Genitourinary Cancer

Incorporating a polygenic risk score into prostate cancer screening could enhance the detection of clinically significant prostate cancer that conventional screening may miss, according to results of the BARCODE 1 clinical trial conducted in the United Kingdom.

The study found that about 72% of participants with high polygenic risk scores were diagnosed with clinically significant prostate cancers, which would not have been detected with prostate-specific antigen (PSA) testing or MRI.

“With this test, it could be possible to turn the tide on prostate cancer,” study author Ros Eeles, PhD, professor of oncogenetics at The Institute of Cancer Research, London, England, said in a statement following the publication of the analysis in The New England Journal of Medicine.

Prostate cancer remains the second most commonly diagnosed cancer among men. As a screening tool, PSA testing has been criticized for leading to a high rate of false positive results and overdiagnosis — defined as a screen-detected cancer that would take longer to progress to clinical cancer than the patient’s lifetime. Both issues can result in overtreatment.

Given prostate cancer’s high heritability and the proliferation of genome-wide association studies identifying common genetic variants, there has been growing interest in using polygenic risk scores to improve risk stratification and guide screening.

“Building on decades of research into the genetic markers of prostate cancer, our study shows that the theory does work in practice — we can identify men at risk of aggressive cancers who need further tests and spare the men who are at lower risk from unnecessary treatments,” said Eeles.

 

An Adjunct to Screening?

The BARCODE 1 study, conducted in the United Kingdom, tested the clinical utility of a polygenic risk score as an adjunct to screening.

The researchers recruited men aged 55-69 years from primary care centers in the United Kingdom. Using germline DNA extracted from saliva, they derived polygenic risk scores from 130 genetic variants known to be associated with an increased risk for prostate cancer.

Among a total of 6393 men who had their scores calculated, 745 (12%) had a score in the top 10% of genetic risk (≥ 90th percentile) and were invited to undergo further screening.

Of these, 468 (63%) accepted the invite and underwent multiparametric MRI and transperineal prostate biopsy, irrespective of the PSA level. Overall, 187 (40%) were diagnosed with prostate cancer following biopsy. Of the 187 men with prostate cancer, 55% (n = 103) had disease classified as intermediate or high risk (Gleason score ≥ 7) per National Comprehensive Cancer Network criteria and therefore warranted further treatment.

Researchers then compared screening that incorporated polygenic risk scores with standard screening with PSA levels and MRI.

When participants’ risk was stratified by their polygenic risk score, 103 patients (55%) with prostate cancer could be classified as intermediate or higher risk, thus warranting treatment. Overall, 74 (71.8%) of those cancers would have been missed using the standard diagnostic pathway in the United Kingdom, which requires patients to have a high PSA level (> 3.0 μg/L) as well as a positive MRI result. These 74 patients either had PSA levels ≤ 3.0 μg/L or negative MRIs, which would mean these patients would typically fall below the action threshold for further testing.

Of the 103 participants warranting treatment, 40 of these men would have been classified as unfavorable intermediate, high, or very high risk, which would require radical treatment. Among this group, roughly 43% would have been missed using the UK diagnostic pathway. 

However, the investigators estimated a rate of overdiagnosis with the use of polygenic risk scores of 16%-21%, similar to the overdiagnosis estimates in two prior PSA-based screening studies, signaling that the addition of polygenic risk scores does not necessarily reduce the risk for overdiagnosis.

Overall, “this study is the strongest evidence to date on the clinical utility of a polygenic score for prostate cancer screening,” commented Michael Inouye, professor of systems genomics & population health, University of Cambridge, Cambridge, England, in a statement from the UK nonprofit Science Media Centre (SMC).

“I suspect we will look back on this as a landmark study that really made the clinical case for polygenic scores as a new tool that moved health systems from disease management to early detection and prevention,” said Inouye, who was not involved in the study.

However, other experts were more cautious about the findings.

Dusko Ilic, MD, professor of stem cell sciences, King’s College London, London, England, said the results are “promising, especially in identifying significant cancers that would otherwise be missed,” but cautioned that “there is no direct evidence yet that using [polygenic risk scores] improves long-term outcomes such as mortality or quality-adjusted life years.”

“Modeling suggests benefit, but empirical confirmation is needed,” Ilic said in the SMC statement.

The hope is that the recently launched TRANSFORM trial will help answer some of these outstanding questions.

The current study suggests that polygenic risk scores for prostate cancer “would be a useful component of a multimodality screening program that assesses age, family history of prostate cancer, PSA, and MRI results as triage tools before biopsy is recommended,” David Hunter, MPH, ScD, with Harvard T. H. Chan School of Public Health, Boston, and University of Oxford, Oxford, England, wrote in an editorial accompanying the study.

“To make this integrated program a reality, however, changes to infrastructure would be needed to make running and analyzing a regulated genome array as easy as requesting a PSA level or ordering an MRI. Clearly, we are far from that future,” Hunter cautioned. 

“A possible first step that would require less infrastructure could be to order a polygenic risk score only for men with a positive PSA result, then use the polygenic risk score to determine who should undergo an MRI, and then use all the information to determine whether biopsy is recommended,” Hunter said.

In his view, the current study is a “first step on a long road to evaluating new components of any disease screening pathway.”

The research received funding from the European Research Council, the Bob Willis Fund, Cancer Research UK, the Peacock Trust, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research. Disclosures for authors and editorialists are available with the original article. Inouye and Ilic reported no relevant disclosures.

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

Incorporating a polygenic risk score into prostate cancer screening could enhance the detection of clinically significant prostate cancer that conventional screening may miss, according to results of the BARCODE 1 clinical trial conducted in the United Kingdom.

The study found that about 72% of participants with high polygenic risk scores were diagnosed with clinically significant prostate cancers, which would not have been detected with prostate-specific antigen (PSA) testing or MRI.

“With this test, it could be possible to turn the tide on prostate cancer,” study author Ros Eeles, PhD, professor of oncogenetics at The Institute of Cancer Research, London, England, said in a statement following the publication of the analysis in The New England Journal of Medicine.

Prostate cancer remains the second most commonly diagnosed cancer among men. As a screening tool, PSA testing has been criticized for leading to a high rate of false positive results and overdiagnosis — defined as a screen-detected cancer that would take longer to progress to clinical cancer than the patient’s lifetime. Both issues can result in overtreatment.

Given prostate cancer’s high heritability and the proliferation of genome-wide association studies identifying common genetic variants, there has been growing interest in using polygenic risk scores to improve risk stratification and guide screening.

“Building on decades of research into the genetic markers of prostate cancer, our study shows that the theory does work in practice — we can identify men at risk of aggressive cancers who need further tests and spare the men who are at lower risk from unnecessary treatments,” said Eeles.

 

An Adjunct to Screening?

The BARCODE 1 study, conducted in the United Kingdom, tested the clinical utility of a polygenic risk score as an adjunct to screening.

