In the JournalsPerspective

Localized prostate cancer treatment options lead to different sexual functioning, quality-of-life outcomes

Men with localized prostate cancer experienced different adverse events and quality-of-life changes according to whether they underwent surgery, radiation or active surveillance, according to two studies published in JAMA.

In one study, Daniel A. Barocas, MD, MPH, urologic surgeon and oncologist in the department of urologic surgery at Vanderbilt University Medical Center, and colleagues found radical prostatectomy was associated with a greater decrease in sexual function and urinary incontinence after 3 years compared with active surveillance and external beam radiation therapy.

Daniel A. Barocas
Ronald C. Chen

“This information may facilitate patient counseling regarding the expected harms of contemporary treatments and their possible effect on quality of life,” the researchers wrote.

In another study, Ronald C. Chen, MD, MPH, associate professor in the department of radiation oncology at University of North Carolina at Chapel Hill, and colleagues showed radical prostatectomy, external beam radiotherapy and brachytherapy were associated with worse sexual dysfunction scores at 3 months compared with active surveillance.

“Patients diagnosed with early-stage prostate cancer — and that's the vast majority of patients with this disease — face many treatment options that are thought to be similarly efficacious,” Chen said in a press release. “Therefore, the quality-of-life differences among these options become an important consideration when patients are trying to make their decisions.”

Patient-reported outcomes

Choosing among options for managing localized prostate cancer — which include radiation, radical prostatectomy and active surveillance — depends on multiple factors, including risk for progression; patient preference; and baseline urinary, sexual and bowel function.

However, comparative data on the effectiveness and harms of these options has been limited because studies have focused on homogenous populations and have not compared contemporary treatments, like robotic radical prostatectomy and intensity-modulated radiotherapy.

Therefore, Barocas and colleagues used five SEER registries and the Cancer of the Prostate Strategic Urologic Research Endeavor registry to evaluate data from 2,550 men (mean age, 63.8 years) diagnosed with localized prostate cancer between 2011 and 2012.

Each patient had PSA levels less than 50 ng/mL and were enrolled 6 months after diagnosis.

Domain scores on the 26-item Expanded Prostate Cancer Index Composite — a score that measures disease-specific function, in which a higher score (range, 0-100) indicates better function — after 36 months served as the study’s primary outcome. Researchers defined a minimum clinically important difference as 10 to 12 points for sexual function, six points for urinary incontinence, five for urinary irritative symptoms, five for bowel function and four for hormonal function.

Researchers collected patient-reported outcomes via mail at enrollment and at 6, 12 and 36 months thereafter.

In total, 1,523 patients underwent radical prostatectomy, 598 underwent external beam radiation therapy and 429 underwent active surveillance. Men treated with external beam radiation therapy were older than men treated with radical prostatectomy (mean age, 68.1 vs. 61.5 years; P < .001) and had worse baseline sexual function (mean score, 52.3 vs. 65.2; P < .001).

At 3 years, patients who underwent radical prostatectomy had a lower adjusted mean sexual domain score than men who underwent external beam radiation therapy (mean difference, –11.9 points; 95% CI, –15.1 to –8.7). Researchers observed no clinically significant difference in sexual domain score among men who received external beam radiation therapy compared with active surveillance (difference, –4.3 points; 95% CI, –9.2 to 0.7).

Urinary incontinence was worse among men who went radical prostatectomy than those who underwent external beam radiation therapy (–18 points; 95% CI, –20.5 to –15.4) or active surveillance (difference, –12.7 points; 95% CI, –16 to –9.3).

However, radical prostatectomy was associated with better urinary irritative symptoms than active surveillance (difference, 5.2 points; 95% CI, 3.2-7.2).

Further, the researchers did not observe clinically significant differences in bowel or hormone function beyond 1 year.

There also were no differences in health-related quality of life or disease-specific survival (range, 99.7%-100%) between the treatment options.

“These findings may facilitate counseling regarding the comparative harms of contemporary treatments for prostate cancer,” the researchers wrote.

Quality - of - life comparison

In their analysis, Chen and colleagues also sought to provide more information for men having to decide among treatment options for localized prostate cancer.

“There has not been a large-scale comparison of the quality-of-life impact for these modern options, until now,” Chen said in a press release. “Existing quality-of-life studies have studied older types of surgery and radiation that are no longer used, and patients need updated information regarding the impact of modern treatment options so they can make informed decisions about the choices they face today.”

