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SUDs rates highest in head, neck, and gastric cancer survivors
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The association between cancer and substance use is well known, but data on the prevalence of different substance use disorders (SUDs) in different types of cancer are limited, Katie F. Jones, PhD, of the VA Boston Healthcare System, and colleagues, wrote in their paper.
“Substance use and use disorders are on the rise in general and among older adults, who represent the majority of people diagnosed with cancer, and SUDs have significant potential to complicate cancer care and negatively impact cancer outcomes,” corresponding author Devon K. Check, PhD, of Duke University, Durham, N.C., said in an interview. “We thought it was important to understand whether SUDs are more common with certain types of cancer. We can use that information to guide resources toward populations where interventions to integrate SUD treatment and cancer treatment are most needed,” he said. “In addition, because different SUDs (opioid use disorder, alcohol use disorder) might complicate cancer treatment in different ways and necessitate different types of interventions, we thought it was important to understand the distribution of specific disorders,” he explained.
In the cross-sectional study published in JAMA Oncology, the researchers reviewed data from 6,101 adult cancer survivors who participated in the National Survey of Drug Use and Health (NSDUH) between 2015 and 2020.
The study population included survivors of solid tumor cancers. SUD was defined as meeting at least one of four criteria for substance abuse or at least 3 of 6 criteria for dependence based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria.
Overall, 3.83% of the participants met criteria for SUD. Survivors of head and neck cancers and survivors of gastric and esophageal cancers had the highest rates of SUDs (approximately 9%), followed by cervical cancer and melanoma survivors (approximately 6%).
Alcohol use disorder was the most common SUD both overall (2.8%) and among survivors of head and neck cancers, cervical cancers, and melanoma.
Cannabis use disorder was the most prevalent SUD among esophageal and gastric cancer survivors (approximately 9%).
The prevalence of SUDs overall and within the past year (active) was approximately 4%, but the prevalence of active SUDs was significantly higher for those with head and neck cancers and cervical cancer (18.73% and 15.70%, respectively). However, the distribution of specific SUDs was different in the newly diagnosed patients. Sedative use disorder took the top spot as the most common SUD for head and neck cancer survivors (9.81%), while alcohol use disorder was the most common SUD among cervical cancer survivors (10.49%).
Limitations and Implications
The findings were limited by several factors, including the nature of the study population and the data source, said Dr. Check.
“The average prevalence of SUD (or the prevalence across cancer types) was lower than we might have expected,” but the results make sense given the mainly older and female study population, he said. SUDs are less common among older adults compared with younger adults and among women compared with men, and the study’s data source (NSDUH) has been shown in other research to underestimate the prevalence of opioid use disorder, he added.
“Otherwise, the study findings were generally consistent with what we would expect,” Dr. Check said in an interview. “For example, alcohol use disorder is the most common SUD in the general U.S. population, and that was true for our study population of cancer survivors as well. In addition, SUD prevalence was higher in cancers such as cervical cancer and head and neck cancers that are causally linked to alcohol and/or tobacco use,” he said.
Integrated care is needed
“Among people diagnosed with certain types of cancers, including cervical and head and neck cancers, the estimated prevalence of SUD is similar to those [with] medical comorbidities such as diabetes and cardiopulmonary conditions,” said Dr. Check. “Within the field, there is an increasing emphasis on ensuring that people diagnosed with cancer have access to integrated care for their comorbid medical conditions. Similar efforts for people who concurrently manage cancer and SUD are largely absent but critically needed; these efforts should prioritize cancer populations where SUD prevalence is high,” he said.
Looking ahead, “We need to understand more about the specific challenges that arise at the intersection of cancer and SUD so we can design interventions and programs to better support both patients who concurrently manage cancer and SUD and the clinicians who care for them,” Dr. Check added.
Recognize risk factors
“It is very important to study overall substance use disorders in patients with cancer, because understanding the risks of developing these issues after treatment helps us develop approaches to best support these patients following their cancer therapies,” Henry S. Park, MD, a radiation oncologist at Yale University, New Haven, Connecticut, said in an interview.
The current study findings “are generally consistent with my experience and intuition, but it is still helpful to see the actual data,” said Dr. Park, who was not involved in the study. “This may be partially because of the baseline elevated risk of preexisting SUDs for certain patients from the higher-prevalence disease sites. However, it may also be related to the intense side effects that survivors of some types of cancers, such as head and neck cancer, gastroesophageal cancer, and cervical cancer, may experience soon after treatment, and even chronically long after treatment,” he said.
Individualize risk assessment
“Ultimately, clinicians should be aware that not all patients with cancer are the same, and that the majority do not necessarily develop SUDs,” Dr. Park said in an interview. “We should be careful to treat symptoms appropriately, and not withhold therapies purely because of an elevated risk of developing SUDs. However, there are some patients who are at higher risk of SUDs who will need extra support and care from physicians, advanced practice providers, nutritionists, social workers, psychologists, dietitians, and survivorship clinics, both in the short-term and long-term,” he emphasized.
As for additional research, “more work needs to be done on which particular patients within each disease subset are most likely to develop SUDs,” said Dr. Park. “Most importantly, once we identify our high-risk group as reliably as possible, we will have to study interventions that rely on supporting and partnering with patients to decrease the risk of developing SUDs as much as possible, while adequately treating residual symptoms and quality-of-life effects following cancer treatment,” he said.
The study received no outside funding. Dr. Check disclosed grants from Duke University during the study period and grants from the National Institutes of Health and AstraZeneca unrelated to the current study. Dr. Park had no financial conflicts to disclose.
.
The association between cancer and substance use is well known, but data on the prevalence of different substance use disorders (SUDs) in different types of cancer are limited, Katie F. Jones, PhD, of the VA Boston Healthcare System, and colleagues, wrote in their paper.
“Substance use and use disorders are on the rise in general and among older adults, who represent the majority of people diagnosed with cancer, and SUDs have significant potential to complicate cancer care and negatively impact cancer outcomes,” corresponding author Devon K. Check, PhD, of Duke University, Durham, N.C., said in an interview. “We thought it was important to understand whether SUDs are more common with certain types of cancer. We can use that information to guide resources toward populations where interventions to integrate SUD treatment and cancer treatment are most needed,” he said. “In addition, because different SUDs (opioid use disorder, alcohol use disorder) might complicate cancer treatment in different ways and necessitate different types of interventions, we thought it was important to understand the distribution of specific disorders,” he explained.
In the cross-sectional study published in JAMA Oncology, the researchers reviewed data from 6,101 adult cancer survivors who participated in the National Survey of Drug Use and Health (NSDUH) between 2015 and 2020.
The study population included survivors of solid tumor cancers. SUD was defined as meeting at least one of four criteria for substance abuse or at least 3 of 6 criteria for dependence based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria.
Overall, 3.83% of the participants met criteria for SUD. Survivors of head and neck cancers and survivors of gastric and esophageal cancers had the highest rates of SUDs (approximately 9%), followed by cervical cancer and melanoma survivors (approximately 6%).
Alcohol use disorder was the most common SUD both overall (2.8%) and among survivors of head and neck cancers, cervical cancers, and melanoma.
Cannabis use disorder was the most prevalent SUD among esophageal and gastric cancer survivors (approximately 9%).
The prevalence of SUDs overall and within the past year (active) was approximately 4%, but the prevalence of active SUDs was significantly higher for those with head and neck cancers and cervical cancer (18.73% and 15.70%, respectively). However, the distribution of specific SUDs was different in the newly diagnosed patients. Sedative use disorder took the top spot as the most common SUD for head and neck cancer survivors (9.81%), while alcohol use disorder was the most common SUD among cervical cancer survivors (10.49%).
Limitations and Implications
The findings were limited by several factors, including the nature of the study population and the data source, said Dr. Check.
“The average prevalence of SUD (or the prevalence across cancer types) was lower than we might have expected,” but the results make sense given the mainly older and female study population, he said. SUDs are less common among older adults compared with younger adults and among women compared with men, and the study’s data source (NSDUH) has been shown in other research to underestimate the prevalence of opioid use disorder, he added.
“Otherwise, the study findings were generally consistent with what we would expect,” Dr. Check said in an interview. “For example, alcohol use disorder is the most common SUD in the general U.S. population, and that was true for our study population of cancer survivors as well. In addition, SUD prevalence was higher in cancers such as cervical cancer and head and neck cancers that are causally linked to alcohol and/or tobacco use,” he said.
Integrated care is needed
“Among people diagnosed with certain types of cancers, including cervical and head and neck cancers, the estimated prevalence of SUD is similar to those [with] medical comorbidities such as diabetes and cardiopulmonary conditions,” said Dr. Check. “Within the field, there is an increasing emphasis on ensuring that people diagnosed with cancer have access to integrated care for their comorbid medical conditions. Similar efforts for people who concurrently manage cancer and SUD are largely absent but critically needed; these efforts should prioritize cancer populations where SUD prevalence is high,” he said.
Looking ahead, “We need to understand more about the specific challenges that arise at the intersection of cancer and SUD so we can design interventions and programs to better support both patients who concurrently manage cancer and SUD and the clinicians who care for them,” Dr. Check added.
Recognize risk factors
“It is very important to study overall substance use disorders in patients with cancer, because understanding the risks of developing these issues after treatment helps us develop approaches to best support these patients following their cancer therapies,” Henry S. Park, MD, a radiation oncologist at Yale University, New Haven, Connecticut, said in an interview.
The current study findings “are generally consistent with my experience and intuition, but it is still helpful to see the actual data,” said Dr. Park, who was not involved in the study. “This may be partially because of the baseline elevated risk of preexisting SUDs for certain patients from the higher-prevalence disease sites. However, it may also be related to the intense side effects that survivors of some types of cancers, such as head and neck cancer, gastroesophageal cancer, and cervical cancer, may experience soon after treatment, and even chronically long after treatment,” he said.
Individualize risk assessment
“Ultimately, clinicians should be aware that not all patients with cancer are the same, and that the majority do not necessarily develop SUDs,” Dr. Park said in an interview. “We should be careful to treat symptoms appropriately, and not withhold therapies purely because of an elevated risk of developing SUDs. However, there are some patients who are at higher risk of SUDs who will need extra support and care from physicians, advanced practice providers, nutritionists, social workers, psychologists, dietitians, and survivorship clinics, both in the short-term and long-term,” he emphasized.
As for additional research, “more work needs to be done on which particular patients within each disease subset are most likely to develop SUDs,” said Dr. Park. “Most importantly, once we identify our high-risk group as reliably as possible, we will have to study interventions that rely on supporting and partnering with patients to decrease the risk of developing SUDs as much as possible, while adequately treating residual symptoms and quality-of-life effects following cancer treatment,” he said.
The study received no outside funding. Dr. Check disclosed grants from Duke University during the study period and grants from the National Institutes of Health and AstraZeneca unrelated to the current study. Dr. Park had no financial conflicts to disclose.
.
The association between cancer and substance use is well known, but data on the prevalence of different substance use disorders (SUDs) in different types of cancer are limited, Katie F. Jones, PhD, of the VA Boston Healthcare System, and colleagues, wrote in their paper.
“Substance use and use disorders are on the rise in general and among older adults, who represent the majority of people diagnosed with cancer, and SUDs have significant potential to complicate cancer care and negatively impact cancer outcomes,” corresponding author Devon K. Check, PhD, of Duke University, Durham, N.C., said in an interview. “We thought it was important to understand whether SUDs are more common with certain types of cancer. We can use that information to guide resources toward populations where interventions to integrate SUD treatment and cancer treatment are most needed,” he said. “In addition, because different SUDs (opioid use disorder, alcohol use disorder) might complicate cancer treatment in different ways and necessitate different types of interventions, we thought it was important to understand the distribution of specific disorders,” he explained.
In the cross-sectional study published in JAMA Oncology, the researchers reviewed data from 6,101 adult cancer survivors who participated in the National Survey of Drug Use and Health (NSDUH) between 2015 and 2020.
The study population included survivors of solid tumor cancers. SUD was defined as meeting at least one of four criteria for substance abuse or at least 3 of 6 criteria for dependence based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria.
Overall, 3.83% of the participants met criteria for SUD. Survivors of head and neck cancers and survivors of gastric and esophageal cancers had the highest rates of SUDs (approximately 9%), followed by cervical cancer and melanoma survivors (approximately 6%).
Alcohol use disorder was the most common SUD both overall (2.8%) and among survivors of head and neck cancers, cervical cancers, and melanoma.
Cannabis use disorder was the most prevalent SUD among esophageal and gastric cancer survivors (approximately 9%).
The prevalence of SUDs overall and within the past year (active) was approximately 4%, but the prevalence of active SUDs was significantly higher for those with head and neck cancers and cervical cancer (18.73% and 15.70%, respectively). However, the distribution of specific SUDs was different in the newly diagnosed patients. Sedative use disorder took the top spot as the most common SUD for head and neck cancer survivors (9.81%), while alcohol use disorder was the most common SUD among cervical cancer survivors (10.49%).
Limitations and Implications
The findings were limited by several factors, including the nature of the study population and the data source, said Dr. Check.
“The average prevalence of SUD (or the prevalence across cancer types) was lower than we might have expected,” but the results make sense given the mainly older and female study population, he said. SUDs are less common among older adults compared with younger adults and among women compared with men, and the study’s data source (NSDUH) has been shown in other research to underestimate the prevalence of opioid use disorder, he added.
“Otherwise, the study findings were generally consistent with what we would expect,” Dr. Check said in an interview. “For example, alcohol use disorder is the most common SUD in the general U.S. population, and that was true for our study population of cancer survivors as well. In addition, SUD prevalence was higher in cancers such as cervical cancer and head and neck cancers that are causally linked to alcohol and/or tobacco use,” he said.
Integrated care is needed
“Among people diagnosed with certain types of cancers, including cervical and head and neck cancers, the estimated prevalence of SUD is similar to those [with] medical comorbidities such as diabetes and cardiopulmonary conditions,” said Dr. Check. “Within the field, there is an increasing emphasis on ensuring that people diagnosed with cancer have access to integrated care for their comorbid medical conditions. Similar efforts for people who concurrently manage cancer and SUD are largely absent but critically needed; these efforts should prioritize cancer populations where SUD prevalence is high,” he said.
Looking ahead, “We need to understand more about the specific challenges that arise at the intersection of cancer and SUD so we can design interventions and programs to better support both patients who concurrently manage cancer and SUD and the clinicians who care for them,” Dr. Check added.
Recognize risk factors
“It is very important to study overall substance use disorders in patients with cancer, because understanding the risks of developing these issues after treatment helps us develop approaches to best support these patients following their cancer therapies,” Henry S. Park, MD, a radiation oncologist at Yale University, New Haven, Connecticut, said in an interview.
The current study findings “are generally consistent with my experience and intuition, but it is still helpful to see the actual data,” said Dr. Park, who was not involved in the study. “This may be partially because of the baseline elevated risk of preexisting SUDs for certain patients from the higher-prevalence disease sites. However, it may also be related to the intense side effects that survivors of some types of cancers, such as head and neck cancer, gastroesophageal cancer, and cervical cancer, may experience soon after treatment, and even chronically long after treatment,” he said.