The researchers recruited men aged 55-69 years from primary care centers in the United Kingdom. Using germline DNA extracted from saliva, they derived polygenic risk scores from 130 genetic variants known to be associated with an increased risk for prostate cancer.

Among a total of 6393 men who had their scores calculated, 745 (12%) had a score in the top 10% of genetic risk (≥ 90th percentile) and were invited to undergo further screening.

Of these, 468 (63%) accepted the invite and underwent multiparametric MRI and transperineal prostate biopsy, irrespective of the PSA level. Overall, 187 (40%) were diagnosed with prostate cancer following biopsy. Of the 187 men with prostate cancer, 55% (n = 103) had disease classified as intermediate or high risk (Gleason score ≥ 7) per National Comprehensive Cancer Network criteria and therefore warranted further treatment.

Researchers then compared screening that incorporated polygenic risk scores with standard screening with PSA levels and MRI.

When participants’ risk was stratified by their polygenic risk score, 103 patients (55%) with prostate cancer could be classified as intermediate or higher risk, thus warranting treatment. Overall, 74 (71.8%) of those cancers would have been missed using the standard diagnostic pathway in the United Kingdom, which requires patients to have a high PSA level (> 3.0 μg/L) as well as a positive MRI result. These 74 patients either had PSA levels ≤ 3.0 μg/L or negative MRIs, which would mean these patients would typically fall below the action threshold for further testing.

Of the 103 participants warranting treatment, 40 of these men would have been classified as unfavorable intermediate, high, or very high risk, which would require radical treatment. Among this group, roughly 43% would have been missed using the UK diagnostic pathway. 

However, the investigators estimated a rate of overdiagnosis with the use of polygenic risk scores of 16%-21%, similar to the overdiagnosis estimates in two prior PSA-based screening studies, signaling that the addition of polygenic risk scores does not necessarily reduce the risk for overdiagnosis.

Overall, “this study is the strongest evidence to date on the clinical utility of a polygenic score for prostate cancer screening,” commented Michael Inouye, professor of systems genomics & population health, University of Cambridge, Cambridge, England, in a statement from the UK nonprofit Science Media Centre (SMC).

“I suspect we will look back on this as a landmark study that really made the clinical case for polygenic scores as a new tool that moved health systems from disease management to early detection and prevention,” said Inouye, who was not involved in the study.

However, other experts were more cautious about the findings.

Dusko Ilic, MD, professor of stem cell sciences, King’s College London, London, England, said the results are “promising, especially in identifying significant cancers that would otherwise be missed,” but cautioned that “there is no direct evidence yet that using [polygenic risk scores] improves long-term outcomes such as mortality or quality-adjusted life years.”

“Modeling suggests benefit, but empirical confirmation is needed,” Ilic said in the SMC statement.

The hope is that the recently launched TRANSFORM trial will help answer some of these outstanding questions.

The current study suggests that polygenic risk scores for prostate cancer “would be a useful component of a multimodality screening program that assesses age, family history of prostate cancer, PSA, and MRI results as triage tools before biopsy is recommended,” David Hunter, MPH, ScD, with Harvard T. H. Chan School of Public Health, Boston, and University of Oxford, Oxford, England, wrote in an editorial accompanying the study.

“To make this integrated program a reality, however, changes to infrastructure would be needed to make running and analyzing a regulated genome array as easy as requesting a PSA level or ordering an MRI. Clearly, we are far from that future,” Hunter cautioned. 

“A possible first step that would require less infrastructure could be to order a polygenic risk score only for men with a positive PSA result, then use the polygenic risk score to determine who should undergo an MRI, and then use all the information to determine whether biopsy is recommended,” Hunter said.

In his view, the current study is a “first step on a long road to evaluating new components of any disease screening pathway.”

The research received funding from the European Research Council, the Bob Willis Fund, Cancer Research UK, the Peacock Trust, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research. Disclosures for authors and editorialists are available with the original article. Inouye and Ilic reported no relevant disclosures.

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

Incorporating a polygenic risk score into prostate cancer screening could enhance the detection of clinically significant prostate cancer that conventional screening may miss, according to results of the BARCODE 1 clinical trial conducted in the United Kingdom.

The study found that about 72% of participants with high polygenic risk scores were diagnosed with clinically significant prostate cancers, which would not have been detected with prostate-specific antigen (PSA) testing or MRI.

“With this test, it could be possible to turn the tide on prostate cancer,” study author Ros Eeles, PhD, professor of oncogenetics at The Institute of Cancer Research, London, England, said in a statement following the publication of the analysis in The New England Journal of Medicine.

Prostate cancer remains the second most commonly diagnosed cancer among men. As a screening tool, PSA testing has been criticized for leading to a high rate of false positive results and overdiagnosis — defined as a screen-detected cancer that would take longer to progress to clinical cancer than the patient’s lifetime. Both issues can result in overtreatment.

Given prostate cancer’s high heritability and the proliferation of genome-wide association studies identifying common genetic variants, there has been growing interest in using polygenic risk scores to improve risk stratification and guide screening.

“Building on decades of research into the genetic markers of prostate cancer, our study shows that the theory does work in practice — we can identify men at risk of aggressive cancers who need further tests and spare the men who are at lower risk from unnecessary treatments,” said Eeles.

 

An Adjunct to Screening?

The BARCODE 1 study, conducted in the United Kingdom, tested the clinical utility of a polygenic risk score as an adjunct to screening.

The researchers recruited men aged 55-69 years from primary care centers in the United Kingdom. Using germline DNA extracted from saliva, they derived polygenic risk scores from 130 genetic variants known to be associated with an increased risk for prostate cancer.

Among a total of 6393 men who had their scores calculated, 745 (12%) had a score in the top 10% of genetic risk (≥ 90th percentile) and were invited to undergo further screening.

Of these, 468 (63%) accepted the invite and underwent multiparametric MRI and transperineal prostate biopsy, irrespective of the PSA level. Overall, 187 (40%) were diagnosed with prostate cancer following biopsy. Of the 187 men with prostate cancer, 55% (n = 103) had disease classified as intermediate or high risk (Gleason score ≥ 7) per National Comprehensive Cancer Network criteria and therefore warranted further treatment.

Researchers then compared screening that incorporated polygenic risk scores with standard screening with PSA levels and MRI.

When participants’ risk was stratified by their polygenic risk score, 103 patients (55%) with prostate cancer could be classified as intermediate or higher risk, thus warranting treatment. Overall, 74 (71.8%) of those cancers would have been missed using the standard diagnostic pathway in the United Kingdom, which requires patients to have a high PSA level (> 3.0 μg/L) as well as a positive MRI result. These 74 patients either had PSA levels ≤ 3.0 μg/L or negative MRIs, which would mean these patients would typically fall below the action threshold for further testing.

