequency and risks associated with dense breasts, different and alternative strategies have been recommended for screening persons who are at average risk with dense breasts. Supplemental screening with MRI, ultrasonography, contrast-enhanced mammography, and molecular breast imaging are all being considered but have not been studied sufficiently to demonstrate mortality benefit or cost-effectiveness.

Of all the supplemental modalities used to screen patients with dense breasts, MRI has been the best studied. A large RCT in the Netherlands evaluated supplemental MRI screening in persons with extremely dense breasts after a negative mammogram.²¹ Compared with no supplemental screening, the MRI group had 17 additional cancers detected per 1,000 screened and a 50% reduction in interval breast cancers; in addition, MRI was associated with a positive predictive value of 26% for biopsies. At present, high cost and limited access to standard breast MRI has not allowed its routine use for persons with dense breasts in the United States, but this may change with more experience and more widespread introduction and experience with abbreviated (or rapid) breast MRI in the future (TABLE 8).

Equitable screening

Black persons who are diagnosed with breast cancer have a 40% higher risk of dying than White patients due to multiple factors, including systemic racial factors (implicit and unconscious bias), reduced access to care, and a lower likelihood of receiving standard of care once diagnosed.^22-24 In addition, Black patients have twice the likelihood of being diagnosed with triple-negative breast cancers, a biologically more aggressive tumor.^22-24 Among Black, Asian, and Hispanic persons diagnosed with breast cancer, one-third are diagnosed younger than age 50, which is higher than for non-Hispanic White persons. Prior to the age of 50, Black, Asian, and Hispanic patients also have a 72% more likelihood of being diagnosed with invasive breast cancer, have a 58% greater risk of advanced-stage disease, and have a 127% higher risk of dying from breast cancer compared with White patients.^25,26 Based on all of these factors, delaying SM until age 50 may adversely affect the Black, Asian, and Hispanic populations.

Persons in the LGBTQ+ community do not present for SM as frequently as the general population, often because they feel threatened or unwelcome.²⁷ Clinicians and breast imaging units should review their inclusivity policies and training to provide a welcoming and respectful environment to all persons in an effort to reduce these barriers. While data are limited and largely depend on expert opinion, current recommendations for screening in the transgender patient depend on sex assigned at birth, the type and duration of hormone use, and surgical history. In patients assigned female sex at birth, average-risk and high-risk screening recommendations are similar to those for the general population unless bilateral mastectomy has been performed.²⁸ In transfeminine patients who have used hormones for longer than 5 years, some groups recommend annual screening starting at age 40, although well-designed studies are lacking.²⁹

Continue to: We have done well, can we do better?...

 

 

We have done well, can we do better?

Screening mammography clearly has been an important and effective tool in the effort to reduce breast cancer mortality, but there are clear limitations. These include moderate sensitivity of mammography, particularly in patients with dense breasts, and a specificity that results in either callbacks (10%), breast biopsies for benign disease (1%), or the reality of overdiagnosis, which becomes increasingly important in older patients.

With the introduction of mammography in the mid-1980s, a one-size-fits-all approach has proved challenging more recently due to an increased recognition of the harms of screening. As a result of this evolving understanding, different recommendations for average-risk screening have emerged. With the advent of breast MRI, risk-based screening is an important but underutilized tool to identify highest-risk individuals, which is associated with improved cancer detection rates, reduced node-positive disease, and fewer diagnosed interval breast cancers. Assuring that nearly all of this highest-risk group is identified through routine breast cancer risk assessment remains a challenge for clinicians.

But what SM recommendations should be offered to persons who fall into an intermediate-risk group (15%–20%), very low-risk groups (<5%), or patients with dense breasts? These are challenges that could be met through novel and individualized approaches (for example, polygenic risk scoring, further research on newer modalities of screening [TABLE 8]), improved screening algorithms for persons with dense breasts, and enhanced clinician engagement to achieve universal breast cancer and BRCA risk assessment of patients by age 25 to 30.

In 2023, best practice and consensus guidelines for intermediate- and low-risk breast cancer groups remain unclear, and one of the many ongoing challenges is to further reduce the impact of breast cancer on the lives of persons affected and the recognized harms of SM.

In the meantime, there is consensus in average-risk patients to provide counseling about SM by age 40. My approach has been to counsel all average-risk patients on the risks and benefits of mammography using the acronym TIP-V:

• Use a Tool to calculate breast cancer risk (TABLE 3). If they are at high risk, provide recommendations for high-risk management (TABLE 7).⁷
• For average-risk patients, counsel that their Incidence of developing breast cancer in the next decade is approximately 1 in 70 (TABLE 6).⁴
• Provide data and guidance on the benefits of SM for patients in their 40s (mortality improvement, decreased treatment) and the likelihood of harm from breast cancer screening (10% callback, 1% benign biopsy, and <1% likelihood of overdiagnosis [TABLE 4]).^4,14,15
• Engage the patient to better understand their relative Values of the benefits and harms and make a shared decision on screening starting at age 40, 45, or 50.

Looking forward

In summary, SM remains an important tool in the effort to decrease the risk of mortality due to breast cancer. Given the limitations of SM, however, newer tools and methods—abbreviated MRI, contrast-enhanced mammography, molecular breast imaging, customized screening intervals depending on individual risk/polygenic risk score, and customized counseling and screening based on risk factors (TABLES 2 and 7)—will play an increased role in recommendations for breast cancer screening in the future. ●

Meaningful progress has been made in reducing deaths due to breast cancer over the last half century, with a 43% decrease in mortality rate (breast cancer deaths per 100,000 population).¹ Screening mammography (SM) has contributed greatly to that success, accounting for 30% to 70% of the reduced mortality rate, with the remainder due to advancements in breast cancer treatment.² Despite these improvements, invasive breast cancer remains the highest incident cancer in the United States and in the world, is the second leading cause of cancer death in the United States, and results in more years of life lost than any other cancer (TABLE 1).^1,3

While the benefits and harms of SM are reasonably well understood, different guidelines groups have approached the relative value of the risks and benefits differently, which has led to challenges in implementation of shared decision making, particularly around the age to initiate routine screening.^4-6 In this article, we will focus on the data behind the controversy, current gaps in knowledge, challenges related to breast density and screening in diverse groups, and emerging technologies to address these gaps and provide a construct for appropriate counseling of the patient across the risk spectrum.

Breast cancer risk

Variables that affect risk

While female sex and older age are the 2 greatest risks for the development of breast cancer, many other factors can either increase or decrease breast cancer risk in a person’s lifetime. The importance of identifying risk factors is 3-fold:

1. to perform risk assessment to determine if individuals would benefit from average-risk versus high-risk breast cancer surveillance
2. to identify persons who might benefit from BRCA genetic counseling and screening, risk reduction medications or procedures, and
3. to allow patients to determine whether any modification in their lifestyle or reproductive choices would make sense to them to reduce their future breast cancer risk.

Most of these risk variables are largely inalterable (for example, family history of breast cancer, carriage of genetic pathogenic variants such as BRCA1 and BRCA2, age of menarche and menopause), but some are potentially modifiable, such as parity, age at first birth, lactation and duration, and dietary factors, among others. TABLE 2 lists common breast cancer risk factors.

Breast cancer risk assessment

Several validated tools have been developed to estimate a person’s breast cancer risk (TABLE 3). These tools combine known risk factors and, depending on the specific tool, can provide estimates of 5-year, 10-year, or lifetime risk of breast cancer. Patients at highest risk can benefit from earlier screening, supplemental screening with breast magnetic resonance imaging (MRI), or risk reduction (see the section, “High-risk screening”). Ideally, a risk assessment should be done by age 30 so that patients at high risk can be identified for earlier or more intensive screening and for possible genetic testing in those at risk for carriage of the BRCA or other breast cancer gene pathogenic variants.^5,7

Continue to: Breast cancer screening: Efficacy and harms...

Breast cancer screening: Efficacy and harms

The earliest studies of breast cancer screening with mammography were randomized controlled trials (RCTs) that compared screened and unscreened patients aged 40 to 74. Nearly all the RCTs and numerous well-designed incidence-based and case-control studies have demonstrated that SM results in a clinically and statistically significant reduction in breast cancer mortality (TABLE 4).^4,6,8 Since the mid-1980s and continuing to the current day, SM programs are routinely recommended in the United States. In addition to the mortality benefit outlined in TABLE 4, SM also is associated with a need for less invasive treatments if breast cancer is diagnosed.^9,10

With several decades of experience, SM programs have demonstrated that multiple harms are associated with SM, including callbacks, false-positive mammograms that result in a benign biopsy, and overdiagnosis of breast cancer (TABLE 4). Overdiagnosis is a mammographic detection of a breast cancer that would not have harmed that woman in her lifetime. Overdiagnosis leads to overtreatment of breast cancers with its attendant side effects, the emotional harms of a breast cancer diagnosis, and the substantial financial cost of cancer treatment. Estimates of overdiagnosis range from 0% to 50%, with the most likely estimate of invasive breast cancer overdiagnosis from SM between 5% and 15%.^11-13 Some of these overdiagnosed cancers are due to very slow growing cancers or breast cancers that may even regress. However, the higher rates of overdiagnosis occur in older persons who are screened and in whom competing causes of mortality become more prevalent. It is estimated that overdiagnosis of invasive breast cancer in patients younger than age 60 is less than 1%, but it exceeds 14% in those older than age 80 (TABLE 4).¹⁴

A structured approach is needed to counsel patients about SM so that they understand both the substantial benefit (earlier-stage diagnosis, reduced need for treatment, reduced breast cancer and all-cause mortality) and the potential harms (callback, false-positive results, and overdiagnosis). Moreover, the relative balance of the benefits and harms are influenced throughout their lifetime by both aging and changes in their personal and family medical history.

Counseling should consider factors beyond just the performance of mammography (sensitivity and specificity), such as the patient’s current health and age (competing causes of mortality), likelihood of developing breast cancer based on risk assessment (more benefit in higher-risk persons), and the individual patient’s values on the importance of the benefits and harms. The differing emphases on mammography performance and the relative value of the benefits and harms have led experts to produce disparate national guideline recommendations (TABLE 5).

Should SM start at age 40, 45, or 50 in average-risk persons?

There is not clear consensus about the age at which to begin to recommend routine SM in patients at average risk. The National Comprehensive Cancer Network (NCCN),⁷ American Cancer Society (ACS),⁴ and the US Preventive Services Task Force (USPSTF)⁵ recommend that those at average risk start SM at age 40, 45, and 50, respectively (TABLE 5). While the guideline groups listed in TABLE 5 agree that there is level 1 evidence that SM reduces breast cancer mortality in the general population for persons starting at age 40, because the incidence of breast cancer is lower in younger persons (TABLE 6),⁴ the net population-based screening benefit is lower in this group, and the number needed to invite to screening to save a single life due to breast cancer varies.

For patients in their 40s, it is estimated that 1,904 individuals need to be invited to SM to save 1 life, whereas for patients in their 50s, it is 1,339.¹⁵ However, for patients in their 40s, the number needed to screen to save 1 life due to breast cancer decreases from 1 in 1,904 if invited to be screened to 1 in 588 if they are actually screened.¹⁶ Furthermore, if a patient is diagnosed with breast cancer at age 40–50, the likelihood of dying is reduced at least 22% and perhaps as high as 48% if her cancer was diagnosed on SM compared with an unscreened individual with a symptomatic presentation (for example, palpable mass).^4,15,17,18 Another benefit of SM in the fifth decade of life (40s) is the decreased need for more extensive treatment, including a higher risk of need for chemotherapy (odds ratio [OR], 2.81; 95% confidence interval [CI], 1.16–6.84); need for mastectomy (OR, 3.41; 95% CI, 1.36–8.52); and need for axillary lymph node dissection (OR, 5.76; 95% CI, 2.40–13.82) in unscreened (compared with screened) patients diagnosed with breast cancer.¹⁰

The harms associated with SM are not inconsequential and include callbacks (approximately 1 in 10), false-positive biopsy (approximately 1 in 100), and overdiagnosis (likely <1% of all breast cancers in persons younger than age 50). Because most patients in their 40s will not develop breast cancer (TABLE 6), the benefit of reduced breast cancer mortality will not be experienced by most in this decade of life, but they are still just as likely to experience a callback, false-positive biopsy, or the possibility of overdiagnosis. Interpretation of this balance on a population level is the crux of the various guideline groups’ development of differing recommendations as to when screening should start. Despite this seeming disagreement, all the guideline groups listed in TABLE 5 concur that persons at average risk for breast cancer should be offered SM if they desire starting at age 40 after a shared decision-making conversation that incorporates the patient’s view on the relative value of the benefits and risks.

Continue to: High-risk screening...

 

 

High-risk screening

Unlike in screening average-risk patients, there is less disagreement about screening in high-risk groups. TABLE 7 outlines the various categories and recommended strategies that qualify for screening at younger ages or more intensive screening. Adding breast MRI to SM in high-risk individuals results in both higher cancer detection rates and less interval breast cancers (cancers diagnosed between screening rounds) diagnosed compared with SM alone.^19,20 Interval breast cancer tends to be more aggressive and is used as a surrogate marker for more recognized factors, such as breast cancer mortality. In addition to less interval breast cancers, high-risk patients are more likely to be diagnosed with node-negative disease if screening breast MRI is added to SM.

Long-term mortality benefit studies using MRI have not been conducted due to the prolonged follow-up times needed. Expense, lower specificity compared with mammography (that is, more false-positive results), and need for the use of gadolinium limit more widespread use of breast MRI screening in average-risk persons.

Screening in patients with dense breasts

Half of patients undergoing SM in the United States have dense breasts (heterogeneously dense breasts, 40%; extremely dense breasts, 10%). Importantly, increasing breast density is associated with a lower cancer detection rate with SM and is an independent risk factor for developing breast cancer. While most states already require patients to be notified if they have dense breasts identified on SM, the US Food and Drug Administration will soon make breast density patient notification a national standard (see: https://delauro.house.gov/media-center/press-releases/delauro-secures-timeline-fda-rollout-breast-density-notification-rule).

Most of the risk assessment tools listed in TABLE 3 incorporate breast density into their calculation of breast cancer risk. If that calculation places a patient into one of the highest-risk groups (based on additional factors like strong family history of breast cancer, reproductive risk factors, BRCA carriage, and so on), more intensive surveillance should be recommended (TABLE 7).⁷ However, once these risk calculations are done, most persons with dense breasts will remain in an average-risk category.

Because of the frequency and risks associated with dense breasts, different and alternative strategies have been recommended for screening persons who are at average risk with dense breasts. Supplemental screening with MRI, ultrasonography, contrast-enhanced mammography, and molecular breast imaging are all being considered but have not been studied sufficiently to demonstrate mortality benefit or cost-effectiveness.

Of all the supplemental modalities used to screen patients with dense breasts, MRI has been the best studied. A large RCT in the Netherlands evaluated supplemental MRI screening in persons with extremely dense breasts after a negative mammogram.²¹ Compared with no supplemental screening, the MRI group had 17 additional cancers detected per 1,000 screened and a 50% reduction in interval breast cancers; in addition, MRI was associated with a positive predictive value of 26% for biopsies. At present, high cost and limited access to standard breast MRI has not allowed its routine use for persons with dense breasts in the United States, but this may change with more experience and more widespread introduction and experience with abbreviated (or rapid) breast MRI in the future (TABLE 8).

Equitable screening

Black persons who are diagnosed with breast cancer have a 40% higher risk of dying than White patients due to multiple factors, including systemic racial factors (implicit and unconscious bias), reduced access to care, and a lower likelihood of receiving standard of care once diagnosed.^22-24 In addition, Black patients have twice the likelihood of being diagnosed with triple-negative breast cancers, a biologically more aggressive tumor.^22-24 Among Black, Asian, and Hispanic persons diagnosed with breast cancer, one-third are diagnosed younger than age 50, which is higher than for non-Hispanic White persons. Prior to the age of 50, Black, Asian, and Hispanic patients also have a 72% more likelihood of being diagnosed with invasive breast cancer, have a 58% greater risk of advanced-stage disease, and have a 127% higher risk of dying from breast cancer compared with White patients.^25,26 Based on all of these factors, delaying SM until age 50 may adversely affect the Black, Asian, and Hispanic populations.

Persons in the LGBTQ+ community do not present for SM as frequently as the general population, often because they feel threatened or unwelcome.²⁷ Clinicians and breast imaging units should review their inclusivity policies and training to provide a welcoming and respectful environment to all persons in an effort to reduce these barriers. While data are limited and largely depend on expert opinion, current recommendations for screening in the transgender patient depend on sex assigned at birth, the type and duration of hormone use, and surgical history. In patients assigned female sex at birth, average-risk and high-risk screening recommendations are similar to those for the general population unless bilateral mastectomy has been performed.²⁸ In transfeminine patients who have used hormones for longer than 5 years, some groups recommend annual screening starting at age 40, although well-designed studies are lacking.²⁹

Continue to: We have done well, can we do better?...

 

 

We have done well, can we do better?

Screening mammography clearly has been an important and effective tool in the effort to reduce breast cancer mortality, but there are clear limitations. These include moderate sensitivity of mammography, particularly in patients with dense breasts, and a specificity that results in either callbacks (10%), breast biopsies for benign disease (1%), or the reality of overdiagnosis, which becomes increasingly important in older patients.

With the introduction of mammography in the mid-1980s, a one-size-fits-all approach has proved challenging more recently due to an increased recognition of the harms of screening. As a result of this evolving understanding, different recommendations for average-risk screening have emerged. With the advent of breast MRI, risk-based screening is an important but underutilized tool to identify highest-risk individuals, which is associated with improved cancer detection rates, reduced node-positive disease, and fewer diagnosed interval breast cancers. Assuring that nearly all of this highest-risk group is identified through routine breast cancer risk assessment remains a challenge for clinicians.