Individualize risk assessment
“Ultimately, clinicians should be aware that not all patients with cancer are the same, and that the majority do not necessarily develop SUDs,” Dr. Park said in an interview. “We should be careful to treat symptoms appropriately, and not withhold therapies purely because of an elevated risk of developing SUDs. However, there are some patients who are at higher risk of SUDs who will need extra support and care from physicians, advanced practice providers, nutritionists, social workers, psychologists, dietitians, and survivorship clinics, both in the short-term and long-term,” he emphasized.
As for additional research, “more work needs to be done on which particular patients within each disease subset are most likely to develop SUDs,” said Dr. Park. “Most importantly, once we identify our high-risk group as reliably as possible, we will have to study interventions that rely on supporting and partnering with patients to decrease the risk of developing SUDs as much as possible, while adequately treating residual symptoms and quality-of-life effects following cancer treatment,” he said.
The study received no outside funding. Dr. Check disclosed grants from Duke University during the study period and grants from the National Institutes of Health and AstraZeneca unrelated to the current study. Dr. Park had no financial conflicts to disclose.
FROM JAMA ONCOLOGY
Side Effects of Local Treatment for Advanced Prostate Cancer May Linger for Years
TOPLINE:
METHODOLOGY:
Recent evidence suggested that in men with advanced prostate cancer, local therapy with radical prostatectomy or radiation may improve survival outcomes; however, data on the long-term side effects from these local options were limited.
The retrospective cohort included 5502 men (mean age, 68 years) diagnosed with advanced (T4, N1, and/or M1) prostate cancer.
A total of 1705 men (31%) received initial local treatment, consisting of radical prostatectomy, (55%), radiation (39%), or both (5.6%), while 3797 (69%) opted for initial nonlocal treatment (hormone therapy, chemotherapy, or both).
The main outcomes were treatment-related adverse effects, including GI, chronic pain, sexual dysfunction, and urinary symptoms, assessed at three timepoints after initial treatment — up to 1 year, between 1 and 2 years, and between 2 and 5 years.
TAKEAWAY:
Overall, 916 men (75%) who had initial local treatment and 897 men (67%) with initial nonlocal therapy reported at least one adverse condition up to 5 years after initial treatment.
In the first year after initial treatment, local therapy was associated with a higher prevalence of GI (9% vs 3%), pain (60% vs 38%), sexual (37% vs 8%), and urinary (46.5% vs 18%) conditions. Men receiving local therapy were more likely to experience GI (adjusted odds ratio [aOR], 4.08), pain (aOR, 1.57), sexual (aOR, 2.96), and urinary (aOR, 2.25) conditions.
Between 2 and 5 years after local therapy, certain conditions remained more prevalent — 7.8% vs 4.2% for GI, 40% vs 13% for sexual, and 40.5% vs 26% for urinary issues. Men receiving local vs nonlocal therapy were more likely to experience GI (aOR, 2.39), sexual (aOR, 3.36), and urinary (aOR, 1.39) issues over the long term.
The researchers found no difference in the prevalence of constitutional conditions such as hot flashes (36.5% vs 34.4%) in the first year following initial local or nonlocal therapy. However, local treatment followed by any secondary treatment was associated with a higher likelihood of developing constitutional conditions at 1-2 years (aOR, 1.50) and 2-5 years (aOR, 1.78) after initial treatment.
IN PRACTICE:
“These results suggest that patients and clinicians should consider the adverse effects of local treatment” alongside the potential for enhanced survival when making treatment decisions in the setting of advanced prostate cancer, the authors explained. Careful informed decision-making by both patients and practitioners is especially important because “there are currently no established guidelines regarding the use of local treatment among men with advanced prostate cancer.”
SOURCE:
The study, with first author Saira Khan, PhD, MPH, Washington University School of Medicine in St. Louis, Missouri, was published online in JAMA Network Open.
LIMITATIONS:
The authors noted that the study was limited by its retrospective design. Men who received local treatment were, on average, younger; older or lesser healthy patients who received local treatment may experience worse adverse effects than observed in the study. The study was limited to US veterans.
DISCLOSURES:
The study was supported by a grant from the US Department of Defense. The authors have no relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
Recent evidence suggested that in men with advanced prostate cancer, local therapy with radical prostatectomy or radiation may improve survival outcomes; however, data on the long-term side effects from these local options were limited.
The retrospective cohort included 5502 men (mean age, 68 years) diagnosed with advanced (T4, N1, and/or M1) prostate cancer.
A total of 1705 men (31%) received initial local treatment, consisting of radical prostatectomy, (55%), radiation (39%), or both (5.6%), while 3797 (69%) opted for initial nonlocal treatment (hormone therapy, chemotherapy, or both).
The main outcomes were treatment-related adverse effects, including GI, chronic pain, sexual dysfunction, and urinary symptoms, assessed at three timepoints after initial treatment — up to 1 year, between 1 and 2 years, and between 2 and 5 years.
TAKEAWAY:
Overall, 916 men (75%) who had initial local treatment and 897 men (67%) with initial nonlocal therapy reported at least one adverse condition up to 5 years after initial treatment.
In the first year after initial treatment, local therapy was associated with a higher prevalence of GI (9% vs 3%), pain (60% vs 38%), sexual (37% vs 8%), and urinary (46.5% vs 18%) conditions. Men receiving local therapy were more likely to experience GI (adjusted odds ratio [aOR], 4.08), pain (aOR, 1.57), sexual (aOR, 2.96), and urinary (aOR, 2.25) conditions.
Between 2 and 5 years after local therapy, certain conditions remained more prevalent — 7.8% vs 4.2% for GI, 40% vs 13% for sexual, and 40.5% vs 26% for urinary issues. Men receiving local vs nonlocal therapy were more likely to experience GI (aOR, 2.39), sexual (aOR, 3.36), and urinary (aOR, 1.39) issues over the long term.
The researchers found no difference in the prevalence of constitutional conditions such as hot flashes (36.5% vs 34.4%) in the first year following initial local or nonlocal therapy. However, local treatment followed by any secondary treatment was associated with a higher likelihood of developing constitutional conditions at 1-2 years (aOR, 1.50) and 2-5 years (aOR, 1.78) after initial treatment.
IN PRACTICE:
“These results suggest that patients and clinicians should consider the adverse effects of local treatment” alongside the potential for enhanced survival when making treatment decisions in the setting of advanced prostate cancer, the authors explained. Careful informed decision-making by both patients and practitioners is especially important because “there are currently no established guidelines regarding the use of local treatment among men with advanced prostate cancer.”
SOURCE:
The study, with first author Saira Khan, PhD, MPH, Washington University School of Medicine in St. Louis, Missouri, was published online in JAMA Network Open.
LIMITATIONS:
The authors noted that the study was limited by its retrospective design. Men who received local treatment were, on average, younger; older or lesser healthy patients who received local treatment may experience worse adverse effects than observed in the study. The study was limited to US veterans.
DISCLOSURES:
The study was supported by a grant from the US Department of Defense. The authors have no relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
Recent evidence suggested that in men with advanced prostate cancer, local therapy with radical prostatectomy or radiation may improve survival outcomes; however, data on the long-term side effects from these local options were limited.
The retrospective cohort included 5502 men (mean age, 68 years) diagnosed with advanced (T4, N1, and/or M1) prostate cancer.
A total of 1705 men (31%) received initial local treatment, consisting of radical prostatectomy, (55%), radiation (39%), or both (5.6%), while 3797 (69%) opted for initial nonlocal treatment (hormone therapy, chemotherapy, or both).
The main outcomes were treatment-related adverse effects, including GI, chronic pain, sexual dysfunction, and urinary symptoms, assessed at three timepoints after initial treatment — up to 1 year, between 1 and 2 years, and between 2 and 5 years.
TAKEAWAY:
Overall, 916 men (75%) who had initial local treatment and 897 men (67%) with initial nonlocal therapy reported at least one adverse condition up to 5 years after initial treatment.
In the first year after initial treatment, local therapy was associated with a higher prevalence of GI (9% vs 3%), pain (60% vs 38%), sexual (37% vs 8%), and urinary (46.5% vs 18%) conditions. Men receiving local therapy were more likely to experience GI (adjusted odds ratio [aOR], 4.08), pain (aOR, 1.57), sexual (aOR, 2.96), and urinary (aOR, 2.25) conditions.
Between 2 and 5 years after local therapy, certain conditions remained more prevalent — 7.8% vs 4.2% for GI, 40% vs 13% for sexual, and 40.5% vs 26% for urinary issues. Men receiving local vs nonlocal therapy were more likely to experience GI (aOR, 2.39), sexual (aOR, 3.36), and urinary (aOR, 1.39) issues over the long term.
The researchers found no difference in the prevalence of constitutional conditions such as hot flashes (36.5% vs 34.4%) in the first year following initial local or nonlocal therapy. However, local treatment followed by any secondary treatment was associated with a higher likelihood of developing constitutional conditions at 1-2 years (aOR, 1.50) and 2-5 years (aOR, 1.78) after initial treatment.
IN PRACTICE:
“These results suggest that patients and clinicians should consider the adverse effects of local treatment” alongside the potential for enhanced survival when making treatment decisions in the setting of advanced prostate cancer, the authors explained. Careful informed decision-making by both patients and practitioners is especially important because “there are currently no established guidelines regarding the use of local treatment among men with advanced prostate cancer.”
SOURCE:
The study, with first author Saira Khan, PhD, MPH, Washington University School of Medicine in St. Louis, Missouri, was published online in JAMA Network Open.
LIMITATIONS:
The authors noted that the study was limited by its retrospective design. Men who received local treatment were, on average, younger; older or lesser healthy patients who received local treatment may experience worse adverse effects than observed in the study. The study was limited to US veterans.
DISCLOSURES:
The study was supported by a grant from the US Department of Defense. The authors have no relevant disclosures.
A version of this article appeared on Medscape.com.
Optimal Follow-up After Fertility-Sparing Cervical Cancer Surgery
TOPLINE:
METHODOLOGY:
- Among patients with early-stage cervical cancer, the optimal follow-up strategy to detect recurrence after fertility-sparing surgery remains unclear. The authors wanted to find out if follow-up could be tailored to the patient’s risk for recurrence instead of using the current inefficient one-size-fits-all approach.
- The retrospective cohort study, which used data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank, included 1462 patients aged 18-40 years with early-stage cervical cancer who received fertility-sparing surgery (large loop excision of the transformation zone, conization, or trachelectomy) between 2000 and 2020.
- The primary endpoint was the cumulative incidence of recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+), including recurrent cervical cancer.
- The authors stratified the likelihood of recurrence by cytology and high-risk HPV results at the first follow-up visit within 12 months of fertility-sparing surgery; they also compared the cumulative incidence of recurrence — the number of new cases divided by all at-risk individuals over a specific interval — at four timepoints in 2 years (6, 12, 18, and 24 months).
TAKEAWAY:
- Overall, the 10-year recurrence-free survival for CIN2+ was 89.3%. Patients with high-grade cytology at the first follow-up had worse 10-year recurrence-free survival for CIN2+ (43.1%) than those who had normal (92.1%) and low-grade cytology (84.6%). Similarly for HPV status, patients positive for high-risk HPV at the first follow-up had worse 10-year recurrence-free survival rates for CIN2+ (73.6%) than those negative for high-risk HPV (91.1%).
- Patients negative for both high-risk HPV and high-grade cytology 6-24 months after fertility-sparing surgery had a cumulative incidence of recurrence of 0.0%-0.7% within 6 months of follow-up compared with 0.0%-33.3% among patients negative for high-risk HPV but who had high-grade cytology.
- By contrast, patients positive for high-risk HPV but not high-grade cytology had a cumulative incidence of recurrence of 0.0%-15.4% within 6 months of any follow-up visit compared with 50.0%-100.0% among those with both high-risk HPV and high-grade cytology.
- Patients who remained free of high-risk HPV and high-grade cytology at their 6-month and 12-month follow-ups had no disease recurrence over the next 6 months.
IN PRACTICE:
“Patients who are negative for high-risk HPV with normal or low-grade cytology at 6-24 months after fertility-sparing surgery could be offered a prolonged follow-up interval of 6 months,” the authors concluded, adding that this “group comprises 80% of all patients receiving fertility-sparing surgery.”
“Reducing the number of follow-up visits, and subsequently the number of follow-up tests, in patients with low risk for recurrence on the basis of co-testing has the potential to substantially reduce healthcare costs,” the authors explained.
SOURCE:
The study, led by Teska N. Schuurman, MD, of the Netherlands Cancer Institute, Amsterdam, was published in the December 2023 issue of The Lancet Oncology.
LIMITATIONS:
The retrospective design of the study meant that analysis was limited to available records, so data on patients’ symptoms, physical examinations, or colposcopic findings were not available. Follow-up biopsies, considered the gold standard for diagnosing recurrence, are not routine in the Netherlands, so recurrence could have been underreported.
DISCLOSURES:
The authors declared no competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Among patients with early-stage cervical cancer, the optimal follow-up strategy to detect recurrence after fertility-sparing surgery remains unclear. The authors wanted to find out if follow-up could be tailored to the patient’s risk for recurrence instead of using the current inefficient one-size-fits-all approach.
- The retrospective cohort study, which used data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank, included 1462 patients aged 18-40 years with early-stage cervical cancer who received fertility-sparing surgery (large loop excision of the transformation zone, conization, or trachelectomy) between 2000 and 2020.
- The primary endpoint was the cumulative incidence of recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+), including recurrent cervical cancer.
- The authors stratified the likelihood of recurrence by cytology and high-risk HPV results at the first follow-up visit within 12 months of fertility-sparing surgery; they also compared the cumulative incidence of recurrence — the number of new cases divided by all at-risk individuals over a specific interval — at four timepoints in 2 years (6, 12, 18, and 24 months).
TAKEAWAY:
- Overall, the 10-year recurrence-free survival for CIN2+ was 89.3%. Patients with high-grade cytology at the first follow-up had worse 10-year recurrence-free survival for CIN2+ (43.1%) than those who had normal (92.1%) and low-grade cytology (84.6%). Similarly for HPV status, patients positive for high-risk HPV at the first follow-up had worse 10-year recurrence-free survival rates for CIN2+ (73.6%) than those negative for high-risk HPV (91.1%).
- Patients negative for both high-risk HPV and high-grade cytology 6-24 months after fertility-sparing surgery had a cumulative incidence of recurrence of 0.0%-0.7% within 6 months of follow-up compared with 0.0%-33.3% among patients negative for high-risk HPV but who had high-grade cytology.
- By contrast, patients positive for high-risk HPV but not high-grade cytology had a cumulative incidence of recurrence of 0.0%-15.4% within 6 months of any follow-up visit compared with 50.0%-100.0% among those with both high-risk HPV and high-grade cytology.
- Patients who remained free of high-risk HPV and high-grade cytology at their 6-month and 12-month follow-ups had no disease recurrence over the next 6 months.
IN PRACTICE:
“Patients who are negative for high-risk HPV with normal or low-grade cytology at 6-24 months after fertility-sparing surgery could be offered a prolonged follow-up interval of 6 months,” the authors concluded, adding that this “group comprises 80% of all patients receiving fertility-sparing surgery.”