Of the 103 participants warranting treatment, 40 of these men would have been classified as unfavorable intermediate, high, or very high risk, which would require radical treatment. Among this group, roughly 43% would have been missed using the UK diagnostic pathway. 

However, the investigators estimated a rate of overdiagnosis with the use of polygenic risk scores of 16%-21%, similar to the overdiagnosis estimates in two prior PSA-based screening studies, signaling that the addition of polygenic risk scores does not necessarily reduce the risk for overdiagnosis.

Overall, “this study is the strongest evidence to date on the clinical utility of a polygenic score for prostate cancer screening,” commented Michael Inouye, professor of systems genomics & population health, University of Cambridge, Cambridge, England, in a statement from the UK nonprofit Science Media Centre (SMC).

“I suspect we will look back on this as a landmark study that really made the clinical case for polygenic scores as a new tool that moved health systems from disease management to early detection and prevention,” said Inouye, who was not involved in the study.

However, other experts were more cautious about the findings.

Dusko Ilic, MD, professor of stem cell sciences, King’s College London, London, England, said the results are “promising, especially in identifying significant cancers that would otherwise be missed,” but cautioned that “there is no direct evidence yet that using [polygenic risk scores] improves long-term outcomes such as mortality or quality-adjusted life years.”

“Modeling suggests benefit, but empirical confirmation is needed,” Ilic said in the SMC statement.

The hope is that the recently launched TRANSFORM trial will help answer some of these outstanding questions.

The current study suggests that polygenic risk scores for prostate cancer “would be a useful component of a multimodality screening program that assesses age, family history of prostate cancer, PSA, and MRI results as triage tools before biopsy is recommended,” David Hunter, MPH, ScD, with Harvard T. H. Chan School of Public Health, Boston, and University of Oxford, Oxford, England, wrote in an editorial accompanying the study.

“To make this integrated program a reality, however, changes to infrastructure would be needed to make running and analyzing a regulated genome array as easy as requesting a PSA level or ordering an MRI. Clearly, we are far from that future,” Hunter cautioned. 

“A possible first step that would require less infrastructure could be to order a polygenic risk score only for men with a positive PSA result, then use the polygenic risk score to determine who should undergo an MRI, and then use all the information to determine whether biopsy is recommended,” Hunter said.

In his view, the current study is a “first step on a long road to evaluating new components of any disease screening pathway.”

The research received funding from the European Research Council, the Bob Willis Fund, Cancer Research UK, the Peacock Trust, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research. Disclosures for authors and editorialists are available with the original article. Inouye and Ilic reported no relevant disclosures.

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

New findings on radiation plus adjuvant chemotherapy in patients with intermediate-risk cervical cancer seem to spell the end for the dual therapy in this group. 

Results from a phase 3 clinical trial of 316 women who’d had radical hysterectomies found that adjuvant chemotherapy as treatment for their early-stage, intermediate-risk cervical carcinoma did not improve outcomes but did increase toxicity. The results were the inverse of the study’s intention. 

The NRG-GOG 0263 (NCT01101451) study failed to reach its endpoint of improving recurrence-free survival through the addition of cisplatin chemotherapy, confirming instead that cisplatin chemotherapy given adjuvantly with radiotherapy is not a superior alternative in this cohort. The results were presented during a plenary session of the Society of Gynecologic Oncology Annual Meeting on Women’s Cancers in Seattle, Washington.

The current standard of care in this cohort is for radiotherapy alone, although the National Comprehensive Cancer Network (NCCN) guidelines place adjuvant chemotherapy in category 2B recommendations. 

“Perhaps the NCCN guidelines will have to change what it says here,” Andrew Berchuck, MD, chief of gynecologic oncology and professor of obstetrics and gynecology at Duke University School of Medicine in Durham, North Carolina, told this news organization. Berchuck was not involved in the clinical trial.

The National Cancer Institute lists adjuvant chemotherapy first in its guidelines for this group.

Another study published online this month in JAMA Oncology concluded that morbidity in these patients could be reduced if the use of chemoradiotherapy were de-escalated. 

This population-based cohort study of 1116 women, conducted by Núria Agustí Garcia, MD, postdoctoral fellow at The University of Texas MD Anderson Cancer Center in Houston, and colleagues, found no significant overall survival benefit of adjuvant chemotherapy in intermediate-risk cervical cancer, and that when it was given, patients tended to have larger tumors and nonsquamous cell history. 

The 5-year survival rate in patients who received chemoradiotherapy was 87%, compared with an 87% 5-year survival rate in those who received radiotherapy alone (hazard ratio = 0.85; 95% CI, 0.59-1.23; P =.38).

If the standard of care in this cohort is radiation only, and outcomes are not better in adjuvant treatment, then why is there a controversy at all, and why are some investigators such as Agustí Garcia attempting to clarify adjuvant treatment’s effects?

Experts say it’s because of the history of adjuvant chemotherapy in more advanced cervical cancer and the extrapolations clinicians made when treating patients with intermediate risk.

 

What Is the History of Adjuvant Treatment in Cervical Cancer?

Concomitant therapies in intermediate-risk cervical cancer began in the late 1990s, at a time when it was found effective in more advanced disease, according to Berchuck, who also was not involved in the population study.

“Say back then, you had a stage IIIb cervical cancer. With external radiation alone, followed by brachytherapy internally, the cure rate for something like that would have been maybe 50 or 60%,” Berchuck said in an interview. “Adding cisplatin improved the cure rate by about 15%.”

That cisplatin improved survival rates in advanced disease, led to using it in less advanced cases, according to Berchuck. “The idea here was that if the pathology report indicated a larger tumor involving the lymphatics, the risk of recurrence went up to about 20%, so by adding chemo to postsurgical radiotherapy, you could improve things more than with just radiation alone,” Berchuck said. 

Studies of adjuvant chemotherapy in advanced cervical cancers confused the matter, according to Agustí Garcia. 

“The theoretical benefit of adding chemotherapy to radiotherapy for patients with intermediate-risk cervical cancer has been extrapolated from studies on locally advanced or high-risk cases, for example, those with parametrial or lymph node metastases,” Agustí Garcia said in an interview.

“However, before its implementation, there was no solid evidence supporting this approach in intermediate-risk patients,” she said. “The oncologic behavior of this subgroup may differ, and in the absence of parametrial or lymph node metastasis, chemotherapy may not be necessary.”

 

Do Both Studies Suggest That Radiotherapy Has Become More Effective Recently?

“Probably. Modern radiation techniques, such as IMRT [intensity-modulated radiation therapy] and IGRT [image-guided radiation therapy] are more effective than historical techniques,” said Amer Karam, MD, a clinical professor of obstetrics and gynecology at Stanford University in Palo Alto, California. Karam was not involved in either study mentioned previously.

Agustí Garcia said that while it’s true radiotherapy techniques have improved, these advancements primarily impact morbidity rather than survival outcomes.

“The lack of survival benefit from concomitant chemotherapy in intermediate-risk patients suggests that such benefit may never have existed in this subgroup,” she said.