But what SM recommendations should be offered to persons who fall into an intermediate-risk group (15%–20%), very low-risk groups (<5%), or patients with dense breasts? These are challenges that could be met through novel and individualized approaches (for example, polygenic risk scoring, further research on newer modalities of screening [TABLE 8]), improved screening algorithms for persons with dense breasts, and enhanced clinician engagement to achieve universal breast cancer and BRCA risk assessment of patients by age 25 to 30.

In 2023, best practice and consensus guidelines for intermediate- and low-risk breast cancer groups remain unclear, and one of the many ongoing challenges is to further reduce the impact of breast cancer on the lives of persons affected and the recognized harms of SM.

In the meantime, there is consensus in average-risk patients to provide counseling about SM by age 40. My approach has been to counsel all average-risk patients on the risks and benefits of mammography using the acronym TIP-V:

• Use a Tool to calculate breast cancer risk (TABLE 3). If they are at high risk, provide recommendations for high-risk management (TABLE 7).⁷
• For average-risk patients, counsel that their Incidence of developing breast cancer in the next decade is approximately 1 in 70 (TABLE 6).⁴
• Provide data and guidance on the benefits of SM for patients in their 40s (mortality improvement, decreased treatment) and the likelihood of harm from breast cancer screening (10% callback, 1% benign biopsy, and <1% likelihood of overdiagnosis [TABLE 4]).^4,14,15
• Engage the patient to better understand their relative Values of the benefits and harms and make a shared decision on screening starting at age 40, 45, or 50.

Looking forward

In summary, SM remains an important tool in the effort to decrease the risk of mortality due to breast cancer. Given the limitations of SM, however, newer tools and methods—abbreviated MRI, contrast-enhanced mammography, molecular breast imaging, customized screening intervals depending on individual risk/polygenic risk score, and customized counseling and screening based on risk factors (TABLES 2 and 7)—will play an increased role in recommendations for breast cancer screening in the future. ●

SAN FRANCISCO – For patients with metastatic castration-resistant prostate cancer (mCRPC) with a BRCA alteration whose disease had already progressed with an androgen receptor pathway inhibitor (ARPI), imaging-based progression-free survival (PFS) was significantly longer through treatment with rucaparib (Rubraca, Clovis) than with any other drug chosen by their physician.

The finding, which comes from the TRITON3 clinical trial, provides evidence of clinical benefit for an indication for rucaparib that was granted an accelerated approval in May 2020.

“Rucaparib reduced the risk of progression or death by half in patients with BRCA alterations,” said lead author Alan H. Bryce, MD, medical director of the Genomic Oncology Clinic at Mayo Clinic Arizona, in Phoenix.

For the subgroup of patients with BRCA alterations, the median PFS was 11.2 months with rucaparib vs. 6.4 months (hazard ratio, 0.50; P < .001) among those who received physician’s choice of therapy, which included docetaxel or a second-generation ARPI, such as abiraterone or enzalutamide.

In another subgroup of patients whose disease had ATM alterations, the median PFS was 8.1 months with rucaparib vs. 6.8 months with physician’s choice of drug. The difference was not statistically significant.

However, the difference was significant in the intention-to-treat (ITT) population (comprising both subgroups), for whom the median PFS was 10.2 months with rucaparib vs. 6.4 months with physician’s choice of drug (HR, 0.61; P < .001 by log-rank test).

Dr. Bryce pointed out that three-quarters of the patients in the physician’s-choice arm who had progressive disease crossed over to rucaparib upon progression and that overall survival (OS) results are immature. At 62 months, median OS did not significantly differ in the BRCA subgroup (24.3 vs. 20.8 months favoring rucaparib; P = .21) or in the ITT group (23.6 vs. 20.9 months; P = .67).

Importantly, rucaparib was well tolerated. In all treatment groups, the most frequent adverse events were asthenia and fatigue, Bryce said. “There were no cases of myelodysplastic syndrome or acute myeloid leukemia reported.”

These results from the TRITON3 trial were presented at the 2023 ASCO Genitourinary Cancers Symposium and were published simultaneously in the New England Journal of Medicine.
 

Suggested benefit

Rucaparib is the first PARP inhibitor approved for use in patients with mCRPC that harbors deleterious BRCA mutations (germline and/or somatic) who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy. This prostate cancer indication was granted an accelerated approval in May 2020 by the U.S. Food and Drug Administration on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial, the forerunner of the current study.

The TRITON2 study was a single-arm clinical trial that involved three cohorts: 62 patients with a BRCA mutation (germline and/or somatic) and measurable disease; 115 patients with a BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency–positive mCRPC.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%. For the patients with measurable disease and a BRCA mutation, the objective response rate was 44%. The objective response rate was similar for those with a germline BRCA mutation.
 

Study details

The current phase 3 randomized TRITON3 clinical trial was conducted to confirm the earlier findings and to expand upon the data in mCRPC. The participants in this trial were patients with mCRPC who had specific gene alterations, including BRCA and ATM alterations, who had experienced disease progression after androgen receptor–directed therapy but who had not yet received chemotherapy.

A total of 270 men were assigned to receive rucaparib (600 mg twice daily); 135 patients received their physician’s choice of medication. Within the two study arms, 302 patients had a BRCA alteration, and 103 patients had an ATM alteration. The ITT population consisted of all the patients who had been randomly assigned to either of the two groups. A prespecified subgroup included patients with a BRCA alteration.

The primary outcome was the median duration of imaging-based PSF, as determined through independent review. Key secondary outcomes were overall survival and objective response rate.

The most common adverse events in the rucaparib group were fatigue, nausea, and anemia or decreased hemoglobin. In the control group, the most common adverse events were fatigue, diarrhea, and neuropathy. The most common events of grade 3 or higher were anemia or decreased hemoglobin, neutropenia or a decreased neutrophil count, and fatigue in the rucaparib group, and fatigue and neutropenia or a decreased neutrophil count among control patients.
 

No changes in standard of care

In a discussion of the study, Elena Castro, MD, PhD, of the Instituto de Investigación Biomédica de Málaga, Campanillas, Spain, emphasized that there is a clear benefit from the use of PARP inhibitors (such as rucaparib) for patients with BRCA alterations.

However, she highlighted the absence of convincing overall survival data and the absence of a clear benefit on PFS in the subgroup of patients with ATM alterations.

“These data raise several questions,” she noted, “such as, do patients with ATM alterations benefit at all? And should PARP inhibitors [such as rucaparib] precede or follow docetaxel therapy?”

Because of the high crossover rate, it may be possible to evaluate the directionality of docetaxel followed by PARP inhibitors and the other way around, she suggested.

Dr. Castro said that patients with BRCA alterations benefit from PARP inhibitors and are likely to derive more benefit from them than from taxanes.

“But those with ATM alterations are unlikely to benefit from rucaparib more than from taxanes,” she said.

In a comment, Hank Ng, MD, medical oncologist, NYU Langone Perlmutter Cancer Center, New York, said he is not convinced that the findings from TRITON 3 represent a new standard of care in BRCA 1/2 mutations or ATM.

“Currently, we know that, for patients with prostate cancer with BRCA1/2 or ATM, the standard of care is an androgen receptor pathway inhibitor (ARPI), such as abiraterone or enzalutamide, then docetaxel, and then a PARP inhibitor like rucaparib,” he said.

(Currently, rucaparib is indicated for use in patients with mCRPC with BRCA alterations after they have already received an ARPI and taxane-based chemotherapy.)

Dr. Ng also questioned the control arm of the TRITON 3 trial. All the participants in the trial had already experienced disease progression after treatment with a second-generation ARPI. But the physician’s choice of therapy allowed them to move on to another ARPI or to docetaxel.

Dr. NG commented that, “in almost all cases, after progression of one ARPI, switching to another ARPI does not provide much benefit – from what is visible from this abstract – and only 56% patients received docetaxel, and thus 44% received a not-beneficial treatment,” he said.

“I am not sure what the docetaxel subgroup showed, but potentially, if those numbers are convincing, we could move this [rucaparib] ahead of docetaxel,” he speculated.

However, he also pointed out that an overall survival benefit has not yet been shown; so far, the benefit that has been shown is with respect to imaging-based PFS.

Dr. Ng does agree that rucaparib is indicated in the second line after progression with one ARPI for patients who are not candidates for chemotherapy. “But this has not yet shown me that we should absolutely be offering rucaparib before docetaxel,” he said.

TRITON3 was supported by Clovis Oncology, manufacturer of rucaparib. Dr. Bryce has relationships with Bayer, Foundation Medicine, Janssen, Merck, Myovant Sciences, and Novartis and holds a patent for therapeutic targeting of cancer patients with NRG1 rearrangements. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis, Pfizer, and Roche.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – For patients with metastatic castration-resistant prostate cancer (mCRPC) with a BRCA alteration whose disease had already progressed with an androgen receptor pathway inhibitor (ARPI), imaging-based progression-free survival (PFS) was significantly longer through treatment with rucaparib (Rubraca, Clovis) than with any other drug chosen by their physician.

The finding, which comes from the TRITON3 clinical trial, provides evidence of clinical benefit for an indication for rucaparib that was granted an accelerated approval in May 2020.

“Rucaparib reduced the risk of progression or death by half in patients with BRCA alterations,” said lead author Alan H. Bryce, MD, medical director of the Genomic Oncology Clinic at Mayo Clinic Arizona, in Phoenix.

For the subgroup of patients with BRCA alterations, the median PFS was 11.2 months with rucaparib vs. 6.4 months (hazard ratio, 0.50; P < .001) among those who received physician’s choice of therapy, which included docetaxel or a second-generation ARPI, such as abiraterone or enzalutamide.

In another subgroup of patients whose disease had ATM alterations, the median PFS was 8.1 months with rucaparib vs. 6.8 months with physician’s choice of drug. The difference was not statistically significant.

However, the difference was significant in the intention-to-treat (ITT) population (comprising both subgroups), for whom the median PFS was 10.2 months with rucaparib vs. 6.4 months with physician’s choice of drug (HR, 0.61; P < .001 by log-rank test).

Dr. Bryce pointed out that three-quarters of the patients in the physician’s-choice arm who had progressive disease crossed over to rucaparib upon progression and that overall survival (OS) results are immature. At 62 months, median OS did not significantly differ in the BRCA subgroup (24.3 vs. 20.8 months favoring rucaparib; P = .21) or in the ITT group (23.6 vs. 20.9 months; P = .67).

Importantly, rucaparib was well tolerated. In all treatment groups, the most frequent adverse events were asthenia and fatigue, Bryce said. “There were no cases of myelodysplastic syndrome or acute myeloid leukemia reported.”

These results from the TRITON3 trial were presented at the 2023 ASCO Genitourinary Cancers Symposium and were published simultaneously in the New England Journal of Medicine.
 

Suggested benefit

Rucaparib is the first PARP inhibitor approved for use in patients with mCRPC that harbors deleterious BRCA mutations (germline and/or somatic) who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy. This prostate cancer indication was granted an accelerated approval in May 2020 by the U.S. Food and Drug Administration on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial, the forerunner of the current study.

The TRITON2 study was a single-arm clinical trial that involved three cohorts: 62 patients with a BRCA mutation (germline and/or somatic) and measurable disease; 115 patients with a BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency–positive mCRPC.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%. For the patients with measurable disease and a BRCA mutation, the objective response rate was 44%. The objective response rate was similar for those with a germline BRCA mutation.
 

Study details

The current phase 3 randomized TRITON3 clinical trial was conducted to confirm the earlier findings and to expand upon the data in mCRPC. The participants in this trial were patients with mCRPC who had specific gene alterations, including BRCA and ATM alterations, who had experienced disease progression after androgen receptor–directed therapy but who had not yet received chemotherapy.

A total of 270 men were assigned to receive rucaparib (600 mg twice daily); 135 patients received their physician’s choice of medication. Within the two study arms, 302 patients had a BRCA alteration, and 103 patients had an ATM alteration. The ITT population consisted of all the patients who had been randomly assigned to either of the two groups. A prespecified subgroup included patients with a BRCA alteration.

The primary outcome was the median duration of imaging-based PSF, as determined through independent review. Key secondary outcomes were overall survival and objective response rate.

The most common adverse events in the rucaparib group were fatigue, nausea, and anemia or decreased hemoglobin. In the control group, the most common adverse events were fatigue, diarrhea, and neuropathy. The most common events of grade 3 or higher were anemia or decreased hemoglobin, neutropenia or a decreased neutrophil count, and fatigue in the rucaparib group, and fatigue and neutropenia or a decreased neutrophil count among control patients.
 

No changes in standard of care

In a discussion of the study, Elena Castro, MD, PhD, of the Instituto de Investigación Biomédica de Málaga, Campanillas, Spain, emphasized that there is a clear benefit from the use of PARP inhibitors (such as rucaparib) for patients with BRCA alterations.

However, she highlighted the absence of convincing overall survival data and the absence of a clear benefit on PFS in the subgroup of patients with ATM alterations.

“These data raise several questions,” she noted, “such as, do patients with ATM alterations benefit at all? And should PARP inhibitors [such as rucaparib] precede or follow docetaxel therapy?”

Because of the high crossover rate, it may be possible to evaluate the directionality of docetaxel followed by PARP inhibitors and the other way around, she suggested.

Dr. Castro said that patients with BRCA alterations benefit from PARP inhibitors and are likely to derive more benefit from them than from taxanes.

“But those with ATM alterations are unlikely to benefit from rucaparib more than from taxanes,” she said.

In a comment, Hank Ng, MD, medical oncologist, NYU Langone Perlmutter Cancer Center, New York, said he is not convinced that the findings from TRITON 3 represent a new standard of care in BRCA 1/2 mutations or ATM.

“Currently, we know that, for patients with prostate cancer with BRCA1/2 or ATM, the standard of care is an androgen receptor pathway inhibitor (ARPI), such as abiraterone or enzalutamide, then docetaxel, and then a PARP inhibitor like rucaparib,” he said.

(Currently, rucaparib is indicated for use in patients with mCRPC with BRCA alterations after they have already received an ARPI and taxane-based chemotherapy.)

Dr. Ng also questioned the control arm of the TRITON 3 trial. All the participants in the trial had already experienced disease progression after treatment with a second-generation ARPI. But the physician’s choice of therapy allowed them to move on to another ARPI or to docetaxel.

Dr. NG commented that, “in almost all cases, after progression of one ARPI, switching to another ARPI does not provide much benefit – from what is visible from this abstract – and only 56% patients received docetaxel, and thus 44% received a not-beneficial treatment,” he said.

“I am not sure what the docetaxel subgroup showed, but potentially, if those numbers are convincing, we could move this [rucaparib] ahead of docetaxel,” he speculated.

However, he also pointed out that an overall survival benefit has not yet been shown; so far, the benefit that has been shown is with respect to imaging-based PFS.

Dr. Ng does agree that rucaparib is indicated in the second line after progression with one ARPI for patients who are not candidates for chemotherapy. “But this has not yet shown me that we should absolutely be offering rucaparib before docetaxel,” he said.

TRITON3 was supported by Clovis Oncology, manufacturer of rucaparib. Dr. Bryce has relationships with Bayer, Foundation Medicine, Janssen, Merck, Myovant Sciences, and Novartis and holds a patent for therapeutic targeting of cancer patients with NRG1 rearrangements. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis, Pfizer, and Roche.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – For patients with metastatic castration-resistant prostate cancer (mCRPC) with a BRCA alteration whose disease had already progressed with an androgen receptor pathway inhibitor (ARPI), imaging-based progression-free survival (PFS) was significantly longer through treatment with rucaparib (Rubraca, Clovis) than with any other drug chosen by their physician.

The finding, which comes from the TRITON3 clinical trial, provides evidence of clinical benefit for an indication for rucaparib that was granted an accelerated approval in May 2020.

“Rucaparib reduced the risk of progression or death by half in patients with BRCA alterations,” said lead author Alan H. Bryce, MD, medical director of the Genomic Oncology Clinic at Mayo Clinic Arizona, in Phoenix.

For the subgroup of patients with BRCA alterations, the median PFS was 11.2 months with rucaparib vs. 6.4 months (hazard ratio, 0.50; P < .001) among those who received physician’s choice of therapy, which included docetaxel or a second-generation ARPI, such as abiraterone or enzalutamide.

In another subgroup of patients whose disease had ATM alterations, the median PFS was 8.1 months with rucaparib vs. 6.8 months with physician’s choice of drug. The difference was not statistically significant.

However, the difference was significant in the intention-to-treat (ITT) population (comprising both subgroups), for whom the median PFS was 10.2 months with rucaparib vs. 6.4 months with physician’s choice of drug (HR, 0.61; P < .001 by log-rank test).

Dr. Bryce pointed out that three-quarters of the patients in the physician’s-choice arm who had progressive disease crossed over to rucaparib upon progression and that overall survival (OS) results are immature. At 62 months, median OS did not significantly differ in the BRCA subgroup (24.3 vs. 20.8 months favoring rucaparib; P = .21) or in the ITT group (23.6 vs. 20.9 months; P = .67).

Importantly, rucaparib was well tolerated. In all treatment groups, the most frequent adverse events were asthenia and fatigue, Bryce said. “There were no cases of myelodysplastic syndrome or acute myeloid leukemia reported.”

These results from the TRITON3 trial were presented at the 2023 ASCO Genitourinary Cancers Symposium and were published simultaneously in the New England Journal of Medicine.
 

Suggested benefit

Rucaparib is the first PARP inhibitor approved for use in patients with mCRPC that harbors deleterious BRCA mutations (germline and/or somatic) who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy. This prostate cancer indication was granted an accelerated approval in May 2020 by the U.S. Food and Drug Administration on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial, the forerunner of the current study.

The TRITON2 study was a single-arm clinical trial that involved three cohorts: 62 patients with a BRCA mutation (germline and/or somatic) and measurable disease; 115 patients with a BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency–positive mCRPC.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%. For the patients with measurable disease and a BRCA mutation, the objective response rate was 44%. The objective response rate was similar for those with a germline BRCA mutation.
 

