Prostate Cancer

For patients with high-risk prostate cancer, treatment with long-term androgen deprivation therapy (ADT) and high-dose radiation was associated with significantly better progression-free, cancer-specific, and overall survival compared with ADT and standard-dose radiation.
The investigators also found that the patients taking long-term ADT and high-dose radiation did not experience additional late urinary tract or gastrointestinal toxicities. Christophe Hennequin, MD, PhD, reported these and other findings of the Radiation Therapy in Treating Patients Receiving Hormone Therapy for Prostate Cancer (GETUG-AFU 18) trial, at the 2024 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium.  
Among 505 patients randomly assigned to be treated with radiation therapy (RT) at either the standard 70 Gy dose or a high, 80 Gy dose followed by 3 years of adjuvant  ADT, the 10-year progression-free survival (PFS) rate was 83.6% for patients who had received the 80 Gy dose, vs. 72.2% for patients who had received the 70 Gy dose. This translated into a hazard ratio (HR) for biochemical or clinical progression of 0.56 (P = .0005). 
This PFS advantage for high-dose radiation was also reflected by an overall survival (OS) advantage, with 10-year OS rates of 77% vs. 65.9%, respectively, translating into a 39% reduction in risk of death (HR 0.61, P = .0039) for patients who had received the higher radiation dose, reported Dr. Hennequin, of the Hospital Saint Louis in Paris, France. 
"We have now Level 1 evidence that high-dose RT with long-term ADT must be the standard of care in high-risk prostate cancer patients," he said at the meeting. 
Dr. Hennequin noted that significantly more patients assigned to high-dose RT were treated with intensity modulated radiation therapy (IMRT) rather than conventional beam radiation, and emphasized that the superior results seen with the higher dose is likely due to the use of IMRT. 

Prior evidence 

Dr. Hennequin pointed to a meta-analysis published in The Lancet in 2022 which showed that among nearly 11,000 patients with a median follow-up of 11.4 years the addition of ADT to RT significantly improved metastasis-free survival, and that longer ADT reduced the risk of metastases by 16% compared with standard schedule ADT. 
He also cited the DART 01/05 trial results, which were published in 2022 in The Lancet: Oncology, which found a clinically relevant benefit for 24 months vs. 4 months of adjuvant ADT following a minimum of 76 Gy radiation in patients with high-risk disease, but not among patients with intermediate-risk disease.   
The GETUG-AFU 18 trial was designed to address the question of whether 80 Gy of radiation could improve outcomes compared with 70 Gy in patients treated with long-term ADT. 

Study details and results 

The investigators enrolled men with high-risk prostate cancer defined as either a prostate-specific antigen (PSA) level 20 ng/ml or greater, Gleason score 8 or higher, or clinical stage T3 or T4 disease, and after stratification by treatment center and lymph node resection randomly assigned them to receive either 70 Gy or 80 Gy RT followed by 3 years of ADT. 
Approximately two-thirds of the patients in each study arm had one risk factor and about one-fourth had two risk factors. The remaining patients had all three high-risk defining factors.  
Approximately 16.5% of patients in each arm had undergone lymph node dissection.  
The median ADT duration was 33.4 months. In all, 82.9% of patients underwent pelvic lymph node radiation; lymph node radiation was not performed in those patients who had negative node dissection results. 
Significantly more patients assigned to the 80 Gy dose were treated with IMRT (80.6% vs. 58.6%, P < .001).   
The cancer-specific survival rate was also higher for the group receiving the 80 Gy dose, with a 10 year rate of 95.6% vs. 90% for patients treated with 70 Gy. This difference translated into a HR of 0.48 (P = .0090).  
 

Comparable safety 

The safety analysis, which included 248 patients who received 80 Gy and 251 who received 70 Gy, showed that the incidence rates of both late genitourinary and gastrointestinal toxicities were low and comparable between the groups. Grade 3 or greater late genitourinary toxicities were seen in 2.0% of patients treated with 80 Gy and 3.2% of those treated with 70 Gy. In both arms, only 1.6% of patients had grade 3 or greater later GI toxicities.  
There were also no differences between the study arms in patient-reported quality of life measures related to either bowel or urinary symptoms. 
Invited discussant Neha Vapiwala, MD, FACR, from Penn Medicine in Philadelphia commented that the results of the GETUG-AFU 18 trial suggest that "if you had even lower-dose systemic therapy that the radiation control at the local level - local-regional level in this case - can in fact contribute to the prevention of distant metastases and can contribute to cancer-specific survival." 
She said that with the efficacy results and the comparable toxicity and quality of life measures, dose-escalated radiation therapy and long-term ADT appear to offer a synergistic benefit. 
The results are "practice-affirming for many, perhaps practice-changing for some if you're not already offering this," she said. 

For patients with high-risk prostate cancer, treatment with long-term androgen deprivation therapy (ADT) and high-dose radiation was associated with significantly better progression-free, cancer-specific, and overall survival compared with ADT and standard-dose radiation.
The investigators also found that the patients taking long-term ADT and high-dose radiation did not experience additional late urinary tract or gastrointestinal toxicities. Christophe Hennequin, MD, PhD, reported these and other findings of the Radiation Therapy in Treating Patients Receiving Hormone Therapy for Prostate Cancer (GETUG-AFU 18) trial, at the 2024 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium.  
Among 505 patients randomly assigned to be treated with radiation therapy (RT) at either the standard 70 Gy dose or a high, 80 Gy dose followed by 3 years of adjuvant  ADT, the 10-year progression-free survival (PFS) rate was 83.6% for patients who had received the 80 Gy dose, vs. 72.2% for patients who had received the 70 Gy dose. This translated into a hazard ratio (HR) for biochemical or clinical progression of 0.56 (P = .0005). 
This PFS advantage for high-dose radiation was also reflected by an overall survival (OS) advantage, with 10-year OS rates of 77% vs. 65.9%, respectively, translating into a 39% reduction in risk of death (HR 0.61, P = .0039) for patients who had received the higher radiation dose, reported Dr. Hennequin, of the Hospital Saint Louis in Paris, France. 
"We have now Level 1 evidence that high-dose RT with long-term ADT must be the standard of care in high-risk prostate cancer patients," he said at the meeting. 
Dr. Hennequin noted that significantly more patients assigned to high-dose RT were treated with intensity modulated radiation therapy (IMRT) rather than conventional beam radiation, and emphasized that the superior results seen with the higher dose is likely due to the use of IMRT. 

Prior evidence 

Dr. Hennequin pointed to a meta-analysis published in The Lancet in 2022 which showed that among nearly 11,000 patients with a median follow-up of 11.4 years the addition of ADT to RT significantly improved metastasis-free survival, and that longer ADT reduced the risk of metastases by 16% compared with standard schedule ADT. 
He also cited the DART 01/05 trial results, which were published in 2022 in The Lancet: Oncology, which found a clinically relevant benefit for 24 months vs. 4 months of adjuvant ADT following a minimum of 76 Gy radiation in patients with high-risk disease, but not among patients with intermediate-risk disease.   
The GETUG-AFU 18 trial was designed to address the question of whether 80 Gy of radiation could improve outcomes compared with 70 Gy in patients treated with long-term ADT. 

Study details and results 

The investigators enrolled men with high-risk prostate cancer defined as either a prostate-specific antigen (PSA) level 20 ng/ml or greater, Gleason score 8 or higher, or clinical stage T3 or T4 disease, and after stratification by treatment center and lymph node resection randomly assigned them to receive either 70 Gy or 80 Gy RT followed by 3 years of ADT. 
Approximately two-thirds of the patients in each study arm had one risk factor and about one-fourth had two risk factors. The remaining patients had all three high-risk defining factors.  
Approximately 16.5% of patients in each arm had undergone lymph node dissection.  
The median ADT duration was 33.4 months. In all, 82.9% of patients underwent pelvic lymph node radiation; lymph node radiation was not performed in those patients who had negative node dissection results. 
Significantly more patients assigned to the 80 Gy dose were treated with IMRT (80.6% vs. 58.6%, P < .001).   
The cancer-specific survival rate was also higher for the group receiving the 80 Gy dose, with a 10 year rate of 95.6% vs. 90% for patients treated with 70 Gy. This difference translated into a HR of 0.48 (P = .0090).  
 

Comparable safety 

The safety analysis, which included 248 patients who received 80 Gy and 251 who received 70 Gy, showed that the incidence rates of both late genitourinary and gastrointestinal toxicities were low and comparable between the groups. Grade 3 or greater late genitourinary toxicities were seen in 2.0% of patients treated with 80 Gy and 3.2% of those treated with 70 Gy. In both arms, only 1.6% of patients had grade 3 or greater later GI toxicities.  
There were also no differences between the study arms in patient-reported quality of life measures related to either bowel or urinary symptoms. 
Invited discussant Neha Vapiwala, MD, FACR, from Penn Medicine in Philadelphia commented that the results of the GETUG-AFU 18 trial suggest that "if you had even lower-dose systemic therapy that the radiation control at the local level - local-regional level in this case - can in fact contribute to the prevention of distant metastases and can contribute to cancer-specific survival." 
She said that with the efficacy results and the comparable toxicity and quality of life measures, dose-escalated radiation therapy and long-term ADT appear to offer a synergistic benefit. 
The results are "practice-affirming for many, perhaps practice-changing for some if you're not already offering this," she said. 

For patients with high-risk prostate cancer, treatment with long-term androgen deprivation therapy (ADT) and high-dose radiation was associated with significantly better progression-free, cancer-specific, and overall survival compared with ADT and standard-dose radiation.
The investigators also found that the patients taking long-term ADT and high-dose radiation did not experience additional late urinary tract or gastrointestinal toxicities. Christophe Hennequin, MD, PhD, reported these and other findings of the Radiation Therapy in Treating Patients Receiving Hormone Therapy for Prostate Cancer (GETUG-AFU 18) trial, at the 2024 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium.  
Among 505 patients randomly assigned to be treated with radiation therapy (RT) at either the standard 70 Gy dose or a high, 80 Gy dose followed by 3 years of adjuvant  ADT, the 10-year progression-free survival (PFS) rate was 83.6% for patients who had received the 80 Gy dose, vs. 72.2% for patients who had received the 70 Gy dose. This translated into a hazard ratio (HR) for biochemical or clinical progression of 0.56 (P = .0005). 
This PFS advantage for high-dose radiation was also reflected by an overall survival (OS) advantage, with 10-year OS rates of 77% vs. 65.9%, respectively, translating into a 39% reduction in risk of death (HR 0.61, P = .0039) for patients who had received the higher radiation dose, reported Dr. Hennequin, of the Hospital Saint Louis in Paris, France. 
"We have now Level 1 evidence that high-dose RT with long-term ADT must be the standard of care in high-risk prostate cancer patients," he said at the meeting. 
Dr. Hennequin noted that significantly more patients assigned to high-dose RT were treated with intensity modulated radiation therapy (IMRT) rather than conventional beam radiation, and emphasized that the superior results seen with the higher dose is likely due to the use of IMRT. 

Prior evidence 

Dr. Hennequin pointed to a meta-analysis published in The Lancet in 2022 which showed that among nearly 11,000 patients with a median follow-up of 11.4 years the addition of ADT to RT significantly improved metastasis-free survival, and that longer ADT reduced the risk of metastases by 16% compared with standard schedule ADT. 
He also cited the DART 01/05 trial results, which were published in 2022 in The Lancet: Oncology, which found a clinically relevant benefit for 24 months vs. 4 months of adjuvant ADT following a minimum of 76 Gy radiation in patients with high-risk disease, but not among patients with intermediate-risk disease.   
The GETUG-AFU 18 trial was designed to address the question of whether 80 Gy of radiation could improve outcomes compared with 70 Gy in patients treated with long-term ADT. 

Study details and results 

The investigators enrolled men with high-risk prostate cancer defined as either a prostate-specific antigen (PSA) level 20 ng/ml or greater, Gleason score 8 or higher, or clinical stage T3 or T4 disease, and after stratification by treatment center and lymph node resection randomly assigned them to receive either 70 Gy or 80 Gy RT followed by 3 years of ADT. 
Approximately two-thirds of the patients in each study arm had one risk factor and about one-fourth had two risk factors. The remaining patients had all three high-risk defining factors.  
Approximately 16.5% of patients in each arm had undergone lymph node dissection.  
The median ADT duration was 33.4 months. In all, 82.9% of patients underwent pelvic lymph node radiation; lymph node radiation was not performed in those patients who had negative node dissection results. 
Significantly more patients assigned to the 80 Gy dose were treated with IMRT (80.6% vs. 58.6%, P < .001).   
The cancer-specific survival rate was also higher for the group receiving the 80 Gy dose, with a 10 year rate of 95.6% vs. 90% for patients treated with 70 Gy. This difference translated into a HR of 0.48 (P = .0090).  
 