“Reducing the number of follow-up visits, and subsequently the number of follow-up tests, in patients with low risk for recurrence on the basis of co-testing has the potential to substantially reduce healthcare costs,” the authors explained.
SOURCE:
The study, led by Teska N. Schuurman, MD, of the Netherlands Cancer Institute, Amsterdam, was published in the December 2023 issue of The Lancet Oncology.
LIMITATIONS:
The retrospective design of the study meant that analysis was limited to available records, so data on patients’ symptoms, physical examinations, or colposcopic findings were not available. Follow-up biopsies, considered the gold standard for diagnosing recurrence, are not routine in the Netherlands, so recurrence could have been underreported.
DISCLOSURES:
The authors declared no competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Among patients with early-stage cervical cancer, the optimal follow-up strategy to detect recurrence after fertility-sparing surgery remains unclear. The authors wanted to find out if follow-up could be tailored to the patient’s risk for recurrence instead of using the current inefficient one-size-fits-all approach.
- The retrospective cohort study, which used data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank, included 1462 patients aged 18-40 years with early-stage cervical cancer who received fertility-sparing surgery (large loop excision of the transformation zone, conization, or trachelectomy) between 2000 and 2020.
- The primary endpoint was the cumulative incidence of recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+), including recurrent cervical cancer.
- The authors stratified the likelihood of recurrence by cytology and high-risk HPV results at the first follow-up visit within 12 months of fertility-sparing surgery; they also compared the cumulative incidence of recurrence — the number of new cases divided by all at-risk individuals over a specific interval — at four timepoints in 2 years (6, 12, 18, and 24 months).
TAKEAWAY:
- Overall, the 10-year recurrence-free survival for CIN2+ was 89.3%. Patients with high-grade cytology at the first follow-up had worse 10-year recurrence-free survival for CIN2+ (43.1%) than those who had normal (92.1%) and low-grade cytology (84.6%). Similarly for HPV status, patients positive for high-risk HPV at the first follow-up had worse 10-year recurrence-free survival rates for CIN2+ (73.6%) than those negative for high-risk HPV (91.1%).
- Patients negative for both high-risk HPV and high-grade cytology 6-24 months after fertility-sparing surgery had a cumulative incidence of recurrence of 0.0%-0.7% within 6 months of follow-up compared with 0.0%-33.3% among patients negative for high-risk HPV but who had high-grade cytology.
- By contrast, patients positive for high-risk HPV but not high-grade cytology had a cumulative incidence of recurrence of 0.0%-15.4% within 6 months of any follow-up visit compared with 50.0%-100.0% among those with both high-risk HPV and high-grade cytology.
- Patients who remained free of high-risk HPV and high-grade cytology at their 6-month and 12-month follow-ups had no disease recurrence over the next 6 months.
IN PRACTICE:
“Patients who are negative for high-risk HPV with normal or low-grade cytology at 6-24 months after fertility-sparing surgery could be offered a prolonged follow-up interval of 6 months,” the authors concluded, adding that this “group comprises 80% of all patients receiving fertility-sparing surgery.”
“Reducing the number of follow-up visits, and subsequently the number of follow-up tests, in patients with low risk for recurrence on the basis of co-testing has the potential to substantially reduce healthcare costs,” the authors explained.
SOURCE:
The study, led by Teska N. Schuurman, MD, of the Netherlands Cancer Institute, Amsterdam, was published in the December 2023 issue of The Lancet Oncology.
LIMITATIONS:
The retrospective design of the study meant that analysis was limited to available records, so data on patients’ symptoms, physical examinations, or colposcopic findings were not available. Follow-up biopsies, considered the gold standard for diagnosing recurrence, are not routine in the Netherlands, so recurrence could have been underreported.
DISCLOSURES:
The authors declared no competing interests.
A version of this article appeared on Medscape.com.
Active Surveillance for Low-Risk PCa: Sprint or Marathon?
Seventeen years ago, Philip Segal, a retired accountant from suburban Toronto, Canada, was diagnosed with prostate cancer in a private clinic. After rejecting brachytherapy recommended by an oncologist, he went on active surveillance to watch, but not treat, the Gleason 6 (grade group 1) tumor. As he approaches his 80th birthday later this year, Mr. Segal said he plans to maintain the status quo. “It definitely brings me some peace of mind. I’d rather do that than not follow it and kick myself if there was a serious change,” he said.
Meanwhile, 2 years ago and 200 miles away in suburban Detroit, Bruno Barrey, a robotics engineer, was diagnosed with three cores of Gleason 6 and went on active surveillance.
Six months after the original diagnosis, however, Mr. Barrey, 57, underwent a follow-up biopsy. This time, all 16 cores were positive, with a mix of low-risk Gleason 6 and more advanced Gleason 3 + 4 lesions. His tumor was so large he underwent radiation therapy in 2023, ending his brief stint on the monitoring approach.
The two cases illustrate the complicated truth of active surveillance. For some men, the strategy can prove to be short-lived, perhaps 5 years or less, or a life-long approach lasting until the man dies from another cause.
Which kind of race a man will run depends on a wide range of factors: His comfort level living with a cancer, or at least a tumor that might well evolve into an aggressive malignancy, changes in his prostate-specific antigen (PSA) level and results of a magnetic resonance imaging test, the volume of his cancer, results of genetic testing of the patient himself and his lesion, and his urologist’s philosophy about surveillance. Where a patient lives matters, too, because variations in surveillance levels exist in different geographic areas, domestically and internationally.
“Active surveillance is a strategy of monitoring until it is necessary to be treated. For some people, it is very short, and for others, essentially indefinite,” said Michael Leapman, MD, clinical lead at Yale Cancer Center in New Haven, Connecticut. “While there are differences, I think they are mainly about who is the ideal patient.”
Most studies show that roughly half of men in the United States who go on active surveillance abandon it within 5 years of diagnosis. Rashid Sayyid, MD, a clinical fellow at the University of Toronto, Canada, found in a paper presented to the American Urological Association in 2022 that the number leaving active surveillance increased to nearly two thirds at 10 years.
Peter Carroll, MD, a urologist at the University of California, San Francisco, and a pioneer in the active surveillance in the late 1990s, said the major reason men abandon the strategy is because monitoring reveals the presence of a more aggressive cancer, typically a grade group 2 (Gleason 3 + 4) lesion. But other reasons include anxiety and other emotional distress and upgrades in blood levels of PSA and increases in the rating scale for MRI for the likelihood of the presence of clinically significant prostate cancer.
Laurence Klotz, MD, of the University of Toronto, Toronto, Ontario, who coined the term active surveillance strategy in 1997 and published the first studies in the early 2000s, said it is important to consider when the data on surveillance were collected.
Since 2013, when MRI began to be adopted as a surveillance modality for men with prostate cancer, the dropout rate began declining. The reason? According to Dr. Klotz, MRIs and targeted biopsies result in greater accuracy in staging the disease, determining which patients need to be biopsied, which helps some men avoid being diagnosed to begin with.
Dr. Klotz cited as an example of the emerging change a 2020 study in the Journal of Urology, which found a 24% dropout rate for surveillance at 5 years, 36% at 10 years, and 42% at 15 years in a series of 2664 grade group 1 patients on active surveillance at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2017.
Dr. Leapman cited a 2023 study in JNCI Cancer Spectrum using the National Cancer Database that found a decline in the percentage of patients who had grade group 1 in biopsies from 45% in 2010 to 25% in 2019.
“There is more judicious use of PSA testing and biopsy in individuals who are more likely to have significant prostate cancer,” Dr. Leapman told this news organization. “And MRI could also play a role by finding more high-grade cancers that would have otherwise been hidden.”
The changing statistics of prostate cancer also may reflect decreases in screening in response to a 2012 statement from the US Preventive Services Task Force advising against PSA testing. The American Cancer Society in January 2023 said that statement could be driving more diagnoses of late-stage disease, which has been surging for the first time in two decades, especially among Black men.
Dr. Sayyid said patients must be selected carefully for active surveillance. And he said urologists should not promise their active surveillance patients that they will avoid treatment. “There are numerous factors at stake that influence the ultimate outcome,” he said.
Progression of Gleason scores is estimated at 1%-2% per year, Dr. Sayyid added. When active surveillance fails in the short to medium term — 5-10 years — the reason usually is that higher-grade cancers with Gleason 3 + 4 or above were initially missed.
Dr. Sayyid said he counsels patients aged 70 years and older differently than those in their 50s, telling younger patients they are more likely to need treatment eventually than the older patients.
Factors that can affect the longevity of active surveillance include the presence or absence of germline mutations and the overall health and life expectancy and comorbidities such as heart disease and diabetes in a given patient, he said.
Urologists hold varying philosophies here, especially involving younger patients and the presence of any level of Gleason 4 cancer.
William Catalona, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, who developed the concept of mass screening with PSA testing, originally opposed active surveillance. In recent years, he has modified his views but still takes a more conservative approach.
“I consider active surveillance a foolish strategy or, at best, a short-term strategy for young, otherwise healthy men, especially those having any Gleason pattern 4 disease.”
“More than half will ultimately convert to active treatment, some too late, and will require multiple treatments with multiple side effects. Some will develop metastases, and some will die of prostate cancer.”
Dr. Sayyid takes a more liberal approach. “I would counsel an eligible patient considering active surveillance that at the current time, I see no strong reason why you should be subjected to treatment and the associated side effects,” he said. “And as long as your overall disease ‘state’ [the combination of grade, volume, PSA, and imaging tests] remains relatively stable, there should be no reason for us to ‘jump ship’. In my practice, another term for active surveillance is ‘active partnership’ — working together to decide if this is a sprint or a lifelong marathon.”
Dr. Carroll reported research funding from the National Institutes of Health.
A version of this article appeared on Medscape.com.
Seventeen years ago, Philip Segal, a retired accountant from suburban Toronto, Canada, was diagnosed with prostate cancer in a private clinic. After rejecting brachytherapy recommended by an oncologist, he went on active surveillance to watch, but not treat, the Gleason 6 (grade group 1) tumor. As he approaches his 80th birthday later this year, Mr. Segal said he plans to maintain the status quo. “It definitely brings me some peace of mind. I’d rather do that than not follow it and kick myself if there was a serious change,” he said.
Meanwhile, 2 years ago and 200 miles away in suburban Detroit, Bruno Barrey, a robotics engineer, was diagnosed with three cores of Gleason 6 and went on active surveillance.
Six months after the original diagnosis, however, Mr. Barrey, 57, underwent a follow-up biopsy. This time, all 16 cores were positive, with a mix of low-risk Gleason 6 and more advanced Gleason 3 + 4 lesions. His tumor was so large he underwent radiation therapy in 2023, ending his brief stint on the monitoring approach.
The two cases illustrate the complicated truth of active surveillance. For some men, the strategy can prove to be short-lived, perhaps 5 years or less, or a life-long approach lasting until the man dies from another cause.
Which kind of race a man will run depends on a wide range of factors: His comfort level living with a cancer, or at least a tumor that might well evolve into an aggressive malignancy, changes in his prostate-specific antigen (PSA) level and results of a magnetic resonance imaging test, the volume of his cancer, results of genetic testing of the patient himself and his lesion, and his urologist’s philosophy about surveillance. Where a patient lives matters, too, because variations in surveillance levels exist in different geographic areas, domestically and internationally.
“Active surveillance is a strategy of monitoring until it is necessary to be treated. For some people, it is very short, and for others, essentially indefinite,” said Michael Leapman, MD, clinical lead at Yale Cancer Center in New Haven, Connecticut. “While there are differences, I think they are mainly about who is the ideal patient.”
Most studies show that roughly half of men in the United States who go on active surveillance abandon it within 5 years of diagnosis. Rashid Sayyid, MD, a clinical fellow at the University of Toronto, Canada, found in a paper presented to the American Urological Association in 2022 that the number leaving active surveillance increased to nearly two thirds at 10 years.
Peter Carroll, MD, a urologist at the University of California, San Francisco, and a pioneer in the active surveillance in the late 1990s, said the major reason men abandon the strategy is because monitoring reveals the presence of a more aggressive cancer, typically a grade group 2 (Gleason 3 + 4) lesion. But other reasons include anxiety and other emotional distress and upgrades in blood levels of PSA and increases in the rating scale for MRI for the likelihood of the presence of clinically significant prostate cancer.
Laurence Klotz, MD, of the University of Toronto, Toronto, Ontario, who coined the term active surveillance strategy in 1997 and published the first studies in the early 2000s, said it is important to consider when the data on surveillance were collected.
Since 2013, when MRI began to be adopted as a surveillance modality for men with prostate cancer, the dropout rate began declining. The reason? According to Dr. Klotz, MRIs and targeted biopsies result in greater accuracy in staging the disease, determining which patients need to be biopsied, which helps some men avoid being diagnosed to begin with.
Dr. Klotz cited as an example of the emerging change a 2020 study in the Journal of Urology, which found a 24% dropout rate for surveillance at 5 years, 36% at 10 years, and 42% at 15 years in a series of 2664 grade group 1 patients on active surveillance at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2017.
Dr. Leapman cited a 2023 study in JNCI Cancer Spectrum using the National Cancer Database that found a decline in the percentage of patients who had grade group 1 in biopsies from 45% in 2010 to 25% in 2019.
“There is more judicious use of PSA testing and biopsy in individuals who are more likely to have significant prostate cancer,” Dr. Leapman told this news organization. “And MRI could also play a role by finding more high-grade cancers that would have otherwise been hidden.”
The changing statistics of prostate cancer also may reflect decreases in screening in response to a 2012 statement from the US Preventive Services Task Force advising against PSA testing. The American Cancer Society in January 2023 said that statement could be driving more diagnoses of late-stage disease, which has been surging for the first time in two decades, especially among Black men.
Dr. Sayyid said patients must be selected carefully for active surveillance. And he said urologists should not promise their active surveillance patients that they will avoid treatment. “There are numerous factors at stake that influence the ultimate outcome,” he said.
Progression of Gleason scores is estimated at 1%-2% per year, Dr. Sayyid added. When active surveillance fails in the short to medium term — 5-10 years — the reason usually is that higher-grade cancers with Gleason 3 + 4 or above were initially missed.
Dr. Sayyid said he counsels patients aged 70 years and older differently than those in their 50s, telling younger patients they are more likely to need treatment eventually than the older patients.
Factors that can affect the longevity of active surveillance include the presence or absence of germline mutations and the overall health and life expectancy and comorbidities such as heart disease and diabetes in a given patient, he said.
Urologists hold varying philosophies here, especially involving younger patients and the presence of any level of Gleason 4 cancer.
William Catalona, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, who developed the concept of mass screening with PSA testing, originally opposed active surveillance. In recent years, he has modified his views but still takes a more conservative approach.
“I consider active surveillance a foolish strategy or, at best, a short-term strategy for young, otherwise healthy men, especially those having any Gleason pattern 4 disease.”
“More than half will ultimately convert to active treatment, some too late, and will require multiple treatments with multiple side effects. Some will develop metastases, and some will die of prostate cancer.”