Study details

The current phase 3 randomized TRITON3 clinical trial was conducted to confirm the earlier findings and to expand upon the data in mCRPC. The participants in this trial were patients with mCRPC who had specific gene alterations, including BRCA and ATM alterations, who had experienced disease progression after androgen receptor–directed therapy but who had not yet received chemotherapy.

A total of 270 men were assigned to receive rucaparib (600 mg twice daily); 135 patients received their physician’s choice of medication. Within the two study arms, 302 patients had a BRCA alteration, and 103 patients had an ATM alteration. The ITT population consisted of all the patients who had been randomly assigned to either of the two groups. A prespecified subgroup included patients with a BRCA alteration.

The primary outcome was the median duration of imaging-based PSF, as determined through independent review. Key secondary outcomes were overall survival and objective response rate.

The most common adverse events in the rucaparib group were fatigue, nausea, and anemia or decreased hemoglobin. In the control group, the most common adverse events were fatigue, diarrhea, and neuropathy. The most common events of grade 3 or higher were anemia or decreased hemoglobin, neutropenia or a decreased neutrophil count, and fatigue in the rucaparib group, and fatigue and neutropenia or a decreased neutrophil count among control patients.
 

No changes in standard of care

In a discussion of the study, Elena Castro, MD, PhD, of the Instituto de Investigación Biomédica de Málaga, Campanillas, Spain, emphasized that there is a clear benefit from the use of PARP inhibitors (such as rucaparib) for patients with BRCA alterations.

However, she highlighted the absence of convincing overall survival data and the absence of a clear benefit on PFS in the subgroup of patients with ATM alterations.

“These data raise several questions,” she noted, “such as, do patients with ATM alterations benefit at all? And should PARP inhibitors [such as rucaparib] precede or follow docetaxel therapy?”

Because of the high crossover rate, it may be possible to evaluate the directionality of docetaxel followed by PARP inhibitors and the other way around, she suggested.

Dr. Castro said that patients with BRCA alterations benefit from PARP inhibitors and are likely to derive more benefit from them than from taxanes.

“But those with ATM alterations are unlikely to benefit from rucaparib more than from taxanes,” she said.

In a comment, Hank Ng, MD, medical oncologist, NYU Langone Perlmutter Cancer Center, New York, said he is not convinced that the findings from TRITON 3 represent a new standard of care in BRCA 1/2 mutations or ATM.

“Currently, we know that, for patients with prostate cancer with BRCA1/2 or ATM, the standard of care is an androgen receptor pathway inhibitor (ARPI), such as abiraterone or enzalutamide, then docetaxel, and then a PARP inhibitor like rucaparib,” he said.

(Currently, rucaparib is indicated for use in patients with mCRPC with BRCA alterations after they have already received an ARPI and taxane-based chemotherapy.)

Dr. Ng also questioned the control arm of the TRITON 3 trial. All the participants in the trial had already experienced disease progression after treatment with a second-generation ARPI. But the physician’s choice of therapy allowed them to move on to another ARPI or to docetaxel.

Dr. NG commented that, “in almost all cases, after progression of one ARPI, switching to another ARPI does not provide much benefit – from what is visible from this abstract – and only 56% patients received docetaxel, and thus 44% received a not-beneficial treatment,” he said.

“I am not sure what the docetaxel subgroup showed, but potentially, if those numbers are convincing, we could move this [rucaparib] ahead of docetaxel,” he speculated.

However, he also pointed out that an overall survival benefit has not yet been shown; so far, the benefit that has been shown is with respect to imaging-based PFS.

Dr. Ng does agree that rucaparib is indicated in the second line after progression with one ARPI for patients who are not candidates for chemotherapy. “But this has not yet shown me that we should absolutely be offering rucaparib before docetaxel,” he said.

TRITON3 was supported by Clovis Oncology, manufacturer of rucaparib. Dr. Bryce has relationships with Bayer, Foundation Medicine, Janssen, Merck, Myovant Sciences, and Novartis and holds a patent for therapeutic targeting of cancer patients with NRG1 rearrangements. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis, Pfizer, and Roche.

A version of this article first appeared on Medscape.com.

Patients with intermediate-risk acute myeloid leukemia (AML) who underwent allogeneic hematopoietic cell transplantation (HCT) after their first complete remission showed improvements in disease-free survival but had similar overall survival rates, compared with patients treated with consolidation chemotherapy alone.

Notably, all patients who relapsed after consolidation chemotherapy were able to receive allogeneic HCT, suggesting that transplantation may be safely delayed in some patients until their first relapse.

“The results of this randomized clinical trial indicate that the probability of survival after [allogeneic] HCT is not superior to that of conventional consolidation chemotherapy” among patients 60 years or younger with intermediate-risk AML, the authors concluded.

However, two experts highlighted several caveats to the study, which suggest the results may not translate to current clinical practice.

The study was published online in JAMA Oncology.

Approximately 50%-70% of patients with AML who receive intensive induction chemotherapy for AML and achieve a first complete remission are referred for post-remission therapy.

While consolidation chemotherapy with high-dose cytarabine has shown a benefit for those with a favorable risk profile, patients considered high-risk with adequate performance status may be candidates for allogeneic HCT.

However, determining the optimal post-remission treatment option for patients who fall into the intermediate-risk category can be more challenging.

To compare outcomes among intermediate-risk patients, researchers from Germany conducted a multicenter trial, enrolling 143 adults aged 60 or younger with intermediate-risk AML who had achieved first complete remission or complete remission with incomplete blood cell count recovery following conventional induction therapy.

The patients, who had a mean age of 48.2 years, were randomly assigned to consolidation treatment with allogeneic HCT (n = 76) or chemotherapy with high-dose cytarabine (n = 67), with the option for salvage HCT in the case of relapse. Overall, 12 patients in the HCT group received one consolidation course of high-dose cytarabine after achieving complete remission to bridge until allogeneic HCT, while all other patients in this group received allogeneic HCT directly after induction therapy.

Overall, disease-free survival at 2 years was significantly higher in the allogeneic HCT group (69%), compared with the consolidation therapy group (40%; P = .001). And the cumulative incidence of relapse at 2 years in the allogeneic HCT group was also lower, at 20%, compared with 58% in the consolidation therapy group (P < .001).

The overall survival data, however, painted a slightly more complex picture. In the intention-to-treat analysis, the probability of survival at 2 years was similar between the allogeneic HCT group (74%, or 56 of 76 patients), compared with consolidation chemotherapy (84%, or 56 of 67 patients; P = .22).

In addition, the rates of nonrelapse mortality at 2 years were higher in the allogeneic HCT group (9%) versus chemotherapy (2%; P = .005).

Although the rate of nonrelapse mortality was higher with allogeneic HCT, the relatively low rate with each treatment strategies was “an important and rewarding finding,” the authors noted. “This achievement is clearly due to the availability of less toxic but still effective conditioning therapies and modern antiviral and antifungal prophylaxis.”

In addition, among the 41 patients who relapsed after consolidation chemotherapy, all received allogeneic HCT, and the authors observed no significant differences between the groups in terms of health-related quality of life measures.
 

Results ‘may not translate to real-life clinical practice’

An important caveat is that the findings do not reflect some key updated strategies currently used in clinical practice, said Diego Adrianzen Herrera, MD, from the University of Vermont’s Larner College of Medicine, Burlington, who was not involved in the study.

“A charitable interpretation of the results is that a clear, large survival benefit of transplant in first complete remission is not apparent, which in turn can inform decision-making in certain circumstances for patients meeting the trial criteria, [including] younger patients with a readily available donor,” he told this news organization.

“However, risk stratification strategies currently used were not followed,” he said.

For instance, molecular risk stratification was not universally used, which may have led the researchers to overrepresent the number of patients considered to have favorable risk disease and “could have skewed the results in favor of the chemotherapy arm,” he explained.

In addition, minimal residual disease surveillance by flow cytometry was not used. Plus, Dr. Herrera added, in practice, not all patients can be salvaged and taken to HCT when in their second complete remission, or even achieve complete remission again.

“Unfortunately, these issues make the clinical significance of these results limited,” he concluded.

Margaret Kasner, MD, who was not associated with the research, agreed that aspects of the study design may not translate to real-life clinical practice, particularly in terms of quality-of-life outcomes.

“Although the [study] showed no difference in quality of life in the patient groups, this is likely due to the patient selection,” Dr. Kasner, of the Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, said in an interview. “Most patients do not allow themselves to be randomized between these two very different strategies, so those who are willing to be randomized may be a different population in terms how their quality of life is affected by relapse.”

The authors acknowledged some of these limitations, adding that the routine use of minimal residual disease monitoring in some patients was only established once the trial was underway, and the number of patients with complete minimal residual disease was therefore limited.

In addition, Dr. Herrera explained that because HCT involves significant disruptions to daily life and extensive follow-up and monitoring, decisions to use the strategy are not taken lightly by clinicians or patients.

“This is a major issue,” he said. “HCT remains a therapeutic option which causes significant apprehension to patients.”

Nevertheless, “in my experience most patients would prefer an upfront strategy if there is a definitive need for transplant,” he added. “I think the main question patients have is whether they absolutely need an HCT and how can we better identify up front who will be in the relapse-free group at 2 years.”

The study received grant funding from the Deutsche Forschungsgemeinschaft. The authors’ disclosures are detailed in the original article. Dr. Herrera and Dr. Kasner report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Patients with intermediate-risk acute myeloid leukemia (AML) who underwent allogeneic hematopoietic cell transplantation (HCT) after their first complete remission showed improvements in disease-free survival but had similar overall survival rates, compared with patients treated with consolidation chemotherapy alone.

Notably, all patients who relapsed after consolidation chemotherapy were able to receive allogeneic HCT, suggesting that transplantation may be safely delayed in some patients until their first relapse.

“The results of this randomized clinical trial indicate that the probability of survival after [allogeneic] HCT is not superior to that of conventional consolidation chemotherapy” among patients 60 years or younger with intermediate-risk AML, the authors concluded.

However, two experts highlighted several caveats to the study, which suggest the results may not translate to current clinical practice.

The study was published online in JAMA Oncology.

Approximately 50%-70% of patients with AML who receive intensive induction chemotherapy for AML and achieve a first complete remission are referred for post-remission therapy.

While consolidation chemotherapy with high-dose cytarabine has shown a benefit for those with a favorable risk profile, patients considered high-risk with adequate performance status may be candidates for allogeneic HCT.

However, determining the optimal post-remission treatment option for patients who fall into the intermediate-risk category can be more challenging.

To compare outcomes among intermediate-risk patients, researchers from Germany conducted a multicenter trial, enrolling 143 adults aged 60 or younger with intermediate-risk AML who had achieved first complete remission or complete remission with incomplete blood cell count recovery following conventional induction therapy.

The patients, who had a mean age of 48.2 years, were randomly assigned to consolidation treatment with allogeneic HCT (n = 76) or chemotherapy with high-dose cytarabine (n = 67), with the option for salvage HCT in the case of relapse. Overall, 12 patients in the HCT group received one consolidation course of high-dose cytarabine after achieving complete remission to bridge until allogeneic HCT, while all other patients in this group received allogeneic HCT directly after induction therapy.

Overall, disease-free survival at 2 years was significantly higher in the allogeneic HCT group (69%), compared with the consolidation therapy group (40%; P = .001). And the cumulative incidence of relapse at 2 years in the allogeneic HCT group was also lower, at 20%, compared with 58% in the consolidation therapy group (P < .001).

The overall survival data, however, painted a slightly more complex picture. In the intention-to-treat analysis, the probability of survival at 2 years was similar between the allogeneic HCT group (74%, or 56 of 76 patients), compared with consolidation chemotherapy (84%, or 56 of 67 patients; P = .22).

In addition, the rates of nonrelapse mortality at 2 years were higher in the allogeneic HCT group (9%) versus chemotherapy (2%; P = .005).

Although the rate of nonrelapse mortality was higher with allogeneic HCT, the relatively low rate with each treatment strategies was “an important and rewarding finding,” the authors noted. “This achievement is clearly due to the availability of less toxic but still effective conditioning therapies and modern antiviral and antifungal prophylaxis.”

In addition, among the 41 patients who relapsed after consolidation chemotherapy, all received allogeneic HCT, and the authors observed no significant differences between the groups in terms of health-related quality of life measures.
 

Results ‘may not translate to real-life clinical practice’

An important caveat is that the findings do not reflect some key updated strategies currently used in clinical practice, said Diego Adrianzen Herrera, MD, from the University of Vermont’s Larner College of Medicine, Burlington, who was not involved in the study.

“A charitable interpretation of the results is that a clear, large survival benefit of transplant in first complete remission is not apparent, which in turn can inform decision-making in certain circumstances for patients meeting the trial criteria, [including] younger patients with a readily available donor,” he told this news organization.

“However, risk stratification strategies currently used were not followed,” he said.

For instance, molecular risk stratification was not universally used, which may have led the researchers to overrepresent the number of patients considered to have favorable risk disease and “could have skewed the results in favor of the chemotherapy arm,” he explained.

In addition, minimal residual disease surveillance by flow cytometry was not used. Plus, Dr. Herrera added, in practice, not all patients can be salvaged and taken to HCT when in their second complete remission, or even achieve complete remission again.

“Unfortunately, these issues make the clinical significance of these results limited,” he concluded.

Margaret Kasner, MD, who was not associated with the research, agreed that aspects of the study design may not translate to real-life clinical practice, particularly in terms of quality-of-life outcomes.

“Although the [study] showed no difference in quality of life in the patient groups, this is likely due to the patient selection,” Dr. Kasner, of the Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, said in an interview. “Most patients do not allow themselves to be randomized between these two very different strategies, so those who are willing to be randomized may be a different population in terms how their quality of life is affected by relapse.”

The authors acknowledged some of these limitations, adding that the routine use of minimal residual disease monitoring in some patients was only established once the trial was underway, and the number of patients with complete minimal residual disease was therefore limited.

In addition, Dr. Herrera explained that because HCT involves significant disruptions to daily life and extensive follow-up and monitoring, decisions to use the strategy are not taken lightly by clinicians or patients.

“This is a major issue,” he said. “HCT remains a therapeutic option which causes significant apprehension to patients.”

Nevertheless, “in my experience most patients would prefer an upfront strategy if there is a definitive need for transplant,” he added. “I think the main question patients have is whether they absolutely need an HCT and how can we better identify up front who will be in the relapse-free group at 2 years.”

The study received grant funding from the Deutsche Forschungsgemeinschaft. The authors’ disclosures are detailed in the original article. Dr. Herrera and Dr. Kasner report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Patients with intermediate-risk acute myeloid leukemia (AML) who underwent allogeneic hematopoietic cell transplantation (HCT) after their first complete remission showed improvements in disease-free survival but had similar overall survival rates, compared with patients treated with consolidation chemotherapy alone.

Notably, all patients who relapsed after consolidation chemotherapy were able to receive allogeneic HCT, suggesting that transplantation may be safely delayed in some patients until their first relapse.

“The results of this randomized clinical trial indicate that the probability of survival after [allogeneic] HCT is not superior to that of conventional consolidation chemotherapy” among patients 60 years or younger with intermediate-risk AML, the authors concluded.

However, two experts highlighted several caveats to the study, which suggest the results may not translate to current clinical practice.

The study was published online in JAMA Oncology.

Approximately 50%-70% of patients with AML who receive intensive induction chemotherapy for AML and achieve a first complete remission are referred for post-remission therapy.

While consolidation chemotherapy with high-dose cytarabine has shown a benefit for those with a favorable risk profile, patients considered high-risk with adequate performance status may be candidates for allogeneic HCT.

However, determining the optimal post-remission treatment option for patients who fall into the intermediate-risk category can be more challenging.

To compare outcomes among intermediate-risk patients, researchers from Germany conducted a multicenter trial, enrolling 143 adults aged 60 or younger with intermediate-risk AML who had achieved first complete remission or complete remission with incomplete blood cell count recovery following conventional induction therapy.

The patients, who had a mean age of 48.2 years, were randomly assigned to consolidation treatment with allogeneic HCT (n = 76) or chemotherapy with high-dose cytarabine (n = 67), with the option for salvage HCT in the case of relapse. Overall, 12 patients in the HCT group received one consolidation course of high-dose cytarabine after achieving complete remission to bridge until allogeneic HCT, while all other patients in this group received allogeneic HCT directly after induction therapy.

Overall, disease-free survival at 2 years was significantly higher in the allogeneic HCT group (69%), compared with the consolidation therapy group (40%; P = .001). And the cumulative incidence of relapse at 2 years in the allogeneic HCT group was also lower, at 20%, compared with 58% in the consolidation therapy group (P < .001).

The overall survival data, however, painted a slightly more complex picture. In the intention-to-treat analysis, the probability of survival at 2 years was similar between the allogeneic HCT group (74%, or 56 of 76 patients), compared with consolidation chemotherapy (84%, or 56 of 67 patients; P = .22).

In addition, the rates of nonrelapse mortality at 2 years were higher in the allogeneic HCT group (9%) versus chemotherapy (2%; P = .005).

Although the rate of nonrelapse mortality was higher with allogeneic HCT, the relatively low rate with each treatment strategies was “an important and rewarding finding,” the authors noted. “This achievement is clearly due to the availability of less toxic but still effective conditioning therapies and modern antiviral and antifungal prophylaxis.”

In addition, among the 41 patients who relapsed after consolidation chemotherapy, all received allogeneic HCT, and the authors observed no significant differences between the groups in terms of health-related quality of life measures.
 

Results ‘may not translate to real-life clinical practice’

An important caveat is that the findings do not reflect some key updated strategies currently used in clinical practice, said Diego Adrianzen Herrera, MD, from the University of Vermont’s Larner College of Medicine, Burlington, who was not involved in the study.