Researchers analyzed quality-of-life changes from enrollment to 2 years following treatment among 1,141 men diagnosed in 2011 or 2012 who underwent radical prostatectomy (n = 469), external beam radiotherapy (n = 249) or brachytherapy (n = 109), compared with active surveillance (n = 314).

Median time from diagnosis to enrollment was 5 weeks. After propensity weighting, median age was 66 to 67 years across treatment groups, and 77% to 80% of men were white.

Researchers used the Prostate Cancer Symptom Indices to measure quality of life at baseline, 3 months, 12 month and 24 months. The instrument measures four domains — sexual dysfunction, urinary obstruction and irritation, urinary incontinence and bowel dysfunction — with scores that range from no dysfunction (0) to maximum dysfunction (100).

For all treatment groups at baseline, propensity-weighted mean scores range from 41.8 to 46.4 for sexual dysfunction; 20.8 to 22.8 for urinary obstruction and irritation; 9.7 to 10.5 for urinary incontinence; and 5.7 to 6.1 for bowel problems.

Compared with men who underwent active surveillance, mean sexual dysfunction scores appeared worse at 3 months for patients who underwent radical prostatectomy (between-group score difference, 36.2; 95% CI, 30.4-42), external beam radiotherapy (13.9; 95% CI, 6.7-21.2) and brachytherapy (17.1; 95% CI, 7.8-26.6).

Further, external beam radiotherapy and brachytherapy appeared linked to short-term urinary tract obstruction and irritation, whereas external beam radiotherapy caused short-term bowel symptoms.

Specifically, men who underwent radical prostatectomy had worse urinary incontinence at 3 months than men who underwent active surveillance (33.6; 95% CI, 27.8-39.2). Acute worsening or urinary obstruction and irritation was associated with treatment with external beam radiotherapy (11.7; 95% CI, 8.7-14.8) and brachytherapy (20.5; 95% CI, 15.1-25.9), and worsened bowel symptoms were associated with external beam radiotherapy (4.9; 95% CI, 2.4-7.4).

At the 24-month assessment, mean scores between the treated patients and active surveillance were not significantly different in most of the domains.

Still, at 2 years, poor sexual function following normal baseline function occurred in 57.1% of men treated with prostatectomy, 27.2% treated with external beam radiotherapy, 34.2% treated with brachytherapy and 25.2% treated with active surveillance.

“With modern robotic surgery, sexual dysfunction and urinary incontinence continue to be some of the side effects that surgery can cause,” Chen said. “While we do see improvement over time, even at the 2-year point, surgery still causes more of these issues than other treatments.”

It may be surprising to patients that at 2 years, quality-of-life appeared similar among men who chose radiotherapy or brachytherapy as those who chose active surveillance, Chen added.

“With all of the modern treatment options, patients should have accurate and realistic expectations about the frequency of side effects from treatment,” he said. “We found that the different treatment options have trade-offs in side effects. Each patient can look at these data to see what they care about most.”

Real-world applications

The findings from both studies — combined with results from the ProtecT trial — can help inform a patient with localized prostate cancer on how to make treatment decisions, Freddie C Hamdy, MD, FMedSci, from the department of surgical sciences at University of Oxford in the United Kingdom, and Jenny L. Donovan, PhD, FMedSci, from University of Bristol in the United Kingdom, wrote in a related editorial.

Results from these studies can now encourage patients to:

Take the time to assess the risk of treatment or active surveillance with their physician, factoring in risk category and their general health;

Be mindful of adverse effects from each treatment and its effect on quality of life for the short term, considering that urinary incontinence and sexual dysfunction appear worse after surgery, bowel problems may persist and become worse after radiation, and sexual dysfunction is mostly related to neoadjuvant androgen deprivation therapy; and

Realize that although adverse events of interventions can initially be avoided with active surveillance, natural declines in urinary and sexual function symptoms occur over time, and the adverse events of radical therapy will be experienced by patients when they are received.

“These new studies provide a useful addition to the evidence, which will help physicians and patients to make difficult decisions about the management of this ubiquitous disease,” Hamdy and Donovan wrote. – by Melinda Stevens

References:

Barocas DA, et al. JAMA. 2017;doi:10.1001/jama.2017.1704.