 

What Explains Why Overall Survival Did Not Significantly Differ Between Patients Who Received Radiotherapy Alone and Those Who Received Chemoradiotherapy?

For Karam, there is a question as to whether chemosensitization mechanisms in radiation therapy, such as reactive oxygen species, inhibition of DNA repair, modulating tumor microenvironment, and cell cycle arrest — all used to induce apoptosis — are as efficacious as once thought.

“Also, systemic chemosensitization may not be as effective at controlling systemic disease beyond the pelvis and radiation field,” he said.

“Radiation is extremely effective in cervical cancer,” said Berchuck. “When you’re giving radiation in a situation like this where there is none, to only microscopic disease, it makes sense that radiation could be effective by itself.”

 

Why in the JAMA Oncology Study Were Larger Tumor Size and Nonsquamous Histology Associated With the Use of Chemoradiotherapy?

All experts agreed this is likely because this subgroup of patients with larger tumors is typically seen as being at higher risk for recurrence. This might be due to what Karam called an “unfavorable histology” and certain tumor characteristics, including depth of invasion.

Yet Agustí Garcia said, in her study, even after propensity score matching, adjuvant chemotherapy did not demonstrate any survival benefit in this subgroup.

“The importance of performing propensity score matching in our analysis was to ensure that populations with comparable baseline recurrence and death risks were being evaluated fairly,” she told this news organization.

 

Do These Findings Change Clinical Practice for Intermediate-Risk Cervical Cancer Treatment?

For Karam, the new evidence in intermediate-risk cervical cancer confirms rather than changes clinical practice. “The standard of care was radiation therapy alone, which is now confirmed, based on the results of GOG 263,” Karam said. “The standard of care for these patients will remain the same.”

Agustí Garcia said her study results can help “refine” clinical practice.

“The results suggest that adjuvant therapy could be safely de-escalated in intermediate-risk cervical cancer,” Agustí Garcia said. 

“We should avoid chemotherapy when there is no evidence-based benefit, reserving its use for locally advanced or high-risk cases, refining clinical guidelines to ensure treatment recommendations are based on higher-quality evidence, thereby standardizing care and reducing overtreatment,” she continued. “Current guidelines lack consensus and rely on lower-quality evidence.”

Agustí Garcia reported grants from Fundación Alfonso Martín Escudero. Berchuck has no disclosures. Karam reported royalties from UpToDate and that he is a speaker for AstraZeneca.

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

New findings on radiation plus adjuvant chemotherapy in patients with intermediate-risk cervical cancer seem to spell the end for the dual therapy in this group. 

Results from a phase 3 clinical trial of 316 women who’d had radical hysterectomies found that adjuvant chemotherapy as treatment for their early-stage, intermediate-risk cervical carcinoma did not improve outcomes but did increase toxicity. The results were the inverse of the study’s intention. 

The NRG-GOG 0263 (NCT01101451) study failed to reach its endpoint of improving recurrence-free survival through the addition of cisplatin chemotherapy, confirming instead that cisplatin chemotherapy given adjuvantly with radiotherapy is not a superior alternative in this cohort. The results were presented during a plenary session of the Society of Gynecologic Oncology Annual Meeting on Women’s Cancers in Seattle, Washington.

The current standard of care in this cohort is for radiotherapy alone, although the National Comprehensive Cancer Network (NCCN) guidelines place adjuvant chemotherapy in category 2B recommendations. 

“Perhaps the NCCN guidelines will have to change what it says here,” Andrew Berchuck, MD, chief of gynecologic oncology and professor of obstetrics and gynecology at Duke University School of Medicine in Durham, North Carolina, told this news organization. Berchuck was not involved in the clinical trial.

The National Cancer Institute lists adjuvant chemotherapy first in its guidelines for this group.

Another study published online this month in JAMA Oncology concluded that morbidity in these patients could be reduced if the use of chemoradiotherapy were de-escalated. 

This population-based cohort study of 1116 women, conducted by Núria Agustí Garcia, MD, postdoctoral fellow at The University of Texas MD Anderson Cancer Center in Houston, and colleagues, found no significant overall survival benefit of adjuvant chemotherapy in intermediate-risk cervical cancer, and that when it was given, patients tended to have larger tumors and nonsquamous cell history. 

The 5-year survival rate in patients who received chemoradiotherapy was 87%, compared with an 87% 5-year survival rate in those who received radiotherapy alone (hazard ratio = 0.85; 95% CI, 0.59-1.23; P =.38).

If the standard of care in this cohort is radiation only, and outcomes are not better in adjuvant treatment, then why is there a controversy at all, and why are some investigators such as Agustí Garcia attempting to clarify adjuvant treatment’s effects?

Experts say it’s because of the history of adjuvant chemotherapy in more advanced cervical cancer and the extrapolations clinicians made when treating patients with intermediate risk.

 

What Is the History of Adjuvant Treatment in Cervical Cancer?

Concomitant therapies in intermediate-risk cervical cancer began in the late 1990s, at a time when it was found effective in more advanced disease, according to Berchuck, who also was not involved in the population study.

“Say back then, you had a stage IIIb cervical cancer. With external radiation alone, followed by brachytherapy internally, the cure rate for something like that would have been maybe 50 or 60%,” Berchuck said in an interview. “Adding cisplatin improved the cure rate by about 15%.”

That cisplatin improved survival rates in advanced disease, led to using it in less advanced cases, according to Berchuck. “The idea here was that if the pathology report indicated a larger tumor involving the lymphatics, the risk of recurrence went up to about 20%, so by adding chemo to postsurgical radiotherapy, you could improve things more than with just radiation alone,” Berchuck said. 

Studies of adjuvant chemotherapy in advanced cervical cancers confused the matter, according to Agustí Garcia. 

“The theoretical benefit of adding chemotherapy to radiotherapy for patients with intermediate-risk cervical cancer has been extrapolated from studies on locally advanced or high-risk cases, for example, those with parametrial or lymph node metastases,” Agustí Garcia said in an interview.

“However, before its implementation, there was no solid evidence supporting this approach in intermediate-risk patients,” she said. “The oncologic behavior of this subgroup may differ, and in the absence of parametrial or lymph node metastasis, chemotherapy may not be necessary.”

 

Do Both Studies Suggest That Radiotherapy Has Become More Effective Recently?

“Probably. Modern radiation techniques, such as IMRT [intensity-modulated radiation therapy] and IGRT [image-guided radiation therapy] are more effective than historical techniques,” said Amer Karam, MD, a clinical professor of obstetrics and gynecology at Stanford University in Palo Alto, California. Karam was not involved in either study mentioned previously.

Agustí Garcia said that while it’s true radiotherapy techniques have improved, these advancements primarily impact morbidity rather than survival outcomes.

“The lack of survival benefit from concomitant chemotherapy in intermediate-risk patients suggests that such benefit may never have existed in this subgroup,” she said.