“A charitable interpretation of the results is that a clear, large survival benefit of transplant in first complete remission is not apparent, which in turn can inform decision-making in certain circumstances for patients meeting the trial criteria, [including] younger patients with a readily available donor,” he told this news organization.

“However, risk stratification strategies currently used were not followed,” he said.

For instance, molecular risk stratification was not universally used, which may have led the researchers to overrepresent the number of patients considered to have favorable risk disease and “could have skewed the results in favor of the chemotherapy arm,” he explained.

In addition, minimal residual disease surveillance by flow cytometry was not used. Plus, Dr. Herrera added, in practice, not all patients can be salvaged and taken to HCT when in their second complete remission, or even achieve complete remission again.

“Unfortunately, these issues make the clinical significance of these results limited,” he concluded.

Margaret Kasner, MD, who was not associated with the research, agreed that aspects of the study design may not translate to real-life clinical practice, particularly in terms of quality-of-life outcomes.

“Although the [study] showed no difference in quality of life in the patient groups, this is likely due to the patient selection,” Dr. Kasner, of the Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, said in an interview. “Most patients do not allow themselves to be randomized between these two very different strategies, so those who are willing to be randomized may be a different population in terms how their quality of life is affected by relapse.”

The authors acknowledged some of these limitations, adding that the routine use of minimal residual disease monitoring in some patients was only established once the trial was underway, and the number of patients with complete minimal residual disease was therefore limited.

In addition, Dr. Herrera explained that because HCT involves significant disruptions to daily life and extensive follow-up and monitoring, decisions to use the strategy are not taken lightly by clinicians or patients.

“This is a major issue,” he said. “HCT remains a therapeutic option which causes significant apprehension to patients.”

Nevertheless, “in my experience most patients would prefer an upfront strategy if there is a definitive need for transplant,” he added. “I think the main question patients have is whether they absolutely need an HCT and how can we better identify up front who will be in the relapse-free group at 2 years.”

The study received grant funding from the Deutsche Forschungsgemeinschaft. The authors’ disclosures are detailed in the original article. Dr. Herrera and Dr. Kasner report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Thanks to treatment advancements, patients with chronic lymphocytic leukemia (CLL) are living much longer – and at greater risk of developing other types of cancer. A new Dutch study has found that patients with CLL face higher risks of second primary malignancies (SPM) than the rest of the population, especially those who were treated with antineoplastic therapy.

The report, which appeared in January in Blood Cancer Journal, found that patients diagnosed with CLL between 1989 and 2019 were 63% more likely to were diagnosed with SPM than a matched population: standardized incidence ratio = 1.63, 95% confidence interval (CI), 1.59-1.68.

“Our results provide patients and their treating physicians with an overview of the risk of SPM development. This information can be used in treatment decision-making and for planning appropriate surveillance activities and interventions,” study lead author Lina van der Straten, MD, PhD, of the Albert Schweitzer Hospital and Erasmus University Medical Center in the Netherlands, said in an interview.

Ohio State University hematologist David Bond, MD, who’s familiar with the findings, said in an interview that “it’s been well-established that patients with CLL are at increased risk for second primary malignancies. This is thought to be due to impaired immune surveillance and possibly carcinogenic effects of CLL treatments.” It’s not clear, he said, “whether the rate of second cancers differs between chemoimmunotherapy-treated patients and those receiving newer oral kinase inhibitors.”

Previous research into CLL and SPM has been sparse, Dr. van der Straten said, and most studies haven’t looked at SPM over time and taken into account the widespread use of chemoimmunotherapy and agents such as ibrutinib and venetoclax.

It’s important to study this topic, she said, since “cancers diagnosed after the CLL diagnosis can outweigh the improved longevity and contribute to excess morbidity and mortality in long-term CLL survivors.”

With the help of the Netherlands Cancer Registry, researchers tracked 24,815 patients with CLL who were diagnosed over the 20-year period; 4,369 developed SPM. “We demonstrated that the risk of SPM development was higher than in the general population with an excess of 125 malignancies per 10,000 person-years in the CLL cohort,” Dr. van der Straten said. “The risk of SPM development was found to be heightened in solid and hematological cancers. Patients with CLL had an increased risk of developing cancers at the following sites or types: skin, acute myeloid leukemia, soft-tissue sarcomas, thyroid, kidney, unknown primary localization, non-Hodgkin lymphomas, lung and bronchus, and colon and rectum.”

Specifically, the study reports that “elevated risk was observed for solid (SIR = 1.67; 95% CI, 1.65-1.75) and hematological SPMs (SIR = 1.42; 95% CI, 1.24-1.62). The highest risk for SPMs was noted beyond 5 years post diagnosis (SIR = 1.70; 95% CI, 1.62-1.77), for male individuals (SIR = 1.70; 95% CI, 1.64-1.77), and patients aged 18-69 years (SR = 1.92; 95% CI, 1.79-2.05).

“Patients with CLL exposed to treatment have a higher risk of SPM development than patients who will never receive therapy,” Dr. van der Straten said. Research has shown that “treatment with fludarabine, cyclophosphamide, and rituximab has been associated with a 2.38 increased risk for SPM development, particularly acute myeloid leukemia. Indeed, we found an increased risk for hematological malignancies in patients diagnosed between 2003-2009 and 2010-2019, which might be explained by the broader administration of fludarabine-based strategies in these calendar periods.”

Multiple factors could explain the higher risk of SPM in patients with CLL, including “a dysregulated immune system, treatment-related effects, and surveillance bias,” Dr. van der Straten said. “In addition, it is proposed that the immune dysfunctional nature of CLL might enhance the effect of common carcinogens, such as UV exposure and smoking, in increasing the probability of skin and respiratory cancers.”

She added that “the risk and the spectrum of SPMs were comparable for the 2003-2009 and 2010-2019 periods, suggesting that both the introduction of chemoimmunotherapy and, in part, targeted therapies did not dramatically alter the SPM landscape. However, due to the short follow-up period for the small cohort of patients receiving targeted therapies, further research is warranted.”

Dr. Bond said the findings “are largely in line with prior studies and strengthen their conclusions. Immune surveillance appears to be critical to reducing the risk for some but not all malignancies including lung cancer and melanoma, and the treatments given for CLL can cause immune suppression and thus may increase the risk.”

Moving forward, he said, “this research highlights the importance of second cancers to patients with CLL. It also highlights the need for secondary cancer screening for CLL patients, patient education to avoid known cancer risk factors including smoking and excess UV light exposure, and the need as a field to continue to invest in research into characteristics of second cancers and mitigation strategies.”

Study funding was not reported. The authors and Dr. Bond report no disclosures.

Thanks to treatment advancements, patients with chronic lymphocytic leukemia (CLL) are living much longer – and at greater risk of developing other types of cancer. A new Dutch study has found that patients with CLL face higher risks of second primary malignancies (SPM) than the rest of the population, especially those who were treated with antineoplastic therapy.

The report, which appeared in January in Blood Cancer Journal, found that patients diagnosed with CLL between 1989 and 2019 were 63% more likely to were diagnosed with SPM than a matched population: standardized incidence ratio = 1.63, 95% confidence interval (CI), 1.59-1.68.

“Our results provide patients and their treating physicians with an overview of the risk of SPM development. This information can be used in treatment decision-making and for planning appropriate surveillance activities and interventions,” study lead author Lina van der Straten, MD, PhD, of the Albert Schweitzer Hospital and Erasmus University Medical Center in the Netherlands, said in an interview.

Ohio State University hematologist David Bond, MD, who’s familiar with the findings, said in an interview that “it’s been well-established that patients with CLL are at increased risk for second primary malignancies. This is thought to be due to impaired immune surveillance and possibly carcinogenic effects of CLL treatments.” It’s not clear, he said, “whether the rate of second cancers differs between chemoimmunotherapy-treated patients and those receiving newer oral kinase inhibitors.”

Previous research into CLL and SPM has been sparse, Dr. van der Straten said, and most studies haven’t looked at SPM over time and taken into account the widespread use of chemoimmunotherapy and agents such as ibrutinib and venetoclax.

It’s important to study this topic, she said, since “cancers diagnosed after the CLL diagnosis can outweigh the improved longevity and contribute to excess morbidity and mortality in long-term CLL survivors.”

With the help of the Netherlands Cancer Registry, researchers tracked 24,815 patients with CLL who were diagnosed over the 20-year period; 4,369 developed SPM. “We demonstrated that the risk of SPM development was higher than in the general population with an excess of 125 malignancies per 10,000 person-years in the CLL cohort,” Dr. van der Straten said. “The risk of SPM development was found to be heightened in solid and hematological cancers. Patients with CLL had an increased risk of developing cancers at the following sites or types: skin, acute myeloid leukemia, soft-tissue sarcomas, thyroid, kidney, unknown primary localization, non-Hodgkin lymphomas, lung and bronchus, and colon and rectum.”

Specifically, the study reports that “elevated risk was observed for solid (SIR = 1.67; 95% CI, 1.65-1.75) and hematological SPMs (SIR = 1.42; 95% CI, 1.24-1.62). The highest risk for SPMs was noted beyond 5 years post diagnosis (SIR = 1.70; 95% CI, 1.62-1.77), for male individuals (SIR = 1.70; 95% CI, 1.64-1.77), and patients aged 18-69 years (SR = 1.92; 95% CI, 1.79-2.05).

“Patients with CLL exposed to treatment have a higher risk of SPM development than patients who will never receive therapy,” Dr. van der Straten said. Research has shown that “treatment with fludarabine, cyclophosphamide, and rituximab has been associated with a 2.38 increased risk for SPM development, particularly acute myeloid leukemia. Indeed, we found an increased risk for hematological malignancies in patients diagnosed between 2003-2009 and 2010-2019, which might be explained by the broader administration of fludarabine-based strategies in these calendar periods.”

Multiple factors could explain the higher risk of SPM in patients with CLL, including “a dysregulated immune system, treatment-related effects, and surveillance bias,” Dr. van der Straten said. “In addition, it is proposed that the immune dysfunctional nature of CLL might enhance the effect of common carcinogens, such as UV exposure and smoking, in increasing the probability of skin and respiratory cancers.”

She added that “the risk and the spectrum of SPMs were comparable for the 2003-2009 and 2010-2019 periods, suggesting that both the introduction of chemoimmunotherapy and, in part, targeted therapies did not dramatically alter the SPM landscape. However, due to the short follow-up period for the small cohort of patients receiving targeted therapies, further research is warranted.”

Dr. Bond said the findings “are largely in line with prior studies and strengthen their conclusions. Immune surveillance appears to be critical to reducing the risk for some but not all malignancies including lung cancer and melanoma, and the treatments given for CLL can cause immune suppression and thus may increase the risk.”

Moving forward, he said, “this research highlights the importance of second cancers to patients with CLL. It also highlights the need for secondary cancer screening for CLL patients, patient education to avoid known cancer risk factors including smoking and excess UV light exposure, and the need as a field to continue to invest in research into characteristics of second cancers and mitigation strategies.”

Study funding was not reported. The authors and Dr. Bond report no disclosures.

Thanks to treatment advancements, patients with chronic lymphocytic leukemia (CLL) are living much longer – and at greater risk of developing other types of cancer. A new Dutch study has found that patients with CLL face higher risks of second primary malignancies (SPM) than the rest of the population, especially those who were treated with antineoplastic therapy.

The report, which appeared in January in Blood Cancer Journal, found that patients diagnosed with CLL between 1989 and 2019 were 63% more likely to were diagnosed with SPM than a matched population: standardized incidence ratio = 1.63, 95% confidence interval (CI), 1.59-1.68.

“Our results provide patients and their treating physicians with an overview of the risk of SPM development. This information can be used in treatment decision-making and for planning appropriate surveillance activities and interventions,” study lead author Lina van der Straten, MD, PhD, of the Albert Schweitzer Hospital and Erasmus University Medical Center in the Netherlands, said in an interview.

Ohio State University hematologist David Bond, MD, who’s familiar with the findings, said in an interview that “it’s been well-established that patients with CLL are at increased risk for second primary malignancies. This is thought to be due to impaired immune surveillance and possibly carcinogenic effects of CLL treatments.” It’s not clear, he said, “whether the rate of second cancers differs between chemoimmunotherapy-treated patients and those receiving newer oral kinase inhibitors.”

Previous research into CLL and SPM has been sparse, Dr. van der Straten said, and most studies haven’t looked at SPM over time and taken into account the widespread use of chemoimmunotherapy and agents such as ibrutinib and venetoclax.

It’s important to study this topic, she said, since “cancers diagnosed after the CLL diagnosis can outweigh the improved longevity and contribute to excess morbidity and mortality in long-term CLL survivors.”

With the help of the Netherlands Cancer Registry, researchers tracked 24,815 patients with CLL who were diagnosed over the 20-year period; 4,369 developed SPM. “We demonstrated that the risk of SPM development was higher than in the general population with an excess of 125 malignancies per 10,000 person-years in the CLL cohort,” Dr. van der Straten said. “The risk of SPM development was found to be heightened in solid and hematological cancers. Patients with CLL had an increased risk of developing cancers at the following sites or types: skin, acute myeloid leukemia, soft-tissue sarcomas, thyroid, kidney, unknown primary localization, non-Hodgkin lymphomas, lung and bronchus, and colon and rectum.”

Specifically, the study reports that “elevated risk was observed for solid (SIR = 1.67; 95% CI, 1.65-1.75) and hematological SPMs (SIR = 1.42; 95% CI, 1.24-1.62). The highest risk for SPMs was noted beyond 5 years post diagnosis (SIR = 1.70; 95% CI, 1.62-1.77), for male individuals (SIR = 1.70; 95% CI, 1.64-1.77), and patients aged 18-69 years (SR = 1.92; 95% CI, 1.79-2.05).

“Patients with CLL exposed to treatment have a higher risk of SPM development than patients who will never receive therapy,” Dr. van der Straten said. Research has shown that “treatment with fludarabine, cyclophosphamide, and rituximab has been associated with a 2.38 increased risk for SPM development, particularly acute myeloid leukemia. Indeed, we found an increased risk for hematological malignancies in patients diagnosed between 2003-2009 and 2010-2019, which might be explained by the broader administration of fludarabine-based strategies in these calendar periods.”

Multiple factors could explain the higher risk of SPM in patients with CLL, including “a dysregulated immune system, treatment-related effects, and surveillance bias,” Dr. van der Straten said. “In addition, it is proposed that the immune dysfunctional nature of CLL might enhance the effect of common carcinogens, such as UV exposure and smoking, in increasing the probability of skin and respiratory cancers.”

She added that “the risk and the spectrum of SPMs were comparable for the 2003-2009 and 2010-2019 periods, suggesting that both the introduction of chemoimmunotherapy and, in part, targeted therapies did not dramatically alter the SPM landscape. However, due to the short follow-up period for the small cohort of patients receiving targeted therapies, further research is warranted.”

Dr. Bond said the findings “are largely in line with prior studies and strengthen their conclusions. Immune surveillance appears to be critical to reducing the risk for some but not all malignancies including lung cancer and melanoma, and the treatments given for CLL can cause immune suppression and thus may increase the risk.”

Moving forward, he said, “this research highlights the importance of second cancers to patients with CLL. It also highlights the need for secondary cancer screening for CLL patients, patient education to avoid known cancer risk factors including smoking and excess UV light exposure, and the need as a field to continue to invest in research into characteristics of second cancers and mitigation strategies.”

Study funding was not reported. The authors and Dr. Bond report no disclosures.

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• Adding hyperthermic intraperitoneal chemotherapy to systemic chemotherapy after radical gastrectomy reduces the occurrence of peritoneal metastases and improves disease-free survival (DFS) for patients with locally advanced gastric cancer.

Why this matters

• Surgery and postoperative chemotherapy are standard of care for advanced gastric cancer, but up to half of patients develop peritoneal metastases with poor prognosis.
• There is no consensus on how to prevent peritoneal metastases.
• With hyperthermic intraperitoneal chemotherapy, the abdominal cavity is bathed in chemotherapy that has been heated, directly killing free cancer cells and micrometastases.
• The findings suggest that adding hyperthermic intraperitoneal chemotherapy to standard treatment greatly reduces the risk of peritoneal metastases.

Study design

• The investigators randomly assigned 134 patients with advanced gastric cancer evenly to receive either systemic chemotherapy alone or systemic chemotherapy plus hyperthermic intraperitoneal chemotherapy after radical gastrectomy.
• The hyperthermic intraperitoneal chemotherapy group had 3 L of heated saline containing 40 mg/m² of cisplatin circulated in their peritoneal cavities for an hour. The procedure was performed twice within 72 hours of surgery.
• Systemic chemotherapy consisted of six to eight cycles of S-1 combined with oxaliplatin (SOX regimen) starting 4-6 weeks after surgery.
• Most patients (90%) had stage III disease, and the rest stage II.
• Median follow-up was 44 months.

Key results

• Overall, the 3-year DFS rate was 73.8% with hyperthermic intraperitoneal chemotherapy versus 61.2% without it (P = .031).
• In addition, 21% of patients in the hyperthermic intraperitoneal chemotherapy group developed peritoneal metastases versus 40.3% with standard care (P = .015)
• The 3-year overall survival was 73.9% in the hyperthermic intraperitoneal chemotherapy group versus 77.6% in the standard care arm, but the difference was not significant (P = .737).
• There were no serious adverse events related to hyperthermic intraperitoneal chemotherapy, and postoperative complications were similar between the groups.
• Grade 3 or 4 adverse events occurred in 14.2% of patients; there were no statistically significant between-group differences.
• Metastases to other sites, such as the liver and distant lymph nodes, were also similar between the two arms.

Limitations

• Follow-up might have been too short to detect a difference in overall survival.
• The trial was conducted at a single-center and was relatively small.

Disclosures

• The study received no external funding, and the investigators did not report any financial relationships.