Chen RC, et al. JAMA. 2017;doi:10.1001/jama.2017.1652.

Hamdy FC and Donovan JL. JAMA. 2017;doi:10.1001/jama.2017.1703.

Disclosures: Barocas reports no relevant financial disclosures. Chen reports grants and personal fees from Accuray, and personal fees from Astellas and Medivation. Please see the full studies for lists of all other researchers’ relevant financial disclosures. Hamdy and Donovan report no relevant financial disclosures.

Men with localized prostate cancer experienced different adverse events and quality-of-life changes according to whether they underwent surgery, radiation or active surveillance, according to two studies published in JAMA.

In one study, Daniel A. Barocas, MD, MPH, urologic surgeon and oncologist in the department of urologic surgery at Vanderbilt University Medical Center, and colleagues found radical prostatectomy was associated with a greater decrease in sexual function and urinary incontinence after 3 years compared with active surveillance and external beam radiation therapy.

Daniel A. Barocas
Ronald C. Chen

“This information may facilitate patient counseling regarding the expected harms of contemporary treatments and their possible effect on quality of life,” the researchers wrote.

In another study, Ronald C. Chen, MD, MPH, associate professor in the department of radiation oncology at University of North Carolina at Chapel Hill, and colleagues showed radical prostatectomy, external beam radiotherapy and brachytherapy were associated with worse sexual dysfunction scores at 3 months compared with active surveillance.

“Patients diagnosed with early-stage prostate cancer — and that's the vast majority of patients with this disease — face many treatment options that are thought to be similarly efficacious,” Chen said in a press release. “Therefore, the quality-of-life differences among these options become an important consideration when patients are trying to make their decisions.”

Patient-reported outcomes

Choosing among options for managing localized prostate cancer — which include radiation, radical prostatectomy and active surveillance — depends on multiple factors, including risk for progression; patient preference; and baseline urinary, sexual and bowel function.

However, comparative data on the effectiveness and harms of these options has been limited because studies have focused on homogenous populations and have not compared contemporary treatments, like robotic radical prostatectomy and intensity-modulated radiotherapy.

Therefore, Barocas and colleagues used five SEER registries and the Cancer of the Prostate Strategic Urologic Research Endeavor registry to evaluate data from 2,550 men (mean age, 63.8 years) diagnosed with localized prostate cancer between 2011 and 2012.

Each patient had PSA levels less than 50 ng/mL and were enrolled 6 months after diagnosis.

Domain scores on the 26-item Expanded Prostate Cancer Index Composite — a score that measures disease-specific function, in which a higher score (range, 0-100) indicates better function — after 36 months served as the study’s primary outcome. Researchers defined a minimum clinically important difference as 10 to 12 points for sexual function, six points for urinary incontinence, five for urinary irritative symptoms, five for bowel function and four for hormonal function.

PAGE BREAK

Researchers collected patient-reported outcomes via mail at enrollment and at 6, 12 and 36 months thereafter.

In total, 1,523 patients underwent radical prostatectomy, 598 underwent external beam radiation therapy and 429 underwent active surveillance. Men treated with external beam radiation therapy were older than men treated with radical prostatectomy (mean age, 68.1 vs. 61.5 years; P < .001) and had worse baseline sexual function (mean score, 52.3 vs. 65.2; P < .001).

At 3 years, patients who underwent radical prostatectomy had a lower adjusted mean sexual domain score than men who underwent external beam radiation therapy (mean difference, –11.9 points; 95% CI, –15.1 to –8.7). Researchers observed no clinically significant difference in sexual domain score among men who received external beam radiation therapy compared with active surveillance (difference, –4.3 points; 95% CI, –9.2 to 0.7).

Urinary incontinence was worse among men who went radical prostatectomy than those who underwent external beam radiation therapy (–18 points; 95% CI, –20.5 to –15.4) or active surveillance (difference, –12.7 points; 95% CI, –16 to –9.3).

However, radical prostatectomy was associated with better urinary irritative symptoms than active surveillance (difference, 5.2 points; 95% CI, 3.2-7.2).

Further, the researchers did not observe clinically significant differences in bowel or hormone function beyond 1 year.

There also were no differences in health-related quality of life or disease-specific survival (range, 99.7%-100%) between the treatment options.

“These findings may facilitate counseling regarding the comparative harms of contemporary treatments for prostate cancer,” the researchers wrote.