Dr. Sayyid takes a more liberal approach. “I would counsel an eligible patient considering active surveillance that at the current time, I see no strong reason why you should be subjected to treatment and the associated side effects,” he said. “And as long as your overall disease ‘state’ [the combination of grade, volume, PSA, and imaging tests] remains relatively stable, there should be no reason for us to ‘jump ship’. In my practice, another term for active surveillance is ‘active partnership’ — working together to decide if this is a sprint or a lifelong marathon.”
Dr. Carroll reported research funding from the National Institutes of Health.
A version of this article appeared on Medscape.com.
Seventeen years ago, Philip Segal, a retired accountant from suburban Toronto, Canada, was diagnosed with prostate cancer in a private clinic. After rejecting brachytherapy recommended by an oncologist, he went on active surveillance to watch, but not treat, the Gleason 6 (grade group 1) tumor. As he approaches his 80th birthday later this year, Mr. Segal said he plans to maintain the status quo. “It definitely brings me some peace of mind. I’d rather do that than not follow it and kick myself if there was a serious change,” he said.
Meanwhile, 2 years ago and 200 miles away in suburban Detroit, Bruno Barrey, a robotics engineer, was diagnosed with three cores of Gleason 6 and went on active surveillance.
Six months after the original diagnosis, however, Mr. Barrey, 57, underwent a follow-up biopsy. This time, all 16 cores were positive, with a mix of low-risk Gleason 6 and more advanced Gleason 3 + 4 lesions. His tumor was so large he underwent radiation therapy in 2023, ending his brief stint on the monitoring approach.
The two cases illustrate the complicated truth of active surveillance. For some men, the strategy can prove to be short-lived, perhaps 5 years or less, or a life-long approach lasting until the man dies from another cause.
Which kind of race a man will run depends on a wide range of factors: His comfort level living with a cancer, or at least a tumor that might well evolve into an aggressive malignancy, changes in his prostate-specific antigen (PSA) level and results of a magnetic resonance imaging test, the volume of his cancer, results of genetic testing of the patient himself and his lesion, and his urologist’s philosophy about surveillance. Where a patient lives matters, too, because variations in surveillance levels exist in different geographic areas, domestically and internationally.
“Active surveillance is a strategy of monitoring until it is necessary to be treated. For some people, it is very short, and for others, essentially indefinite,” said Michael Leapman, MD, clinical lead at Yale Cancer Center in New Haven, Connecticut. “While there are differences, I think they are mainly about who is the ideal patient.”
Most studies show that roughly half of men in the United States who go on active surveillance abandon it within 5 years of diagnosis. Rashid Sayyid, MD, a clinical fellow at the University of Toronto, Canada, found in a paper presented to the American Urological Association in 2022 that the number leaving active surveillance increased to nearly two thirds at 10 years.
Peter Carroll, MD, a urologist at the University of California, San Francisco, and a pioneer in the active surveillance in the late 1990s, said the major reason men abandon the strategy is because monitoring reveals the presence of a more aggressive cancer, typically a grade group 2 (Gleason 3 + 4) lesion. But other reasons include anxiety and other emotional distress and upgrades in blood levels of PSA and increases in the rating scale for MRI for the likelihood of the presence of clinically significant prostate cancer.
Laurence Klotz, MD, of the University of Toronto, Toronto, Ontario, who coined the term active surveillance strategy in 1997 and published the first studies in the early 2000s, said it is important to consider when the data on surveillance were collected.
Since 2013, when MRI began to be adopted as a surveillance modality for men with prostate cancer, the dropout rate began declining. The reason? According to Dr. Klotz, MRIs and targeted biopsies result in greater accuracy in staging the disease, determining which patients need to be biopsied, which helps some men avoid being diagnosed to begin with.
Dr. Klotz cited as an example of the emerging change a 2020 study in the Journal of Urology, which found a 24% dropout rate for surveillance at 5 years, 36% at 10 years, and 42% at 15 years in a series of 2664 grade group 1 patients on active surveillance at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2017.
Dr. Leapman cited a 2023 study in JNCI Cancer Spectrum using the National Cancer Database that found a decline in the percentage of patients who had grade group 1 in biopsies from 45% in 2010 to 25% in 2019.
“There is more judicious use of PSA testing and biopsy in individuals who are more likely to have significant prostate cancer,” Dr. Leapman told this news organization. “And MRI could also play a role by finding more high-grade cancers that would have otherwise been hidden.”
The changing statistics of prostate cancer also may reflect decreases in screening in response to a 2012 statement from the US Preventive Services Task Force advising against PSA testing. The American Cancer Society in January 2023 said that statement could be driving more diagnoses of late-stage disease, which has been surging for the first time in two decades, especially among Black men.
Dr. Sayyid said patients must be selected carefully for active surveillance. And he said urologists should not promise their active surveillance patients that they will avoid treatment. “There are numerous factors at stake that influence the ultimate outcome,” he said.
Progression of Gleason scores is estimated at 1%-2% per year, Dr. Sayyid added. When active surveillance fails in the short to medium term — 5-10 years — the reason usually is that higher-grade cancers with Gleason 3 + 4 or above were initially missed.
Dr. Sayyid said he counsels patients aged 70 years and older differently than those in their 50s, telling younger patients they are more likely to need treatment eventually than the older patients.
Factors that can affect the longevity of active surveillance include the presence or absence of germline mutations and the overall health and life expectancy and comorbidities such as heart disease and diabetes in a given patient, he said.
Urologists hold varying philosophies here, especially involving younger patients and the presence of any level of Gleason 4 cancer.
William Catalona, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, who developed the concept of mass screening with PSA testing, originally opposed active surveillance. In recent years, he has modified his views but still takes a more conservative approach.
“I consider active surveillance a foolish strategy or, at best, a short-term strategy for young, otherwise healthy men, especially those having any Gleason pattern 4 disease.”
“More than half will ultimately convert to active treatment, some too late, and will require multiple treatments with multiple side effects. Some will develop metastases, and some will die of prostate cancer.”
Dr. Sayyid takes a more liberal approach. “I would counsel an eligible patient considering active surveillance that at the current time, I see no strong reason why you should be subjected to treatment and the associated side effects,” he said. “And as long as your overall disease ‘state’ [the combination of grade, volume, PSA, and imaging tests] remains relatively stable, there should be no reason for us to ‘jump ship’. In my practice, another term for active surveillance is ‘active partnership’ — working together to decide if this is a sprint or a lifelong marathon.”
Dr. Carroll reported research funding from the National Institutes of Health.
A version of this article appeared on Medscape.com.
ASCO details how to manage ongoing cancer drug shortage
As of November 30, the US Food and Drug Administration lists 16 commonly used oncology drugs currently in shortage, including methotrexate, capecitabine, vinblastine, carboplatin, and cisplatin, along with another 13 discontinued agents.
The ASCO guidance, which is updated regularly on ASCO’s drug shortage website, covers dozens of clinical situations involving breast, gastrointestinal, genitourinary, gynecologic, thoracic, and head & neck cancers, as well as Hodgkin lymphoma.
The recommendations, published earlier in JCO Oncology Practice, represent the work of a Drug Shortages Advisory Group with over 40 oncologists, ethicists, and patient advocates brought together by ASCO in collaboration with the Society for Gynecologic Oncology.
In the guidance, the advisory group also provides some context about why these shortage issues have persisted, including a paucity of generic options, quality control issues, and reluctance among manufacturers to produce older drugs with slim profit margins.
And “while ASCO continues to work to address the root causes of the shortages, this guidance document aims to support clinicians, as they navigate the complexities of treatment planning amid the drug shortage, and patients with cancer who are already enduring physical and emotional hardships,” the advisory group writes.
The overall message in the guidance: conserve oncology drugs in limited supply to use when needed most.
The recommendations highlight alternative regimens, when available, and what to do in situations when there are no alternatives, advice that has become particularly relevant for the oncology workhorses cisplatin and carboplatin.
More generally, when ranges of acceptable doses and dose frequencies exist for drugs in short supply, clinicians should opt for the lowest dose at the longest interval. Dose rounding and multi-use vials should also be used to eliminate waste, and alternatives should be used whenever possible. If an alternative agent with similar efficacy and safety is available, the agent in limited supply should not be ordered.
In certain settings where no reasonable alternatives to platinum regimens exist, the advisory group recommends patients travel to where platinum agents are available. The group noted this strategy specifically for patients with non–small cell lung cancer or testicular germ cell cancers, but also acknowledged that this option “may cause additional financial toxicity, hardship, and distress.”
Other, more granular advice includes holding carboplatin in reserve for patients with early-stage triple-negative breast cancer on neoadjuvant therapy who don’t respond well to upfront doxorubicin, cyclophosphamide, and pembrolizumab.
In addition to providing strategies to manage the ongoing cancer drug shortages, ASCO advises counseling for patients and clinicians struggling with the “psychological or moral distress” from the ongoing shortages.
“Unfortunately, drug shortages place the patient and the provider in a challenging situation, possibly resulting in inferior outcomes, delayed or denied care, and increased adverse events,” the advisory group writes. “ASCO will continue to respond to the oncology drug shortage crisis through policy and advocacy efforts, provide ethical guidance for allocation and prioritization decisions, and maintain shortage-specific clinical guidance as long as necessary.”
A version of this article appeared on Medscape.com.
As of November 30, the US Food and Drug Administration lists 16 commonly used oncology drugs currently in shortage, including methotrexate, capecitabine, vinblastine, carboplatin, and cisplatin, along with another 13 discontinued agents.
The ASCO guidance, which is updated regularly on ASCO’s drug shortage website, covers dozens of clinical situations involving breast, gastrointestinal, genitourinary, gynecologic, thoracic, and head & neck cancers, as well as Hodgkin lymphoma.
The recommendations, published earlier in JCO Oncology Practice, represent the work of a Drug Shortages Advisory Group with over 40 oncologists, ethicists, and patient advocates brought together by ASCO in collaboration with the Society for Gynecologic Oncology.
In the guidance, the advisory group also provides some context about why these shortage issues have persisted, including a paucity of generic options, quality control issues, and reluctance among manufacturers to produce older drugs with slim profit margins.
And “while ASCO continues to work to address the root causes of the shortages, this guidance document aims to support clinicians, as they navigate the complexities of treatment planning amid the drug shortage, and patients with cancer who are already enduring physical and emotional hardships,” the advisory group writes.
The overall message in the guidance: conserve oncology drugs in limited supply to use when needed most.
The recommendations highlight alternative regimens, when available, and what to do in situations when there are no alternatives, advice that has become particularly relevant for the oncology workhorses cisplatin and carboplatin.
More generally, when ranges of acceptable doses and dose frequencies exist for drugs in short supply, clinicians should opt for the lowest dose at the longest interval. Dose rounding and multi-use vials should also be used to eliminate waste, and alternatives should be used whenever possible. If an alternative agent with similar efficacy and safety is available, the agent in limited supply should not be ordered.
In certain settings where no reasonable alternatives to platinum regimens exist, the advisory group recommends patients travel to where platinum agents are available. The group noted this strategy specifically for patients with non–small cell lung cancer or testicular germ cell cancers, but also acknowledged that this option “may cause additional financial toxicity, hardship, and distress.”
Other, more granular advice includes holding carboplatin in reserve for patients with early-stage triple-negative breast cancer on neoadjuvant therapy who don’t respond well to upfront doxorubicin, cyclophosphamide, and pembrolizumab.
In addition to providing strategies to manage the ongoing cancer drug shortages, ASCO advises counseling for patients and clinicians struggling with the “psychological or moral distress” from the ongoing shortages.
“Unfortunately, drug shortages place the patient and the provider in a challenging situation, possibly resulting in inferior outcomes, delayed or denied care, and increased adverse events,” the advisory group writes. “ASCO will continue to respond to the oncology drug shortage crisis through policy and advocacy efforts, provide ethical guidance for allocation and prioritization decisions, and maintain shortage-specific clinical guidance as long as necessary.”
A version of this article appeared on Medscape.com.
As of November 30, the US Food and Drug Administration lists 16 commonly used oncology drugs currently in shortage, including methotrexate, capecitabine, vinblastine, carboplatin, and cisplatin, along with another 13 discontinued agents.
The ASCO guidance, which is updated regularly on ASCO’s drug shortage website, covers dozens of clinical situations involving breast, gastrointestinal, genitourinary, gynecologic, thoracic, and head & neck cancers, as well as Hodgkin lymphoma.
The recommendations, published earlier in JCO Oncology Practice, represent the work of a Drug Shortages Advisory Group with over 40 oncologists, ethicists, and patient advocates brought together by ASCO in collaboration with the Society for Gynecologic Oncology.
In the guidance, the advisory group also provides some context about why these shortage issues have persisted, including a paucity of generic options, quality control issues, and reluctance among manufacturers to produce older drugs with slim profit margins.
And “while ASCO continues to work to address the root causes of the shortages, this guidance document aims to support clinicians, as they navigate the complexities of treatment planning amid the drug shortage, and patients with cancer who are already enduring physical and emotional hardships,” the advisory group writes.
The overall message in the guidance: conserve oncology drugs in limited supply to use when needed most.
The recommendations highlight alternative regimens, when available, and what to do in situations when there are no alternatives, advice that has become particularly relevant for the oncology workhorses cisplatin and carboplatin.
More generally, when ranges of acceptable doses and dose frequencies exist for drugs in short supply, clinicians should opt for the lowest dose at the longest interval. Dose rounding and multi-use vials should also be used to eliminate waste, and alternatives should be used whenever possible. If an alternative agent with similar efficacy and safety is available, the agent in limited supply should not be ordered.
In certain settings where no reasonable alternatives to platinum regimens exist, the advisory group recommends patients travel to where platinum agents are available. The group noted this strategy specifically for patients with non–small cell lung cancer or testicular germ cell cancers, but also acknowledged that this option “may cause additional financial toxicity, hardship, and distress.”
Other, more granular advice includes holding carboplatin in reserve for patients with early-stage triple-negative breast cancer on neoadjuvant therapy who don’t respond well to upfront doxorubicin, cyclophosphamide, and pembrolizumab.
In addition to providing strategies to manage the ongoing cancer drug shortages, ASCO advises counseling for patients and clinicians struggling with the “psychological or moral distress” from the ongoing shortages.
“Unfortunately, drug shortages place the patient and the provider in a challenging situation, possibly resulting in inferior outcomes, delayed or denied care, and increased adverse events,” the advisory group writes. “ASCO will continue to respond to the oncology drug shortage crisis through policy and advocacy efforts, provide ethical guidance for allocation and prioritization decisions, and maintain shortage-specific clinical guidance as long as necessary.”
A version of this article appeared on Medscape.com.
FROM JCO ONCOLOGY PRACTICE
MRIs, MRI-guided biopsies detect prostate cancer affordably
TOPLINE:
published online in JAMA Network Open.
METHODOLOGY:
- Investigators ran a simulation of a hypothetical group of 65-year-old men who were at risk for the cancer, as indicated by their prostate-specific antigen (PSA) levels.
- The costs and benefits of periodic ultrasound biopsies were modeled in comparison with those of an annual MRI plus MRI-guided biopsies using epidemiologic and clinical data.
- The investigators compared the cost-effectiveness of each biopsy approach over a decade, as measured by the cost of procedures divided by the projected gain in life-years.
- Cost-effectiveness was defined as less than $100,000 for each life-year gain using an MRI in comparison with ultrasound.