This is a summary of a preprint research study, “Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Plus Systemic Chemotherapy Versus Systemic Chemotherapy Alone in Locally Advanced Gastric Cancer After D2 Radical Resection: A Randomized Controlled Study,” led by Pengfei Yu of the Zhejiang Cancer Hospital, Hangzhou, China. The study has not been peer reviewed. The full text can be found at researchsquare.com.

A version of this article first appeared on Medscape.com.

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• Adding hyperthermic intraperitoneal chemotherapy to systemic chemotherapy after radical gastrectomy reduces the occurrence of peritoneal metastases and improves disease-free survival (DFS) for patients with locally advanced gastric cancer.

Why this matters

• Surgery and postoperative chemotherapy are standard of care for advanced gastric cancer, but up to half of patients develop peritoneal metastases with poor prognosis.
• There is no consensus on how to prevent peritoneal metastases.
• With hyperthermic intraperitoneal chemotherapy, the abdominal cavity is bathed in chemotherapy that has been heated, directly killing free cancer cells and micrometastases.
• The findings suggest that adding hyperthermic intraperitoneal chemotherapy to standard treatment greatly reduces the risk of peritoneal metastases.

Study design

• The investigators randomly assigned 134 patients with advanced gastric cancer evenly to receive either systemic chemotherapy alone or systemic chemotherapy plus hyperthermic intraperitoneal chemotherapy after radical gastrectomy.
• The hyperthermic intraperitoneal chemotherapy group had 3 L of heated saline containing 40 mg/m² of cisplatin circulated in their peritoneal cavities for an hour. The procedure was performed twice within 72 hours of surgery.
• Systemic chemotherapy consisted of six to eight cycles of S-1 combined with oxaliplatin (SOX regimen) starting 4-6 weeks after surgery.
• Most patients (90%) had stage III disease, and the rest stage II.
• Median follow-up was 44 months.

Key results

• Overall, the 3-year DFS rate was 73.8% with hyperthermic intraperitoneal chemotherapy versus 61.2% without it (P = .031).
• In addition, 21% of patients in the hyperthermic intraperitoneal chemotherapy group developed peritoneal metastases versus 40.3% with standard care (P = .015)
• The 3-year overall survival was 73.9% in the hyperthermic intraperitoneal chemotherapy group versus 77.6% in the standard care arm, but the difference was not significant (P = .737).
• There were no serious adverse events related to hyperthermic intraperitoneal chemotherapy, and postoperative complications were similar between the groups.
• Grade 3 or 4 adverse events occurred in 14.2% of patients; there were no statistically significant between-group differences.
• Metastases to other sites, such as the liver and distant lymph nodes, were also similar between the two arms.

Limitations

• Follow-up might have been too short to detect a difference in overall survival.
• The trial was conducted at a single-center and was relatively small.

Disclosures

• The study received no external funding, and the investigators did not report any financial relationships.

This is a summary of a preprint research study, “Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Plus Systemic Chemotherapy Versus Systemic Chemotherapy Alone in Locally Advanced Gastric Cancer After D2 Radical Resection: A Randomized Controlled Study,” led by Pengfei Yu of the Zhejiang Cancer Hospital, Hangzhou, China. The study has not been peer reviewed. The full text can be found at researchsquare.com.

A version of this article first appeared on Medscape.com.

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• Adding hyperthermic intraperitoneal chemotherapy to systemic chemotherapy after radical gastrectomy reduces the occurrence of peritoneal metastases and improves disease-free survival (DFS) for patients with locally advanced gastric cancer.

Why this matters

• Surgery and postoperative chemotherapy are standard of care for advanced gastric cancer, but up to half of patients develop peritoneal metastases with poor prognosis.
• There is no consensus on how to prevent peritoneal metastases.
• With hyperthermic intraperitoneal chemotherapy, the abdominal cavity is bathed in chemotherapy that has been heated, directly killing free cancer cells and micrometastases.
• The findings suggest that adding hyperthermic intraperitoneal chemotherapy to standard treatment greatly reduces the risk of peritoneal metastases.

Study design

• The investigators randomly assigned 134 patients with advanced gastric cancer evenly to receive either systemic chemotherapy alone or systemic chemotherapy plus hyperthermic intraperitoneal chemotherapy after radical gastrectomy.
• The hyperthermic intraperitoneal chemotherapy group had 3 L of heated saline containing 40 mg/m² of cisplatin circulated in their peritoneal cavities for an hour. The procedure was performed twice within 72 hours of surgery.
• Systemic chemotherapy consisted of six to eight cycles of S-1 combined with oxaliplatin (SOX regimen) starting 4-6 weeks after surgery.
• Most patients (90%) had stage III disease, and the rest stage II.
• Median follow-up was 44 months.

Key results

• Overall, the 3-year DFS rate was 73.8% with hyperthermic intraperitoneal chemotherapy versus 61.2% without it (P = .031).
• In addition, 21% of patients in the hyperthermic intraperitoneal chemotherapy group developed peritoneal metastases versus 40.3% with standard care (P = .015)
• The 3-year overall survival was 73.9% in the hyperthermic intraperitoneal chemotherapy group versus 77.6% in the standard care arm, but the difference was not significant (P = .737).
• There were no serious adverse events related to hyperthermic intraperitoneal chemotherapy, and postoperative complications were similar between the groups.
• Grade 3 or 4 adverse events occurred in 14.2% of patients; there were no statistically significant between-group differences.
• Metastases to other sites, such as the liver and distant lymph nodes, were also similar between the two arms.

Limitations

• Follow-up might have been too short to detect a difference in overall survival.
• The trial was conducted at a single-center and was relatively small.

Disclosures

• The study received no external funding, and the investigators did not report any financial relationships.

This is a summary of a preprint research study, “Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Plus Systemic Chemotherapy Versus Systemic Chemotherapy Alone in Locally Advanced Gastric Cancer After D2 Radical Resection: A Randomized Controlled Study,” led by Pengfei Yu of the Zhejiang Cancer Hospital, Hangzhou, China. The study has not been peer reviewed. The full text can be found at researchsquare.com.

A version of this article first appeared on Medscape.com.

Modifiable chronic health conditions and socioeconomic factors may raise the risk for death in adult survivors of childhood cancer, according to new data from the St. Jude Lifetime Cohort.

Survivors with a greater number and severity of modifiable chronic health conditions as well as those living in the most versus least resource-deprived areas had a significantly higher risk of all-cause and health-related late death.

Finding ways to mitigate these factors “will be important to improving health outcomes and developing risk-stratification strategies to optimize care delivery to survivors at varying risk of adverse health events,” the researchers wrote.

The study indicates that treating chronic health conditions alone may not be enough to increase a cancer survivor’s lifespan; improving local environments matters too.

“It is important for clinicians to ask patients about their specific situation,” first author Matthew J. Ehrhardt, MD, department of oncology, St. Jude Children’s Research Hospital, Memphis, said in a news release. “It’s easy to prescribe medications or to tell people to exercise. It takes more time and more thoughtfulness to sit and understand environments in which they are residing.”

“As clinicians, we may have limited ability to modify some of those factors. But we can work closely with the rest of the health care team, such as social workers, for example, to help survivors to identify and access local resources,” Dr. Ehrhardt added.

The study was published online in JAMA Network Open.

A growing population of childhood cancer survivors faces an increased risk for premature death in the years following their diagnosis. However, associations between social determinants of health, modifiable health conditions, and late mortality in childhood cancer survivors remain unclear.

To assess late mortality, the study team analyzed data on 9,440 participants (median age at assessment, 27.5 years; range, 5.3-71.9 years) who lived at least 5 years after being diagnosed with a childhood cancer between 1962 and 2012.

During a median follow-up of about 18 years, childhood cancer survivors had an increased rate of both all-cause and health-related late mortality (standardized mortality rate, 7.6 for both). Among specific health-related causes of death, SMRs were 16.0 for subsequent neoplasms, 9.0 for pulmonary causes, 4.2 for cardiac causes, and 4.3 for other health-related causes.

To evaluate ties between modifiable chronic health conditions, social determinants, and late mortality, the researchers restricted their analysis to 3,407 adult study participants for whom relevant data were available. Modifiable chronic health conditions included dyslipidemia, hypertension, diabetes, underweight or obesity, bone mineral deficiency, and hypothyroidism.

After adjusting for individual factors, including age at diagnosis and treatment, as well as neighborhood-level factors, the researchers observed a significantly increased risk for death among survivors with one or more modifiable chronic health conditions of grade 2 or higher (relative risk, 2.2), two chronic health conditions of grade 2 or higher (RR, 2.6) or three chronic health conditions of grade 2 or higher (RR, 3.6).

These findings suggest that “increased late mortality experienced by childhood cancer survivors in adulthood may not be predetermined by treatment-related risk factors alone,” the researchers said.

In addition, survivors living in the most disadvantaged areas, as measured by the area deprivation index (ADI), had a five- to eightfold increased risk of late death from any cause compared with those living in the least disadvantaged areas, even after adjusting for modifiable chronic health conditions, cancer treatment, demographics, and individual socioeconomic factors.

The findings have important public health implications, Dr. Ehrhardt and colleagues said. The results can, for instance, help identify and stratify cancer survivors at higher lifetime risk for specific chronic conditions and late death. 

This risk-stratified approach to care, however, is “relatively static” and does not account for risk factors acquired after cancer diagnosis and treatment, such as social determinants of health.

That is why also focusing on socioeconomic factors is important, and transitional care services following cancer treatment should consider that survivors in disadvantaged neighborhoods may lack supportive resources to address health issues, potentially leading to increased risk for death, the researchers said.

The knowledge that living in a resource-poor neighborhood may raise the risk for late death in childhood cancer survivors “strengthens support for public health policies that will direct resources to such regions and facilitate a multipronged approach to risk mitigation,” the authors concluded.

This study was supported by grants from the National Institutes of Health and the American Lebanese Syrian Associated Charities. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Modifiable chronic health conditions and socioeconomic factors may raise the risk for death in adult survivors of childhood cancer, according to new data from the St. Jude Lifetime Cohort.

Survivors with a greater number and severity of modifiable chronic health conditions as well as those living in the most versus least resource-deprived areas had a significantly higher risk of all-cause and health-related late death.

Finding ways to mitigate these factors “will be important to improving health outcomes and developing risk-stratification strategies to optimize care delivery to survivors at varying risk of adverse health events,” the researchers wrote.

The study indicates that treating chronic health conditions alone may not be enough to increase a cancer survivor’s lifespan; improving local environments matters too.

“It is important for clinicians to ask patients about their specific situation,” first author Matthew J. Ehrhardt, MD, department of oncology, St. Jude Children’s Research Hospital, Memphis, said in a news release. “It’s easy to prescribe medications or to tell people to exercise. It takes more time and more thoughtfulness to sit and understand environments in which they are residing.”

“As clinicians, we may have limited ability to modify some of those factors. But we can work closely with the rest of the health care team, such as social workers, for example, to help survivors to identify and access local resources,” Dr. Ehrhardt added.

The study was published online in JAMA Network Open.

A growing population of childhood cancer survivors faces an increased risk for premature death in the years following their diagnosis. However, associations between social determinants of health, modifiable health conditions, and late mortality in childhood cancer survivors remain unclear.

To assess late mortality, the study team analyzed data on 9,440 participants (median age at assessment, 27.5 years; range, 5.3-71.9 years) who lived at least 5 years after being diagnosed with a childhood cancer between 1962 and 2012.

During a median follow-up of about 18 years, childhood cancer survivors had an increased rate of both all-cause and health-related late mortality (standardized mortality rate, 7.6 for both). Among specific health-related causes of death, SMRs were 16.0 for subsequent neoplasms, 9.0 for pulmonary causes, 4.2 for cardiac causes, and 4.3 for other health-related causes.

To evaluate ties between modifiable chronic health conditions, social determinants, and late mortality, the researchers restricted their analysis to 3,407 adult study participants for whom relevant data were available. Modifiable chronic health conditions included dyslipidemia, hypertension, diabetes, underweight or obesity, bone mineral deficiency, and hypothyroidism.

After adjusting for individual factors, including age at diagnosis and treatment, as well as neighborhood-level factors, the researchers observed a significantly increased risk for death among survivors with one or more modifiable chronic health conditions of grade 2 or higher (relative risk, 2.2), two chronic health conditions of grade 2 or higher (RR, 2.6) or three chronic health conditions of grade 2 or higher (RR, 3.6).

These findings suggest that “increased late mortality experienced by childhood cancer survivors in adulthood may not be predetermined by treatment-related risk factors alone,” the researchers said.

In addition, survivors living in the most disadvantaged areas, as measured by the area deprivation index (ADI), had a five- to eightfold increased risk of late death from any cause compared with those living in the least disadvantaged areas, even after adjusting for modifiable chronic health conditions, cancer treatment, demographics, and individual socioeconomic factors.

The findings have important public health implications, Dr. Ehrhardt and colleagues said. The results can, for instance, help identify and stratify cancer survivors at higher lifetime risk for specific chronic conditions and late death. 

This risk-stratified approach to care, however, is “relatively static” and does not account for risk factors acquired after cancer diagnosis and treatment, such as social determinants of health.

That is why also focusing on socioeconomic factors is important, and transitional care services following cancer treatment should consider that survivors in disadvantaged neighborhoods may lack supportive resources to address health issues, potentially leading to increased risk for death, the researchers said.

The knowledge that living in a resource-poor neighborhood may raise the risk for late death in childhood cancer survivors “strengthens support for public health policies that will direct resources to such regions and facilitate a multipronged approach to risk mitigation,” the authors concluded.

This study was supported by grants from the National Institutes of Health and the American Lebanese Syrian Associated Charities. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Modifiable chronic health conditions and socioeconomic factors may raise the risk for death in adult survivors of childhood cancer, according to new data from the St. Jude Lifetime Cohort.

Survivors with a greater number and severity of modifiable chronic health conditions as well as those living in the most versus least resource-deprived areas had a significantly higher risk of all-cause and health-related late death.

Finding ways to mitigate these factors “will be important to improving health outcomes and developing risk-stratification strategies to optimize care delivery to survivors at varying risk of adverse health events,” the researchers wrote.

The study indicates that treating chronic health conditions alone may not be enough to increase a cancer survivor’s lifespan; improving local environments matters too.

“It is important for clinicians to ask patients about their specific situation,” first author Matthew J. Ehrhardt, MD, department of oncology, St. Jude Children’s Research Hospital, Memphis, said in a news release. “It’s easy to prescribe medications or to tell people to exercise. It takes more time and more thoughtfulness to sit and understand environments in which they are residing.”

“As clinicians, we may have limited ability to modify some of those factors. But we can work closely with the rest of the health care team, such as social workers, for example, to help survivors to identify and access local resources,” Dr. Ehrhardt added.

The study was published online in JAMA Network Open.

A growing population of childhood cancer survivors faces an increased risk for premature death in the years following their diagnosis. However, associations between social determinants of health, modifiable health conditions, and late mortality in childhood cancer survivors remain unclear.

To assess late mortality, the study team analyzed data on 9,440 participants (median age at assessment, 27.5 years; range, 5.3-71.9 years) who lived at least 5 years after being diagnosed with a childhood cancer between 1962 and 2012.

During a median follow-up of about 18 years, childhood cancer survivors had an increased rate of both all-cause and health-related late mortality (standardized mortality rate, 7.6 for both). Among specific health-related causes of death, SMRs were 16.0 for subsequent neoplasms, 9.0 for pulmonary causes, 4.2 for cardiac causes, and 4.3 for other health-related causes.

To evaluate ties between modifiable chronic health conditions, social determinants, and late mortality, the researchers restricted their analysis to 3,407 adult study participants for whom relevant data were available. Modifiable chronic health conditions included dyslipidemia, hypertension, diabetes, underweight or obesity, bone mineral deficiency, and hypothyroidism.

After adjusting for individual factors, including age at diagnosis and treatment, as well as neighborhood-level factors, the researchers observed a significantly increased risk for death among survivors with one or more modifiable chronic health conditions of grade 2 or higher (relative risk, 2.2), two chronic health conditions of grade 2 or higher (RR, 2.6) or three chronic health conditions of grade 2 or higher (RR, 3.6).

These findings suggest that “increased late mortality experienced by childhood cancer survivors in adulthood may not be predetermined by treatment-related risk factors alone,” the researchers said.

In addition, survivors living in the most disadvantaged areas, as measured by the area deprivation index (ADI), had a five- to eightfold increased risk of late death from any cause compared with those living in the least disadvantaged areas, even after adjusting for modifiable chronic health conditions, cancer treatment, demographics, and individual socioeconomic factors.

The findings have important public health implications, Dr. Ehrhardt and colleagues said. The results can, for instance, help identify and stratify cancer survivors at higher lifetime risk for specific chronic conditions and late death. 

This risk-stratified approach to care, however, is “relatively static” and does not account for risk factors acquired after cancer diagnosis and treatment, such as social determinants of health.

That is why also focusing on socioeconomic factors is important, and transitional care services following cancer treatment should consider that survivors in disadvantaged neighborhoods may lack supportive resources to address health issues, potentially leading to increased risk for death, the researchers said.

The knowledge that living in a resource-poor neighborhood may raise the risk for late death in childhood cancer survivors “strengthens support for public health policies that will direct resources to such regions and facilitate a multipronged approach to risk mitigation,” the authors concluded.

This study was supported by grants from the National Institutes of Health and the American Lebanese Syrian Associated Charities. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

It was Friday, and oncologist Coral Olazagasti, MD, faced a ticking clock.

Her patient had taken his last prescription antinausea pill. Without a refill of ondansetron, he faced a long, painful weekend.

The patient – a man with HPV-related oropharyngeal cancer – was experiencing severe side effects from standard chemoradiation with weekly cisplatin. Intense nausea and grade 3 mucositis, in particular, left him struggling to swallow or take in any food or fluids.

He was on 8 mg of ondansetron (Zofran) every 8 hours, as needed, to keep the nausea at bay. The pills along with a feeding tube helped, but his symptoms were so intense, neither was quite enough.