Comparable safety 

The safety analysis, which included 248 patients who received 80 Gy and 251 who received 70 Gy, showed that the incidence rates of both late genitourinary and gastrointestinal toxicities were low and comparable between the groups. Grade 3 or greater late genitourinary toxicities were seen in 2.0% of patients treated with 80 Gy and 3.2% of those treated with 70 Gy. In both arms, only 1.6% of patients had grade 3 or greater later GI toxicities.  
There were also no differences between the study arms in patient-reported quality of life measures related to either bowel or urinary symptoms. 
Invited discussant Neha Vapiwala, MD, FACR, from Penn Medicine in Philadelphia commented that the results of the GETUG-AFU 18 trial suggest that "if you had even lower-dose systemic therapy that the radiation control at the local level - local-regional level in this case - can in fact contribute to the prevention of distant metastases and can contribute to cancer-specific survival." 
She said that with the efficacy results and the comparable toxicity and quality of life measures, dose-escalated radiation therapy and long-term ADT appear to offer a synergistic benefit. 
The results are "practice-affirming for many, perhaps practice-changing for some if you're not already offering this," she said. 

Men with localized prostate cancer face a number of treatment choices, including radical prostatectomy, radiotherapy with or without androgen deprivation therapy, and active surveillance. Understanding the likely functional outcomes of each treatment over time is important, as most patients are expected to live at least 15 years after diagnosis.

New research published Jan. 23 in JAMA parses functional outcome results from a population-based study of men diagnosed with localized prostate cancer. For their research, Bashir Al Hussein Al Awamlh, MD, of Vanderbilt University in Nashville, Tennessee, and his colleagues, looked at sexual function, urinary health, bowel function, hormonal function, and other outcomes in this cohort at 10 years’ follow-up.

Courtesy Vanderbilt University

Among 2455 patients for whom 10-year data were available, 1877 were deemed at baseline to have a favorable prognosis (defined as cT1-cT2bN0M0, prostate-specific antigen level less than 20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. The men in the study were all younger than 80 years, and three-quarters of them were White.

At 10 years, outcomes differed based on the amount of time that had passed since diagnosis (they found different results at 3 and 5 year follow up, for example) and which treatment a patient received.

Among men with favorable prognoses at diagnosis, 20% underwent active surveillance for at least 1 year, while 56% received radical prostatectomy, 19% had external beam radiotherapy (EBRT) without ADT, and 5% had brachytherapy. Nearly a third of men originally opting for surveillance went on to undergo a therapeutic intervention by 10 years.

Dr. Al Hussein Al Awamlh and his colleagues found that while 3- and 5-year follow-up studies in this cohort had shown declines in sexual function among men who underwent surgery compared with those who had radiation or active surveillance, by 10 years those differences had faded, with no clinically meaningful differences in sexual function scores between the surgery and surveillance groups. In an interview, Dr. Al Hussein Al Awamlh said that this finding likely reflected mainly age-related declines in function across the study population — though it could also reflect declines after converting from surveillance to surgery or gradual decline with radiation treatment, he acknowledged.

Men with favorable prognoses at baseline who underwent surgery saw significantly worse urinary incontinence at 10 years compared with those started on radiotherapy or active surveillance. And EBRT was associated with fewer incontinence issues compared with active surveillance.

Among the group of men with an unfavorable prognosis at baseline, 64% of whom underwent radical prostatectomy and 36% EBRT with ADT, surgery was associated with worse urinary incontinence but not worse sexual function throughout 10 years of follow up, compared to radiotherapy with androgen deprivation therapy.

Radiation-treated patients with unfavorable prognoses, meanwhile, saw significantly worse bowel function and hormone function at 10 years compared with patients who had undergone surgery.

Dr. Al Hussein Al Awamlh said that a strength of this study was that “we had enough patients to stratify functional outcomes based on disease prognosis.” Another key finding was that some of the outcomes changed over time. “For example, among the patients with unfavorable prognoses, at 10-year follow-up there was slightly worse bowel and hormone function seen associated with radiation with ADT compared with surgery,” he said — something not seen at earlier follow-up points.

The findings may help offer a more nuanced way to counsel patients, Dr. Al Hussein Al Awamlh noted. For example, the side effects associated with sexual function “are not as relevant for those with unfavorable disease,” he said.

While current prostate cancer guidelines do address quality of life in shared decision-making, he said, “hopefully this data may provide more insight on that.” For patients with favorable prognosis, the findings reinforce that “active surveillance is a great option because it avoids the effects associated with those other treatments.”

Ultimately, Dr. Al Hussein Al Awamlh said, “this is a patient preference issue. It’s important for patients to understand how different functions are affected and to decide what is better for them — what they can live with and what they cannot, provided all the options are oncologically safe.”

The study authors disclosed as limitations of their study its observational design, the potential for response bias among study participants, and small numbers for some of the measured outcomes.

In an interview, urologist Mark S. Litwin, MD, of the University of California Los Angeles, characterized the study as “a well-conducted very-long-term longitudinal cohort that tracked men long past the initial diagnosis and treatment. That empowered the Vanderbilt team to find differences in quality of life many years later and compare them to other older men who had not received treatment.”

The new findings, Dr. Litwin said, “are critical in showing that most men with prostate cancer do not die from it; hence, the quality-of-life effects end up being the key issues for decision-making.”

Dr. Al Hussein Al Awamlh and colleagues’ study was funded by grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. Several coauthors disclosed funding from pharmaceutical and/or device manufacturers. Dr. Litwin disclosed no conflicts of interest related to his comment.

Men with localized prostate cancer face a number of treatment choices, including radical prostatectomy, radiotherapy with or without androgen deprivation therapy, and active surveillance. Understanding the likely functional outcomes of each treatment over time is important, as most patients are expected to live at least 15 years after diagnosis.

New research published Jan. 23 in JAMA parses functional outcome results from a population-based study of men diagnosed with localized prostate cancer. For their research, Bashir Al Hussein Al Awamlh, MD, of Vanderbilt University in Nashville, Tennessee, and his colleagues, looked at sexual function, urinary health, bowel function, hormonal function, and other outcomes in this cohort at 10 years’ follow-up.

Courtesy Vanderbilt University

Among 2455 patients for whom 10-year data were available, 1877 were deemed at baseline to have a favorable prognosis (defined as cT1-cT2bN0M0, prostate-specific antigen level less than 20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. The men in the study were all younger than 80 years, and three-quarters of them were White.

At 10 years, outcomes differed based on the amount of time that had passed since diagnosis (they found different results at 3 and 5 year follow up, for example) and which treatment a patient received.

Among men with favorable prognoses at diagnosis, 20% underwent active surveillance for at least 1 year, while 56% received radical prostatectomy, 19% had external beam radiotherapy (EBRT) without ADT, and 5% had brachytherapy. Nearly a third of men originally opting for surveillance went on to undergo a therapeutic intervention by 10 years.

Dr. Al Hussein Al Awamlh and his colleagues found that while 3- and 5-year follow-up studies in this cohort had shown declines in sexual function among men who underwent surgery compared with those who had radiation or active surveillance, by 10 years those differences had faded, with no clinically meaningful differences in sexual function scores between the surgery and surveillance groups. In an interview, Dr. Al Hussein Al Awamlh said that this finding likely reflected mainly age-related declines in function across the study population — though it could also reflect declines after converting from surveillance to surgery or gradual decline with radiation treatment, he acknowledged.

Men with favorable prognoses at baseline who underwent surgery saw significantly worse urinary incontinence at 10 years compared with those started on radiotherapy or active surveillance. And EBRT was associated with fewer incontinence issues compared with active surveillance.

Among the group of men with an unfavorable prognosis at baseline, 64% of whom underwent radical prostatectomy and 36% EBRT with ADT, surgery was associated with worse urinary incontinence but not worse sexual function throughout 10 years of follow up, compared to radiotherapy with androgen deprivation therapy.

Radiation-treated patients with unfavorable prognoses, meanwhile, saw significantly worse bowel function and hormone function at 10 years compared with patients who had undergone surgery.

Dr. Al Hussein Al Awamlh said that a strength of this study was that “we had enough patients to stratify functional outcomes based on disease prognosis.” Another key finding was that some of the outcomes changed over time. “For example, among the patients with unfavorable prognoses, at 10-year follow-up there was slightly worse bowel and hormone function seen associated with radiation with ADT compared with surgery,” he said — something not seen at earlier follow-up points.

The findings may help offer a more nuanced way to counsel patients, Dr. Al Hussein Al Awamlh noted. For example, the side effects associated with sexual function “are not as relevant for those with unfavorable disease,” he said.

While current prostate cancer guidelines do address quality of life in shared decision-making, he said, “hopefully this data may provide more insight on that.” For patients with favorable prognosis, the findings reinforce that “active surveillance is a great option because it avoids the effects associated with those other treatments.”

Ultimately, Dr. Al Hussein Al Awamlh said, “this is a patient preference issue. It’s important for patients to understand how different functions are affected and to decide what is better for them — what they can live with and what they cannot, provided all the options are oncologically safe.”

The study authors disclosed as limitations of their study its observational design, the potential for response bias among study participants, and small numbers for some of the measured outcomes.

In an interview, urologist Mark S. Litwin, MD, of the University of California Los Angeles, characterized the study as “a well-conducted very-long-term longitudinal cohort that tracked men long past the initial diagnosis and treatment. That empowered the Vanderbilt team to find differences in quality of life many years later and compare them to other older men who had not received treatment.”

The new findings, Dr. Litwin said, “are critical in showing that most men with prostate cancer do not die from it; hence, the quality-of-life effects end up being the key issues for decision-making.”

Dr. Al Hussein Al Awamlh and colleagues’ study was funded by grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. Several coauthors disclosed funding from pharmaceutical and/or device manufacturers. Dr. Litwin disclosed no conflicts of interest related to his comment.

Men with localized prostate cancer face a number of treatment choices, including radical prostatectomy, radiotherapy with or without androgen deprivation therapy, and active surveillance. Understanding the likely functional outcomes of each treatment over time is important, as most patients are expected to live at least 15 years after diagnosis.

New research published Jan. 23 in JAMA parses functional outcome results from a population-based study of men diagnosed with localized prostate cancer. For their research, Bashir Al Hussein Al Awamlh, MD, of Vanderbilt University in Nashville, Tennessee, and his colleagues, looked at sexual function, urinary health, bowel function, hormonal function, and other outcomes in this cohort at 10 years’ follow-up.

Courtesy Vanderbilt University

Among 2455 patients for whom 10-year data were available, 1877 were deemed at baseline to have a favorable prognosis (defined as cT1-cT2bN0M0, prostate-specific antigen level less than 20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. The men in the study were all younger than 80 years, and three-quarters of them were White.

At 10 years, outcomes differed based on the amount of time that had passed since diagnosis (they found different results at 3 and 5 year follow up, for example) and which treatment a patient received.

Among men with favorable prognoses at diagnosis, 20% underwent active surveillance for at least 1 year, while 56% received radical prostatectomy, 19% had external beam radiotherapy (EBRT) without ADT, and 5% had brachytherapy. Nearly a third of men originally opting for surveillance went on to undergo a therapeutic intervention by 10 years.

Dr. Al Hussein Al Awamlh and his colleagues found that while 3- and 5-year follow-up studies in this cohort had shown declines in sexual function among men who underwent surgery compared with those who had radiation or active surveillance, by 10 years those differences had faded, with no clinically meaningful differences in sexual function scores between the surgery and surveillance groups. In an interview, Dr. Al Hussein Al Awamlh said that this finding likely reflected mainly age-related declines in function across the study population — though it could also reflect declines after converting from surveillance to surgery or gradual decline with radiation treatment, he acknowledged.

Men with favorable prognoses at baseline who underwent surgery saw significantly worse urinary incontinence at 10 years compared with those started on radiotherapy or active surveillance. And EBRT was associated with fewer incontinence issues compared with active surveillance.

Among the group of men with an unfavorable prognosis at baseline, 64% of whom underwent radical prostatectomy and 36% EBRT with ADT, surgery was associated with worse urinary incontinence but not worse sexual function throughout 10 years of follow up, compared to radiotherapy with androgen deprivation therapy.