- They stratified the cost-effectiveness of the MRI approach by severity of PSA level: less than 2.5 ng/mL, 2.5-4.0 ng/mL, 4.1-10.0 ng/mL, and greater than 10.0 ng/mL.
TAKEAWAY:
- For three of the four PSA levels (2.5-4.0 ng/mL, 4.1-10.0 ng/mL, and greater than 10.0 ng/mL) the combination of MRI plus MRI-guided biopsy was cost effective.
- The MRI-based approach cost $6,000 more than ultrasound for each life-year gained at the highest PSA level of greater than 10.0 ng/mL, which was significantly below the $100,000 threshold.
- At the lowest PSA level of less than 2.5 ng/mL, the difference between MRI and ultrasound was $187,000, which was above the threshold.
IN PRACTICE:
The researchers wrote that there is “a growing consensus that the use of MRI and potential MRI-guided biopsy is cost effective.”
SOURCE:
Ali Jalali, PhD, a health economist at Weill Cornell Medicine, New York, is the senior author of the study. Simulation data come from the National Vital Statistics Report of the Centers for Disease Control and Prevention and the Medicare fee schedule.
LIMITATIONS:
The study is a hypothetical simulation of what could happen under different conditions, not an analysis of data developed over time in clinical practice. It also assumes that PSA levels remain constant over time.
DISCLOSURES:
One author receives grants from Siemens Healthineers for MRI technology development, and another author consults for Promaxo, which develops MRI tools.
A version of this article first appeared on Medscape.com.
TOPLINE:
published online in JAMA Network Open.
METHODOLOGY:
- Investigators ran a simulation of a hypothetical group of 65-year-old men who were at risk for the cancer, as indicated by their prostate-specific antigen (PSA) levels.
- The costs and benefits of periodic ultrasound biopsies were modeled in comparison with those of an annual MRI plus MRI-guided biopsies using epidemiologic and clinical data.
- The investigators compared the cost-effectiveness of each biopsy approach over a decade, as measured by the cost of procedures divided by the projected gain in life-years.
- Cost-effectiveness was defined as less than $100,000 for each life-year gain using an MRI in comparison with ultrasound.
- They stratified the cost-effectiveness of the MRI approach by severity of PSA level: less than 2.5 ng/mL, 2.5-4.0 ng/mL, 4.1-10.0 ng/mL, and greater than 10.0 ng/mL.
TAKEAWAY:
- For three of the four PSA levels (2.5-4.0 ng/mL, 4.1-10.0 ng/mL, and greater than 10.0 ng/mL) the combination of MRI plus MRI-guided biopsy was cost effective.
- The MRI-based approach cost $6,000 more than ultrasound for each life-year gained at the highest PSA level of greater than 10.0 ng/mL, which was significantly below the $100,000 threshold.
- At the lowest PSA level of less than 2.5 ng/mL, the difference between MRI and ultrasound was $187,000, which was above the threshold.
IN PRACTICE:
The researchers wrote that there is “a growing consensus that the use of MRI and potential MRI-guided biopsy is cost effective.”
SOURCE:
Ali Jalali, PhD, a health economist at Weill Cornell Medicine, New York, is the senior author of the study. Simulation data come from the National Vital Statistics Report of the Centers for Disease Control and Prevention and the Medicare fee schedule.
LIMITATIONS:
The study is a hypothetical simulation of what could happen under different conditions, not an analysis of data developed over time in clinical practice. It also assumes that PSA levels remain constant over time.
DISCLOSURES:
One author receives grants from Siemens Healthineers for MRI technology development, and another author consults for Promaxo, which develops MRI tools.
A version of this article first appeared on Medscape.com.
TOPLINE:
published online in JAMA Network Open.
METHODOLOGY:
- Investigators ran a simulation of a hypothetical group of 65-year-old men who were at risk for the cancer, as indicated by their prostate-specific antigen (PSA) levels.
- The costs and benefits of periodic ultrasound biopsies were modeled in comparison with those of an annual MRI plus MRI-guided biopsies using epidemiologic and clinical data.
- The investigators compared the cost-effectiveness of each biopsy approach over a decade, as measured by the cost of procedures divided by the projected gain in life-years.
- Cost-effectiveness was defined as less than $100,000 for each life-year gain using an MRI in comparison with ultrasound.
- They stratified the cost-effectiveness of the MRI approach by severity of PSA level: less than 2.5 ng/mL, 2.5-4.0 ng/mL, 4.1-10.0 ng/mL, and greater than 10.0 ng/mL.
TAKEAWAY:
- For three of the four PSA levels (2.5-4.0 ng/mL, 4.1-10.0 ng/mL, and greater than 10.0 ng/mL) the combination of MRI plus MRI-guided biopsy was cost effective.
- The MRI-based approach cost $6,000 more than ultrasound for each life-year gained at the highest PSA level of greater than 10.0 ng/mL, which was significantly below the $100,000 threshold.
- At the lowest PSA level of less than 2.5 ng/mL, the difference between MRI and ultrasound was $187,000, which was above the threshold.
IN PRACTICE:
The researchers wrote that there is “a growing consensus that the use of MRI and potential MRI-guided biopsy is cost effective.”
SOURCE:
Ali Jalali, PhD, a health economist at Weill Cornell Medicine, New York, is the senior author of the study. Simulation data come from the National Vital Statistics Report of the Centers for Disease Control and Prevention and the Medicare fee schedule.
LIMITATIONS:
The study is a hypothetical simulation of what could happen under different conditions, not an analysis of data developed over time in clinical practice. It also assumes that PSA levels remain constant over time.
DISCLOSURES:
One author receives grants from Siemens Healthineers for MRI technology development, and another author consults for Promaxo, which develops MRI tools.
A version of this article first appeared on Medscape.com.
Black men are at higher risk of prostate cancer at younger ages, lower PSA levels
Black men are at higher risk of prostate cancer than their White counterparts at younger ages and lower prostate-specific antigen (PSA) levels, a large new study conducted in a Veterans Affairs health care system suggests.
The findings suggest the need for PSA biopsy thresholds that are set with better understanding of patients’ risk factors, said the authors, led by Kyung Min Lee, PhD, with VA Informatics and Computing Infrastructure, at Salt Lake City Health Care System.
The study, which included more than 280,000 veterans, was published online in Cancer.
Risk higher, regardless of PSA level before biopsy
The researchers found that self-identified Black men are more likely than White men to be diagnosed with prostate cancer on their first prostate biopsy after controlling for age, prebiopsy PSA count, statin use, smoking status, and several socioeconomic variables.
Among the highlighted results are that a Black man who had a PSA level of 4.0 ng/mL before biopsy “had the same risk of prostate cancer as a White man with a PSA level 3.4 times higher [13.4 ng/mL].”
The gap was even more evident at younger ages. “Among men aged 60 years or younger, a Black man with a prebiopsy PSA level of 4.0 ng/mL had the same risk of prostate cancer as a White man with PSA level 3.7 times higher,” they wrote.
Researchers also found that Black veterans sought PSA screening and underwent their first diagnostic prostate biopsy at a younger age than did their White counterparts. Logistic regression models were used to predict the likelihood of a prostate cancer diagnosis on the first biopsy for 75,295 Black and 207,658 White male veterans.
U.S. Black men have an 80% higher risk of prostate cancer that White men
Previous research has shown that, in the United States, Black men have an 80% higher risk than White men of developing prostate cancer and are 220% more likely to die from it. Rigorous early screening has been suggested to decrease deaths from prostate cancer in Black men, but because that population group is underrepresented in randomized controlled trials, evidence for this has been lacking, the authors wrote.
Different national screening guidelines reflect the lack of clarity about best protocols. The U.S. Preventive Services Task Force acknowledges the higher risk but doesn’t make specific screening recommendations for Black men or those at higher risk. Conversely, the National Comprehensive Cancer Network “explicitly recommends earlier PSA screening and a shorter retest interval at lower PSA levels for populations at greater than average risk (including Black men). However, it does not otherwise recommend a different screening protocol.”
Social determinants of health may play a role
The reasons for the higher risk in Black men is unclear, the authors said, pointing out that recent studies suggest that “Black men may have higher genetic risk as assessed by polygenic scores.”
The authors wrote that nongenetic causes, such as access to care, mistrust of the health system, and environmental exposures may also be driving the association of Black race or ethnicity with higher risk of prostate cancer.
“Identifying and addressing these risk factors could further reduce racial disparities in prostate cancer outcomes,” they wrote.
The authors acknowledged that they are limited in their ability to account for socioeconomic status individually and used ZIP codes as proxies. Also, veterans generally have more comorbidities and mortality risks, compared with the general population.
The authors declared no relevant conflicts of interest.
Black men are at higher risk of prostate cancer than their White counterparts at younger ages and lower prostate-specific antigen (PSA) levels, a large new study conducted in a Veterans Affairs health care system suggests.
The findings suggest the need for PSA biopsy thresholds that are set with better understanding of patients’ risk factors, said the authors, led by Kyung Min Lee, PhD, with VA Informatics and Computing Infrastructure, at Salt Lake City Health Care System.
The study, which included more than 280,000 veterans, was published online in Cancer.
Risk higher, regardless of PSA level before biopsy
The researchers found that self-identified Black men are more likely than White men to be diagnosed with prostate cancer on their first prostate biopsy after controlling for age, prebiopsy PSA count, statin use, smoking status, and several socioeconomic variables.
Among the highlighted results are that a Black man who had a PSA level of 4.0 ng/mL before biopsy “had the same risk of prostate cancer as a White man with a PSA level 3.4 times higher [13.4 ng/mL].”
The gap was even more evident at younger ages. “Among men aged 60 years or younger, a Black man with a prebiopsy PSA level of 4.0 ng/mL had the same risk of prostate cancer as a White man with PSA level 3.7 times higher,” they wrote.
Researchers also found that Black veterans sought PSA screening and underwent their first diagnostic prostate biopsy at a younger age than did their White counterparts. Logistic regression models were used to predict the likelihood of a prostate cancer diagnosis on the first biopsy for 75,295 Black and 207,658 White male veterans.
U.S. Black men have an 80% higher risk of prostate cancer that White men
Previous research has shown that, in the United States, Black men have an 80% higher risk than White men of developing prostate cancer and are 220% more likely to die from it. Rigorous early screening has been suggested to decrease deaths from prostate cancer in Black men, but because that population group is underrepresented in randomized controlled trials, evidence for this has been lacking, the authors wrote.
Different national screening guidelines reflect the lack of clarity about best protocols. The U.S. Preventive Services Task Force acknowledges the higher risk but doesn’t make specific screening recommendations for Black men or those at higher risk. Conversely, the National Comprehensive Cancer Network “explicitly recommends earlier PSA screening and a shorter retest interval at lower PSA levels for populations at greater than average risk (including Black men). However, it does not otherwise recommend a different screening protocol.”
Social determinants of health may play a role
The reasons for the higher risk in Black men is unclear, the authors said, pointing out that recent studies suggest that “Black men may have higher genetic risk as assessed by polygenic scores.”
The authors wrote that nongenetic causes, such as access to care, mistrust of the health system, and environmental exposures may also be driving the association of Black race or ethnicity with higher risk of prostate cancer.
“Identifying and addressing these risk factors could further reduce racial disparities in prostate cancer outcomes,” they wrote.
The authors acknowledged that they are limited in their ability to account for socioeconomic status individually and used ZIP codes as proxies. Also, veterans generally have more comorbidities and mortality risks, compared with the general population.
The authors declared no relevant conflicts of interest.
Black men are at higher risk of prostate cancer than their White counterparts at younger ages and lower prostate-specific antigen (PSA) levels, a large new study conducted in a Veterans Affairs health care system suggests.
The findings suggest the need for PSA biopsy thresholds that are set with better understanding of patients’ risk factors, said the authors, led by Kyung Min Lee, PhD, with VA Informatics and Computing Infrastructure, at Salt Lake City Health Care System.
The study, which included more than 280,000 veterans, was published online in Cancer.
Risk higher, regardless of PSA level before biopsy
The researchers found that self-identified Black men are more likely than White men to be diagnosed with prostate cancer on their first prostate biopsy after controlling for age, prebiopsy PSA count, statin use, smoking status, and several socioeconomic variables.
Among the highlighted results are that a Black man who had a PSA level of 4.0 ng/mL before biopsy “had the same risk of prostate cancer as a White man with a PSA level 3.4 times higher [13.4 ng/mL].”
The gap was even more evident at younger ages. “Among men aged 60 years or younger, a Black man with a prebiopsy PSA level of 4.0 ng/mL had the same risk of prostate cancer as a White man with PSA level 3.7 times higher,” they wrote.
Researchers also found that Black veterans sought PSA screening and underwent their first diagnostic prostate biopsy at a younger age than did their White counterparts. Logistic regression models were used to predict the likelihood of a prostate cancer diagnosis on the first biopsy for 75,295 Black and 207,658 White male veterans.
U.S. Black men have an 80% higher risk of prostate cancer that White men
Previous research has shown that, in the United States, Black men have an 80% higher risk than White men of developing prostate cancer and are 220% more likely to die from it. Rigorous early screening has been suggested to decrease deaths from prostate cancer in Black men, but because that population group is underrepresented in randomized controlled trials, evidence for this has been lacking, the authors wrote.
Different national screening guidelines reflect the lack of clarity about best protocols. The U.S. Preventive Services Task Force acknowledges the higher risk but doesn’t make specific screening recommendations for Black men or those at higher risk. Conversely, the National Comprehensive Cancer Network “explicitly recommends earlier PSA screening and a shorter retest interval at lower PSA levels for populations at greater than average risk (including Black men). However, it does not otherwise recommend a different screening protocol.”
Social determinants of health may play a role
The reasons for the higher risk in Black men is unclear, the authors said, pointing out that recent studies suggest that “Black men may have higher genetic risk as assessed by polygenic scores.”
The authors wrote that nongenetic causes, such as access to care, mistrust of the health system, and environmental exposures may also be driving the association of Black race or ethnicity with higher risk of prostate cancer.
“Identifying and addressing these risk factors could further reduce racial disparities in prostate cancer outcomes,” they wrote.
The authors acknowledged that they are limited in their ability to account for socioeconomic status individually and used ZIP codes as proxies. Also, veterans generally have more comorbidities and mortality risks, compared with the general population.
The authors declared no relevant conflicts of interest.
FROM CANCER
Enfortumab vedotin/pembrolizumab hailed as new standard for upfront mUC
following a phase 3 trial presented at the 2023 European Society for Medical Oncology annual meeting.
The combination soundly beat the current standard of care – platinum-based chemotherapy – with a median overall survival of 31.5 months among 442 subjects versus 16.1 months among 444 randomized to gemcitabine with cisplatin or carboplatin, an unprecedented 53% drop in the risk of mortality (P < .00001).
The elimination of chemotherapy also meant that there were substantially fewer grade 3 or higher adverse events with the new combination.
“This is the first time we’ve managed to beat chemotherapy in the first-line setting for overall survival despite multiple previous attempts.” The 30% remission rate with enfortumab vedotin plus pembrolizumab “is not something we’ve seen before,” said lead investigator Thomas Powles, MBBS, MD, a urologic oncologist and researcher at the University of London, who presented the findings.