“He still needed to be hospitalized twice for dehydration,” said Dr. Olazagasti, who specializes in head and neck medical cancer at Sylvester Comprehensive Cancer Center in Miami.

But when it came time to renew his ondansetron prescription, his insurance company denied it.

The reasoning: “The company had only approved 30 tablets a month and, for them, it was unjustifiable to approve anything above that amount,” Dr. Olazagasti explained.

After Dr. Olazagasti called the insurance company to resolve the issue, a company representative told her to fill out a prior authorization form.

But it was already after 7:30 p.m. ET on Friday.

At that point, finding the prior authorization documents, filling them out, and submitting them would take more time – and the paperwork couldn’t be filed until Monday.

“My patient was at home with zero tablets left and horrible symptoms. He couldn’t keep anything down,” Dr. Olazagasti said.

On Monday, the oncology team sent the prior authorization request, and her patient received his medication a few days later.

“My patient had to wait about 5 days to get the nausea meds he needed,” she said. In the meantime, he was in pain. “Having a refill of this simple supportive care medication rejected was infuriating.”

When Dr. Olazagasti vented her frustrations on Twitter, several people chimed in, suggesting purchasing the drug at a discount through GoodRx or Cost Plus instead of going through the insurance company.

At Cost Plus, for instance, 30 8-mg pills would cost $6.30, but ordering from the online pharmacy would mean waiting several days for delivery.

Discounts through GoodRx may provide a potentially faster solution in a pinch, but the pharmacy matters. In Miami, 30 8-mg pills would cost $19.99 at Costco with a GoodRx coupon, but $233.56 at CVS and $253.60 at Walgreens.

Although potentially useful, these options may not be the obvious choice for oncologists and patients, especially when a drug has already been approved and covered by the insurer. In this case, the denial was also a surprise, which left Dr. Olazagasti and her patient scrambling right before the weekend.

In addition, companies providing discounted generic drugs may only have a limited number of oncology-related medications. Cost Plus, for instance, now sells more than 1,000 generic prescription drugs at a fraction of what insurance companies charge, but only about 7 are cancer drugs.

On a broader level, Dr. Olazagasti noted, “insurance companies have a responsibility to cover these drugs. If we all get so fed up that we start relying on alternate routes to get patients their treatments, then insurance companies are let off the hook.”

However, using an alternative option like GoodRx or CostPlus could mean bypassing insurance company obstacles in certain cases.

“The hurdles someone may have to go through to get a generic drug approved are very frustrating,” said Stacie B. Dusetzina, PhD, professor of health policy and a professor of cancer research at Vanderbilt University in Nashville, Tenn.

In a weekend emergency situation, if the drug is discounted through GoodRx, “it can be a good backup strategy to send the prescription to the pharmacy” and more generally “worth it for patients to check if they can get a better deal on generic drugs through these companies.”

A version of this article first appeared on Medscape.com.

It was Friday, and oncologist Coral Olazagasti, MD, faced a ticking clock.

Her patient had taken his last prescription antinausea pill. Without a refill of ondansetron, he faced a long, painful weekend.

The patient – a man with HPV-related oropharyngeal cancer – was experiencing severe side effects from standard chemoradiation with weekly cisplatin. Intense nausea and grade 3 mucositis, in particular, left him struggling to swallow or take in any food or fluids.

He was on 8 mg of ondansetron (Zofran) every 8 hours, as needed, to keep the nausea at bay. The pills along with a feeding tube helped, but his symptoms were so intense, neither was quite enough.

“He still needed to be hospitalized twice for dehydration,” said Dr. Olazagasti, who specializes in head and neck medical cancer at Sylvester Comprehensive Cancer Center in Miami.

But when it came time to renew his ondansetron prescription, his insurance company denied it.

The reasoning: “The company had only approved 30 tablets a month and, for them, it was unjustifiable to approve anything above that amount,” Dr. Olazagasti explained.

After Dr. Olazagasti called the insurance company to resolve the issue, a company representative told her to fill out a prior authorization form.

But it was already after 7:30 p.m. ET on Friday.

At that point, finding the prior authorization documents, filling them out, and submitting them would take more time – and the paperwork couldn’t be filed until Monday.

“My patient was at home with zero tablets left and horrible symptoms. He couldn’t keep anything down,” Dr. Olazagasti said.

On Monday, the oncology team sent the prior authorization request, and her patient received his medication a few days later.

“My patient had to wait about 5 days to get the nausea meds he needed,” she said. In the meantime, he was in pain. “Having a refill of this simple supportive care medication rejected was infuriating.”

When Dr. Olazagasti vented her frustrations on Twitter, several people chimed in, suggesting purchasing the drug at a discount through GoodRx or Cost Plus instead of going through the insurance company.

At Cost Plus, for instance, 30 8-mg pills would cost $6.30, but ordering from the online pharmacy would mean waiting several days for delivery.

Discounts through GoodRx may provide a potentially faster solution in a pinch, but the pharmacy matters. In Miami, 30 8-mg pills would cost $19.99 at Costco with a GoodRx coupon, but $233.56 at CVS and $253.60 at Walgreens.

Although potentially useful, these options may not be the obvious choice for oncologists and patients, especially when a drug has already been approved and covered by the insurer. In this case, the denial was also a surprise, which left Dr. Olazagasti and her patient scrambling right before the weekend.

In addition, companies providing discounted generic drugs may only have a limited number of oncology-related medications. Cost Plus, for instance, now sells more than 1,000 generic prescription drugs at a fraction of what insurance companies charge, but only about 7 are cancer drugs.

On a broader level, Dr. Olazagasti noted, “insurance companies have a responsibility to cover these drugs. If we all get so fed up that we start relying on alternate routes to get patients their treatments, then insurance companies are let off the hook.”

However, using an alternative option like GoodRx or CostPlus could mean bypassing insurance company obstacles in certain cases.

“The hurdles someone may have to go through to get a generic drug approved are very frustrating,” said Stacie B. Dusetzina, PhD, professor of health policy and a professor of cancer research at Vanderbilt University in Nashville, Tenn.

In a weekend emergency situation, if the drug is discounted through GoodRx, “it can be a good backup strategy to send the prescription to the pharmacy” and more generally “worth it for patients to check if they can get a better deal on generic drugs through these companies.”

A version of this article first appeared on Medscape.com.

It was Friday, and oncologist Coral Olazagasti, MD, faced a ticking clock.

Her patient had taken his last prescription antinausea pill. Without a refill of ondansetron, he faced a long, painful weekend.

The patient – a man with HPV-related oropharyngeal cancer – was experiencing severe side effects from standard chemoradiation with weekly cisplatin. Intense nausea and grade 3 mucositis, in particular, left him struggling to swallow or take in any food or fluids.

He was on 8 mg of ondansetron (Zofran) every 8 hours, as needed, to keep the nausea at bay. The pills along with a feeding tube helped, but his symptoms were so intense, neither was quite enough.

“He still needed to be hospitalized twice for dehydration,” said Dr. Olazagasti, who specializes in head and neck medical cancer at Sylvester Comprehensive Cancer Center in Miami.

But when it came time to renew his ondansetron prescription, his insurance company denied it.

The reasoning: “The company had only approved 30 tablets a month and, for them, it was unjustifiable to approve anything above that amount,” Dr. Olazagasti explained.

After Dr. Olazagasti called the insurance company to resolve the issue, a company representative told her to fill out a prior authorization form.

But it was already after 7:30 p.m. ET on Friday.

At that point, finding the prior authorization documents, filling them out, and submitting them would take more time – and the paperwork couldn’t be filed until Monday.

“My patient was at home with zero tablets left and horrible symptoms. He couldn’t keep anything down,” Dr. Olazagasti said.

On Monday, the oncology team sent the prior authorization request, and her patient received his medication a few days later.

“My patient had to wait about 5 days to get the nausea meds he needed,” she said. In the meantime, he was in pain. “Having a refill of this simple supportive care medication rejected was infuriating.”

When Dr. Olazagasti vented her frustrations on Twitter, several people chimed in, suggesting purchasing the drug at a discount through GoodRx or Cost Plus instead of going through the insurance company.

At Cost Plus, for instance, 30 8-mg pills would cost $6.30, but ordering from the online pharmacy would mean waiting several days for delivery.

Discounts through GoodRx may provide a potentially faster solution in a pinch, but the pharmacy matters. In Miami, 30 8-mg pills would cost $19.99 at Costco with a GoodRx coupon, but $233.56 at CVS and $253.60 at Walgreens.

Although potentially useful, these options may not be the obvious choice for oncologists and patients, especially when a drug has already been approved and covered by the insurer. In this case, the denial was also a surprise, which left Dr. Olazagasti and her patient scrambling right before the weekend.

In addition, companies providing discounted generic drugs may only have a limited number of oncology-related medications. Cost Plus, for instance, now sells more than 1,000 generic prescription drugs at a fraction of what insurance companies charge, but only about 7 are cancer drugs.

On a broader level, Dr. Olazagasti noted, “insurance companies have a responsibility to cover these drugs. If we all get so fed up that we start relying on alternate routes to get patients their treatments, then insurance companies are let off the hook.”

However, using an alternative option like GoodRx or CostPlus could mean bypassing insurance company obstacles in certain cases.

“The hurdles someone may have to go through to get a generic drug approved are very frustrating,” said Stacie B. Dusetzina, PhD, professor of health policy and a professor of cancer research at Vanderbilt University in Nashville, Tenn.

In a weekend emergency situation, if the drug is discounted through GoodRx, “it can be a good backup strategy to send the prescription to the pharmacy” and more generally “worth it for patients to check if they can get a better deal on generic drugs through these companies.”

A version of this article first appeared on Medscape.com.

Treatment for breast cancer exacts a high financial toll on patients, not just in the United States and other high-income countries but in low- and middle-income countries as well, a meta-analysis found.

Although the rate of financial toxicity was much higher in low- and middle-income countries – affecting 79% of patients – more than 35% of patients in high-income countries also incurred financial hardship, the study team found.

The findings highlight the need for policies to offset the burden of direct and indirect costs for breast cancer care and improve the financial health of vulnerable patients, said the study authors, led by Kavitha Ranganathan, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston.

The study was published online in JAMA Network Open.

 

The most expensive malignancy?

Patients with breast cancer may be particularly burdened by costs of care, with one study showing substantially higher out-of-pocket costs for patients with breast cancer than colorectal, lung, and prostate cancer combined.

A Lancet Oncology Commission report revealed that breast cancer was the most expensive cancer in the United States in 2010, accounting for $16.5 billion, or 13% of all cancer-related spending. A separate analysis found that individual direct medical costs of breast cancer care can reach $100,000.

In high-income countries, the financial burden of breast cancer care may be the result of novel and costly cancer therapeutics and interventions, overuse of services, increased willingness to pay, and varying insurance coverage. In low- and middle-income countries, women may experience delayed diagnosis because of limited access to screening and high-quality diagnostic services, leading to more later-stage diagnoses requiring more extensive treatments. Lower baseline income, limited insurance coverage, and greater distance to treatment centers may also be factors.

“Establishing the global extent of financial toxicity and comparing the economic burden of disease in different populations is imperative to help policy makers prioritize funding of breast cancer care infrastructure,” Dr. Ranganathan and colleagues write.

In their meta-analysis of 18 studies – 14 from high-income countries and 4 from low – published from 2008 to 2021, the authors found that the definition of financial toxicity varied widely across studies.

For example, some used specific numerical criteria for defining financial toxicity, such as medical cost exceeding 40% of household capacity to pay or potential income or out-of-pocket costs exceeding 30% of annual household income.

Others used patient-reported outcome measures instruments evaluating subjective statements of financial difficulty, such as an affirmative answer to having financial difficulty or trouble paying medical bills, or paying more for medical care than is affordable.

In other studies, financial toxicity was defined according to a patient’s report of specific, objective financial consequences of care, including losing income or a job; having to borrow money or go into debt; having trouble paying for food, rent, or transportation; or having to forgo any type of medical care because of cost.

In their analysis, the pooled rate of financial toxicity among patients with breast cancer was 35.3% in high-income countries and 78.8% in low/middle-income countries, both demonstrating high heterogeneity or variability (P for heterogeneity < .001). In contrast, typical financial toxicity rates across all health conditions in low-income countries ranged from 6% to 12%, the investigators noted.

One study assessing quality of life measures in Egypt found that 47.5% of patients were food insecure, 66% needed financial assistance, 34% used savings to pay for treatment, and 41.2% lacked savings altogether.
 

Burden reduction

Given the high rates of financial toxicity associated with breast cancer, what strategies might reduce this cost burden?

When exploring potential factors associated with financial toxicity, the researchers found no clear association between financial toxicity and race, employment status, and age, and could draw no firm conclusions about the impact of comorbidities and urban vs. rural place of residence. In addition, cancer stage and treatments were “extremely” heterogeneous across studies and the authors found no clear association between either factor and financial toxicity.

But the authors noted that the highest-priority patients are typically those who have low education, have low socioeconomic status, lack health insurance, and live in low-resource areas.

To reduce financial toxicity and improve outcomes among patients with breast cancer, the study team recommended four potential strategies:

• Use targeted educational campaigns to raise awareness about the signs and symptoms of breast cancer and the importance of early diagnosis and treatment.
• Expand health care coverage to minimize direct medical out-of-pocket costs.
• Develop programs to assist with direct nonmedical and indirect costs, such as transportation to and lodging near treatment centers and childcare.
• Improve screening, referral, and treatment infrastructure for breast cancer care.

The researchers also noted that their data highlight the value of universal health care coverage as a policy strategy, with evidence of lower financial toxicity rates in countries with universal health coverage.

Support for the study was provided in part by the National Cancer Institute, United Nations Institute for Training and Research and the Global Surgery Foundation, Harvard Global Health Institute, Connors Center for Women’s Health and Gender Biology, the Center for Surgery and Public Health, and the National Endowment for Plastic Surgery. Dr. Ranganathan reports no relevant financial relationships. Several coauthors have disclosures; the full list can be found with the original article.

A version of this article originally appeared on Medscape.com.

Treatment for breast cancer exacts a high financial toll on patients, not just in the United States and other high-income countries but in low- and middle-income countries as well, a meta-analysis found.

Although the rate of financial toxicity was much higher in low- and middle-income countries – affecting 79% of patients – more than 35% of patients in high-income countries also incurred financial hardship, the study team found.

The findings highlight the need for policies to offset the burden of direct and indirect costs for breast cancer care and improve the financial health of vulnerable patients, said the study authors, led by Kavitha Ranganathan, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston.

The study was published online in JAMA Network Open.

 

The most expensive malignancy?

Patients with breast cancer may be particularly burdened by costs of care, with one study showing substantially higher out-of-pocket costs for patients with breast cancer than colorectal, lung, and prostate cancer combined.

A Lancet Oncology Commission report revealed that breast cancer was the most expensive cancer in the United States in 2010, accounting for $16.5 billion, or 13% of all cancer-related spending. A separate analysis found that individual direct medical costs of breast cancer care can reach $100,000.

In high-income countries, the financial burden of breast cancer care may be the result of novel and costly cancer therapeutics and interventions, overuse of services, increased willingness to pay, and varying insurance coverage. In low- and middle-income countries, women may experience delayed diagnosis because of limited access to screening and high-quality diagnostic services, leading to more later-stage diagnoses requiring more extensive treatments. Lower baseline income, limited insurance coverage, and greater distance to treatment centers may also be factors.

“Establishing the global extent of financial toxicity and comparing the economic burden of disease in different populations is imperative to help policy makers prioritize funding of breast cancer care infrastructure,” Dr. Ranganathan and colleagues write.

In their meta-analysis of 18 studies – 14 from high-income countries and 4 from low – published from 2008 to 2021, the authors found that the definition of financial toxicity varied widely across studies.

For example, some used specific numerical criteria for defining financial toxicity, such as medical cost exceeding 40% of household capacity to pay or potential income or out-of-pocket costs exceeding 30% of annual household income.

Others used patient-reported outcome measures instruments evaluating subjective statements of financial difficulty, such as an affirmative answer to having financial difficulty or trouble paying medical bills, or paying more for medical care than is affordable.

In other studies, financial toxicity was defined according to a patient’s report of specific, objective financial consequences of care, including losing income or a job; having to borrow money or go into debt; having trouble paying for food, rent, or transportation; or having to forgo any type of medical care because of cost.

In their analysis, the pooled rate of financial toxicity among patients with breast cancer was 35.3% in high-income countries and 78.8% in low/middle-income countries, both demonstrating high heterogeneity or variability (P for heterogeneity < .001). In contrast, typical financial toxicity rates across all health conditions in low-income countries ranged from 6% to 12%, the investigators noted.

One study assessing quality of life measures in Egypt found that 47.5% of patients were food insecure, 66% needed financial assistance, 34% used savings to pay for treatment, and 41.2% lacked savings altogether.
 

Burden reduction

Given the high rates of financial toxicity associated with breast cancer, what strategies might reduce this cost burden?

When exploring potential factors associated with financial toxicity, the researchers found no clear association between financial toxicity and race, employment status, and age, and could draw no firm conclusions about the impact of comorbidities and urban vs. rural place of residence. In addition, cancer stage and treatments were “extremely” heterogeneous across studies and the authors found no clear association between either factor and financial toxicity.

But the authors noted that the highest-priority patients are typically those who have low education, have low socioeconomic status, lack health insurance, and live in low-resource areas.

To reduce financial toxicity and improve outcomes among patients with breast cancer, the study team recommended four potential strategies:

• Use targeted educational campaigns to raise awareness about the signs and symptoms of breast cancer and the importance of early diagnosis and treatment.
• Expand health care coverage to minimize direct medical out-of-pocket costs.
• Develop programs to assist with direct nonmedical and indirect costs, such as transportation to and lodging near treatment centers and childcare.
• Improve screening, referral, and treatment infrastructure for breast cancer care.

The researchers also noted that their data highlight the value of universal health care coverage as a policy strategy, with evidence of lower financial toxicity rates in countries with universal health coverage.