Radiation-treated patients with unfavorable prognoses, meanwhile, saw significantly worse bowel function and hormone function at 10 years compared with patients who had undergone surgery.

Dr. Al Hussein Al Awamlh said that a strength of this study was that “we had enough patients to stratify functional outcomes based on disease prognosis.” Another key finding was that some of the outcomes changed over time. “For example, among the patients with unfavorable prognoses, at 10-year follow-up there was slightly worse bowel and hormone function seen associated with radiation with ADT compared with surgery,” he said — something not seen at earlier follow-up points.

The findings may help offer a more nuanced way to counsel patients, Dr. Al Hussein Al Awamlh noted. For example, the side effects associated with sexual function “are not as relevant for those with unfavorable disease,” he said.

While current prostate cancer guidelines do address quality of life in shared decision-making, he said, “hopefully this data may provide more insight on that.” For patients with favorable prognosis, the findings reinforce that “active surveillance is a great option because it avoids the effects associated with those other treatments.”

Ultimately, Dr. Al Hussein Al Awamlh said, “this is a patient preference issue. It’s important for patients to understand how different functions are affected and to decide what is better for them — what they can live with and what they cannot, provided all the options are oncologically safe.”

The study authors disclosed as limitations of their study its observational design, the potential for response bias among study participants, and small numbers for some of the measured outcomes.

In an interview, urologist Mark S. Litwin, MD, of the University of California Los Angeles, characterized the study as “a well-conducted very-long-term longitudinal cohort that tracked men long past the initial diagnosis and treatment. That empowered the Vanderbilt team to find differences in quality of life many years later and compare them to other older men who had not received treatment.”

The new findings, Dr. Litwin said, “are critical in showing that most men with prostate cancer do not die from it; hence, the quality-of-life effects end up being the key issues for decision-making.”

Dr. Al Hussein Al Awamlh and colleagues’ study was funded by grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. Several coauthors disclosed funding from pharmaceutical and/or device manufacturers. Dr. Litwin disclosed no conflicts of interest related to his comment.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

Medicare will now cover the use of an AI-based test for prostate cancer that can predict which men will benefit from potentially disabling androgen deprivation therapy.

The Centers for Medicare & Medicare Services (CMS) on January 1 approved the payment rate for ArteraAI as a clinical diagnostic laboratory test. The test is the first that can both predict therapeutic benefit and prognosticate long-term outcomes in localized prostate cancer. 

Daniel Spratt, MD, chair of radiation oncology at UH Seidman Cancer Center in Cleveland, who has been involved in researching ArteraAI, told this news organization that the test improves risk stratification or prognostication over standard clinical and pathologic tools, such as prostate-specific antigen, Gleason score, and T-stage, or risk groupings such as those from the National Comprehensive Cancer Network (NCCN).

“Medicare approval allows this test to reach more patients without the financial burden of covering the test out of pocket. The test is found among other tests in NCCN guidelines as a tool to improve risk stratification and personalization of treatment,” said Dr. Spratt, who serves on the network’s prostate cancer panel.

ArteraAI combines a patient’s standard clinical and pathologic information into an algorithm, alongside a digitized image analysis of the patients’ prostate biopsy. The result is a score that estimates a patient’s risk of developing metastasis or dying from prostate cancer.

Dr. Spratt was the lead author of article last June in NEJM Evidence that validated ArteraAI. He said ArteraAI is 80% accurate as a prognostic test compared with 65% accuracy using NCCN stratification systems. 

The AI test spares about two thirds of men with intermediate-risk prostate cancer who are starting radiation therapy from androgen deprivation and its side effects, such as weight gain, breast enlargement, hot flashes, heart disease, and brain problems, Dr. Spratt added. 

Andre Esteva, CEO and co-founder of San Francisco-based ArteraAI, said, “After someone is diagnosed with localized prostate cancer, deciding on a treatment can feel very overwhelming as there are so many factors to consider. During this time, knowledge is power, and having detailed, personalized information can increase confidence when making these challenging decisions. The ArteraAI Prostate Test was developed with this in mind and can predict whether a patient will benefit from hormone therapy and estimate long-term outcomes.”

Bruno Barrey is one of Dr. Spratt’s patients. Barrey, a robotics engineer from suburban Detroit who was transitioning from active surveillance with Gleason 3+4 intermediate-risk prostate cancer to radiation therapy, said, “I was concerned about the side effects from androgen-deprivation therapy. I was relieved that the AI test allowed me to avoid hormone therapy.”

Dr. Spratt reported working with NRG Oncology, a clinical trials group funded by the National Cancer Institute, and as an academic collaborator with ArteraAI. 

A version of this article appeared on Medscape.com.

Medicare will now cover the use of an AI-based test for prostate cancer that can predict which men will benefit from potentially disabling androgen deprivation therapy.

The Centers for Medicare & Medicare Services (CMS) on January 1 approved the payment rate for ArteraAI as a clinical diagnostic laboratory test. The test is the first that can both predict therapeutic benefit and prognosticate long-term outcomes in localized prostate cancer. 

Daniel Spratt, MD, chair of radiation oncology at UH Seidman Cancer Center in Cleveland, who has been involved in researching ArteraAI, told this news organization that the test improves risk stratification or prognostication over standard clinical and pathologic tools, such as prostate-specific antigen, Gleason score, and T-stage, or risk groupings such as those from the National Comprehensive Cancer Network (NCCN).

“Medicare approval allows this test to reach more patients without the financial burden of covering the test out of pocket. The test is found among other tests in NCCN guidelines as a tool to improve risk stratification and personalization of treatment,” said Dr. Spratt, who serves on the network’s prostate cancer panel.

ArteraAI combines a patient’s standard clinical and pathologic information into an algorithm, alongside a digitized image analysis of the patients’ prostate biopsy. The result is a score that estimates a patient’s risk of developing metastasis or dying from prostate cancer.

Dr. Spratt was the lead author of article last June in NEJM Evidence that validated ArteraAI. He said ArteraAI is 80% accurate as a prognostic test compared with 65% accuracy using NCCN stratification systems. 

The AI test spares about two thirds of men with intermediate-risk prostate cancer who are starting radiation therapy from androgen deprivation and its side effects, such as weight gain, breast enlargement, hot flashes, heart disease, and brain problems, Dr. Spratt added. 

Andre Esteva, CEO and co-founder of San Francisco-based ArteraAI, said, “After someone is diagnosed with localized prostate cancer, deciding on a treatment can feel very overwhelming as there are so many factors to consider. During this time, knowledge is power, and having detailed, personalized information can increase confidence when making these challenging decisions. The ArteraAI Prostate Test was developed with this in mind and can predict whether a patient will benefit from hormone therapy and estimate long-term outcomes.”

Bruno Barrey is one of Dr. Spratt’s patients. Barrey, a robotics engineer from suburban Detroit who was transitioning from active surveillance with Gleason 3+4 intermediate-risk prostate cancer to radiation therapy, said, “I was concerned about the side effects from androgen-deprivation therapy. I was relieved that the AI test allowed me to avoid hormone therapy.”

Dr. Spratt reported working with NRG Oncology, a clinical trials group funded by the National Cancer Institute, and as an academic collaborator with ArteraAI. 

A version of this article appeared on Medscape.com.

Medicare will now cover the use of an AI-based test for prostate cancer that can predict which men will benefit from potentially disabling androgen deprivation therapy.

The Centers for Medicare & Medicare Services (CMS) on January 1 approved the payment rate for ArteraAI as a clinical diagnostic laboratory test. The test is the first that can both predict therapeutic benefit and prognosticate long-term outcomes in localized prostate cancer. 

Daniel Spratt, MD, chair of radiation oncology at UH Seidman Cancer Center in Cleveland, who has been involved in researching ArteraAI, told this news organization that the test improves risk stratification or prognostication over standard clinical and pathologic tools, such as prostate-specific antigen, Gleason score, and T-stage, or risk groupings such as those from the National Comprehensive Cancer Network (NCCN).

“Medicare approval allows this test to reach more patients without the financial burden of covering the test out of pocket. The test is found among other tests in NCCN guidelines as a tool to improve risk stratification and personalization of treatment,” said Dr. Spratt, who serves on the network’s prostate cancer panel.

ArteraAI combines a patient’s standard clinical and pathologic information into an algorithm, alongside a digitized image analysis of the patients’ prostate biopsy. The result is a score that estimates a patient’s risk of developing metastasis or dying from prostate cancer.

Dr. Spratt was the lead author of article last June in NEJM Evidence that validated ArteraAI. He said ArteraAI is 80% accurate as a prognostic test compared with 65% accuracy using NCCN stratification systems. 

The AI test spares about two thirds of men with intermediate-risk prostate cancer who are starting radiation therapy from androgen deprivation and its side effects, such as weight gain, breast enlargement, hot flashes, heart disease, and brain problems, Dr. Spratt added. 

Andre Esteva, CEO and co-founder of San Francisco-based ArteraAI, said, “After someone is diagnosed with localized prostate cancer, deciding on a treatment can feel very overwhelming as there are so many factors to consider. During this time, knowledge is power, and having detailed, personalized information can increase confidence when making these challenging decisions. The ArteraAI Prostate Test was developed with this in mind and can predict whether a patient will benefit from hormone therapy and estimate long-term outcomes.”

Bruno Barrey is one of Dr. Spratt’s patients. Barrey, a robotics engineer from suburban Detroit who was transitioning from active surveillance with Gleason 3+4 intermediate-risk prostate cancer to radiation therapy, said, “I was concerned about the side effects from androgen-deprivation therapy. I was relieved that the AI test allowed me to avoid hormone therapy.”

Dr. Spratt reported working with NRG Oncology, a clinical trials group funded by the National Cancer Institute, and as an academic collaborator with ArteraAI. 

A version of this article appeared on Medscape.com.

TOPLINE:

Testosterone replacement therapy in middle-aged and older men with hypogonadism does not increase the risk for high-grade or any prostate cancer, new data confirmed.

METHODOLOGY:

• The relationship between testosterone replacement therapy and prostate cancer risk remains unclear.
• Epidemiologic studies have shown inconsistent findings, and clinical trials have not examined prostate safety. As a result, guidelines generally advise against testosterone replacement therapy in men with a history of or increased risk for prostate cancer.
• The current placebo-controlled, double-blind, parallel-group randomized study included 5204 men, ages 45-80, who had two fasting testosterone concentrations < 300 ng/dL, one or more hypogonadal symptoms, and a history of cardiovascular disease or increased . Patients were randomly assigned 1:1 to receive either testosterone replacement therapy or placebo.
• The primary prostate safety endpoint was incident high-grade prostate cancer (Gleason score 4 + 3 or higher).
• Secondary endpoints included incidence of any prostate cancer, acute urinary retention, invasive procedure for , , and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• The incidence of high-grade prostate cancer did not differ significantly between groups. Over a mean follow-up of 33 months, only 0.19% (5 of 2596 participants) in the testosterone replacement therapy group and 0.12% (3 of 2602) in the placebo group were diagnosed with high-grade disease (hazard ratio [HR], 1.62; P = .51).
• The rate of any prostate cancer also did not differ significantly between the testosterone vs placebo groups (0.46% vs 0.42%; HR, 1.07; P = .87).
• The rates of acute urinary retention (0.77% vs 0.61%; HR, 1.25; P = .50), invasive procedures for benign prostatic hyperplasia (0.89% vs 0.46%; HR, 1.91; P = .07), prostate biopsy (0.62% vs 0.54%; HR, 1.13; P = .74), or new treatment for lower urinary tract symptoms (3.89% vs 3.34%; HR, 1.16; P = .32) did not differ significantly between the testosterone vs placebo groups.
• Compared with placebo, testosterone therapy did increase prostate-specific antigen (PSA) levels, but the differences were small and did not increase after 12 months.

IN PRACTICE:

In a population of middle-aged and older men with hypogonadism, “the incidences of high-grade or any prostate cancer and other prostate events were low and did not differ significantly between testosterone- and placebo-treated men,” the authors concluded. “The study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

This study, led by Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, was published online in JAMA Network Open.

LIMITATIONS:

These study findings do not apply to men with known prostate cancer, higher PSA values, or those without confirmed hypogonadism. The study design did not include prostate imaging or other biomarker tests after PSA testing, which may have affected the decision to perform a biopsy. Also, the rates of treatment discontinuation and loss to follow-up were high.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories. Bhasin, Lincoff, and Khera reported receiving grants and consulting and personal fees from various sources. The remaining authors disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Testosterone replacement therapy in middle-aged and older men with hypogonadism does not increase the risk for high-grade or any prostate cancer, new data confirmed.