“We welcome a new standard of care in the management of advanced, metastatic urothelial carcinoma, enfortumab vedotin plus pembrolizumab,” said Andrea Apolo, MD, a urologic oncology researcher at the National Cancer Institute in Bethesda, Md., and discussant on the trial, dubbed EV-302/KEYNOTE-A39.
The news overshadowed a second trial presented immediately after Dr. Powles’ that also showed improvement in overall survival versus standard platinum-based chemotherapy, CheckMate 901.
Instead of replacing chemotherapy, CheckMate 901 added nivolumab. With 304 patients randomized to each arm, nivolumab add-on led to a median overall survival of 21.7 months versus 18.9 months with stand-alone gemcitabine/cisplatin, a 22% drop in the risk of mortality (P = .0171).
It’s the first time that adding immunotherapy to first-line chemotherapy improved survival in metastatic urothelial carcinoma, said lead investigator Michiel van der Heijden, MD, PhD, a urologic oncologist and researcher at the Netherlands Cancer Institute, Amsterdam.
After decades of stagnation, Dr. Apolo said, it’s “monumental for our field” to have two trials that beat chemotherapy in the first-line setting.
However, she said that the much better survival with enfortumab vedotin/pembrolizumab means that the combination now “takes first place as the best first-line regimen in urothelial carcinoma.”
Major disruptions in the treatment paradigm
The crowning of a new first-line standard for locally advanced/metastatic urothelial carcinoma means that everything else in the treatment paradigm has to shift, Dr. Apolo said, and there are many new questions that need to be answered.
Among the most pressing, should the previous first-line standard – platinum-based chemotherapy – now move to the second line and be considered the treatment of choice after progression? Also, is there still a role for the previous second-line standards, pembrolizumab and other immunotherapies, if pembrolizumab fails in the first line?
Dr. Apolo said investigators also need to figure out if there is a role for enfortumab vedotin/pembrolizumab in earlier-stage disease, such as muscle-invasive bladder cancer, and if the dose and duration of enfortumab vedotin can be reduced to limit its peculiar ocular and other toxicities.
Finally, “we must discuss cost,” she said. Enfortumab vedotin plus pembrolizumab (EV+P) is expensive. “Will payers be able to afford” it?
Dr. Powles, the lead investigator on EV-302/KEYNOTE-A39, said he doesn’t know how negotiations are going with payers, but that he hopes they move quickly. “We’ve seen transformative results” with the combination for even aggressive cancers in very sick people. “I think it’s going to be a challenge with patients not to talk about these data.”
EV-302/KEYNOTE-059 details
Merck, the maker of pembrolizumab, and the makers/marketers of enfortumab vedotin, Astellas and Seagen, said they will use EV-302/KEYNOTE-059 to seek a first-line indication for locally advanced/metastatic urothelial carcinoma from the U.S. Food and Drug Administration and other regulators.
They also said the results serve as the confirmation FDA required when it gave accelerated approval to the combination in April 2023 for cisplatin-ineligible patients based on tumor response rates and response durability, according to press releases from the companies.
Pembrolizumab (P) in the trial was dosed at 200 mg on the first day of 3-week treatment cycles to a maximum of 35 cycles; enfortumab vedotin (EV) was given on the first and eighth day of the cycle with no limit in the number of cycles until progression or unacceptable toxicity.
Cisplatin or carboplatin (C) in the control arm was delivered on the first day and gemcitabine (G) on the first and eighth days for up to six 3-week cycles.
Patients in both arms were split about equally between performance statuses of 0 or 1; less than 4% in each group had statuses of 2.
Echoing the overall survival (OS) results, progression-free survival (PFS) was a median of 12.5 months with EV-P versus 6.3 months with GC, a 55% drop in the risk of progression or death (P < .00001).
The results held regardless of PD-L1 expression, cisplatin eligibility, and the presence or absence of visceral metastases.
Follow-up treatments in the trial begin to address Dr. Apolo’s questions: Almost 60% of GC patients went on to a PD-1/L1 for subsequent maintenance or progression, and almost a quarter of EV+P patients went on to subsequent platinum-based chemotherapy.
Grade 3 or higher adverse events occurred in 55.9% of subjects in the EV+P group versus 69.5% in the GC arm.
The most common in the chemotherapy arm were anemia, neutropenia, thrombocytopenia, fatigue, and nausea. The most common with EV+P were skin reactions, hyperglycemia, neutropenia, peripheral neuropathy, diarrhea, and anemia,
CheckMate 901 details
In CheckMate 901, gemcitabine and cisplatin were administered on the first day of 3-week treatment cycles for up to 6 cycles; subjects randomized to nivolumab add-on received 360 mg on day 1 of each cycle, followed by 480 mg every 4 weeks until disease progression or unacceptable toxicity for up to 2 years.
PFS results again mirrored OS, with a median PFS of 7.9 months in the nivolumab arm versus 7.6 months with stand-alone chemotherapy, a 28% drop in the risk of progression or death (P = .0012).
Although OS and PFS benefits were statistically significant overall, they were not significant in subgroup analyses of patients 65 years and older, women, or in patients with liver metastases.
Trends in OS and PFS actually favored chemotherapy in the 40 U.S. subjects (HR OS, 1.92; 95% confidence interval, 0.95-3.88).
The rate of grade 3 or higher adverse events was 61.8% with nivolumab add-on versus 51.7% with chemotherapy alone. Anemia and neutropenia were the most common in both arms, and higher in the nivolumab group.
EV-302/KEYNOTE-A39 was funded by Seagen, Astellas, and Merck. CheckMate 901 was funded by Bristol-Myers Squibb, the maker of nivolumab.
Dr. Powles reported extensive financial ties to pharmaceutical companies, including being an advisor to and receiving research funding from Bristol-Myers Squibb, Merck, SeaGen, and Astellas, as well as travel expenses from Merck. Among other disclosures, Dr. Heijden is an advisor to Seagen and an advisor and researcher for Bristol-Myers Squibb. Dr. Apolo is an unpaid consultant to Merck, Astellas, Seagen, Bristol-Myers Squibb, and other companies.
following a phase 3 trial presented at the 2023 European Society for Medical Oncology annual meeting.
The combination soundly beat the current standard of care – platinum-based chemotherapy – with a median overall survival of 31.5 months among 442 subjects versus 16.1 months among 444 randomized to gemcitabine with cisplatin or carboplatin, an unprecedented 53% drop in the risk of mortality (P < .00001).
The elimination of chemotherapy also meant that there were substantially fewer grade 3 or higher adverse events with the new combination.
“This is the first time we’ve managed to beat chemotherapy in the first-line setting for overall survival despite multiple previous attempts.” The 30% remission rate with enfortumab vedotin plus pembrolizumab “is not something we’ve seen before,” said lead investigator Thomas Powles, MBBS, MD, a urologic oncologist and researcher at the University of London, who presented the findings.
“We welcome a new standard of care in the management of advanced, metastatic urothelial carcinoma, enfortumab vedotin plus pembrolizumab,” said Andrea Apolo, MD, a urologic oncology researcher at the National Cancer Institute in Bethesda, Md., and discussant on the trial, dubbed EV-302/KEYNOTE-A39.
The news overshadowed a second trial presented immediately after Dr. Powles’ that also showed improvement in overall survival versus standard platinum-based chemotherapy, CheckMate 901.
Instead of replacing chemotherapy, CheckMate 901 added nivolumab. With 304 patients randomized to each arm, nivolumab add-on led to a median overall survival of 21.7 months versus 18.9 months with stand-alone gemcitabine/cisplatin, a 22% drop in the risk of mortality (P = .0171).
It’s the first time that adding immunotherapy to first-line chemotherapy improved survival in metastatic urothelial carcinoma, said lead investigator Michiel van der Heijden, MD, PhD, a urologic oncologist and researcher at the Netherlands Cancer Institute, Amsterdam.
After decades of stagnation, Dr. Apolo said, it’s “monumental for our field” to have two trials that beat chemotherapy in the first-line setting.
However, she said that the much better survival with enfortumab vedotin/pembrolizumab means that the combination now “takes first place as the best first-line regimen in urothelial carcinoma.”
Major disruptions in the treatment paradigm
The crowning of a new first-line standard for locally advanced/metastatic urothelial carcinoma means that everything else in the treatment paradigm has to shift, Dr. Apolo said, and there are many new questions that need to be answered.
Among the most pressing, should the previous first-line standard – platinum-based chemotherapy – now move to the second line and be considered the treatment of choice after progression? Also, is there still a role for the previous second-line standards, pembrolizumab and other immunotherapies, if pembrolizumab fails in the first line?
Dr. Apolo said investigators also need to figure out if there is a role for enfortumab vedotin/pembrolizumab in earlier-stage disease, such as muscle-invasive bladder cancer, and if the dose and duration of enfortumab vedotin can be reduced to limit its peculiar ocular and other toxicities.
Finally, “we must discuss cost,” she said. Enfortumab vedotin plus pembrolizumab (EV+P) is expensive. “Will payers be able to afford” it?
Dr. Powles, the lead investigator on EV-302/KEYNOTE-A39, said he doesn’t know how negotiations are going with payers, but that he hopes they move quickly. “We’ve seen transformative results” with the combination for even aggressive cancers in very sick people. “I think it’s going to be a challenge with patients not to talk about these data.”
EV-302/KEYNOTE-059 details
Merck, the maker of pembrolizumab, and the makers/marketers of enfortumab vedotin, Astellas and Seagen, said they will use EV-302/KEYNOTE-059 to seek a first-line indication for locally advanced/metastatic urothelial carcinoma from the U.S. Food and Drug Administration and other regulators.
They also said the results serve as the confirmation FDA required when it gave accelerated approval to the combination in April 2023 for cisplatin-ineligible patients based on tumor response rates and response durability, according to press releases from the companies.
Pembrolizumab (P) in the trial was dosed at 200 mg on the first day of 3-week treatment cycles to a maximum of 35 cycles; enfortumab vedotin (EV) was given on the first and eighth day of the cycle with no limit in the number of cycles until progression or unacceptable toxicity.
Cisplatin or carboplatin (C) in the control arm was delivered on the first day and gemcitabine (G) on the first and eighth days for up to six 3-week cycles.
Patients in both arms were split about equally between performance statuses of 0 or 1; less than 4% in each group had statuses of 2.
Echoing the overall survival (OS) results, progression-free survival (PFS) was a median of 12.5 months with EV-P versus 6.3 months with GC, a 55% drop in the risk of progression or death (P < .00001).
The results held regardless of PD-L1 expression, cisplatin eligibility, and the presence or absence of visceral metastases.
Follow-up treatments in the trial begin to address Dr. Apolo’s questions: Almost 60% of GC patients went on to a PD-1/L1 for subsequent maintenance or progression, and almost a quarter of EV+P patients went on to subsequent platinum-based chemotherapy.
Grade 3 or higher adverse events occurred in 55.9% of subjects in the EV+P group versus 69.5% in the GC arm.
The most common in the chemotherapy arm were anemia, neutropenia, thrombocytopenia, fatigue, and nausea. The most common with EV+P were skin reactions, hyperglycemia, neutropenia, peripheral neuropathy, diarrhea, and anemia,
CheckMate 901 details
In CheckMate 901, gemcitabine and cisplatin were administered on the first day of 3-week treatment cycles for up to 6 cycles; subjects randomized to nivolumab add-on received 360 mg on day 1 of each cycle, followed by 480 mg every 4 weeks until disease progression or unacceptable toxicity for up to 2 years.
PFS results again mirrored OS, with a median PFS of 7.9 months in the nivolumab arm versus 7.6 months with stand-alone chemotherapy, a 28% drop in the risk of progression or death (P = .0012).
Although OS and PFS benefits were statistically significant overall, they were not significant in subgroup analyses of patients 65 years and older, women, or in patients with liver metastases.
Trends in OS and PFS actually favored chemotherapy in the 40 U.S. subjects (HR OS, 1.92; 95% confidence interval, 0.95-3.88).
The rate of grade 3 or higher adverse events was 61.8% with nivolumab add-on versus 51.7% with chemotherapy alone. Anemia and neutropenia were the most common in both arms, and higher in the nivolumab group.
EV-302/KEYNOTE-A39 was funded by Seagen, Astellas, and Merck. CheckMate 901 was funded by Bristol-Myers Squibb, the maker of nivolumab.
Dr. Powles reported extensive financial ties to pharmaceutical companies, including being an advisor to and receiving research funding from Bristol-Myers Squibb, Merck, SeaGen, and Astellas, as well as travel expenses from Merck. Among other disclosures, Dr. Heijden is an advisor to Seagen and an advisor and researcher for Bristol-Myers Squibb. Dr. Apolo is an unpaid consultant to Merck, Astellas, Seagen, Bristol-Myers Squibb, and other companies.
following a phase 3 trial presented at the 2023 European Society for Medical Oncology annual meeting.
The combination soundly beat the current standard of care – platinum-based chemotherapy – with a median overall survival of 31.5 months among 442 subjects versus 16.1 months among 444 randomized to gemcitabine with cisplatin or carboplatin, an unprecedented 53% drop in the risk of mortality (P < .00001).
The elimination of chemotherapy also meant that there were substantially fewer grade 3 or higher adverse events with the new combination.
“This is the first time we’ve managed to beat chemotherapy in the first-line setting for overall survival despite multiple previous attempts.” The 30% remission rate with enfortumab vedotin plus pembrolizumab “is not something we’ve seen before,” said lead investigator Thomas Powles, MBBS, MD, a urologic oncologist and researcher at the University of London, who presented the findings.
“We welcome a new standard of care in the management of advanced, metastatic urothelial carcinoma, enfortumab vedotin plus pembrolizumab,” said Andrea Apolo, MD, a urologic oncology researcher at the National Cancer Institute in Bethesda, Md., and discussant on the trial, dubbed EV-302/KEYNOTE-A39.
The news overshadowed a second trial presented immediately after Dr. Powles’ that also showed improvement in overall survival versus standard platinum-based chemotherapy, CheckMate 901.
Instead of replacing chemotherapy, CheckMate 901 added nivolumab. With 304 patients randomized to each arm, nivolumab add-on led to a median overall survival of 21.7 months versus 18.9 months with stand-alone gemcitabine/cisplatin, a 22% drop in the risk of mortality (P = .0171).
It’s the first time that adding immunotherapy to first-line chemotherapy improved survival in metastatic urothelial carcinoma, said lead investigator Michiel van der Heijden, MD, PhD, a urologic oncologist and researcher at the Netherlands Cancer Institute, Amsterdam.
After decades of stagnation, Dr. Apolo said, it’s “monumental for our field” to have two trials that beat chemotherapy in the first-line setting.
However, she said that the much better survival with enfortumab vedotin/pembrolizumab means that the combination now “takes first place as the best first-line regimen in urothelial carcinoma.”
Major disruptions in the treatment paradigm
The crowning of a new first-line standard for locally advanced/metastatic urothelial carcinoma means that everything else in the treatment paradigm has to shift, Dr. Apolo said, and there are many new questions that need to be answered.
Among the most pressing, should the previous first-line standard – platinum-based chemotherapy – now move to the second line and be considered the treatment of choice after progression? Also, is there still a role for the previous second-line standards, pembrolizumab and other immunotherapies, if pembrolizumab fails in the first line?