Support for the study was provided in part by the National Cancer Institute, United Nations Institute for Training and Research and the Global Surgery Foundation, Harvard Global Health Institute, Connors Center for Women’s Health and Gender Biology, the Center for Surgery and Public Health, and the National Endowment for Plastic Surgery. Dr. Ranganathan reports no relevant financial relationships. Several coauthors have disclosures; the full list can be found with the original article.

A version of this article originally appeared on Medscape.com.

Treatment for breast cancer exacts a high financial toll on patients, not just in the United States and other high-income countries but in low- and middle-income countries as well, a meta-analysis found.

Although the rate of financial toxicity was much higher in low- and middle-income countries – affecting 79% of patients – more than 35% of patients in high-income countries also incurred financial hardship, the study team found.

The findings highlight the need for policies to offset the burden of direct and indirect costs for breast cancer care and improve the financial health of vulnerable patients, said the study authors, led by Kavitha Ranganathan, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston.

The study was published online in JAMA Network Open.

 

The most expensive malignancy?

Patients with breast cancer may be particularly burdened by costs of care, with one study showing substantially higher out-of-pocket costs for patients with breast cancer than colorectal, lung, and prostate cancer combined.

A Lancet Oncology Commission report revealed that breast cancer was the most expensive cancer in the United States in 2010, accounting for $16.5 billion, or 13% of all cancer-related spending. A separate analysis found that individual direct medical costs of breast cancer care can reach $100,000.

In high-income countries, the financial burden of breast cancer care may be the result of novel and costly cancer therapeutics and interventions, overuse of services, increased willingness to pay, and varying insurance coverage. In low- and middle-income countries, women may experience delayed diagnosis because of limited access to screening and high-quality diagnostic services, leading to more later-stage diagnoses requiring more extensive treatments. Lower baseline income, limited insurance coverage, and greater distance to treatment centers may also be factors.

“Establishing the global extent of financial toxicity and comparing the economic burden of disease in different populations is imperative to help policy makers prioritize funding of breast cancer care infrastructure,” Dr. Ranganathan and colleagues write.

In their meta-analysis of 18 studies – 14 from high-income countries and 4 from low – published from 2008 to 2021, the authors found that the definition of financial toxicity varied widely across studies.

For example, some used specific numerical criteria for defining financial toxicity, such as medical cost exceeding 40% of household capacity to pay or potential income or out-of-pocket costs exceeding 30% of annual household income.

Others used patient-reported outcome measures instruments evaluating subjective statements of financial difficulty, such as an affirmative answer to having financial difficulty or trouble paying medical bills, or paying more for medical care than is affordable.

In other studies, financial toxicity was defined according to a patient’s report of specific, objective financial consequences of care, including losing income or a job; having to borrow money or go into debt; having trouble paying for food, rent, or transportation; or having to forgo any type of medical care because of cost.

In their analysis, the pooled rate of financial toxicity among patients with breast cancer was 35.3% in high-income countries and 78.8% in low/middle-income countries, both demonstrating high heterogeneity or variability (P for heterogeneity < .001). In contrast, typical financial toxicity rates across all health conditions in low-income countries ranged from 6% to 12%, the investigators noted.

One study assessing quality of life measures in Egypt found that 47.5% of patients were food insecure, 66% needed financial assistance, 34% used savings to pay for treatment, and 41.2% lacked savings altogether.
 

Burden reduction

Given the high rates of financial toxicity associated with breast cancer, what strategies might reduce this cost burden?

When exploring potential factors associated with financial toxicity, the researchers found no clear association between financial toxicity and race, employment status, and age, and could draw no firm conclusions about the impact of comorbidities and urban vs. rural place of residence. In addition, cancer stage and treatments were “extremely” heterogeneous across studies and the authors found no clear association between either factor and financial toxicity.

But the authors noted that the highest-priority patients are typically those who have low education, have low socioeconomic status, lack health insurance, and live in low-resource areas.

To reduce financial toxicity and improve outcomes among patients with breast cancer, the study team recommended four potential strategies:

• Use targeted educational campaigns to raise awareness about the signs and symptoms of breast cancer and the importance of early diagnosis and treatment.
• Expand health care coverage to minimize direct medical out-of-pocket costs.
• Develop programs to assist with direct nonmedical and indirect costs, such as transportation to and lodging near treatment centers and childcare.
• Improve screening, referral, and treatment infrastructure for breast cancer care.

The researchers also noted that their data highlight the value of universal health care coverage as a policy strategy, with evidence of lower financial toxicity rates in countries with universal health coverage.

Support for the study was provided in part by the National Cancer Institute, United Nations Institute for Training and Research and the Global Surgery Foundation, Harvard Global Health Institute, Connors Center for Women’s Health and Gender Biology, the Center for Surgery and Public Health, and the National Endowment for Plastic Surgery. Dr. Ranganathan reports no relevant financial relationships. Several coauthors have disclosures; the full list can be found with the original article.

A version of this article originally appeared on Medscape.com.

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• A few key factors predict when gallbladder cancer will be found on routine cholecystectomy, allowing for better surgical planning and treatment.

Why this matters

• More than 60% of gallbladder cancers are diagnosed incidentally following cholecystectomy for benign reasons.
• Identifying predictors allows surgeons to send high-risk individuals for oncologic evaluation beforehand and to prepare for intraoperative frozen pathology and more appropriate surgery, including extended cholecystectomy and lymph node dissection.

Study design

• The investigators analyzed 403,443 cholecystectomies in the American College of Surgeons’ NSQIP database from 2007 to 2017.
• They used multivariable logistic regression to identify risk factors for gallbladder cancers.
• Patients undergoing cholecystectomy for suspected or confirmed gallbladder cancer were excluded.

Key results

• The incidence of gallbladder cancer was 0.11% (441 of 403,443 patients).
• Preoperative factors significantly associated with gallbladder cancer included age older than 60 years (odds ratio [OR], 6.51), female sex (OR, 1.75), weight loss (OR, 2.58), and elevated alkaline phosphatase level (OR, 1.67).
• Starting with or converting to an open approach – both potential indicators of more complex disease – were associated with seven times’ higher odds of gallbladder cancer (OR, 7.33; P < .001), as were longer operative times (127 minutes vs. 70.7 minutes; P < .001).

Limitations

• There is a risk of selection bias regarding which patients were included in the database.
• Presenting symptoms, preoperative imaging findings, and pathologic staging were not available.
• The database did not record the reasons for choosing open surgery rather than laparoscopic surgery or for converting to an open approach.

Disclosures

• There was no funding for the work, and the investigators did not disclose any relevant financial relationships.

This is a summary of a preprint research study, “Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors,” led by Elizabeth Olecki of Penn State University, State College. The study has not been peer reviewed. The full text can be found at researchsquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• A few key factors predict when gallbladder cancer will be found on routine cholecystectomy, allowing for better surgical planning and treatment.

Why this matters

• More than 60% of gallbladder cancers are diagnosed incidentally following cholecystectomy for benign reasons.
• Identifying predictors allows surgeons to send high-risk individuals for oncologic evaluation beforehand and to prepare for intraoperative frozen pathology and more appropriate surgery, including extended cholecystectomy and lymph node dissection.

Study design

• The investigators analyzed 403,443 cholecystectomies in the American College of Surgeons’ NSQIP database from 2007 to 2017.
• They used multivariable logistic regression to identify risk factors for gallbladder cancers.
• Patients undergoing cholecystectomy for suspected or confirmed gallbladder cancer were excluded.

Key results

• The incidence of gallbladder cancer was 0.11% (441 of 403,443 patients).
• Preoperative factors significantly associated with gallbladder cancer included age older than 60 years (odds ratio [OR], 6.51), female sex (OR, 1.75), weight loss (OR, 2.58), and elevated alkaline phosphatase level (OR, 1.67).
• Starting with or converting to an open approach – both potential indicators of more complex disease – were associated with seven times’ higher odds of gallbladder cancer (OR, 7.33; P < .001), as were longer operative times (127 minutes vs. 70.7 minutes; P < .001).

Limitations

• There is a risk of selection bias regarding which patients were included in the database.
• Presenting symptoms, preoperative imaging findings, and pathologic staging were not available.
• The database did not record the reasons for choosing open surgery rather than laparoscopic surgery or for converting to an open approach.

Disclosures

• There was no funding for the work, and the investigators did not disclose any relevant financial relationships.

This is a summary of a preprint research study, “Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors,” led by Elizabeth Olecki of Penn State University, State College. The study has not been peer reviewed. The full text can be found at researchsquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• A few key factors predict when gallbladder cancer will be found on routine cholecystectomy, allowing for better surgical planning and treatment.

Why this matters

• More than 60% of gallbladder cancers are diagnosed incidentally following cholecystectomy for benign reasons.
• Identifying predictors allows surgeons to send high-risk individuals for oncologic evaluation beforehand and to prepare for intraoperative frozen pathology and more appropriate surgery, including extended cholecystectomy and lymph node dissection.

Study design

• The investigators analyzed 403,443 cholecystectomies in the American College of Surgeons’ NSQIP database from 2007 to 2017.
• They used multivariable logistic regression to identify risk factors for gallbladder cancers.
• Patients undergoing cholecystectomy for suspected or confirmed gallbladder cancer were excluded.

Key results

• The incidence of gallbladder cancer was 0.11% (441 of 403,443 patients).
• Preoperative factors significantly associated with gallbladder cancer included age older than 60 years (odds ratio [OR], 6.51), female sex (OR, 1.75), weight loss (OR, 2.58), and elevated alkaline phosphatase level (OR, 1.67).
• Starting with or converting to an open approach – both potential indicators of more complex disease – were associated with seven times’ higher odds of gallbladder cancer (OR, 7.33; P < .001), as were longer operative times (127 minutes vs. 70.7 minutes; P < .001).

Limitations

• There is a risk of selection bias regarding which patients were included in the database.
• Presenting symptoms, preoperative imaging findings, and pathologic staging were not available.
• The database did not record the reasons for choosing open surgery rather than laparoscopic surgery or for converting to an open approach.

Disclosures

• There was no funding for the work, and the investigators did not disclose any relevant financial relationships.

This is a summary of a preprint research study, “Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors,” led by Elizabeth Olecki of Penn State University, State College. The study has not been peer reviewed. The full text can be found at researchsquare.com. A version of this article first appeared on Medscape.com.

John Whyte, MD: Hello, I’m Dr. John Whyte, the Chief Medical Officer of WebMD. The American Cancer Society released some encouraging data recently that showed a decline in some cancers. One of those cancers was pancreatic cancer, which historically has had a very low survival rate. What’s going on here? Are we doing better with diagnosis, treatment, a combination?

Joining me today is Dr. Lynn Matrisian. She is PanCAN’s chief science officer. Dr. Matrisian, thanks for joining me today. It’s great to see you.

Lynn Matrisian, PhD, MBA: Great to be here. Thank you.

Dr. Whyte: Well, tell me what your first reaction was when you saw the recent data from the American Cancer Society. What one word would you use?

Dr. Matrisian: Hopeful. I think hopeful in general that survival rates are increasing, not for all cancers, but for many cancers. We continue to make progress. Research is making a difference. And we’re making progress against cancer in general.

Dr. Whyte: You’re passionate, as our viewers know, about pancreatic cancer. And that’s been one of the hardest cancers to treat, and one of the lowest survival rates. But there’s some encouraging news that we saw, didn’t we?

Dr. Matrisian: Yes. So the 5-year survival rate for pancreatic cancer went up a whole percentage. It’s at 12% now. And what’s really good is it was at 11% last year. It was at 10% the year before. So that’s 2 years in a row that we’ve had an increase in the 5-year survival rate for pancreatic cancer. So we’re hopeful that’s a trajectory that we can really capitalize on is how fast we’re making progress in this disease.

Dr. Whyte: I want to put it into context, Lynn. Because some people might be thinking, 1%? Like you’re excited about 1%? That doesn’t seem that much. But correct me if I’m wrong. A one percentage point increase means 641 more loved ones will enjoy life’s moments, as you put it, 5 years after their diagnosis that otherwise wouldn’t have. What does that practically mean to viewers?

Dr. Matrisian: That means that more than 600 people in the United States will hug a loved one 5 years after that diagnosis of pancreatic cancer. It is a very deadly disease. But we’re going to, by continuing to make progress, it gives those moments to those people. And it means that we’re making progress against the disease in general.

Dr. Whyte: So even 1%, and 1% each year, does have value.

Dr. Matrisian: It has a lot of value.

Dr. Whyte: What’s driving this improvement? Is it better screening? And we’re not so great still in screening a pancreatic cancer. Is it the innovation in cancer treatments? What do you think is accounting for what we hope is this trajectory of increases in 5-year survival?

Dr. Matrisian: Right, so the nice thing the reason that we like looking at 5-year survival rates is because it takes into account all of those things. And we have actually made progress in all of those things. So by looking at those that are diagnosed with pancreatic cancer in general as a whole, and looking at their survival, we are looking at better treatments. People who are getting pancreatic cancer later are living longer as a result of better treatments.

But it’s not just that. It’s also, if you’re diagnosed earlier, your 5-year survival rate is higher. More people who are diagnosed early live to five years than those that are diagnosed later. So within that statistic, there are more people who are diagnosed earlier. And those people also live longer. So it takes into account all of those things, which is why we really like to look at that five-year survival rate for a disease like pancreatic cancer.

Dr. Whyte: Where are we on screening? Because we always want to catch people early. That gives them that greatest chance of survival. Have we made much improvements there? And if we have, what are they?

Dr. Matrisian: Well we have made improvements there are more people that are now diagnosed with localized disease than there were 20 years ago. So that is increasing. And we’re still doing it really by being aware of the symptoms right now. Being aware that kind of chronic indigestion, lower back pain that won’t go away, these are signs and symptoms. And especially things like jaundice ...

Dr. Whyte: That yellow color that they might see.

Dr. Matrisian: Yes, that yellow colors in your eye, that’s a really important symptom that would certainly send people to the doctor in order to look at this. So some of it is being more aware and finding the disease earlier. But what we’re really hoping for is some sort of blood test or some sort of other way of looking through medical records and identifying those people that need to go and be checked.

Dr. Whyte: Now we chatted about that almost two years ago. So tell me the progress that we’ve made. How are we doing?

Dr. Matrisian: Yeah, well there’s a number of companies now that have blood tests that are available. They still need more work. They still need more studies to really understand how good they are at finding pancreatic cancer early. But we didn’t have them a couple of years ago. And so it’s really a very exciting time in the field, that there’s companies that were taking advantage of research for many years and actually turning it into a commercial product that is available for people to check.

Dr. Whyte: And then what about treatments? More treatment options today than there were just a few years ago, but still a lot of progress to be made. So when we talk about even 12% 5-year survival, we’d love to see it much more. And you talk about, I don’t want to misquote, so correct me if I’m wrong. Your goal is 20%. Five-year survival by 2030. That’s not too far. So, Lynn, how are we going to get there?

Dr. Matrisian: Okay, well this is our mission. And that’s exactly our goal, 20% by 2030. So we’ve got some work to do. And we are working at both fronts. You’re right, we need better treatments. And so we’ve set up a clinical trial platform where we can look at a lot of different treatments much more efficiently, much faster, kind of taking advantage of an infrastructure to do that. And that’s called Precision Promise. And we’re excited about that as a way to get new treatments for advanced pancreatic cancer.

And then we’re also working on the early detection end. We think an important symptom of pancreatic cancer that isn’t often recognized is new onset diabetes, sudden diabetes in those over 50 where that person did not have diabetes before. So it’s new, looks like type 2 diabetes, but it’s actually caused by pancreatic cancer.

And so we have an initiative, The Early Detection Initiative, that is taking advantage of that. And seeing if we image people right away based on that symptom, can we find pancreatic cancer early? So we think it’s important to look both at trying to diagnose it earlier, as well as trying to treat it better for advanced disease.

Dr. Whyte: Yeah. You know, at WebMD we’re always trying to empower people with better information so they can also become advocates for their health. You’re an expert in advocacy on pancreatic cancer. So what’s your advice to listeners as to how they become good advocates for themselves or advocates in general for loved ones who have pancreatic cancer?

Dr. Matrisian: Yeah. Yeah. Well certainly, knowledge is power. And so the real thing to do is to call the Pancreatic Cancer Action Network. This is what we do. We stay up on the most current information. We have very experienced case managers who can help navigate the complexities of pancreatic cancer at every stage of the journey.

Or if you have questions about pancreatic cancer, call PanCAN. Go to PanCAN.org and give us a call. Because it’s really that knowledge, knowing what it is that you need to get more knowledge about, how to advocate for yourself is very important in a disease, in any disease, but in particular a disease like pancreatic cancer.

Dr. Whyte: And I don’t want to dismiss the progress that we’ve made, that you’ve just referenced in terms of the increased survival. But there’s still a long way to go. We need a lot more dollars for research. We need a lot more clinical trials to take place. What’s your message to a viewer who’s been diagnosed with pancreatic cancer or a loved one? What’s your message, Lynn, today for them?

Dr. Matrisian: Well, first, get as much knowledge as you can. Call PanCAN, and let us help you help your loved one. But then help us. Let’s do research. Let’s do more research. Let’s understand this disease better so we can make those kinds of progress in both treatment and early detection.

And PanCAN works very hard at understanding the disease and setting up research programs that are going to make a difference, that are going to get us to that aggressive goal of 20% survival by 2030. So there is a lot of things that can be done, raise awareness to your friends and neighbors about the disease, lots of things that will help this whole field.

Dr. Whyte: What’s your feeling on second opinions? Given that this can be a difficult cancer to treat, given that there’s emerging therapies that are always developing, when you have a diagnosis of pancreatic cancer, is it important to consider getting a second opinion?

Dr. Matrisian: Yes. Yes, it is. And our case managers will help with that process. We do think it’s important.