 

What Explains Why Overall Survival Did Not Significantly Differ Between Patients Who Received Radiotherapy Alone and Those Who Received Chemoradiotherapy?

For Karam, there is a question as to whether chemosensitization mechanisms in radiation therapy, such as reactive oxygen species, inhibition of DNA repair, modulating tumor microenvironment, and cell cycle arrest — all used to induce apoptosis — are as efficacious as once thought.

“Also, systemic chemosensitization may not be as effective at controlling systemic disease beyond the pelvis and radiation field,” he said.

“Radiation is extremely effective in cervical cancer,” said Berchuck. “When you’re giving radiation in a situation like this where there is none, to only microscopic disease, it makes sense that radiation could be effective by itself.”

 

Why in the JAMA Oncology Study Were Larger Tumor Size and Nonsquamous Histology Associated With the Use of Chemoradiotherapy?

All experts agreed this is likely because this subgroup of patients with larger tumors is typically seen as being at higher risk for recurrence. This might be due to what Karam called an “unfavorable histology” and certain tumor characteristics, including depth of invasion.

Yet Agustí Garcia said, in her study, even after propensity score matching, adjuvant chemotherapy did not demonstrate any survival benefit in this subgroup.

“The importance of performing propensity score matching in our analysis was to ensure that populations with comparable baseline recurrence and death risks were being evaluated fairly,” she told this news organization.

 

Do These Findings Change Clinical Practice for Intermediate-Risk Cervical Cancer Treatment?

For Karam, the new evidence in intermediate-risk cervical cancer confirms rather than changes clinical practice. “The standard of care was radiation therapy alone, which is now confirmed, based on the results of GOG 263,” Karam said. “The standard of care for these patients will remain the same.”

Agustí Garcia said her study results can help “refine” clinical practice.

“The results suggest that adjuvant therapy could be safely de-escalated in intermediate-risk cervical cancer,” Agustí Garcia said. 

“We should avoid chemotherapy when there is no evidence-based benefit, reserving its use for locally advanced or high-risk cases, refining clinical guidelines to ensure treatment recommendations are based on higher-quality evidence, thereby standardizing care and reducing overtreatment,” she continued. “Current guidelines lack consensus and rely on lower-quality evidence.”

Agustí Garcia reported grants from Fundación Alfonso Martín Escudero. Berchuck has no disclosures. Karam reported royalties from UpToDate and that he is a speaker for AstraZeneca.

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

New findings on radiation plus adjuvant chemotherapy in patients with intermediate-risk cervical cancer seem to spell the end for the dual therapy in this group. 

Results from a phase 3 clinical trial of 316 women who’d had radical hysterectomies found that adjuvant chemotherapy as treatment for their early-stage, intermediate-risk cervical carcinoma did not improve outcomes but did increase toxicity. The results were the inverse of the study’s intention. 

The NRG-GOG 0263 (NCT01101451) study failed to reach its endpoint of improving recurrence-free survival through the addition of cisplatin chemotherapy, confirming instead that cisplatin chemotherapy given adjuvantly with radiotherapy is not a superior alternative in this cohort. The results were presented during a plenary session of the Society of Gynecologic Oncology Annual Meeting on Women’s Cancers in Seattle, Washington.

The current standard of care in this cohort is for radiotherapy alone, although the National Comprehensive Cancer Network (NCCN) guidelines place adjuvant chemotherapy in category 2B recommendations. 

“Perhaps the NCCN guidelines will have to change what it says here,” Andrew Berchuck, MD, chief of gynecologic oncology and professor of obstetrics and gynecology at Duke University School of Medicine in Durham, North Carolina, told this news organization. Berchuck was not involved in the clinical trial.

The National Cancer Institute lists adjuvant chemotherapy first in its guidelines for this group.

Another study published online this month in JAMA Oncology concluded that morbidity in these patients could be reduced if the use of chemoradiotherapy were de-escalated. 

This population-based cohort study of 1116 women, conducted by Núria Agustí Garcia, MD, postdoctoral fellow at The University of Texas MD Anderson Cancer Center in Houston, and colleagues, found no significant overall survival benefit of adjuvant chemotherapy in intermediate-risk cervical cancer, and that when it was given, patients tended to have larger tumors and nonsquamous cell history. 

The 5-year survival rate in patients who received chemoradiotherapy was 87%, compared with an 87% 5-year survival rate in those who received radiotherapy alone (hazard ratio = 0.85; 95% CI, 0.59-1.23; P =.38).

If the standard of care in this cohort is radiation only, and outcomes are not better in adjuvant treatment, then why is there a controversy at all, and why are some investigators such as Agustí Garcia attempting to clarify adjuvant treatment’s effects?

Experts say it’s because of the history of adjuvant chemotherapy in more advanced cervical cancer and the extrapolations clinicians made when treating patients with intermediate risk.

 

What Is the History of Adjuvant Treatment in Cervical Cancer?

Concomitant therapies in intermediate-risk cervical cancer began in the late 1990s, at a time when it was found effective in more advanced disease, according to Berchuck, who also was not involved in the population study.

“Say back then, you had a stage IIIb cervical cancer. With external radiation alone, followed by brachytherapy internally, the cure rate for something like that would have been maybe 50 or 60%,” Berchuck said in an interview. “Adding cisplatin improved the cure rate by about 15%.”

That cisplatin improved survival rates in advanced disease, led to using it in less advanced cases, according to Berchuck. “The idea here was that if the pathology report indicated a larger tumor involving the lymphatics, the risk of recurrence went up to about 20%, so by adding chemo to postsurgical radiotherapy, you could improve things more than with just radiation alone,” Berchuck said. 

Studies of adjuvant chemotherapy in advanced cervical cancers confused the matter, according to Agustí Garcia. 

“The theoretical benefit of adding chemotherapy to radiotherapy for patients with intermediate-risk cervical cancer has been extrapolated from studies on locally advanced or high-risk cases, for example, those with parametrial or lymph node metastases,” Agustí Garcia said in an interview.

“However, before its implementation, there was no solid evidence supporting this approach in intermediate-risk patients,” she said. “The oncologic behavior of this subgroup may differ, and in the absence of parametrial or lymph node metastasis, chemotherapy may not be necessary.”

 

Do Both Studies Suggest That Radiotherapy Has Become More Effective Recently?

“Probably. Modern radiation techniques, such as IMRT [intensity-modulated radiation therapy] and IGRT [image-guided radiation therapy] are more effective than historical techniques,” said Amer Karam, MD, a clinical professor of obstetrics and gynecology at Stanford University in Palo Alto, California. Karam was not involved in either study mentioned previously.

Agustí Garcia said that while it’s true radiotherapy techniques have improved, these advancements primarily impact morbidity rather than survival outcomes.

“The lack of survival benefit from concomitant chemotherapy in intermediate-risk patients suggests that such benefit may never have existed in this subgroup,” she said.