METHODOLOGY:

• The relationship between testosterone replacement therapy and prostate cancer risk remains unclear.
• Epidemiologic studies have shown inconsistent findings, and clinical trials have not examined prostate safety. As a result, guidelines generally advise against testosterone replacement therapy in men with a history of or increased risk for prostate cancer.
• The current placebo-controlled, double-blind, parallel-group randomized study included 5204 men, ages 45-80, who had two fasting testosterone concentrations < 300 ng/dL, one or more hypogonadal symptoms, and a history of cardiovascular disease or increased . Patients were randomly assigned 1:1 to receive either testosterone replacement therapy or placebo.
• The primary prostate safety endpoint was incident high-grade prostate cancer (Gleason score 4 + 3 or higher).
• Secondary endpoints included incidence of any prostate cancer, acute urinary retention, invasive procedure for , , and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• The incidence of high-grade prostate cancer did not differ significantly between groups. Over a mean follow-up of 33 months, only 0.19% (5 of 2596 participants) in the testosterone replacement therapy group and 0.12% (3 of 2602) in the placebo group were diagnosed with high-grade disease (hazard ratio [HR], 1.62; P = .51).
• The rate of any prostate cancer also did not differ significantly between the testosterone vs placebo groups (0.46% vs 0.42%; HR, 1.07; P = .87).
• The rates of acute urinary retention (0.77% vs 0.61%; HR, 1.25; P = .50), invasive procedures for benign prostatic hyperplasia (0.89% vs 0.46%; HR, 1.91; P = .07), prostate biopsy (0.62% vs 0.54%; HR, 1.13; P = .74), or new treatment for lower urinary tract symptoms (3.89% vs 3.34%; HR, 1.16; P = .32) did not differ significantly between the testosterone vs placebo groups.
• Compared with placebo, testosterone therapy did increase prostate-specific antigen (PSA) levels, but the differences were small and did not increase after 12 months.

IN PRACTICE:

In a population of middle-aged and older men with hypogonadism, “the incidences of high-grade or any prostate cancer and other prostate events were low and did not differ significantly between testosterone- and placebo-treated men,” the authors concluded. “The study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

This study, led by Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, was published online in JAMA Network Open.

LIMITATIONS:

These study findings do not apply to men with known prostate cancer, higher PSA values, or those without confirmed hypogonadism. The study design did not include prostate imaging or other biomarker tests after PSA testing, which may have affected the decision to perform a biopsy. Also, the rates of treatment discontinuation and loss to follow-up were high.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories. Bhasin, Lincoff, and Khera reported receiving grants and consulting and personal fees from various sources. The remaining authors disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Testosterone replacement therapy in middle-aged and older men with hypogonadism does not increase the risk for high-grade or any prostate cancer, new data confirmed.

METHODOLOGY:

• The relationship between testosterone replacement therapy and prostate cancer risk remains unclear.
• Epidemiologic studies have shown inconsistent findings, and clinical trials have not examined prostate safety. As a result, guidelines generally advise against testosterone replacement therapy in men with a history of or increased risk for prostate cancer.
• The current placebo-controlled, double-blind, parallel-group randomized study included 5204 men, ages 45-80, who had two fasting testosterone concentrations < 300 ng/dL, one or more hypogonadal symptoms, and a history of cardiovascular disease or increased . Patients were randomly assigned 1:1 to receive either testosterone replacement therapy or placebo.
• The primary prostate safety endpoint was incident high-grade prostate cancer (Gleason score 4 + 3 or higher).
• Secondary endpoints included incidence of any prostate cancer, acute urinary retention, invasive procedure for , , and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• The incidence of high-grade prostate cancer did not differ significantly between groups. Over a mean follow-up of 33 months, only 0.19% (5 of 2596 participants) in the testosterone replacement therapy group and 0.12% (3 of 2602) in the placebo group were diagnosed with high-grade disease (hazard ratio [HR], 1.62; P = .51).
• The rate of any prostate cancer also did not differ significantly between the testosterone vs placebo groups (0.46% vs 0.42%; HR, 1.07; P = .87).
• The rates of acute urinary retention (0.77% vs 0.61%; HR, 1.25; P = .50), invasive procedures for benign prostatic hyperplasia (0.89% vs 0.46%; HR, 1.91; P = .07), prostate biopsy (0.62% vs 0.54%; HR, 1.13; P = .74), or new treatment for lower urinary tract symptoms (3.89% vs 3.34%; HR, 1.16; P = .32) did not differ significantly between the testosterone vs placebo groups.
• Compared with placebo, testosterone therapy did increase prostate-specific antigen (PSA) levels, but the differences were small and did not increase after 12 months.

IN PRACTICE:

In a population of middle-aged and older men with hypogonadism, “the incidences of high-grade or any prostate cancer and other prostate events were low and did not differ significantly between testosterone- and placebo-treated men,” the authors concluded. “The study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

This study, led by Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, was published online in JAMA Network Open.

LIMITATIONS:

These study findings do not apply to men with known prostate cancer, higher PSA values, or those without confirmed hypogonadism. The study design did not include prostate imaging or other biomarker tests after PSA testing, which may have affected the decision to perform a biopsy. Also, the rates of treatment discontinuation and loss to follow-up were high.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories. Bhasin, Lincoff, and Khera reported receiving grants and consulting and personal fees from various sources. The remaining authors disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Surgery or radiation for advanced prostate cancer may improve survival but at the cost of treatment-related adverse effects, including gastrointestinal (GI) as well as sexual and urinary conditions, that may persist for years, a study of US veterans showed.

METHODOLOGY:

Recent evidence suggested that in men with advanced prostate cancer, local therapy with radical prostatectomy or radiation may improve survival outcomes; however, data on the long-term side effects from these local options were limited.

The retrospective cohort included 5502 men (mean age, 68 years) diagnosed with advanced (T4, N1, and/or M1) prostate cancer.

A total of 1705 men (31%) received initial local treatment, consisting of radical prostatectomy, (55%), radiation (39%), or both (5.6%), while 3797 (69%) opted for initial nonlocal treatment (hormone therapy, chemotherapy, or both). 

The main outcomes were treatment-related adverse effects, including GI, chronic pain, sexual dysfunction, and urinary symptoms, assessed at three timepoints after initial treatment — up to 1 year, between 1 and 2 years, and between 2 and 5 years.

TAKEAWAY:

Overall, 916 men (75%) who had initial local treatment and 897 men (67%) with initial nonlocal therapy reported at least one adverse condition up to 5 years after initial treatment.

In the first year after initial treatment, local therapy was associated with a higher prevalence of GI (9% vs 3%), pain (60% vs 38%), sexual (37% vs 8%), and urinary (46.5% vs 18%) conditions. Men receiving local therapy were more likely to experience GI (adjusted odds ratio [aOR], 4.08), pain (aOR, 1.57), sexual (aOR, 2.96), and urinary (aOR, 2.25) conditions.

Between 2 and 5 years after local therapy, certain conditions remained more prevalent — 7.8% vs 4.2% for GI, 40% vs 13% for sexual, and 40.5% vs 26% for urinary issues. Men receiving local vs nonlocal therapy were more likely to experience GI (aOR, 2.39), sexual (aOR, 3.36), and urinary (aOR, 1.39) issues over the long term.

The researchers found no difference in the prevalence of constitutional conditions such as hot flashes (36.5% vs 34.4%) in the first year following initial local or nonlocal therapy. However, local treatment followed by any secondary treatment was associated with a higher likelihood of developing constitutional conditions at 1-2 years (aOR, 1.50) and 2-5 years (aOR, 1.78) after initial treatment.

IN PRACTICE:

“These results suggest that patients and clinicians should consider the adverse effects of local treatment” alongside the potential for enhanced survival when making treatment decisions in the setting of advanced prostate cancer, the authors explained. Careful informed decision-making by both patients and practitioners is especially important because “there are currently no established guidelines regarding the use of local treatment among men with advanced prostate cancer.”

SOURCE:

The study, with first author Saira Khan, PhD, MPH, Washington University School of Medicine in St. Louis, Missouri, was published online in JAMA Network Open.

LIMITATIONS:

The authors noted that the study was limited by its retrospective design. Men who received local treatment were, on average, younger; older or lesser healthy patients who received local treatment may experience worse adverse effects than observed in the study. The study was limited to US veterans.

DISCLOSURES:

The study was supported by a grant from the US Department of Defense. The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Surgery or radiation for advanced prostate cancer may improve survival but at the cost of treatment-related adverse effects, including gastrointestinal (GI) as well as sexual and urinary conditions, that may persist for years, a study of US veterans showed.

METHODOLOGY:

Recent evidence suggested that in men with advanced prostate cancer, local therapy with radical prostatectomy or radiation may improve survival outcomes; however, data on the long-term side effects from these local options were limited.

The retrospective cohort included 5502 men (mean age, 68 years) diagnosed with advanced (T4, N1, and/or M1) prostate cancer.

A total of 1705 men (31%) received initial local treatment, consisting of radical prostatectomy, (55%), radiation (39%), or both (5.6%), while 3797 (69%) opted for initial nonlocal treatment (hormone therapy, chemotherapy, or both). 

The main outcomes were treatment-related adverse effects, including GI, chronic pain, sexual dysfunction, and urinary symptoms, assessed at three timepoints after initial treatment — up to 1 year, between 1 and 2 years, and between 2 and 5 years.

TAKEAWAY:

Overall, 916 men (75%) who had initial local treatment and 897 men (67%) with initial nonlocal therapy reported at least one adverse condition up to 5 years after initial treatment.

In the first year after initial treatment, local therapy was associated with a higher prevalence of GI (9% vs 3%), pain (60% vs 38%), sexual (37% vs 8%), and urinary (46.5% vs 18%) conditions. Men receiving local therapy were more likely to experience GI (adjusted odds ratio [aOR], 4.08), pain (aOR, 1.57), sexual (aOR, 2.96), and urinary (aOR, 2.25) conditions.

Between 2 and 5 years after local therapy, certain conditions remained more prevalent — 7.8% vs 4.2% for GI, 40% vs 13% for sexual, and 40.5% vs 26% for urinary issues. Men receiving local vs nonlocal therapy were more likely to experience GI (aOR, 2.39), sexual (aOR, 3.36), and urinary (aOR, 1.39) issues over the long term.

The researchers found no difference in the prevalence of constitutional conditions such as hot flashes (36.5% vs 34.4%) in the first year following initial local or nonlocal therapy. However, local treatment followed by any secondary treatment was associated with a higher likelihood of developing constitutional conditions at 1-2 years (aOR, 1.50) and 2-5 years (aOR, 1.78) after initial treatment.

IN PRACTICE:

“These results suggest that patients and clinicians should consider the adverse effects of local treatment” alongside the potential for enhanced survival when making treatment decisions in the setting of advanced prostate cancer, the authors explained. Careful informed decision-making by both patients and practitioners is especially important because “there are currently no established guidelines regarding the use of local treatment among men with advanced prostate cancer.”

SOURCE:

The study, with first author Saira Khan, PhD, MPH, Washington University School of Medicine in St. Louis, Missouri, was published online in JAMA Network Open.

LIMITATIONS:

The authors noted that the study was limited by its retrospective design. Men who received local treatment were, on average, younger; older or lesser healthy patients who received local treatment may experience worse adverse effects than observed in the study. The study was limited to US veterans.

DISCLOSURES:

The study was supported by a grant from the US Department of Defense. The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Surgery or radiation for advanced prostate cancer may improve survival but at the cost of treatment-related adverse effects, including gastrointestinal (GI) as well as sexual and urinary conditions, that may persist for years, a study of US veterans showed.

METHODOLOGY:

Recent evidence suggested that in men with advanced prostate cancer, local therapy with radical prostatectomy or radiation may improve survival outcomes; however, data on the long-term side effects from these local options were limited.

The retrospective cohort included 5502 men (mean age, 68 years) diagnosed with advanced (T4, N1, and/or M1) prostate cancer.

A total of 1705 men (31%) received initial local treatment, consisting of radical prostatectomy, (55%), radiation (39%), or both (5.6%), while 3797 (69%) opted for initial nonlocal treatment (hormone therapy, chemotherapy, or both). 

The main outcomes were treatment-related adverse effects, including GI, chronic pain, sexual dysfunction, and urinary symptoms, assessed at three timepoints after initial treatment — up to 1 year, between 1 and 2 years, and between 2 and 5 years.