Dr. Apolo said investigators also need to figure out if there is a role for enfortumab vedotin/pembrolizumab in earlier-stage disease, such as muscle-invasive bladder cancer, and if the dose and duration of enfortumab vedotin can be reduced to limit its peculiar ocular and other toxicities.
Finally, “we must discuss cost,” she said. Enfortumab vedotin plus pembrolizumab (EV+P) is expensive. “Will payers be able to afford” it?
Dr. Powles, the lead investigator on EV-302/KEYNOTE-A39, said he doesn’t know how negotiations are going with payers, but that he hopes they move quickly. “We’ve seen transformative results” with the combination for even aggressive cancers in very sick people. “I think it’s going to be a challenge with patients not to talk about these data.”
EV-302/KEYNOTE-059 details
Merck, the maker of pembrolizumab, and the makers/marketers of enfortumab vedotin, Astellas and Seagen, said they will use EV-302/KEYNOTE-059 to seek a first-line indication for locally advanced/metastatic urothelial carcinoma from the U.S. Food and Drug Administration and other regulators.
They also said the results serve as the confirmation FDA required when it gave accelerated approval to the combination in April 2023 for cisplatin-ineligible patients based on tumor response rates and response durability, according to press releases from the companies.
Pembrolizumab (P) in the trial was dosed at 200 mg on the first day of 3-week treatment cycles to a maximum of 35 cycles; enfortumab vedotin (EV) was given on the first and eighth day of the cycle with no limit in the number of cycles until progression or unacceptable toxicity.
Cisplatin or carboplatin (C) in the control arm was delivered on the first day and gemcitabine (G) on the first and eighth days for up to six 3-week cycles.
Patients in both arms were split about equally between performance statuses of 0 or 1; less than 4% in each group had statuses of 2.
Echoing the overall survival (OS) results, progression-free survival (PFS) was a median of 12.5 months with EV-P versus 6.3 months with GC, a 55% drop in the risk of progression or death (P < .00001).
The results held regardless of PD-L1 expression, cisplatin eligibility, and the presence or absence of visceral metastases.
Follow-up treatments in the trial begin to address Dr. Apolo’s questions: Almost 60% of GC patients went on to a PD-1/L1 for subsequent maintenance or progression, and almost a quarter of EV+P patients went on to subsequent platinum-based chemotherapy.
Grade 3 or higher adverse events occurred in 55.9% of subjects in the EV+P group versus 69.5% in the GC arm.
The most common in the chemotherapy arm were anemia, neutropenia, thrombocytopenia, fatigue, and nausea. The most common with EV+P were skin reactions, hyperglycemia, neutropenia, peripheral neuropathy, diarrhea, and anemia,
CheckMate 901 details
In CheckMate 901, gemcitabine and cisplatin were administered on the first day of 3-week treatment cycles for up to 6 cycles; subjects randomized to nivolumab add-on received 360 mg on day 1 of each cycle, followed by 480 mg every 4 weeks until disease progression or unacceptable toxicity for up to 2 years.
PFS results again mirrored OS, with a median PFS of 7.9 months in the nivolumab arm versus 7.6 months with stand-alone chemotherapy, a 28% drop in the risk of progression or death (P = .0012).
Although OS and PFS benefits were statistically significant overall, they were not significant in subgroup analyses of patients 65 years and older, women, or in patients with liver metastases.
Trends in OS and PFS actually favored chemotherapy in the 40 U.S. subjects (HR OS, 1.92; 95% confidence interval, 0.95-3.88).
The rate of grade 3 or higher adverse events was 61.8% with nivolumab add-on versus 51.7% with chemotherapy alone. Anemia and neutropenia were the most common in both arms, and higher in the nivolumab group.
EV-302/KEYNOTE-A39 was funded by Seagen, Astellas, and Merck. CheckMate 901 was funded by Bristol-Myers Squibb, the maker of nivolumab.
Dr. Powles reported extensive financial ties to pharmaceutical companies, including being an advisor to and receiving research funding from Bristol-Myers Squibb, Merck, SeaGen, and Astellas, as well as travel expenses from Merck. Among other disclosures, Dr. Heijden is an advisor to Seagen and an advisor and researcher for Bristol-Myers Squibb. Dr. Apolo is an unpaid consultant to Merck, Astellas, Seagen, Bristol-Myers Squibb, and other companies.
FROM ESMO 2023
Enzalutamide improves metastasis-free survival, QoL in prostate cancer
Adding enzalutamide (Xtandi) to androgen deprivation therapy (ADT) can extend metastasis-free survival (MFS) while maintaining quality of life in men with prostate cancer who have a high risk for biochemical recurrence, according to new research presented at the European Society of Medical Oncology meeting in Madrid.
, while 80% of those receiving only enzalutamide and about 71% of those receiving only leuprolide were metastasis-free.
In a related analysis of patient-reported outcomes, investigators found that patients who received enzalutamide did not appear to have worse quality of life, compared with those treated with leuprolide alone.
“This could be a game-changer for one of the most common disease states in prostate cancer,” lead author Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer, Los Angeles, said. The study was published online in the New England Journal of Medicine.
The results “confirm that in this population, as in men with more advanced stages, adding an androgen-receptor inhibitor [enzalutamide] increases the efficacy of androgen deprivation therapy,” Ana Aparicio, MD, from University of Texas MD Anderson Cancer Center, Houston, wrote in an accompanying editorial.
Standard care in this patient population relies on ADT to suppress testosterone, which would otherwise stimulate cancer cell growth. However, Dr. Freedland explained that “when you go on androgen deprivation therapy, the testosterone level in the blood is reduced but not completely eliminated. The concern is that the testosterone that remains may still be enough to stimulate tumor growth.”
Enzalutamide, an oral androgen receptor inhibitor, has already shown benefits in patients with metastases, and the current EMBARK trial explored whether the inhibitor can help men with earlier-stage disease who are at risk for metastases.
The findings from the phase 3 EMBARK trial, also published in NEJM Evidence, included 1,068 patients with prostate cancer at high-risk for biochemical recurrence. Patients, who had a median age of 69 years, spanned 244 sites across 17 countries.
Patients had a median prostate-specific antigen (PSA) doubling time of 4.9 months, with a median PSA of 5.2 ng/mL. Those with PSA doubling times of 9 months or less are considered at high-risk for biochemical recurrence and increased risk for death from prostate cancer.
Dr. Freedland and colleagues randomly assigned patients to three groups – enzalutamide 160 mg plus leuprolide every 12 weeks (n = 355), enzalutamide monotherapy (n = 355), and placebo plus leuprolide (n = 358). Patients received treatment for 38.7 months on average.
At 5-years, 87.3% of men in the combination group were metastasis-free, compared with 80% in the monotherapy group and 71.4% in the leuprolide-only group. Compared with leuprolide alone, combining enzalutamide and leuprolide reduced the risk for metastasis or death by 58% (hazard ratio, 0.42; P < .001). And compared with enzalutamide monotherapy, the combination also significantly reduced the risk for metastasis or death, compared with leuprolide alone (HR, 0.63; P = .005).
The estimated proportion of patients free from PSA progression at 5 years was 97.4% in the combination group, 88.9% in the monotherapy group, and 70% in the leuprolide-only group.
At the time of data cutoff, 33 (9%) patients in the combination group, 42 (12%) in the monotherapy group, and 55 (15%) in the leuprolide-only group had died.
Nearly all (97%) patients experienced adverse events, most of which (86.4%) were treatment-related. Overall, 46.5% of patients in the combination group experienced a grade 3 or higher adverse event, compared with 50% in the enzalutamide monotherapy group and 42.7% in the leuprolide-only group. Clustered adverse effects occurred in 80% or more patients in all three groups, with the most common cluster combining fatigue, falls, fractures, hypertension, and musculoskeletal events.
The most common adverse events in the enzalutamide monotherapy group, occurring in at least 30% of patients, included gynecomastia, joint pain, hot flashes, and fatigue. Nipple pain and breast tenderness were also common side effects in the enzalutamide monotherapy arm – occurring in 15.3% and 14.4% of patients, respectively – compared with the combination (3.1% and 1.1%) or leuprolide-only (1.1% and 1.1%) groups.
However, Dr. Freedland explained, “our quality-of-life data show that you don’t need to sacrifice global quality of life to get these cancer benefits.”
Patient-reported outcomes from EMBARK revealed that both enzalutamide combination and monotherapy versus leuprolide alone preserved high health-related quality of life in patients with a high-risk for biochemical recurrence.
More specifically, Dr. Freedland and colleagues found no differences in the time to first clinically meaningful deterioration based on questionnaires that rated pain and functional status. Functional status measures included physical, social, and emotional well-being as well as symptom severity.
However, some differences emerged. For instance, time to confirmed clinically meaningful deterioration in physical well-being score was significantly shorter among patients receiving enzalutamide, compared with leuprolide monotherapy – 24.8 months in the combination group and 27.6 months in the enzalutamide-only group versus 49.8 months in the leuprolide-only group (HR, 1.41 and 1.35, respectively).
However, sexual activity appeared to be better preserved among patients receiving enzalutamide monotherapy, compared with leuprolide alone. The median time to confirmed clinically meaningful deterioration in sexual activity score was 5.6 months with enzalutamide monotherapy versus 3 months for leuprolide alone (HR, 0.76).
Given the slightly different side-effect profiles in the enzalutamide combination and monotherapy groups, Dr. Freedland noted that “it will be up to patients and care providers to decide which is the right choice for them. I think the important message is that both are a major step forward from the current standard of care, which is androgen deprivation therapy alone.”
Pedro Barata, MD, who was not involved in the research, also noted that “this is the first time we have seen this kind of results with a novel hormonal therapy without castration.”
Overall, “the findings of this trial confirm the benefit of adding a novel hormonal therapy such as enzalutamide earlier in the course of this disease,” said Dr. Barata, a medical oncologist and director of the Clinical Genitourinary Medical Oncology Research Program at University Hospitals Seidman Cancer Center, Cleveland.
However, he explained that many patients with “rising PSA and short doubling time are known to have metastatic disease as detected by PSMA PET and are already being offered a novel hormonal therapy combined with castration. Perhaps it will be an opportunity for men who don’t want to be castrated to be offered an anti–androgen-like enzalutamide by itself without castration in this patient population.”
Research was funded by Pfizer and Astellas Pharma, manufacturers of enzalutamide.
A version of this article first appeared on Medscape.com.
Adding enzalutamide (Xtandi) to androgen deprivation therapy (ADT) can extend metastasis-free survival (MFS) while maintaining quality of life in men with prostate cancer who have a high risk for biochemical recurrence, according to new research presented at the European Society of Medical Oncology meeting in Madrid.
, while 80% of those receiving only enzalutamide and about 71% of those receiving only leuprolide were metastasis-free.
In a related analysis of patient-reported outcomes, investigators found that patients who received enzalutamide did not appear to have worse quality of life, compared with those treated with leuprolide alone.
“This could be a game-changer for one of the most common disease states in prostate cancer,” lead author Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer, Los Angeles, said. The study was published online in the New England Journal of Medicine.
The results “confirm that in this population, as in men with more advanced stages, adding an androgen-receptor inhibitor [enzalutamide] increases the efficacy of androgen deprivation therapy,” Ana Aparicio, MD, from University of Texas MD Anderson Cancer Center, Houston, wrote in an accompanying editorial.
Standard care in this patient population relies on ADT to suppress testosterone, which would otherwise stimulate cancer cell growth. However, Dr. Freedland explained that “when you go on androgen deprivation therapy, the testosterone level in the blood is reduced but not completely eliminated. The concern is that the testosterone that remains may still be enough to stimulate tumor growth.”
Enzalutamide, an oral androgen receptor inhibitor, has already shown benefits in patients with metastases, and the current EMBARK trial explored whether the inhibitor can help men with earlier-stage disease who are at risk for metastases.
The findings from the phase 3 EMBARK trial, also published in NEJM Evidence, included 1,068 patients with prostate cancer at high-risk for biochemical recurrence. Patients, who had a median age of 69 years, spanned 244 sites across 17 countries.
Patients had a median prostate-specific antigen (PSA) doubling time of 4.9 months, with a median PSA of 5.2 ng/mL. Those with PSA doubling times of 9 months or less are considered at high-risk for biochemical recurrence and increased risk for death from prostate cancer.
Dr. Freedland and colleagues randomly assigned patients to three groups – enzalutamide 160 mg plus leuprolide every 12 weeks (n = 355), enzalutamide monotherapy (n = 355), and placebo plus leuprolide (n = 358). Patients received treatment for 38.7 months on average.
At 5-years, 87.3% of men in the combination group were metastasis-free, compared with 80% in the monotherapy group and 71.4% in the leuprolide-only group. Compared with leuprolide alone, combining enzalutamide and leuprolide reduced the risk for metastasis or death by 58% (hazard ratio, 0.42; P < .001). And compared with enzalutamide monotherapy, the combination also significantly reduced the risk for metastasis or death, compared with leuprolide alone (HR, 0.63; P = .005).
The estimated proportion of patients free from PSA progression at 5 years was 97.4% in the combination group, 88.9% in the monotherapy group, and 70% in the leuprolide-only group.
At the time of data cutoff, 33 (9%) patients in the combination group, 42 (12%) in the monotherapy group, and 55 (15%) in the leuprolide-only group had died.
Nearly all (97%) patients experienced adverse events, most of which (86.4%) were treatment-related. Overall, 46.5% of patients in the combination group experienced a grade 3 or higher adverse event, compared with 50% in the enzalutamide monotherapy group and 42.7% in the leuprolide-only group. Clustered adverse effects occurred in 80% or more patients in all three groups, with the most common cluster combining fatigue, falls, fractures, hypertension, and musculoskeletal events.
The most common adverse events in the enzalutamide monotherapy group, occurring in at least 30% of patients, included gynecomastia, joint pain, hot flashes, and fatigue. Nipple pain and breast tenderness were also common side effects in the enzalutamide monotherapy arm – occurring in 15.3% and 14.4% of patients, respectively – compared with the combination (3.1% and 1.1%) or leuprolide-only (1.1% and 1.1%) groups.
However, Dr. Freedland explained, “our quality-of-life data show that you don’t need to sacrifice global quality of life to get these cancer benefits.”
Patient-reported outcomes from EMBARK revealed that both enzalutamide combination and monotherapy versus leuprolide alone preserved high health-related quality of life in patients with a high-risk for biochemical recurrence.
More specifically, Dr. Freedland and colleagues found no differences in the time to first clinically meaningful deterioration based on questionnaires that rated pain and functional status. Functional status measures included physical, social, and emotional well-being as well as symptom severity.
However, some differences emerged. For instance, time to confirmed clinically meaningful deterioration in physical well-being score was significantly shorter among patients receiving enzalutamide, compared with leuprolide monotherapy – 24.8 months in the combination group and 27.6 months in the enzalutamide-only group versus 49.8 months in the leuprolide-only group (HR, 1.41 and 1.35, respectively).
However, sexual activity appeared to be better preserved among patients receiving enzalutamide monotherapy, compared with leuprolide alone. The median time to confirmed clinically meaningful deterioration in sexual activity score was 5.6 months with enzalutamide monotherapy versus 3 months for leuprolide alone (HR, 0.76).