 

What Explains Why Overall Survival Did Not Significantly Differ Between Patients Who Received Radiotherapy Alone and Those Who Received Chemoradiotherapy?

For Karam, there is a question as to whether chemosensitization mechanisms in radiation therapy, such as reactive oxygen species, inhibition of DNA repair, modulating tumor microenvironment, and cell cycle arrest — all used to induce apoptosis — are as efficacious as once thought.

“Also, systemic chemosensitization may not be as effective at controlling systemic disease beyond the pelvis and radiation field,” he said.

“Radiation is extremely effective in cervical cancer,” said Berchuck. “When you’re giving radiation in a situation like this where there is none, to only microscopic disease, it makes sense that radiation could be effective by itself.”

 

Why in the JAMA Oncology Study Were Larger Tumor Size and Nonsquamous Histology Associated With the Use of Chemoradiotherapy?

All experts agreed this is likely because this subgroup of patients with larger tumors is typically seen as being at higher risk for recurrence. This might be due to what Karam called an “unfavorable histology” and certain tumor characteristics, including depth of invasion.

Yet Agustí Garcia said, in her study, even after propensity score matching, adjuvant chemotherapy did not demonstrate any survival benefit in this subgroup.

“The importance of performing propensity score matching in our analysis was to ensure that populations with comparable baseline recurrence and death risks were being evaluated fairly,” she told this news organization.

 

Do These Findings Change Clinical Practice for Intermediate-Risk Cervical Cancer Treatment?

For Karam, the new evidence in intermediate-risk cervical cancer confirms rather than changes clinical practice. “The standard of care was radiation therapy alone, which is now confirmed, based on the results of GOG 263,” Karam said. “The standard of care for these patients will remain the same.”

Agustí Garcia said her study results can help “refine” clinical practice.

“The results suggest that adjuvant therapy could be safely de-escalated in intermediate-risk cervical cancer,” Agustí Garcia said. 

“We should avoid chemotherapy when there is no evidence-based benefit, reserving its use for locally advanced or high-risk cases, refining clinical guidelines to ensure treatment recommendations are based on higher-quality evidence, thereby standardizing care and reducing overtreatment,” she continued. “Current guidelines lack consensus and rely on lower-quality evidence.”

Agustí Garcia reported grants from Fundación Alfonso Martín Escudero. Berchuck has no disclosures. Karam reported royalties from UpToDate and that he is a speaker for AstraZeneca.

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

A diet high in omega-3 and low in omega-6 fatty acids, alongside fish oil supplements, may curb the growth of prostate cancer cells in men with early-stage disease, new data showed.

Among men on active surveillance for prostate cancer, consuming this diet for a year led to a significant decrease in the prostate cancer tissue Ki-67 index, a biomarker for prostate cancer progression, metastasis, and death, according to findings from the phase 2 CAPFISH-3 study presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.

“This data is certainly intriguing and supports studies looking at this further in prostate cancer,” Bradley Alexander McGregor, MD, from Dana-Farber Cancer Institute, Boston, Massachusetts, who wasn’t involved in the study, told this news organization. But, McGregor noted, patients were on the diet for 1 year, and the long-term implications of this diet are not known.

 

Growing Evidence on Diet

Diets that include fried and processed foods tend to be high in omega 6s, while those that include salmon and tuna are higher in omega 3s.

Research has shown that consuming more omega-3 fatty acids is associated with a lower risk for mortality from prostate cancer, explained study investigator William Aronson, MD, with David Geffen School of Medicine at University of California, Los Angeles (UCLA). Research suggests that ingesting more omega-6 accelerates the growth of human tumors in mice, while raising omega-3 levels lowers it. High omega-3 and low omega-6 are also known to have an inhibitory effect on M2-like macrophages, which are the predominant immune cell type in prostate cancer metastasis.

To investigate the impact of these fatty acids on early-stage prostate cancer, Aronson and colleagues conducted a single-center, phase 2, randomized, open-label study in 100 men with grade 1/2 prostate cancer who elected active surveillance.

Patients were randomly allocated 1:1 to a control group that continued their normal diet (minus fish oil) or to an intervention group that followed a low omega-6/high omega-3 diet, supplemented with fish oil (2.2 g/d), for 1 year.

The primary endpoint was the change in Ki-67 index from baseline to 1 year from same-site biopsies between the groups.

For the primary endpoint, the Ki-67 index decreased in the intervention group by 15% from baseline to 1 year and increased in the control group by 24%. The difference between groups was statistically significant (P = .043).

For the secondary endpoints, the intervention led to a reduction in triglyceride levels and macrophage colony stimulating factor but no change in tumor volume grade group, PSA level, or Decipher 22 gene score.

Aronson said the findings support future phase 3 trials incorporating this intervention among men on active surveillance for prostate cancer.

McGregor said it’s important to note that this was “an aggressive intervention with dietary changes and addition of fish oil and patients need to be highly motivated.” Four men discontinued due to adverse effects — primarily gastrointestinal adverse effects such as diarrhea and nausea — larger sample sizes will be key to better understand the tolerability.

Bottom line, said McGregor, “based on this data alone, it should not be recommended but can be considered for highly motivated patients after discussion of the limitations of available data and side effects.”

The study was funded in part by the National Cancer Institute, the UCLA Health Jonsson Comprehensive Cancer Center, Howard B. Klein, and the Seafood Industry Research Fund. Aronson disclosed relationships with AstraZeneca, Bayer, Blue Earth Diagnostics, Janssen Oncology, and Pfizer/Astellas. McGregor disclosed relationships with Arcus Biosciences, Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo/AstraZeneca, Eisai, Exelixis, Genmab, Gilead Sciences, Loxo/Lilly, Pfizer, and Seattle Genetics/Astellas.

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

A diet high in omega-3 and low in omega-6 fatty acids, alongside fish oil supplements, may curb the growth of prostate cancer cells in men with early-stage disease, new data showed.

Among men on active surveillance for prostate cancer, consuming this diet for a year led to a significant decrease in the prostate cancer tissue Ki-67 index, a biomarker for prostate cancer progression, metastasis, and death, according to findings from the phase 2 CAPFISH-3 study presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.

“This data is certainly intriguing and supports studies looking at this further in prostate cancer,” Bradley Alexander McGregor, MD, from Dana-Farber Cancer Institute, Boston, Massachusetts, who wasn’t involved in the study, told this news organization. But, McGregor noted, patients were on the diet for 1 year, and the long-term implications of this diet are not known.

 

Growing Evidence on Diet

Diets that include fried and processed foods tend to be high in omega 6s, while those that include salmon and tuna are higher in omega 3s.