TAKEAWAY:

Overall, 916 men (75%) who had initial local treatment and 897 men (67%) with initial nonlocal therapy reported at least one adverse condition up to 5 years after initial treatment.

In the first year after initial treatment, local therapy was associated with a higher prevalence of GI (9% vs 3%), pain (60% vs 38%), sexual (37% vs 8%), and urinary (46.5% vs 18%) conditions. Men receiving local therapy were more likely to experience GI (adjusted odds ratio [aOR], 4.08), pain (aOR, 1.57), sexual (aOR, 2.96), and urinary (aOR, 2.25) conditions.

Between 2 and 5 years after local therapy, certain conditions remained more prevalent — 7.8% vs 4.2% for GI, 40% vs 13% for sexual, and 40.5% vs 26% for urinary issues. Men receiving local vs nonlocal therapy were more likely to experience GI (aOR, 2.39), sexual (aOR, 3.36), and urinary (aOR, 1.39) issues over the long term.

The researchers found no difference in the prevalence of constitutional conditions such as hot flashes (36.5% vs 34.4%) in the first year following initial local or nonlocal therapy. However, local treatment followed by any secondary treatment was associated with a higher likelihood of developing constitutional conditions at 1-2 years (aOR, 1.50) and 2-5 years (aOR, 1.78) after initial treatment.

IN PRACTICE:

“These results suggest that patients and clinicians should consider the adverse effects of local treatment” alongside the potential for enhanced survival when making treatment decisions in the setting of advanced prostate cancer, the authors explained. Careful informed decision-making by both patients and practitioners is especially important because “there are currently no established guidelines regarding the use of local treatment among men with advanced prostate cancer.”

SOURCE:

The study, with first author Saira Khan, PhD, MPH, Washington University School of Medicine in St. Louis, Missouri, was published online in JAMA Network Open.

LIMITATIONS:

The authors noted that the study was limited by its retrospective design. Men who received local treatment were, on average, younger; older or lesser healthy patients who received local treatment may experience worse adverse effects than observed in the study. The study was limited to US veterans.

DISCLOSURES:

The study was supported by a grant from the US Department of Defense. The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

Seventeen years ago, Philip Segal, a retired accountant from suburban Toronto, Canada, was diagnosed with prostate cancer in a private clinic. After rejecting brachytherapy recommended by an oncologist, he went on active surveillance to watch, but not treat, the Gleason 6 (grade group 1) tumor. As he approaches his 80th birthday later this year, Mr. Segal said he plans to maintain the status quo. “It definitely brings me some peace of mind. I’d rather do that than not follow it and kick myself if there was a serious change,” he said.

Meanwhile, 2 years ago and 200 miles away in suburban Detroit, Bruno Barrey, a robotics engineer, was diagnosed with three cores of Gleason 6 and went on active surveillance.

Six months after the original diagnosis, however, Mr. Barrey, 57, underwent a follow-up biopsy. This time, all 16 cores were positive, with a mix of low-risk Gleason 6 and more advanced Gleason 3 + 4 lesions. His tumor was so large he underwent radiation therapy in 2023, ending his brief stint on the monitoring approach.

The two cases illustrate the complicated truth of active surveillance. For some men, the strategy can prove to be short-lived, perhaps 5 years or less, or a life-long approach lasting until the man dies from another cause.

Which kind of race a man will run depends on a wide range of factors: His comfort level living with a cancer, or at least a tumor that might well evolve into an aggressive malignancy, changes in his prostate-specific antigen (PSA) level and results of a magnetic resonance imaging test, the volume of his cancer, results of genetic testing of the patient himself and his lesion, and his urologist’s philosophy about surveillance. Where a patient lives matters, too, because variations in surveillance levels exist in different geographic areas, domestically and internationally.

“Active surveillance is a strategy of monitoring until it is necessary to be treated. For some people, it is very short, and for others, essentially indefinite,” said Michael Leapman, MD, clinical lead at Yale Cancer Center in New Haven, Connecticut. “While there are differences, I think they are mainly about who is the ideal patient.”

Most studies show that roughly half of men in the United States who go on active surveillance abandon it within 5 years of diagnosis. Rashid Sayyid, MD, a clinical fellow at the University of Toronto, Canada, found in a paper presented to the American Urological Association in 2022 that the number leaving active surveillance increased to nearly two thirds at 10 years.

Peter Carroll, MD, a urologist at the University of California, San Francisco, and a pioneer in the active surveillance in the late 1990s, said the major reason men abandon the strategy is because monitoring reveals the presence of a more aggressive cancer, typically a grade group 2 (Gleason 3 + 4) lesion. But other reasons include anxiety and other emotional distress and upgrades in blood levels of PSA and increases in the rating scale for MRI for the likelihood of the presence of clinically significant prostate cancer.

Laurence Klotz, MD, of the University of Toronto, Toronto, Ontario, who coined the term active surveillance strategy in 1997 and published the first studies in the early 2000s, said it is important to consider when the data on surveillance were collected.

Since 2013, when MRI began to be adopted as a surveillance modality for men with prostate cancer, the dropout rate began declining. The reason? According to Dr. Klotz, MRIs and targeted biopsies result in greater accuracy in staging the disease, determining which patients need to be biopsied, which helps some men avoid being diagnosed to begin with.

Dr. Klotz cited as an example of the emerging change a 2020 study in the Journal of Urology, which found a 24% dropout rate for surveillance at 5 years, 36% at 10 years, and 42% at 15 years in a series of 2664 grade group 1 patients on active surveillance at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2017.

Dr. Leapman cited a 2023 study in JNCI Cancer Spectrum using the National Cancer Database that found a decline in the percentage of patients who had grade group 1 in biopsies from 45% in 2010 to 25% in 2019.

“There is more judicious use of PSA testing and biopsy in individuals who are more likely to have significant prostate cancer,” Dr. Leapman told this news organization. “And MRI could also play a role by finding more high-grade cancers that would have otherwise been hidden.”

The changing statistics of prostate cancer also may reflect decreases in screening in response to a 2012 statement from the US Preventive Services Task Force advising against PSA testing. The American Cancer Society in January 2023 said that statement could be driving more diagnoses of late-stage disease, which has been surging for the first time in two decades, especially among Black men.

Dr. Sayyid said patients must be selected carefully for active surveillance. And he said urologists should not promise their active surveillance patients that they will avoid treatment. “There are numerous factors at stake that influence the ultimate outcome,” he said.

Progression of Gleason scores is estimated at 1%-2% per year, Dr. Sayyid added. When active surveillance fails in the short to medium term — 5-10 years — the reason usually is that higher-grade cancers with Gleason 3 + 4 or above were initially missed.

Dr. Sayyid said he counsels patients aged 70 years and older differently than those in their 50s, telling younger patients they are more likely to need treatment eventually than the older patients.

Factors that can affect the longevity of active surveillance include the presence or absence of germline mutations and the overall health and life expectancy and comorbidities such as heart disease and diabetes in a given patient, he said.

Urologists hold varying philosophies here, especially involving younger patients and the presence of any level of Gleason 4 cancer.

William Catalona, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, who developed the concept of mass screening with PSA testing, originally opposed active surveillance. In recent years, he has modified his views but still takes a more conservative approach.

“I consider active surveillance a foolish strategy or, at best, a short-term strategy for young, otherwise healthy men, especially those having any Gleason pattern 4 disease.”

“More than half will ultimately convert to active treatment, some too late, and will require multiple treatments with multiple side effects. Some will develop metastases, and some will die of prostate cancer.”

Dr. Sayyid takes a more liberal approach. “I would counsel an eligible patient considering active surveillance that at the current time, I see no strong reason why you should be subjected to treatment and the associated side effects,” he said. “And as long as your overall disease ‘state’ [the combination of grade, volume, PSA, and imaging tests] remains relatively stable, there should be no reason for us to ‘jump ship’. In my practice, another term for active surveillance is ‘active partnership’ — working together to decide if this is a sprint or a lifelong marathon.”

Dr. Carroll reported research funding from the National Institutes of Health.

A version of this article appeared on Medscape.com.

Seventeen years ago, Philip Segal, a retired accountant from suburban Toronto, Canada, was diagnosed with prostate cancer in a private clinic. After rejecting brachytherapy recommended by an oncologist, he went on active surveillance to watch, but not treat, the Gleason 6 (grade group 1) tumor. As he approaches his 80th birthday later this year, Mr. Segal said he plans to maintain the status quo. “It definitely brings me some peace of mind. I’d rather do that than not follow it and kick myself if there was a serious change,” he said.

Meanwhile, 2 years ago and 200 miles away in suburban Detroit, Bruno Barrey, a robotics engineer, was diagnosed with three cores of Gleason 6 and went on active surveillance.

Six months after the original diagnosis, however, Mr. Barrey, 57, underwent a follow-up biopsy. This time, all 16 cores were positive, with a mix of low-risk Gleason 6 and more advanced Gleason 3 + 4 lesions. His tumor was so large he underwent radiation therapy in 2023, ending his brief stint on the monitoring approach.

The two cases illustrate the complicated truth of active surveillance. For some men, the strategy can prove to be short-lived, perhaps 5 years or less, or a life-long approach lasting until the man dies from another cause.

Which kind of race a man will run depends on a wide range of factors: His comfort level living with a cancer, or at least a tumor that might well evolve into an aggressive malignancy, changes in his prostate-specific antigen (PSA) level and results of a magnetic resonance imaging test, the volume of his cancer, results of genetic testing of the patient himself and his lesion, and his urologist’s philosophy about surveillance. Where a patient lives matters, too, because variations in surveillance levels exist in different geographic areas, domestically and internationally.

“Active surveillance is a strategy of monitoring until it is necessary to be treated. For some people, it is very short, and for others, essentially indefinite,” said Michael Leapman, MD, clinical lead at Yale Cancer Center in New Haven, Connecticut. “While there are differences, I think they are mainly about who is the ideal patient.”

Most studies show that roughly half of men in the United States who go on active surveillance abandon it within 5 years of diagnosis. Rashid Sayyid, MD, a clinical fellow at the University of Toronto, Canada, found in a paper presented to the American Urological Association in 2022 that the number leaving active surveillance increased to nearly two thirds at 10 years.

Peter Carroll, MD, a urologist at the University of California, San Francisco, and a pioneer in the active surveillance in the late 1990s, said the major reason men abandon the strategy is because monitoring reveals the presence of a more aggressive cancer, typically a grade group 2 (Gleason 3 + 4) lesion. But other reasons include anxiety and other emotional distress and upgrades in blood levels of PSA and increases in the rating scale for MRI for the likelihood of the presence of clinically significant prostate cancer.

Laurence Klotz, MD, of the University of Toronto, Toronto, Ontario, who coined the term active surveillance strategy in 1997 and published the first studies in the early 2000s, said it is important to consider when the data on surveillance were collected.

Since 2013, when MRI began to be adopted as a surveillance modality for men with prostate cancer, the dropout rate began declining. The reason? According to Dr. Klotz, MRIs and targeted biopsies result in greater accuracy in staging the disease, determining which patients need to be biopsied, which helps some men avoid being diagnosed to begin with.

Dr. Klotz cited as an example of the emerging change a 2020 study in the Journal of Urology, which found a 24% dropout rate for surveillance at 5 years, 36% at 10 years, and 42% at 15 years in a series of 2664 grade group 1 patients on active surveillance at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2017.

Dr. Leapman cited a 2023 study in JNCI Cancer Spectrum using the National Cancer Database that found a decline in the percentage of patients who had grade group 1 in biopsies from 45% in 2010 to 25% in 2019.

“There is more judicious use of PSA testing and biopsy in individuals who are more likely to have significant prostate cancer,” Dr. Leapman told this news organization. “And MRI could also play a role by finding more high-grade cancers that would have otherwise been hidden.”

The changing statistics of prostate cancer also may reflect decreases in screening in response to a 2012 statement from the US Preventive Services Task Force advising against PSA testing. The American Cancer Society in January 2023 said that statement could be driving more diagnoses of late-stage disease, which has been surging for the first time in two decades, especially among Black men.

Dr. Sayyid said patients must be selected carefully for active surveillance. And he said urologists should not promise their active surveillance patients that they will avoid treatment. “There are numerous factors at stake that influence the ultimate outcome,” he said.

Progression of Gleason scores is estimated at 1%-2% per year, Dr. Sayyid added. When active surveillance fails in the short to medium term — 5-10 years — the reason usually is that higher-grade cancers with Gleason 3 + 4 or above were initially missed.

Dr. Sayyid said he counsels patients aged 70 years and older differently than those in their 50s, telling younger patients they are more likely to need treatment eventually than the older patients.