Given the slightly different side-effect profiles in the enzalutamide combination and monotherapy groups, Dr. Freedland noted that “it will be up to patients and care providers to decide which is the right choice for them. I think the important message is that both are a major step forward from the current standard of care, which is androgen deprivation therapy alone.”
Pedro Barata, MD, who was not involved in the research, also noted that “this is the first time we have seen this kind of results with a novel hormonal therapy without castration.”
Overall, “the findings of this trial confirm the benefit of adding a novel hormonal therapy such as enzalutamide earlier in the course of this disease,” said Dr. Barata, a medical oncologist and director of the Clinical Genitourinary Medical Oncology Research Program at University Hospitals Seidman Cancer Center, Cleveland.
However, he explained that many patients with “rising PSA and short doubling time are known to have metastatic disease as detected by PSMA PET and are already being offered a novel hormonal therapy combined with castration. Perhaps it will be an opportunity for men who don’t want to be castrated to be offered an anti–androgen-like enzalutamide by itself without castration in this patient population.”
Research was funded by Pfizer and Astellas Pharma, manufacturers of enzalutamide.
A version of this article first appeared on Medscape.com.
Adding enzalutamide (Xtandi) to androgen deprivation therapy (ADT) can extend metastasis-free survival (MFS) while maintaining quality of life in men with prostate cancer who have a high risk for biochemical recurrence, according to new research presented at the European Society of Medical Oncology meeting in Madrid.
, while 80% of those receiving only enzalutamide and about 71% of those receiving only leuprolide were metastasis-free.
In a related analysis of patient-reported outcomes, investigators found that patients who received enzalutamide did not appear to have worse quality of life, compared with those treated with leuprolide alone.
“This could be a game-changer for one of the most common disease states in prostate cancer,” lead author Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer, Los Angeles, said. The study was published online in the New England Journal of Medicine.
The results “confirm that in this population, as in men with more advanced stages, adding an androgen-receptor inhibitor [enzalutamide] increases the efficacy of androgen deprivation therapy,” Ana Aparicio, MD, from University of Texas MD Anderson Cancer Center, Houston, wrote in an accompanying editorial.
Standard care in this patient population relies on ADT to suppress testosterone, which would otherwise stimulate cancer cell growth. However, Dr. Freedland explained that “when you go on androgen deprivation therapy, the testosterone level in the blood is reduced but not completely eliminated. The concern is that the testosterone that remains may still be enough to stimulate tumor growth.”
Enzalutamide, an oral androgen receptor inhibitor, has already shown benefits in patients with metastases, and the current EMBARK trial explored whether the inhibitor can help men with earlier-stage disease who are at risk for metastases.
The findings from the phase 3 EMBARK trial, also published in NEJM Evidence, included 1,068 patients with prostate cancer at high-risk for biochemical recurrence. Patients, who had a median age of 69 years, spanned 244 sites across 17 countries.
Patients had a median prostate-specific antigen (PSA) doubling time of 4.9 months, with a median PSA of 5.2 ng/mL. Those with PSA doubling times of 9 months or less are considered at high-risk for biochemical recurrence and increased risk for death from prostate cancer.
Dr. Freedland and colleagues randomly assigned patients to three groups – enzalutamide 160 mg plus leuprolide every 12 weeks (n = 355), enzalutamide monotherapy (n = 355), and placebo plus leuprolide (n = 358). Patients received treatment for 38.7 months on average.
At 5-years, 87.3% of men in the combination group were metastasis-free, compared with 80% in the monotherapy group and 71.4% in the leuprolide-only group. Compared with leuprolide alone, combining enzalutamide and leuprolide reduced the risk for metastasis or death by 58% (hazard ratio, 0.42; P < .001). And compared with enzalutamide monotherapy, the combination also significantly reduced the risk for metastasis or death, compared with leuprolide alone (HR, 0.63; P = .005).
The estimated proportion of patients free from PSA progression at 5 years was 97.4% in the combination group, 88.9% in the monotherapy group, and 70% in the leuprolide-only group.
At the time of data cutoff, 33 (9%) patients in the combination group, 42 (12%) in the monotherapy group, and 55 (15%) in the leuprolide-only group had died.
Nearly all (97%) patients experienced adverse events, most of which (86.4%) were treatment-related. Overall, 46.5% of patients in the combination group experienced a grade 3 or higher adverse event, compared with 50% in the enzalutamide monotherapy group and 42.7% in the leuprolide-only group. Clustered adverse effects occurred in 80% or more patients in all three groups, with the most common cluster combining fatigue, falls, fractures, hypertension, and musculoskeletal events.
The most common adverse events in the enzalutamide monotherapy group, occurring in at least 30% of patients, included gynecomastia, joint pain, hot flashes, and fatigue. Nipple pain and breast tenderness were also common side effects in the enzalutamide monotherapy arm – occurring in 15.3% and 14.4% of patients, respectively – compared with the combination (3.1% and 1.1%) or leuprolide-only (1.1% and 1.1%) groups.
However, Dr. Freedland explained, “our quality-of-life data show that you don’t need to sacrifice global quality of life to get these cancer benefits.”
Patient-reported outcomes from EMBARK revealed that both enzalutamide combination and monotherapy versus leuprolide alone preserved high health-related quality of life in patients with a high-risk for biochemical recurrence.
More specifically, Dr. Freedland and colleagues found no differences in the time to first clinically meaningful deterioration based on questionnaires that rated pain and functional status. Functional status measures included physical, social, and emotional well-being as well as symptom severity.
However, some differences emerged. For instance, time to confirmed clinically meaningful deterioration in physical well-being score was significantly shorter among patients receiving enzalutamide, compared with leuprolide monotherapy – 24.8 months in the combination group and 27.6 months in the enzalutamide-only group versus 49.8 months in the leuprolide-only group (HR, 1.41 and 1.35, respectively).
However, sexual activity appeared to be better preserved among patients receiving enzalutamide monotherapy, compared with leuprolide alone. The median time to confirmed clinically meaningful deterioration in sexual activity score was 5.6 months with enzalutamide monotherapy versus 3 months for leuprolide alone (HR, 0.76).
Given the slightly different side-effect profiles in the enzalutamide combination and monotherapy groups, Dr. Freedland noted that “it will be up to patients and care providers to decide which is the right choice for them. I think the important message is that both are a major step forward from the current standard of care, which is androgen deprivation therapy alone.”
Pedro Barata, MD, who was not involved in the research, also noted that “this is the first time we have seen this kind of results with a novel hormonal therapy without castration.”
Overall, “the findings of this trial confirm the benefit of adding a novel hormonal therapy such as enzalutamide earlier in the course of this disease,” said Dr. Barata, a medical oncologist and director of the Clinical Genitourinary Medical Oncology Research Program at University Hospitals Seidman Cancer Center, Cleveland.
However, he explained that many patients with “rising PSA and short doubling time are known to have metastatic disease as detected by PSMA PET and are already being offered a novel hormonal therapy combined with castration. Perhaps it will be an opportunity for men who don’t want to be castrated to be offered an anti–androgen-like enzalutamide by itself without castration in this patient population.”
Research was funded by Pfizer and Astellas Pharma, manufacturers of enzalutamide.
A version of this article first appeared on Medscape.com.
Active surveillance preferred in low-risk prostate cancer
TOPLINE:
When provided detailed information on options, most men with low-risk prostate cancer chose active surveillance over treatment, and there was no difference in outcomes, new research from Italy shows.
METHODOLOGY:
- Active surveillance for patients with low-risk prostate cancer has been recommended for years, but its adoption often varies within and between countries.
- The current study, based in Italy, aimed to promote the adoption of active surveillance in two regions in Northern Italy and to understand patient acceptance and outcomes in comparison with active treatment.
- Men newly diagnosed with low-risk prostate cancer between June 2015 and December 2021 were eligible. All were informed of treatment options and were offered active surveillance.
- Multilevel models identified factors associated with choosing active surveillance over active treatment, which consisted of either radical prostatectomy or radiation therapy.
TAKEAWAY:
- Overall, 83% (706 of 852) men chose active surveillance over immediate treatment. There was an upward trend over time, from 78% in 2015-2017 to 90% in 2020-2021.
- Patients who chose active surveillance over any radical treatment were more likely to be aged 75 years or older (odds ratio, 4.27), to have a Charlson Comorbidity Index ≥ 2 (OR, 1.98), to have undergone independent revision of the first biopsy (OR, 2.35), and to have undergone multidisciplinary assessment (OR, 2.65).
- Worse prostate cancer prognostic factors, such as stage T2a (OR, 0.54) and Gleason Score 3+4 (OR, 0.20), were associated with lower odds of choosing active surveillance than any radical treatment.
- In an adjusted intention-to-treat analysis, among patients who initially chose active surveillance, overall survival was not worse in comparison with those who chose any radical treatment (hazard ratio, 0.86; 95% confidence interval, 0.41-1.79) or in comparison with those who chose radical prostatectomy (HR, 0.90; 95% CI, 0.37-2.20).
IN PRACTICE:
“The main remarkable finding of [the trial] is represented by the widespread adoption of active surveillance in our [Regional Oncology Network] since the beginning of the study, and the increasing trend over time, reaching approximately 90% of eligible patients in 2020 to 2021,” the authors wrote.
SOURCE:
The study, with first author Giovannino Ciccone, MD, PhD, AOU City of Health and Science of Turin, Italy, was published online in JAMA Network Open.
LIMITATIONS:
Key limitations include the relatively short follow-up (median, 57 months), variability between centers in terms of enrolling patients and discussing their choices, and the high rate of patients who abandoned active surveillance by year 2 of follow-up. Overall, about 281 patients (~40%) abandoned active surveillance by year 2, most commonly because of biochemical progression.
DISCLOSURES:
The START project was funded by the Fondazione Compagnia di San Paolo and partially by Rete Oncologica del Piemonte e Valle d’Aosta, Turin, Italy. Dr. Ciccone has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
When provided detailed information on options, most men with low-risk prostate cancer chose active surveillance over treatment, and there was no difference in outcomes, new research from Italy shows.
METHODOLOGY:
- Active surveillance for patients with low-risk prostate cancer has been recommended for years, but its adoption often varies within and between countries.
- The current study, based in Italy, aimed to promote the adoption of active surveillance in two regions in Northern Italy and to understand patient acceptance and outcomes in comparison with active treatment.
- Men newly diagnosed with low-risk prostate cancer between June 2015 and December 2021 were eligible. All were informed of treatment options and were offered active surveillance.
- Multilevel models identified factors associated with choosing active surveillance over active treatment, which consisted of either radical prostatectomy or radiation therapy.
TAKEAWAY:
- Overall, 83% (706 of 852) men chose active surveillance over immediate treatment. There was an upward trend over time, from 78% in 2015-2017 to 90% in 2020-2021.
- Patients who chose active surveillance over any radical treatment were more likely to be aged 75 years or older (odds ratio, 4.27), to have a Charlson Comorbidity Index ≥ 2 (OR, 1.98), to have undergone independent revision of the first biopsy (OR, 2.35), and to have undergone multidisciplinary assessment (OR, 2.65).
- Worse prostate cancer prognostic factors, such as stage T2a (OR, 0.54) and Gleason Score 3+4 (OR, 0.20), were associated with lower odds of choosing active surveillance than any radical treatment.
- In an adjusted intention-to-treat analysis, among patients who initially chose active surveillance, overall survival was not worse in comparison with those who chose any radical treatment (hazard ratio, 0.86; 95% confidence interval, 0.41-1.79) or in comparison with those who chose radical prostatectomy (HR, 0.90; 95% CI, 0.37-2.20).
IN PRACTICE:
“The main remarkable finding of [the trial] is represented by the widespread adoption of active surveillance in our [Regional Oncology Network] since the beginning of the study, and the increasing trend over time, reaching approximately 90% of eligible patients in 2020 to 2021,” the authors wrote.
SOURCE:
The study, with first author Giovannino Ciccone, MD, PhD, AOU City of Health and Science of Turin, Italy, was published online in JAMA Network Open.
LIMITATIONS:
Key limitations include the relatively short follow-up (median, 57 months), variability between centers in terms of enrolling patients and discussing their choices, and the high rate of patients who abandoned active surveillance by year 2 of follow-up. Overall, about 281 patients (~40%) abandoned active surveillance by year 2, most commonly because of biochemical progression.
DISCLOSURES:
The START project was funded by the Fondazione Compagnia di San Paolo and partially by Rete Oncologica del Piemonte e Valle d’Aosta, Turin, Italy. Dr. Ciccone has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
When provided detailed information on options, most men with low-risk prostate cancer chose active surveillance over treatment, and there was no difference in outcomes, new research from Italy shows.
METHODOLOGY:
- Active surveillance for patients with low-risk prostate cancer has been recommended for years, but its adoption often varies within and between countries.
- The current study, based in Italy, aimed to promote the adoption of active surveillance in two regions in Northern Italy and to understand patient acceptance and outcomes in comparison with active treatment.
- Men newly diagnosed with low-risk prostate cancer between June 2015 and December 2021 were eligible. All were informed of treatment options and were offered active surveillance.
- Multilevel models identified factors associated with choosing active surveillance over active treatment, which consisted of either radical prostatectomy or radiation therapy.
TAKEAWAY:
- Overall, 83% (706 of 852) men chose active surveillance over immediate treatment. There was an upward trend over time, from 78% in 2015-2017 to 90% in 2020-2021.
- Patients who chose active surveillance over any radical treatment were more likely to be aged 75 years or older (odds ratio, 4.27), to have a Charlson Comorbidity Index ≥ 2 (OR, 1.98), to have undergone independent revision of the first biopsy (OR, 2.35), and to have undergone multidisciplinary assessment (OR, 2.65).
- Worse prostate cancer prognostic factors, such as stage T2a (OR, 0.54) and Gleason Score 3+4 (OR, 0.20), were associated with lower odds of choosing active surveillance than any radical treatment.
- In an adjusted intention-to-treat analysis, among patients who initially chose active surveillance, overall survival was not worse in comparison with those who chose any radical treatment (hazard ratio, 0.86; 95% confidence interval, 0.41-1.79) or in comparison with those who chose radical prostatectomy (HR, 0.90; 95% CI, 0.37-2.20).
IN PRACTICE:
“The main remarkable finding of [the trial] is represented by the widespread adoption of active surveillance in our [Regional Oncology Network] since the beginning of the study, and the increasing trend over time, reaching approximately 90% of eligible patients in 2020 to 2021,” the authors wrote.
SOURCE:
The study, with first author Giovannino Ciccone, MD, PhD, AOU City of Health and Science of Turin, Italy, was published online in JAMA Network Open.
LIMITATIONS:
Key limitations include the relatively short follow-up (median, 57 months), variability between centers in terms of enrolling patients and discussing their choices, and the high rate of patients who abandoned active surveillance by year 2 of follow-up. Overall, about 281 patients (~40%) abandoned active surveillance by year 2, most commonly because of biochemical progression.
DISCLOSURES:
The START project was funded by the Fondazione Compagnia di San Paolo and partially by Rete Oncologica del Piemonte e Valle d’Aosta, Turin, Italy. Dr. Ciccone has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.