Research has shown that consuming more omega-3 fatty acids is associated with a lower risk for mortality from prostate cancer, explained study investigator William Aronson, MD, with David Geffen School of Medicine at University of California, Los Angeles (UCLA). Research suggests that ingesting more omega-6 accelerates the growth of human tumors in mice, while raising omega-3 levels lowers it. High omega-3 and low omega-6 are also known to have an inhibitory effect on M2-like macrophages, which are the predominant immune cell type in prostate cancer metastasis.

To investigate the impact of these fatty acids on early-stage prostate cancer, Aronson and colleagues conducted a single-center, phase 2, randomized, open-label study in 100 men with grade 1/2 prostate cancer who elected active surveillance.

Patients were randomly allocated 1:1 to a control group that continued their normal diet (minus fish oil) or to an intervention group that followed a low omega-6/high omega-3 diet, supplemented with fish oil (2.2 g/d), for 1 year.

The primary endpoint was the change in Ki-67 index from baseline to 1 year from same-site biopsies between the groups.

For the primary endpoint, the Ki-67 index decreased in the intervention group by 15% from baseline to 1 year and increased in the control group by 24%. The difference between groups was statistically significant (P = .043).

For the secondary endpoints, the intervention led to a reduction in triglyceride levels and macrophage colony stimulating factor but no change in tumor volume grade group, PSA level, or Decipher 22 gene score.

Aronson said the findings support future phase 3 trials incorporating this intervention among men on active surveillance for prostate cancer.

McGregor said it’s important to note that this was “an aggressive intervention with dietary changes and addition of fish oil and patients need to be highly motivated.” Four men discontinued due to adverse effects — primarily gastrointestinal adverse effects such as diarrhea and nausea — larger sample sizes will be key to better understand the tolerability.

Bottom line, said McGregor, “based on this data alone, it should not be recommended but can be considered for highly motivated patients after discussion of the limitations of available data and side effects.”

The study was funded in part by the National Cancer Institute, the UCLA Health Jonsson Comprehensive Cancer Center, Howard B. Klein, and the Seafood Industry Research Fund. Aronson disclosed relationships with AstraZeneca, Bayer, Blue Earth Diagnostics, Janssen Oncology, and Pfizer/Astellas. McGregor disclosed relationships with Arcus Biosciences, Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo/AstraZeneca, Eisai, Exelixis, Genmab, Gilead Sciences, Loxo/Lilly, Pfizer, and Seattle Genetics/Astellas.

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

A diet high in omega-3 and low in omega-6 fatty acids, alongside fish oil supplements, may curb the growth of prostate cancer cells in men with early-stage disease, new data showed.

Among men on active surveillance for prostate cancer, consuming this diet for a year led to a significant decrease in the prostate cancer tissue Ki-67 index, a biomarker for prostate cancer progression, metastasis, and death, according to findings from the phase 2 CAPFISH-3 study presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.

“This data is certainly intriguing and supports studies looking at this further in prostate cancer,” Bradley Alexander McGregor, MD, from Dana-Farber Cancer Institute, Boston, Massachusetts, who wasn’t involved in the study, told this news organization. But, McGregor noted, patients were on the diet for 1 year, and the long-term implications of this diet are not known.

 

Growing Evidence on Diet

Diets that include fried and processed foods tend to be high in omega 6s, while those that include salmon and tuna are higher in omega 3s.

Research has shown that consuming more omega-3 fatty acids is associated with a lower risk for mortality from prostate cancer, explained study investigator William Aronson, MD, with David Geffen School of Medicine at University of California, Los Angeles (UCLA). Research suggests that ingesting more omega-6 accelerates the growth of human tumors in mice, while raising omega-3 levels lowers it. High omega-3 and low omega-6 are also known to have an inhibitory effect on M2-like macrophages, which are the predominant immune cell type in prostate cancer metastasis.

To investigate the impact of these fatty acids on early-stage prostate cancer, Aronson and colleagues conducted a single-center, phase 2, randomized, open-label study in 100 men with grade 1/2 prostate cancer who elected active surveillance.

Patients were randomly allocated 1:1 to a control group that continued their normal diet (minus fish oil) or to an intervention group that followed a low omega-6/high omega-3 diet, supplemented with fish oil (2.2 g/d), for 1 year.

The primary endpoint was the change in Ki-67 index from baseline to 1 year from same-site biopsies between the groups.

For the primary endpoint, the Ki-67 index decreased in the intervention group by 15% from baseline to 1 year and increased in the control group by 24%. The difference between groups was statistically significant (P = .043).

For the secondary endpoints, the intervention led to a reduction in triglyceride levels and macrophage colony stimulating factor but no change in tumor volume grade group, PSA level, or Decipher 22 gene score.

Aronson said the findings support future phase 3 trials incorporating this intervention among men on active surveillance for prostate cancer.

McGregor said it’s important to note that this was “an aggressive intervention with dietary changes and addition of fish oil and patients need to be highly motivated.” Four men discontinued due to adverse effects — primarily gastrointestinal adverse effects such as diarrhea and nausea — larger sample sizes will be key to better understand the tolerability.

Bottom line, said McGregor, “based on this data alone, it should not be recommended but can be considered for highly motivated patients after discussion of the limitations of available data and side effects.”

The study was funded in part by the National Cancer Institute, the UCLA Health Jonsson Comprehensive Cancer Center, Howard B. Klein, and the Seafood Industry Research Fund. Aronson disclosed relationships with AstraZeneca, Bayer, Blue Earth Diagnostics, Janssen Oncology, and Pfizer/Astellas. McGregor disclosed relationships with Arcus Biosciences, Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo/AstraZeneca, Eisai, Exelixis, Genmab, Gilead Sciences, Loxo/Lilly, Pfizer, and Seattle Genetics/Astellas.

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

This article is a based on a video essay. The transcript has been edited for clarity.

I’d like to discuss what I think is a very interesting analysis that we need to see much more of. It’s perhaps not surprising, but the data, I think, are sobering. The paper was published in JAMA Network Open, entitled, “Trends and Disparities in Next-Generation Sequencing in Metastatic Prostate and Urothelial Cancers.”

As I think most of the listening audience is aware, we are in the midst of an ongoing — I would argue, accelerating — revolution in our understanding of cancer, its development and treatments, based upon our characterization at the molecular level of individual cancers.

This, of course, is changing the treatment paradigms and the drugs that we might have available in the first-, second-, and third-line settings. The question to be asked is, how are we, at a clinical level, keeping up with all of these changes, like those approved by the US Food and Drug Administration, and new diagnostic testing with a variety of molecular platforms?

This particular analysis looked at that specific question in metastatic prostate cancer and urothelial malignancies, obviously including bladder cancer. With the new approvals — including tumor agnostic testing, very specific testing, and very molecularly based drugs that are approved for particular abnormalities — they looked at the percentages of patients and the potential disparities in terms of the testing that has been performed.

There were 11,927 patients with prostate cancer. There were 6490 patients with advanced urothelial malignancies; the majority of these were male, but there were females included in this group.