Factors that can affect the longevity of active surveillance include the presence or absence of germline mutations and the overall health and life expectancy and comorbidities such as heart disease and diabetes in a given patient, he said.

Urologists hold varying philosophies here, especially involving younger patients and the presence of any level of Gleason 4 cancer.

William Catalona, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, who developed the concept of mass screening with PSA testing, originally opposed active surveillance. In recent years, he has modified his views but still takes a more conservative approach.

“I consider active surveillance a foolish strategy or, at best, a short-term strategy for young, otherwise healthy men, especially those having any Gleason pattern 4 disease.”

“More than half will ultimately convert to active treatment, some too late, and will require multiple treatments with multiple side effects. Some will develop metastases, and some will die of prostate cancer.”

Dr. Sayyid takes a more liberal approach. “I would counsel an eligible patient considering active surveillance that at the current time, I see no strong reason why you should be subjected to treatment and the associated side effects,” he said. “And as long as your overall disease ‘state’ [the combination of grade, volume, PSA, and imaging tests] remains relatively stable, there should be no reason for us to ‘jump ship’. In my practice, another term for active surveillance is ‘active partnership’ — working together to decide if this is a sprint or a lifelong marathon.”

Dr. Carroll reported research funding from the National Institutes of Health.

A version of this article appeared on Medscape.com.

Seventeen years ago, Philip Segal, a retired accountant from suburban Toronto, Canada, was diagnosed with prostate cancer in a private clinic. After rejecting brachytherapy recommended by an oncologist, he went on active surveillance to watch, but not treat, the Gleason 6 (grade group 1) tumor. As he approaches his 80th birthday later this year, Mr. Segal said he plans to maintain the status quo. “It definitely brings me some peace of mind. I’d rather do that than not follow it and kick myself if there was a serious change,” he said.

Meanwhile, 2 years ago and 200 miles away in suburban Detroit, Bruno Barrey, a robotics engineer, was diagnosed with three cores of Gleason 6 and went on active surveillance.

Six months after the original diagnosis, however, Mr. Barrey, 57, underwent a follow-up biopsy. This time, all 16 cores were positive, with a mix of low-risk Gleason 6 and more advanced Gleason 3 + 4 lesions. His tumor was so large he underwent radiation therapy in 2023, ending his brief stint on the monitoring approach.

The two cases illustrate the complicated truth of active surveillance. For some men, the strategy can prove to be short-lived, perhaps 5 years or less, or a life-long approach lasting until the man dies from another cause.

Which kind of race a man will run depends on a wide range of factors: His comfort level living with a cancer, or at least a tumor that might well evolve into an aggressive malignancy, changes in his prostate-specific antigen (PSA) level and results of a magnetic resonance imaging test, the volume of his cancer, results of genetic testing of the patient himself and his lesion, and his urologist’s philosophy about surveillance. Where a patient lives matters, too, because variations in surveillance levels exist in different geographic areas, domestically and internationally.

“Active surveillance is a strategy of monitoring until it is necessary to be treated. For some people, it is very short, and for others, essentially indefinite,” said Michael Leapman, MD, clinical lead at Yale Cancer Center in New Haven, Connecticut. “While there are differences, I think they are mainly about who is the ideal patient.”

Most studies show that roughly half of men in the United States who go on active surveillance abandon it within 5 years of diagnosis. Rashid Sayyid, MD, a clinical fellow at the University of Toronto, Canada, found in a paper presented to the American Urological Association in 2022 that the number leaving active surveillance increased to nearly two thirds at 10 years.

Peter Carroll, MD, a urologist at the University of California, San Francisco, and a pioneer in the active surveillance in the late 1990s, said the major reason men abandon the strategy is because monitoring reveals the presence of a more aggressive cancer, typically a grade group 2 (Gleason 3 + 4) lesion. But other reasons include anxiety and other emotional distress and upgrades in blood levels of PSA and increases in the rating scale for MRI for the likelihood of the presence of clinically significant prostate cancer.

Laurence Klotz, MD, of the University of Toronto, Toronto, Ontario, who coined the term active surveillance strategy in 1997 and published the first studies in the early 2000s, said it is important to consider when the data on surveillance were collected.

Since 2013, when MRI began to be adopted as a surveillance modality for men with prostate cancer, the dropout rate began declining. The reason? According to Dr. Klotz, MRIs and targeted biopsies result in greater accuracy in staging the disease, determining which patients need to be biopsied, which helps some men avoid being diagnosed to begin with.

Dr. Klotz cited as an example of the emerging change a 2020 study in the Journal of Urology, which found a 24% dropout rate for surveillance at 5 years, 36% at 10 years, and 42% at 15 years in a series of 2664 grade group 1 patients on active surveillance at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2017.

Dr. Leapman cited a 2023 study in JNCI Cancer Spectrum using the National Cancer Database that found a decline in the percentage of patients who had grade group 1 in biopsies from 45% in 2010 to 25% in 2019.

“There is more judicious use of PSA testing and biopsy in individuals who are more likely to have significant prostate cancer,” Dr. Leapman told this news organization. “And MRI could also play a role by finding more high-grade cancers that would have otherwise been hidden.”

The changing statistics of prostate cancer also may reflect decreases in screening in response to a 2012 statement from the US Preventive Services Task Force advising against PSA testing. The American Cancer Society in January 2023 said that statement could be driving more diagnoses of late-stage disease, which has been surging for the first time in two decades, especially among Black men.

Dr. Sayyid said patients must be selected carefully for active surveillance. And he said urologists should not promise their active surveillance patients that they will avoid treatment. “There are numerous factors at stake that influence the ultimate outcome,” he said.

Progression of Gleason scores is estimated at 1%-2% per year, Dr. Sayyid added. When active surveillance fails in the short to medium term — 5-10 years — the reason usually is that higher-grade cancers with Gleason 3 + 4 or above were initially missed.

Dr. Sayyid said he counsels patients aged 70 years and older differently than those in their 50s, telling younger patients they are more likely to need treatment eventually than the older patients.

Factors that can affect the longevity of active surveillance include the presence or absence of germline mutations and the overall health and life expectancy and comorbidities such as heart disease and diabetes in a given patient, he said.

Urologists hold varying philosophies here, especially involving younger patients and the presence of any level of Gleason 4 cancer.

William Catalona, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, who developed the concept of mass screening with PSA testing, originally opposed active surveillance. In recent years, he has modified his views but still takes a more conservative approach.

“I consider active surveillance a foolish strategy or, at best, a short-term strategy for young, otherwise healthy men, especially those having any Gleason pattern 4 disease.”

“More than half will ultimately convert to active treatment, some too late, and will require multiple treatments with multiple side effects. Some will develop metastases, and some will die of prostate cancer.”

Dr. Sayyid takes a more liberal approach. “I would counsel an eligible patient considering active surveillance that at the current time, I see no strong reason why you should be subjected to treatment and the associated side effects,” he said. “And as long as your overall disease ‘state’ [the combination of grade, volume, PSA, and imaging tests] remains relatively stable, there should be no reason for us to ‘jump ship’. In my practice, another term for active surveillance is ‘active partnership’ — working together to decide if this is a sprint or a lifelong marathon.”

Dr. Carroll reported research funding from the National Institutes of Health.

A version of this article appeared on Medscape.com.

A novel DNA test system that assesses a person’s genetic predisposition for certain cancers – the first of its kind granted marketing authorization by the Food and Drug Administration – may become a valuable new public health tool.

The Common Hereditary Cancers Panel (Invitae) was approved late September following FDA review under the De Novo process, a regulatory pathway for new types of low- to moderate-risk devices.

Jezperklauzen/ThinkStock

Validation of the prescription-only in vitro test was based on assessments of more than 9,000 clinical samples, which demonstrated accuracy of at least 99% for all tested variants in 47 genes known to be associated with an increased risk of developing certain cancers, including breast, ovarian, uterine, prostate, colorectal, gastric, pancreatic as well as melanoma.
 

How the test system works

Next-generation sequencing assesses germline human genomic DNA extracted from a single blood sample collected at the point of care, such as a doctor’s office, and is sent to a laboratory for analysis.

Specifically, the system aims to detect substitutions, small insertion and deletion alterations, and copy number variants in the panel of 47 targeted genes.

This technology “can provide an important public health tool that offers individuals more information about their health, including possible predisposition for certain cancers,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological health, explained in an FDA press release announcing the marketing authorization.

Clinical interpretation is based on evidence from the published literature, prediction programs, public databases, and Invitae’s own variants database, the FDA statement explained.
 

What the test can do

Not only can the Common Hereditary Cancer Panel identify genetic variants that increase an individual’s risk of certain cancers, the panel can also help identify potential cancer-related hereditary variants in patients already diagnosed with cancer.

The most clinically significant genes the test system can detect include BRCA1 and BRCA2, which have known associations with hereditary breast and ovarian cancer syndrome; Lynch syndrome–associated genes including MLH1, MSH2, MSH6, PMS2, and EPCAM; CDH1, which is largely associated with hereditary diffuse gastric cancer and lobular breast cancer; and STK11, which is associated with Peutz-Jeghers syndrome.

“Patients should speak with a health care professional, such as a genetic counselor, to discuss any personal/family history of cancer, as such information can be helpful in interpreting test results,” the FDA advised.
 

What the test can’t do

The test is not intended to identify or evaluate all known genes tied to a person’s potential predisposition for cancer. The test is also not intended for cancer screening or prenatal testing. 

For these reasons, and because genetics are not the only factor associated with developing cancer, negative test results could lead to misunderstanding among some patients about their cancer risk.

“Results are intended to be interpreted within the context of additional laboratory results, family history, and clinical findings,” the company wrote in a statement.
 

Test safety

Risks associated with the test include the possibility of false positive and false negative results and the potential for people to misunderstand what the results mean about their risk for cancer.

A false sense of assurance after a false negative result might, for instance, lead patients to forgo recommended surveillance or clinical management, whereas false positive test results could lead to inappropriate decision-making and undesirable consequences.

“These risks are mitigated by the analytical performance validation, clinical validation, and appropriate labeling of this test,” the agency explained.

Along with the De Novo authorization, the FDA is establishing special controls to define requirements for these tests. For instance, accuracy must be 99% or higher for positive agreement and at least 99.9% for negative agreement with a validated, independent method.
 

Public health implications

The information gleaned from this tool can “help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants,” Dr. Shuren said.

The marketing authorization of Invitae’s test established a new regulatory category, which “means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process,” the FDA explained.

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

A novel DNA test system that assesses a person’s genetic predisposition for certain cancers – the first of its kind granted marketing authorization by the Food and Drug Administration – may become a valuable new public health tool.

The Common Hereditary Cancers Panel (Invitae) was approved late September following FDA review under the De Novo process, a regulatory pathway for new types of low- to moderate-risk devices.

Jezperklauzen/ThinkStock

Validation of the prescription-only in vitro test was based on assessments of more than 9,000 clinical samples, which demonstrated accuracy of at least 99% for all tested variants in 47 genes known to be associated with an increased risk of developing certain cancers, including breast, ovarian, uterine, prostate, colorectal, gastric, pancreatic as well as melanoma.
 

How the test system works

Next-generation sequencing assesses germline human genomic DNA extracted from a single blood sample collected at the point of care, such as a doctor’s office, and is sent to a laboratory for analysis.

Specifically, the system aims to detect substitutions, small insertion and deletion alterations, and copy number variants in the panel of 47 targeted genes.

This technology “can provide an important public health tool that offers individuals more information about their health, including possible predisposition for certain cancers,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological health, explained in an FDA press release announcing the marketing authorization.

Clinical interpretation is based on evidence from the published literature, prediction programs, public databases, and Invitae’s own variants database, the FDA statement explained.
 

What the test can do

Not only can the Common Hereditary Cancer Panel identify genetic variants that increase an individual’s risk of certain cancers, the panel can also help identify potential cancer-related hereditary variants in patients already diagnosed with cancer.

The most clinically significant genes the test system can detect include BRCA1 and BRCA2, which have known associations with hereditary breast and ovarian cancer syndrome; Lynch syndrome–associated genes including MLH1, MSH2, MSH6, PMS2, and EPCAM; CDH1, which is largely associated with hereditary diffuse gastric cancer and lobular breast cancer; and STK11, which is associated with Peutz-Jeghers syndrome.

“Patients should speak with a health care professional, such as a genetic counselor, to discuss any personal/family history of cancer, as such information can be helpful in interpreting test results,” the FDA advised.
 