Dr. Whyte: Because sometimes, Lynn, people just want to get started, right? Get it out of me. Get treatment. And sometimes getting a second opinion, doing some genomic testing can take time. So what’s your response to that?

Dr. Matrisian: Yeah. Yeah. Well we say, your care team is very important. Who is on your care team, and it may take a little time to find the right people on your care team. But that is an incredibly important step. Sometimes it’s not just one person. Sometimes you need more than one doctor, more than one nurse, more than one type of specialty to help you deal with this. And taking the time to do that is incredibly important.

Yes, you need to – you do need to act. But act smart. And do it with knowledge. Do it really understanding what your options are, and advocate for yourself.

Dr. Whyte: And surround yourself as you reference with that right care team for you, because that’s the most important thing when you have any type of cancer diagnosis. Dr. Lynn Matrisian, I want to thank you for taking time today.

Dr. Matrisian: Thank you so much, John.

A version of this article first appeared on Medscape.com.

John Whyte, MD: Hello, I’m Dr. John Whyte, the Chief Medical Officer of WebMD. The American Cancer Society released some encouraging data recently that showed a decline in some cancers. One of those cancers was pancreatic cancer, which historically has had a very low survival rate. What’s going on here? Are we doing better with diagnosis, treatment, a combination?

Joining me today is Dr. Lynn Matrisian. She is PanCAN’s chief science officer. Dr. Matrisian, thanks for joining me today. It’s great to see you.

Lynn Matrisian, PhD, MBA: Great to be here. Thank you.

Dr. Whyte: Well, tell me what your first reaction was when you saw the recent data from the American Cancer Society. What one word would you use?

Dr. Matrisian: Hopeful. I think hopeful in general that survival rates are increasing, not for all cancers, but for many cancers. We continue to make progress. Research is making a difference. And we’re making progress against cancer in general.

Dr. Whyte: You’re passionate, as our viewers know, about pancreatic cancer. And that’s been one of the hardest cancers to treat, and one of the lowest survival rates. But there’s some encouraging news that we saw, didn’t we?

Dr. Matrisian: Yes. So the 5-year survival rate for pancreatic cancer went up a whole percentage. It’s at 12% now. And what’s really good is it was at 11% last year. It was at 10% the year before. So that’s 2 years in a row that we’ve had an increase in the 5-year survival rate for pancreatic cancer. So we’re hopeful that’s a trajectory that we can really capitalize on is how fast we’re making progress in this disease.

Dr. Whyte: I want to put it into context, Lynn. Because some people might be thinking, 1%? Like you’re excited about 1%? That doesn’t seem that much. But correct me if I’m wrong. A one percentage point increase means 641 more loved ones will enjoy life’s moments, as you put it, 5 years after their diagnosis that otherwise wouldn’t have. What does that practically mean to viewers?

Dr. Matrisian: That means that more than 600 people in the United States will hug a loved one 5 years after that diagnosis of pancreatic cancer. It is a very deadly disease. But we’re going to, by continuing to make progress, it gives those moments to those people. And it means that we’re making progress against the disease in general.

Dr. Whyte: So even 1%, and 1% each year, does have value.

Dr. Matrisian: It has a lot of value.

Dr. Whyte: What’s driving this improvement? Is it better screening? And we’re not so great still in screening a pancreatic cancer. Is it the innovation in cancer treatments? What do you think is accounting for what we hope is this trajectory of increases in 5-year survival?

Dr. Matrisian: Right, so the nice thing the reason that we like looking at 5-year survival rates is because it takes into account all of those things. And we have actually made progress in all of those things. So by looking at those that are diagnosed with pancreatic cancer in general as a whole, and looking at their survival, we are looking at better treatments. People who are getting pancreatic cancer later are living longer as a result of better treatments.

But it’s not just that. It’s also, if you’re diagnosed earlier, your 5-year survival rate is higher. More people who are diagnosed early live to five years than those that are diagnosed later. So within that statistic, there are more people who are diagnosed earlier. And those people also live longer. So it takes into account all of those things, which is why we really like to look at that five-year survival rate for a disease like pancreatic cancer.

Dr. Whyte: Where are we on screening? Because we always want to catch people early. That gives them that greatest chance of survival. Have we made much improvements there? And if we have, what are they?

Dr. Matrisian: Well we have made improvements there are more people that are now diagnosed with localized disease than there were 20 years ago. So that is increasing. And we’re still doing it really by being aware of the symptoms right now. Being aware that kind of chronic indigestion, lower back pain that won’t go away, these are signs and symptoms. And especially things like jaundice ...

Dr. Whyte: That yellow color that they might see.

Dr. Matrisian: Yes, that yellow colors in your eye, that’s a really important symptom that would certainly send people to the doctor in order to look at this. So some of it is being more aware and finding the disease earlier. But what we’re really hoping for is some sort of blood test or some sort of other way of looking through medical records and identifying those people that need to go and be checked.

Dr. Whyte: Now we chatted about that almost two years ago. So tell me the progress that we’ve made. How are we doing?

Dr. Matrisian: Yeah, well there’s a number of companies now that have blood tests that are available. They still need more work. They still need more studies to really understand how good they are at finding pancreatic cancer early. But we didn’t have them a couple of years ago. And so it’s really a very exciting time in the field, that there’s companies that were taking advantage of research for many years and actually turning it into a commercial product that is available for people to check.

Dr. Whyte: And then what about treatments? More treatment options today than there were just a few years ago, but still a lot of progress to be made. So when we talk about even 12% 5-year survival, we’d love to see it much more. And you talk about, I don’t want to misquote, so correct me if I’m wrong. Your goal is 20%. Five-year survival by 2030. That’s not too far. So, Lynn, how are we going to get there?

Dr. Matrisian: Okay, well this is our mission. And that’s exactly our goal, 20% by 2030. So we’ve got some work to do. And we are working at both fronts. You’re right, we need better treatments. And so we’ve set up a clinical trial platform where we can look at a lot of different treatments much more efficiently, much faster, kind of taking advantage of an infrastructure to do that. And that’s called Precision Promise. And we’re excited about that as a way to get new treatments for advanced pancreatic cancer.

And then we’re also working on the early detection end. We think an important symptom of pancreatic cancer that isn’t often recognized is new onset diabetes, sudden diabetes in those over 50 where that person did not have diabetes before. So it’s new, looks like type 2 diabetes, but it’s actually caused by pancreatic cancer.

And so we have an initiative, The Early Detection Initiative, that is taking advantage of that. And seeing if we image people right away based on that symptom, can we find pancreatic cancer early? So we think it’s important to look both at trying to diagnose it earlier, as well as trying to treat it better for advanced disease.

Dr. Whyte: Yeah. You know, at WebMD we’re always trying to empower people with better information so they can also become advocates for their health. You’re an expert in advocacy on pancreatic cancer. So what’s your advice to listeners as to how they become good advocates for themselves or advocates in general for loved ones who have pancreatic cancer?

Dr. Matrisian: Yeah. Yeah. Well certainly, knowledge is power. And so the real thing to do is to call the Pancreatic Cancer Action Network. This is what we do. We stay up on the most current information. We have very experienced case managers who can help navigate the complexities of pancreatic cancer at every stage of the journey.

Or if you have questions about pancreatic cancer, call PanCAN. Go to PanCAN.org and give us a call. Because it’s really that knowledge, knowing what it is that you need to get more knowledge about, how to advocate for yourself is very important in a disease, in any disease, but in particular a disease like pancreatic cancer.

Dr. Whyte: And I don’t want to dismiss the progress that we’ve made, that you’ve just referenced in terms of the increased survival. But there’s still a long way to go. We need a lot more dollars for research. We need a lot more clinical trials to take place. What’s your message to a viewer who’s been diagnosed with pancreatic cancer or a loved one? What’s your message, Lynn, today for them?

Dr. Matrisian: Well, first, get as much knowledge as you can. Call PanCAN, and let us help you help your loved one. But then help us. Let’s do research. Let’s do more research. Let’s understand this disease better so we can make those kinds of progress in both treatment and early detection.

And PanCAN works very hard at understanding the disease and setting up research programs that are going to make a difference, that are going to get us to that aggressive goal of 20% survival by 2030. So there is a lot of things that can be done, raise awareness to your friends and neighbors about the disease, lots of things that will help this whole field.

Dr. Whyte: What’s your feeling on second opinions? Given that this can be a difficult cancer to treat, given that there’s emerging therapies that are always developing, when you have a diagnosis of pancreatic cancer, is it important to consider getting a second opinion?

Dr. Matrisian: Yes. Yes, it is. And our case managers will help with that process. We do think it’s important.

Dr. Whyte: Because sometimes, Lynn, people just want to get started, right? Get it out of me. Get treatment. And sometimes getting a second opinion, doing some genomic testing can take time. So what’s your response to that?

Dr. Matrisian: Yeah. Yeah. Well we say, your care team is very important. Who is on your care team, and it may take a little time to find the right people on your care team. But that is an incredibly important step. Sometimes it’s not just one person. Sometimes you need more than one doctor, more than one nurse, more than one type of specialty to help you deal with this. And taking the time to do that is incredibly important.

Yes, you need to – you do need to act. But act smart. And do it with knowledge. Do it really understanding what your options are, and advocate for yourself.

Dr. Whyte: And surround yourself as you reference with that right care team for you, because that’s the most important thing when you have any type of cancer diagnosis. Dr. Lynn Matrisian, I want to thank you for taking time today.

Dr. Matrisian: Thank you so much, John.

A version of this article first appeared on Medscape.com.

John Whyte, MD: Hello, I’m Dr. John Whyte, the Chief Medical Officer of WebMD. The American Cancer Society released some encouraging data recently that showed a decline in some cancers. One of those cancers was pancreatic cancer, which historically has had a very low survival rate. What’s going on here? Are we doing better with diagnosis, treatment, a combination?

Joining me today is Dr. Lynn Matrisian. She is PanCAN’s chief science officer. Dr. Matrisian, thanks for joining me today. It’s great to see you.

Lynn Matrisian, PhD, MBA: Great to be here. Thank you.

Dr. Whyte: Well, tell me what your first reaction was when you saw the recent data from the American Cancer Society. What one word would you use?

Dr. Matrisian: Hopeful. I think hopeful in general that survival rates are increasing, not for all cancers, but for many cancers. We continue to make progress. Research is making a difference. And we’re making progress against cancer in general.

Dr. Whyte: You’re passionate, as our viewers know, about pancreatic cancer. And that’s been one of the hardest cancers to treat, and one of the lowest survival rates. But there’s some encouraging news that we saw, didn’t we?

Dr. Matrisian: Yes. So the 5-year survival rate for pancreatic cancer went up a whole percentage. It’s at 12% now. And what’s really good is it was at 11% last year. It was at 10% the year before. So that’s 2 years in a row that we’ve had an increase in the 5-year survival rate for pancreatic cancer. So we’re hopeful that’s a trajectory that we can really capitalize on is how fast we’re making progress in this disease.

Dr. Whyte: I want to put it into context, Lynn. Because some people might be thinking, 1%? Like you’re excited about 1%? That doesn’t seem that much. But correct me if I’m wrong. A one percentage point increase means 641 more loved ones will enjoy life’s moments, as you put it, 5 years after their diagnosis that otherwise wouldn’t have. What does that practically mean to viewers?

Dr. Matrisian: That means that more than 600 people in the United States will hug a loved one 5 years after that diagnosis of pancreatic cancer. It is a very deadly disease. But we’re going to, by continuing to make progress, it gives those moments to those people. And it means that we’re making progress against the disease in general.

Dr. Whyte: So even 1%, and 1% each year, does have value.

Dr. Matrisian: It has a lot of value.

Dr. Whyte: What’s driving this improvement? Is it better screening? And we’re not so great still in screening a pancreatic cancer. Is it the innovation in cancer treatments? What do you think is accounting for what we hope is this trajectory of increases in 5-year survival?

Dr. Matrisian: Right, so the nice thing the reason that we like looking at 5-year survival rates is because it takes into account all of those things. And we have actually made progress in all of those things. So by looking at those that are diagnosed with pancreatic cancer in general as a whole, and looking at their survival, we are looking at better treatments. People who are getting pancreatic cancer later are living longer as a result of better treatments.

But it’s not just that. It’s also, if you’re diagnosed earlier, your 5-year survival rate is higher. More people who are diagnosed early live to five years than those that are diagnosed later. So within that statistic, there are more people who are diagnosed earlier. And those people also live longer. So it takes into account all of those things, which is why we really like to look at that five-year survival rate for a disease like pancreatic cancer.

Dr. Whyte: Where are we on screening? Because we always want to catch people early. That gives them that greatest chance of survival. Have we made much improvements there? And if we have, what are they?

Dr. Matrisian: Well we have made improvements there are more people that are now diagnosed with localized disease than there were 20 years ago. So that is increasing. And we’re still doing it really by being aware of the symptoms right now. Being aware that kind of chronic indigestion, lower back pain that won’t go away, these are signs and symptoms. And especially things like jaundice ...

Dr. Whyte: That yellow color that they might see.

Dr. Matrisian: Yes, that yellow colors in your eye, that’s a really important symptom that would certainly send people to the doctor in order to look at this. So some of it is being more aware and finding the disease earlier. But what we’re really hoping for is some sort of blood test or some sort of other way of looking through medical records and identifying those people that need to go and be checked.

Dr. Whyte: Now we chatted about that almost two years ago. So tell me the progress that we’ve made. How are we doing?

Dr. Matrisian: Yeah, well there’s a number of companies now that have blood tests that are available. They still need more work. They still need more studies to really understand how good they are at finding pancreatic cancer early. But we didn’t have them a couple of years ago. And so it’s really a very exciting time in the field, that there’s companies that were taking advantage of research for many years and actually turning it into a commercial product that is available for people to check.

Dr. Whyte: And then what about treatments? More treatment options today than there were just a few years ago, but still a lot of progress to be made. So when we talk about even 12% 5-year survival, we’d love to see it much more. And you talk about, I don’t want to misquote, so correct me if I’m wrong. Your goal is 20%. Five-year survival by 2030. That’s not too far. So, Lynn, how are we going to get there?

Dr. Matrisian: Okay, well this is our mission. And that’s exactly our goal, 20% by 2030. So we’ve got some work to do. And we are working at both fronts. You’re right, we need better treatments. And so we’ve set up a clinical trial platform where we can look at a lot of different treatments much more efficiently, much faster, kind of taking advantage of an infrastructure to do that. And that’s called Precision Promise. And we’re excited about that as a way to get new treatments for advanced pancreatic cancer.

And then we’re also working on the early detection end. We think an important symptom of pancreatic cancer that isn’t often recognized is new onset diabetes, sudden diabetes in those over 50 where that person did not have diabetes before. So it’s new, looks like type 2 diabetes, but it’s actually caused by pancreatic cancer.

And so we have an initiative, The Early Detection Initiative, that is taking advantage of that. And seeing if we image people right away based on that symptom, can we find pancreatic cancer early? So we think it’s important to look both at trying to diagnose it earlier, as well as trying to treat it better for advanced disease.

Dr. Whyte: Yeah. You know, at WebMD we’re always trying to empower people with better information so they can also become advocates for their health. You’re an expert in advocacy on pancreatic cancer. So what’s your advice to listeners as to how they become good advocates for themselves or advocates in general for loved ones who have pancreatic cancer?

Dr. Matrisian: Yeah. Yeah. Well certainly, knowledge is power. And so the real thing to do is to call the Pancreatic Cancer Action Network. This is what we do. We stay up on the most current information. We have very experienced case managers who can help navigate the complexities of pancreatic cancer at every stage of the journey.

Or if you have questions about pancreatic cancer, call PanCAN. Go to PanCAN.org and give us a call. Because it’s really that knowledge, knowing what it is that you need to get more knowledge about, how to advocate for yourself is very important in a disease, in any disease, but in particular a disease like pancreatic cancer.

Dr. Whyte: And I don’t want to dismiss the progress that we’ve made, that you’ve just referenced in terms of the increased survival. But there’s still a long way to go. We need a lot more dollars for research. We need a lot more clinical trials to take place. What’s your message to a viewer who’s been diagnosed with pancreatic cancer or a loved one? What’s your message, Lynn, today for them?

Dr. Matrisian: Well, first, get as much knowledge as you can. Call PanCAN, and let us help you help your loved one. But then help us. Let’s do research. Let’s do more research. Let’s understand this disease better so we can make those kinds of progress in both treatment and early detection.

And PanCAN works very hard at understanding the disease and setting up research programs that are going to make a difference, that are going to get us to that aggressive goal of 20% survival by 2030. So there is a lot of things that can be done, raise awareness to your friends and neighbors about the disease, lots of things that will help this whole field.

Dr. Whyte: What’s your feeling on second opinions? Given that this can be a difficult cancer to treat, given that there’s emerging therapies that are always developing, when you have a diagnosis of pancreatic cancer, is it important to consider getting a second opinion?

Dr. Matrisian: Yes. Yes, it is. And our case managers will help with that process. We do think it’s important.

Dr. Whyte: Because sometimes, Lynn, people just want to get started, right? Get it out of me. Get treatment. And sometimes getting a second opinion, doing some genomic testing can take time. So what’s your response to that?

Dr. Matrisian: Yeah. Yeah. Well we say, your care team is very important. Who is on your care team, and it may take a little time to find the right people on your care team. But that is an incredibly important step. Sometimes it’s not just one person. Sometimes you need more than one doctor, more than one nurse, more than one type of specialty to help you deal with this. And taking the time to do that is incredibly important.

Yes, you need to – you do need to act. But act smart. And do it with knowledge. Do it really understanding what your options are, and advocate for yourself.

Dr. Whyte: And surround yourself as you reference with that right care team for you, because that’s the most important thing when you have any type of cancer diagnosis. Dr. Lynn Matrisian, I want to thank you for taking time today.

Dr. Matrisian: Thank you so much, John.

A version of this article first appeared on Medscape.com.