The researchers looked at 2015 vs 2022 data. It’s not 2024 data, but it goes all the way to the end of 2022, so, not that long ago. In the metastatic prostate cancer group, 19% of patients had undergone molecular testing or next-generation sequencing in 2015.

By 2022, that number had increased, but only to 27%. Three out of four patients with metastatic prostate cancer had not undergone testing to know whether they were potential candidates for specific therapies. I won’t even get into the question of potential germline abnormalities that might be observed that are relevant for other discussions.

Among patients with urothelial cancer, in 2015, 14% had undergone such testing. By 2022, this number was substantially increased to 46.6%, but still, that’s less than 1 out of 2 patients. More than 50% of patients had not undergone the testing, and yet we have therapy that might be available for these populations based on such testing.

I should add that the population of Black, African American, and Hispanic patients was actually considerably lower, percentage-wise, than the numbers that I’ve quoted.

Clearly, there are explanations. There are socioeconomic explanations and insurance coverage explanations. However, the bottom line is that we have therapies available today, and we’ll have more in the future, that are based on knowledge of this testing.

Based on these data, which most recently included 2022 — we’ll see where we are in 2024 and 2025, and with other types — more than half of patients are not getting the testing to know if this is relevant for them and their care.

These are major questions that need to be addressed. Hopefully, answers will be forthcoming and we will see in the future that these percentages will be much higher for the benefit of our patients.

Dr Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships with GlaxoSmithKline and AstraZeneca.

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

This article is a based on a video essay. The transcript has been edited for clarity.

I’d like to discuss what I think is a very interesting analysis that we need to see much more of. It’s perhaps not surprising, but the data, I think, are sobering. The paper was published in JAMA Network Open, entitled, “Trends and Disparities in Next-Generation Sequencing in Metastatic Prostate and Urothelial Cancers.”

As I think most of the listening audience is aware, we are in the midst of an ongoing — I would argue, accelerating — revolution in our understanding of cancer, its development and treatments, based upon our characterization at the molecular level of individual cancers.

This, of course, is changing the treatment paradigms and the drugs that we might have available in the first-, second-, and third-line settings. The question to be asked is, how are we, at a clinical level, keeping up with all of these changes, like those approved by the US Food and Drug Administration, and new diagnostic testing with a variety of molecular platforms?

This particular analysis looked at that specific question in metastatic prostate cancer and urothelial malignancies, obviously including bladder cancer. With the new approvals — including tumor agnostic testing, very specific testing, and very molecularly based drugs that are approved for particular abnormalities — they looked at the percentages of patients and the potential disparities in terms of the testing that has been performed.

There were 11,927 patients with prostate cancer. There were 6490 patients with advanced urothelial malignancies; the majority of these were male, but there were females included in this group.

The researchers looked at 2015 vs 2022 data. It’s not 2024 data, but it goes all the way to the end of 2022, so, not that long ago. In the metastatic prostate cancer group, 19% of patients had undergone molecular testing or next-generation sequencing in 2015.

By 2022, that number had increased, but only to 27%. Three out of four patients with metastatic prostate cancer had not undergone testing to know whether they were potential candidates for specific therapies. I won’t even get into the question of potential germline abnormalities that might be observed that are relevant for other discussions.

Among patients with urothelial cancer, in 2015, 14% had undergone such testing. By 2022, this number was substantially increased to 46.6%, but still, that’s less than 1 out of 2 patients. More than 50% of patients had not undergone the testing, and yet we have therapy that might be available for these populations based on such testing.

I should add that the population of Black, African American, and Hispanic patients was actually considerably lower, percentage-wise, than the numbers that I’ve quoted.

Clearly, there are explanations. There are socioeconomic explanations and insurance coverage explanations. However, the bottom line is that we have therapies available today, and we’ll have more in the future, that are based on knowledge of this testing.

Based on these data, which most recently included 2022 — we’ll see where we are in 2024 and 2025, and with other types — more than half of patients are not getting the testing to know if this is relevant for them and their care.

These are major questions that need to be addressed. Hopefully, answers will be forthcoming and we will see in the future that these percentages will be much higher for the benefit of our patients.

Dr Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships with GlaxoSmithKline and AstraZeneca.

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

This article is a based on a video essay. The transcript has been edited for clarity.

I’d like to discuss what I think is a very interesting analysis that we need to see much more of. It’s perhaps not surprising, but the data, I think, are sobering. The paper was published in JAMA Network Open, entitled, “Trends and Disparities in Next-Generation Sequencing in Metastatic Prostate and Urothelial Cancers.”

As I think most of the listening audience is aware, we are in the midst of an ongoing — I would argue, accelerating — revolution in our understanding of cancer, its development and treatments, based upon our characterization at the molecular level of individual cancers.

This, of course, is changing the treatment paradigms and the drugs that we might have available in the first-, second-, and third-line settings. The question to be asked is, how are we, at a clinical level, keeping up with all of these changes, like those approved by the US Food and Drug Administration, and new diagnostic testing with a variety of molecular platforms?

This particular analysis looked at that specific question in metastatic prostate cancer and urothelial malignancies, obviously including bladder cancer. With the new approvals — including tumor agnostic testing, very specific testing, and very molecularly based drugs that are approved for particular abnormalities — they looked at the percentages of patients and the potential disparities in terms of the testing that has been performed.

There were 11,927 patients with prostate cancer. There were 6490 patients with advanced urothelial malignancies; the majority of these were male, but there were females included in this group.

The researchers looked at 2015 vs 2022 data. It’s not 2024 data, but it goes all the way to the end of 2022, so, not that long ago. In the metastatic prostate cancer group, 19% of patients had undergone molecular testing or next-generation sequencing in 2015.

By 2022, that number had increased, but only to 27%. Three out of four patients with metastatic prostate cancer had not undergone testing to know whether they were potential candidates for specific therapies. I won’t even get into the question of potential germline abnormalities that might be observed that are relevant for other discussions.

Among patients with urothelial cancer, in 2015, 14% had undergone such testing. By 2022, this number was substantially increased to 46.6%, but still, that’s less than 1 out of 2 patients. More than 50% of patients had not undergone the testing, and yet we have therapy that might be available for these populations based on such testing.

I should add that the population of Black, African American, and Hispanic patients was actually considerably lower, percentage-wise, than the numbers that I’ve quoted.

Clearly, there are explanations. There are socioeconomic explanations and insurance coverage explanations. However, the bottom line is that we have therapies available today, and we’ll have more in the future, that are based on knowledge of this testing.

Based on these data, which most recently included 2022 — we’ll see where we are in 2024 and 2025, and with other types — more than half of patients are not getting the testing to know if this is relevant for them and their care.

These are major questions that need to be addressed. Hopefully, answers will be forthcoming and we will see in the future that these percentages will be much higher for the benefit of our patients.

Dr Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships with GlaxoSmithKline and AstraZeneca.

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

Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

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

Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

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

Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

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

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.