What the test can’t do

The test is not intended to identify or evaluate all known genes tied to a person’s potential predisposition for cancer. The test is also not intended for cancer screening or prenatal testing. 

For these reasons, and because genetics are not the only factor associated with developing cancer, negative test results could lead to misunderstanding among some patients about their cancer risk.

“Results are intended to be interpreted within the context of additional laboratory results, family history, and clinical findings,” the company wrote in a statement.
 

Test safety

Risks associated with the test include the possibility of false positive and false negative results and the potential for people to misunderstand what the results mean about their risk for cancer.

A false sense of assurance after a false negative result might, for instance, lead patients to forgo recommended surveillance or clinical management, whereas false positive test results could lead to inappropriate decision-making and undesirable consequences.

“These risks are mitigated by the analytical performance validation, clinical validation, and appropriate labeling of this test,” the agency explained.

Along with the De Novo authorization, the FDA is establishing special controls to define requirements for these tests. For instance, accuracy must be 99% or higher for positive agreement and at least 99.9% for negative agreement with a validated, independent method.
 

Public health implications

The information gleaned from this tool can “help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants,” Dr. Shuren said.

The marketing authorization of Invitae’s test established a new regulatory category, which “means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process,” the FDA explained.

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

A novel DNA test system that assesses a person’s genetic predisposition for certain cancers – the first of its kind granted marketing authorization by the Food and Drug Administration – may become a valuable new public health tool.

The Common Hereditary Cancers Panel (Invitae) was approved late September following FDA review under the De Novo process, a regulatory pathway for new types of low- to moderate-risk devices.

Jezperklauzen/ThinkStock

Validation of the prescription-only in vitro test was based on assessments of more than 9,000 clinical samples, which demonstrated accuracy of at least 99% for all tested variants in 47 genes known to be associated with an increased risk of developing certain cancers, including breast, ovarian, uterine, prostate, colorectal, gastric, pancreatic as well as melanoma.
 

How the test system works

Next-generation sequencing assesses germline human genomic DNA extracted from a single blood sample collected at the point of care, such as a doctor’s office, and is sent to a laboratory for analysis.

Specifically, the system aims to detect substitutions, small insertion and deletion alterations, and copy number variants in the panel of 47 targeted genes.

This technology “can provide an important public health tool that offers individuals more information about their health, including possible predisposition for certain cancers,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological health, explained in an FDA press release announcing the marketing authorization.

Clinical interpretation is based on evidence from the published literature, prediction programs, public databases, and Invitae’s own variants database, the FDA statement explained.
 

What the test can do

Not only can the Common Hereditary Cancer Panel identify genetic variants that increase an individual’s risk of certain cancers, the panel can also help identify potential cancer-related hereditary variants in patients already diagnosed with cancer.

The most clinically significant genes the test system can detect include BRCA1 and BRCA2, which have known associations with hereditary breast and ovarian cancer syndrome; Lynch syndrome–associated genes including MLH1, MSH2, MSH6, PMS2, and EPCAM; CDH1, which is largely associated with hereditary diffuse gastric cancer and lobular breast cancer; and STK11, which is associated with Peutz-Jeghers syndrome.

“Patients should speak with a health care professional, such as a genetic counselor, to discuss any personal/family history of cancer, as such information can be helpful in interpreting test results,” the FDA advised.
 

What the test can’t do

The test is not intended to identify or evaluate all known genes tied to a person’s potential predisposition for cancer. The test is also not intended for cancer screening or prenatal testing. 

For these reasons, and because genetics are not the only factor associated with developing cancer, negative test results could lead to misunderstanding among some patients about their cancer risk.

“Results are intended to be interpreted within the context of additional laboratory results, family history, and clinical findings,” the company wrote in a statement.
 

Test safety

Risks associated with the test include the possibility of false positive and false negative results and the potential for people to misunderstand what the results mean about their risk for cancer.

A false sense of assurance after a false negative result might, for instance, lead patients to forgo recommended surveillance or clinical management, whereas false positive test results could lead to inappropriate decision-making and undesirable consequences.

“These risks are mitigated by the analytical performance validation, clinical validation, and appropriate labeling of this test,” the agency explained.

Along with the De Novo authorization, the FDA is establishing special controls to define requirements for these tests. For instance, accuracy must be 99% or higher for positive agreement and at least 99.9% for negative agreement with a validated, independent method.
 

Public health implications

The information gleaned from this tool can “help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants,” Dr. Shuren said.

The marketing authorization of Invitae’s test established a new regulatory category, which “means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process,” the FDA explained.

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

SAN DIEGO – With just five fractions of stereotactic body radiation therapy (SBRT), men with low- or intermediate-risk prostate cancer can have 5-year disease control as good as that provided by conventional external-beam radiation therapy delivered at higher doses in 20-39 fractions, according to new data from the phase 3 randomized PACE-B trial.

Overall, the 5-year event-free survival rates were 95.8% among patients who received SBRT and 94.6% among those who had conventional radiation. The incidence of adverse events was also low in both groups, with no significant differences observed between the trial arms.

The similar event-free survival and toxicity profiles in both groups provide more support for SBRT, which treats prostate cancer with larger radiation fractions over a shorter time period.

“I think we can also say now with a high level of confidence that SBRT can be considered a new standard of care for low and favorable intermediate-risk prostate cancer,” said Nicholas van As, MD, MB, from the Royal Marsden NHS Foundation Trust and Institute of Cancer Research in London, who presented efficacy and safety results from the noninferiority trial at the American Society for Radiation Oncology (ASTRO) annual meeting. SBRT is more convenient for patients and more cost-effective for health care providers, Dr. Van As added.

Invited discussant Alejandro Berlin, MD, MSc, from Princess Margaret Cancer Centre and the University of Toronto, agreed “that this should be a standard of care for low and favorable intermediate-risk prostate cancer,” an option already endorsed by relevant guidelines.

But, Dr. Berlin noted, SBRT requires careful attention to technique to achieve the desired results. Further research will be needed to identify and potentially reduce variability among radiation oncology practice regarding margins, dosimetry goals, dose heterogeneity, treatment schedules, and other factors, he said.
 

An international trial

PACE-B is one of three branches of a multi-center collaboration among 37 radiation therapy centers in the United Kingdom, Ireland, and Canada.

In the trial, investigators enrolled 874 patients with T1c or T2c prostate cancer, Gleason score of 3+4 or less, prostate-specific antigen (PSA) level no higher than 20 ng/mL, MRI staging, and no prior androgen deprivation therapy. Investigators then randomly assigned them on a 1:1 basis to receive either conventional radiation (n = 441) or SBRT (n = 433).

At the start of the trial, patients who were assigned to the conventional radiation group received 78 Gy in 39 fractions over 4-8 weeks. However, after results from the CHHiP trial, which showed that a 60-Gy, 20-fraction regimen was not inferior to a 74-Gy, 37-fraction regimen, the PACE-B investigators modified the protocol to 62 Gy delivered in 20 fractions.

Patients assigned to SBRT received 36.25 Gy divided into give fractions delivered over 1-2 weeks, with 40 Gy to the clinical target volume.

The primary outcome was noninferiority of SBRT, measured as whether patients remained free of biochemical clinical failure. Biochemical clinical failure was defined as evidence that the cancer was returning, such as an increase in PSA levels or distant metastases or death from prostate cancer.

At a median follow-up of 73.1 months, 5-year event-free survival rates were 94.6% for patients who received conventional radiation therapy and 95.8% for patients who received SBRT, meeting the prespecified criteria for noninferiority of SBRT (P = .007).

Freedom from biochemical and clinical failure, the trial’s primary endpoint, “was significantly better on both arms than our original power calculation, where we expected control rates of approximately 85%,” Dr. Van As said in an ASTRO plenary session.

Toxicity rates were also low in both study arms. The rate of grade 2 or greater urogenital side effects at 5 years was 5.5% in the SBRT arm and 3.2% in the conventional therapy arm. Grade 2 or greater gastrointestinal side effects occurred in only two patients, one in each study arm.

Given the findings, “I think it’s now imperative that our surgeons discuss this data with their patients before they perform prostatectomies,” Dr. Van As said.

Neha Vapiwala, MD, president-elect of ASTRO who moderated a media briefing where Dr. Van As summarized the PACE-B data, commented that “this study was conducted very rigorously, with excellent quality assurance.”

The study also highlights that clinicians in the United States have considerable catching up to do, said Dr. Vapiwala, from the Hospital of the University of Pennsylvania, Philadelphia.

In the United States, “we are way behind our colleagues on the other side of the pond,” she said. “We are way behind in our uptake of ultra-hypofractionated radiation [such as SBRT], and I do believe that some of that comes from the lack of feeling comfortable with the techniques that are needed and the expertise that is needed.”

PACE-B was funded by Accuray. Dr. Van As disclosed research grants from the company and consulting fees from Varian. Dr. Berlin reported no conflict of interest relevant to the study. Dr. Vapiwala has disclosed a consulting or advisory role with Bayer.

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

SAN DIEGO – With just five fractions of stereotactic body radiation therapy (SBRT), men with low- or intermediate-risk prostate cancer can have 5-year disease control as good as that provided by conventional external-beam radiation therapy delivered at higher doses in 20-39 fractions, according to new data from the phase 3 randomized PACE-B trial.

Overall, the 5-year event-free survival rates were 95.8% among patients who received SBRT and 94.6% among those who had conventional radiation. The incidence of adverse events was also low in both groups, with no significant differences observed between the trial arms.

The similar event-free survival and toxicity profiles in both groups provide more support for SBRT, which treats prostate cancer with larger radiation fractions over a shorter time period.

“I think we can also say now with a high level of confidence that SBRT can be considered a new standard of care for low and favorable intermediate-risk prostate cancer,” said Nicholas van As, MD, MB, from the Royal Marsden NHS Foundation Trust and Institute of Cancer Research in London, who presented efficacy and safety results from the noninferiority trial at the American Society for Radiation Oncology (ASTRO) annual meeting. SBRT is more convenient for patients and more cost-effective for health care providers, Dr. Van As added.

Invited discussant Alejandro Berlin, MD, MSc, from Princess Margaret Cancer Centre and the University of Toronto, agreed “that this should be a standard of care for low and favorable intermediate-risk prostate cancer,” an option already endorsed by relevant guidelines.

But, Dr. Berlin noted, SBRT requires careful attention to technique to achieve the desired results. Further research will be needed to identify and potentially reduce variability among radiation oncology practice regarding margins, dosimetry goals, dose heterogeneity, treatment schedules, and other factors, he said.
 

An international trial

PACE-B is one of three branches of a multi-center collaboration among 37 radiation therapy centers in the United Kingdom, Ireland, and Canada.

In the trial, investigators enrolled 874 patients with T1c or T2c prostate cancer, Gleason score of 3+4 or less, prostate-specific antigen (PSA) level no higher than 20 ng/mL, MRI staging, and no prior androgen deprivation therapy. Investigators then randomly assigned them on a 1:1 basis to receive either conventional radiation (n = 441) or SBRT (n = 433).

At the start of the trial, patients who were assigned to the conventional radiation group received 78 Gy in 39 fractions over 4-8 weeks. However, after results from the CHHiP trial, which showed that a 60-Gy, 20-fraction regimen was not inferior to a 74-Gy, 37-fraction regimen, the PACE-B investigators modified the protocol to 62 Gy delivered in 20 fractions.

Patients assigned to SBRT received 36.25 Gy divided into give fractions delivered over 1-2 weeks, with 40 Gy to the clinical target volume.

The primary outcome was noninferiority of SBRT, measured as whether patients remained free of biochemical clinical failure. Biochemical clinical failure was defined as evidence that the cancer was returning, such as an increase in PSA levels or distant metastases or death from prostate cancer.

At a median follow-up of 73.1 months, 5-year event-free survival rates were 94.6% for patients who received conventional radiation therapy and 95.8% for patients who received SBRT, meeting the prespecified criteria for noninferiority of SBRT (P = .007).

Freedom from biochemical and clinical failure, the trial’s primary endpoint, “was significantly better on both arms than our original power calculation, where we expected control rates of approximately 85%,” Dr. Van As said in an ASTRO plenary session.

Toxicity rates were also low in both study arms. The rate of grade 2 or greater urogenital side effects at 5 years was 5.5% in the SBRT arm and 3.2% in the conventional therapy arm. Grade 2 or greater gastrointestinal side effects occurred in only two patients, one in each study arm.

Given the findings, “I think it’s now imperative that our surgeons discuss this data with their patients before they perform prostatectomies,” Dr. Van As said.

Neha Vapiwala, MD, president-elect of ASTRO who moderated a media briefing where Dr. Van As summarized the PACE-B data, commented that “this study was conducted very rigorously, with excellent quality assurance.”

The study also highlights that clinicians in the United States have considerable catching up to do, said Dr. Vapiwala, from the Hospital of the University of Pennsylvania, Philadelphia.

In the United States, “we are way behind our colleagues on the other side of the pond,” she said. “We are way behind in our uptake of ultra-hypofractionated radiation [such as SBRT], and I do believe that some of that comes from the lack of feeling comfortable with the techniques that are needed and the expertise that is needed.”

PACE-B was funded by Accuray. Dr. Van As disclosed research grants from the company and consulting fees from Varian. Dr. Berlin reported no conflict of interest relevant to the study. Dr. Vapiwala has disclosed a consulting or advisory role with Bayer.

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

SAN DIEGO – With just five fractions of stereotactic body radiation therapy (SBRT), men with low- or intermediate-risk prostate cancer can have 5-year disease control as good as that provided by conventional external-beam radiation therapy delivered at higher doses in 20-39 fractions, according to new data from the phase 3 randomized PACE-B trial.

Overall, the 5-year event-free survival rates were 95.8% among patients who received SBRT and 94.6% among those who had conventional radiation. The incidence of adverse events was also low in both groups, with no significant differences observed between the trial arms.

The similar event-free survival and toxicity profiles in both groups provide more support for SBRT, which treats prostate cancer with larger radiation fractions over a shorter time period.

“I think we can also say now with a high level of confidence that SBRT can be considered a new standard of care for low and favorable intermediate-risk prostate cancer,” said Nicholas van As, MD, MB, from the Royal Marsden NHS Foundation Trust and Institute of Cancer Research in London, who presented efficacy and safety results from the noninferiority trial at the American Society for Radiation Oncology (ASTRO) annual meeting. SBRT is more convenient for patients and more cost-effective for health care providers, Dr. Van As added.

Invited discussant Alejandro Berlin, MD, MSc, from Princess Margaret Cancer Centre and the University of Toronto, agreed “that this should be a standard of care for low and favorable intermediate-risk prostate cancer,” an option already endorsed by relevant guidelines.

But, Dr. Berlin noted, SBRT requires careful attention to technique to achieve the desired results. Further research will be needed to identify and potentially reduce variability among radiation oncology practice regarding margins, dosimetry goals, dose heterogeneity, treatment schedules, and other factors, he said.
 

An international trial

PACE-B is one of three branches of a multi-center collaboration among 37 radiation therapy centers in the United Kingdom, Ireland, and Canada.

In the trial, investigators enrolled 874 patients with T1c or T2c prostate cancer, Gleason score of 3+4 or less, prostate-specific antigen (PSA) level no higher than 20 ng/mL, MRI staging, and no prior androgen deprivation therapy. Investigators then randomly assigned them on a 1:1 basis to receive either conventional radiation (n = 441) or SBRT (n = 433).

At the start of the trial, patients who were assigned to the conventional radiation group received 78 Gy in 39 fractions over 4-8 weeks. However, after results from the CHHiP trial, which showed that a 60-Gy, 20-fraction regimen was not inferior to a 74-Gy, 37-fraction regimen, the PACE-B investigators modified the protocol to 62 Gy delivered in 20 fractions.

Patients assigned to SBRT received 36.25 Gy divided into give fractions delivered over 1-2 weeks, with 40 Gy to the clinical target volume.

The primary outcome was noninferiority of SBRT, measured as whether patients remained free of biochemical clinical failure. Biochemical clinical failure was defined as evidence that the cancer was returning, such as an increase in PSA levels or distant metastases or death from prostate cancer.

At a median follow-up of 73.1 months, 5-year event-free survival rates were 94.6% for patients who received conventional radiation therapy and 95.8% for patients who received SBRT, meeting the prespecified criteria for noninferiority of SBRT (P = .007).

Freedom from biochemical and clinical failure, the trial’s primary endpoint, “was significantly better on both arms than our original power calculation, where we expected control rates of approximately 85%,” Dr. Van As said in an ASTRO plenary session.

Toxicity rates were also low in both study arms. The rate of grade 2 or greater urogenital side effects at 5 years was 5.5% in the SBRT arm and 3.2% in the conventional therapy arm. Grade 2 or greater gastrointestinal side effects occurred in only two patients, one in each study arm.

Given the findings, “I think it’s now imperative that our surgeons discuss this data with their patients before they perform prostatectomies,” Dr. Van As said.

Neha Vapiwala, MD, president-elect of ASTRO who moderated a media briefing where Dr. Van As summarized the PACE-B data, commented that “this study was conducted very rigorously, with excellent quality assurance.”

The study also highlights that clinicians in the United States have considerable catching up to do, said Dr. Vapiwala, from the Hospital of the University of Pennsylvania, Philadelphia.

In the United States, “we are way behind our colleagues on the other side of the pond,” she said. “We are way behind in our uptake of ultra-hypofractionated radiation [such as SBRT], and I do believe that some of that comes from the lack of feeling comfortable with the techniques that are needed and the expertise that is needed.”

PACE-B was funded by Accuray. Dr. Van As disclosed research grants from the company and consulting fees from Varian. Dr. Berlin reported no conflict of interest relevant to the study. Dr. Vapiwala has disclosed a consulting or advisory role with Bayer.

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

TOPLINE:

When patients deal directly with their insurance companies for answers about copayments and other issues, they are more likely to experience delays in cancer care and to be nonadherent.

METHODOLOGY:

• Navigating the complexities of insurance coverage is difficult for cancer patients, and the clinical impact of managing these intricacies remains unclear.
• To understand the issue, investigators surveyed 510 insured cancer patients in the United States about how often they estimate out-of-pocket costs for medications, doctors’ visits, and lab tests and scans, as well as how often they ask their insurance company to help them understand their coverage and how often they appeal coverage decisions.
• The team then correlated the answers with how often patients reported postponing or skipping doctors’ appointments and lab tests and how often they delayed filling prescriptions or skipped doses.
• Breast, colorectal, lung, and prostate cancer were the most common diagnoses among respondents.

TAKEAWAY:

• Overall, 55% of participants said they “never” or “rarely” engaged in any insurance-related cost tasks. The most frequently performed administrative tasks included finding out the cost before filling a prescription (28%) or before undergoing lab tests or scans (20%), as well as estimating the cost before agreeing to a treatment (20%), asking an insurance company for help understanding coverage (18%), or appealing a denial (17%).
• After adjusting for age, race/ethnicity, education, and monthly out-of-pocket costs, participants who engaged in any cost task were 18% more likely to experience treatment delays or forgo care.
• Every additional cost task or increase in frequency of a cost task was associated with 32% higher frequency of treatment delay or nonadherence.
• Age, race, and monthly out-of-pocket costs were more strongly associated with treatment delays/nonadherence than cost-task burden. Younger patients and Black patients were more likely than others to experience cost-related delays/nonadherence.

IN PRACTICE:

• “Reductions to administrative burden on patients, whether through patient-level education interventions, the adaptation of hospital-based navigation programs, or policy-focused changes to insurance systems, will be crucial” for helping patients with cancer to overcome administrative burdens and improve access to care, the authors said.

SOURCE:

• The study, led by Meredith Doherty, PhD, of the University of Pennsylvania, Philadelphia, was published in Cancer Epidemiology, Biomarkers and Prevention.

LIMITATIONS:

The survey was voluntary, which raises the possibility of self-selection bias. Recall bias may also have occurred, particularly among patients farther out from diagnosis and treatment. The investigators did not include uninsured patients and did not stratify patients by insurance type, and they did not measure or account for health care literacy.

DISCLOSURES:

The study was funded by the American Cancer Society. The investigators have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

When patients deal directly with their insurance companies for answers about copayments and other issues, they are more likely to experience delays in cancer care and to be nonadherent.

METHODOLOGY:

• Navigating the complexities of insurance coverage is difficult for cancer patients, and the clinical impact of managing these intricacies remains unclear.
• To understand the issue, investigators surveyed 510 insured cancer patients in the United States about how often they estimate out-of-pocket costs for medications, doctors’ visits, and lab tests and scans, as well as how often they ask their insurance company to help them understand their coverage and how often they appeal coverage decisions.
• The team then correlated the answers with how often patients reported postponing or skipping doctors’ appointments and lab tests and how often they delayed filling prescriptions or skipped doses.
• Breast, colorectal, lung, and prostate cancer were the most common diagnoses among respondents.

TAKEAWAY:

• Overall, 55% of participants said they “never” or “rarely” engaged in any insurance-related cost tasks. The most frequently performed administrative tasks included finding out the cost before filling a prescription (28%) or before undergoing lab tests or scans (20%), as well as estimating the cost before agreeing to a treatment (20%), asking an insurance company for help understanding coverage (18%), or appealing a denial (17%).
• After adjusting for age, race/ethnicity, education, and monthly out-of-pocket costs, participants who engaged in any cost task were 18% more likely to experience treatment delays or forgo care.
• Every additional cost task or increase in frequency of a cost task was associated with 32% higher frequency of treatment delay or nonadherence.
• Age, race, and monthly out-of-pocket costs were more strongly associated with treatment delays/nonadherence than cost-task burden. Younger patients and Black patients were more likely than others to experience cost-related delays/nonadherence.

IN PRACTICE:

• “Reductions to administrative burden on patients, whether through patient-level education interventions, the adaptation of hospital-based navigation programs, or policy-focused changes to insurance systems, will be crucial” for helping patients with cancer to overcome administrative burdens and improve access to care, the authors said.

SOURCE:

• The study, led by Meredith Doherty, PhD, of the University of Pennsylvania, Philadelphia, was published in Cancer Epidemiology, Biomarkers and Prevention.

LIMITATIONS:

The survey was voluntary, which raises the possibility of self-selection bias. Recall bias may also have occurred, particularly among patients farther out from diagnosis and treatment. The investigators did not include uninsured patients and did not stratify patients by insurance type, and they did not measure or account for health care literacy.

DISCLOSURES:

The study was funded by the American Cancer Society. The investigators have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

When patients deal directly with their insurance companies for answers about copayments and other issues, they are more likely to experience delays in cancer care and to be nonadherent.

METHODOLOGY:

• Navigating the complexities of insurance coverage is difficult for cancer patients, and the clinical impact of managing these intricacies remains unclear.
• To understand the issue, investigators surveyed 510 insured cancer patients in the United States about how often they estimate out-of-pocket costs for medications, doctors’ visits, and lab tests and scans, as well as how often they ask their insurance company to help them understand their coverage and how often they appeal coverage decisions.
• The team then correlated the answers with how often patients reported postponing or skipping doctors’ appointments and lab tests and how often they delayed filling prescriptions or skipped doses.
• Breast, colorectal, lung, and prostate cancer were the most common diagnoses among respondents.

TAKEAWAY:

• Overall, 55% of participants said they “never” or “rarely” engaged in any insurance-related cost tasks. The most frequently performed administrative tasks included finding out the cost before filling a prescription (28%) or before undergoing lab tests or scans (20%), as well as estimating the cost before agreeing to a treatment (20%), asking an insurance company for help understanding coverage (18%), or appealing a denial (17%).
• After adjusting for age, race/ethnicity, education, and monthly out-of-pocket costs, participants who engaged in any cost task were 18% more likely to experience treatment delays or forgo care.
• Every additional cost task or increase in frequency of a cost task was associated with 32% higher frequency of treatment delay or nonadherence.
• Age, race, and monthly out-of-pocket costs were more strongly associated with treatment delays/nonadherence than cost-task burden. Younger patients and Black patients were more likely than others to experience cost-related delays/nonadherence.

IN PRACTICE:

• “Reductions to administrative burden on patients, whether through patient-level education interventions, the adaptation of hospital-based navigation programs, or policy-focused changes to insurance systems, will be crucial” for helping patients with cancer to overcome administrative burdens and improve access to care, the authors said.

SOURCE:

• The study, led by Meredith Doherty, PhD, of the University of Pennsylvania, Philadelphia, was published in Cancer Epidemiology, Biomarkers and Prevention.

LIMITATIONS:

The survey was voluntary, which raises the possibility of self-selection bias. Recall bias may also have occurred, particularly among patients farther out from diagnosis and treatment. The investigators did not include uninsured patients and did not stratify patients by insurance type, and they did not measure or account for health care literacy.

DISCLOSURES:

The study was funded by the American Cancer Society. The investigators have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.