Quality - of - life comparison

In their analysis, Chen and colleagues also sought to provide more information for men having to decide among treatment options for localized prostate cancer.

“There has not been a large-scale comparison of the quality-of-life impact for these modern options, until now,” Chen said in a press release. “Existing quality-of-life studies have studied older types of surgery and radiation that are no longer used, and patients need updated information regarding the impact of modern treatment options so they can make informed decisions about the choices they face today.”

Researchers analyzed quality-of-life changes from enrollment to 2 years following treatment among 1,141 men diagnosed in 2011 or 2012 who underwent radical prostatectomy (n = 469), external beam radiotherapy (n = 249) or brachytherapy (n = 109), compared with active surveillance (n = 314).

Median time from diagnosis to enrollment was 5 weeks. After propensity weighting, median age was 66 to 67 years across treatment groups, and 77% to 80% of men were white.

PAGE BREAK

Researchers used the Prostate Cancer Symptom Indices to measure quality of life at baseline, 3 months, 12 month and 24 months. The instrument measures four domains — sexual dysfunction, urinary obstruction and irritation, urinary incontinence and bowel dysfunction — with scores that range from no dysfunction (0) to maximum dysfunction (100).

For all treatment groups at baseline, propensity-weighted mean scores range from 41.8 to 46.4 for sexual dysfunction; 20.8 to 22.8 for urinary obstruction and irritation; 9.7 to 10.5 for urinary incontinence; and 5.7 to 6.1 for bowel problems.

Compared with men who underwent active surveillance, mean sexual dysfunction scores appeared worse at 3 months for patients who underwent radical prostatectomy (between-group score difference, 36.2; 95% CI, 30.4-42), external beam radiotherapy (13.9; 95% CI, 6.7-21.2) and brachytherapy (17.1; 95% CI, 7.8-26.6).

Further, external beam radiotherapy and brachytherapy appeared linked to short-term urinary tract obstruction and irritation, whereas external beam radiotherapy caused short-term bowel symptoms.

Specifically, men who underwent radical prostatectomy had worse urinary incontinence at 3 months than men who underwent active surveillance (33.6; 95% CI, 27.8-39.2). Acute worsening or urinary obstruction and irritation was associated with treatment with external beam radiotherapy (11.7; 95% CI, 8.7-14.8) and brachytherapy (20.5; 95% CI, 15.1-25.9), and worsened bowel symptoms were associated with external beam radiotherapy (4.9; 95% CI, 2.4-7.4).

At the 24-month assessment, mean scores between the treated patients and active surveillance were not significantly different in most of the domains.

Still, at 2 years, poor sexual function following normal baseline function occurred in 57.1% of men treated with prostatectomy, 27.2% treated with external beam radiotherapy, 34.2% treated with brachytherapy and 25.2% treated with active surveillance.

“With modern robotic surgery, sexual dysfunction and urinary incontinence continue to be some of the side effects that surgery can cause,” Chen said. “While we do see improvement over time, even at the 2-year point, surgery still causes more of these issues than other treatments.”

It may be surprising to patients that at 2 years, quality-of-life appeared similar among men who chose radiotherapy or brachytherapy as those who chose active surveillance, Chen added.

“With all of the modern treatment options, patients should have accurate and realistic expectations about the frequency of side effects from treatment,” he said. “We found that the different treatment options have trade-offs in side effects. Each patient can look at these data to see what they care about most.”

PAGE BREAK

Real-world applications

The findings from both studies — combined with results from the ProtecT trial — can help inform a patient with localized prostate cancer on how to make treatment decisions, Freddie C Hamdy, MD, FMedSci, from the department of surgical sciences at University of Oxford in the United Kingdom, and Jenny L. Donovan, PhD, FMedSci, from University of Bristol in the United Kingdom, wrote in a related editorial.

Results from these studies can now encourage patients to:

Take the time to assess the risk of treatment or active surveillance with their physician, factoring in risk category and their general health;

Be mindful of adverse effects from each treatment and its effect on quality of life for the short term, considering that urinary incontinence and sexual dysfunction appear worse after surgery, bowel problems may persist and become worse after radiation, and sexual dysfunction is mostly related to neoadjuvant androgen deprivation therapy; and

Realize that although adverse events of interventions can initially be avoided with active surveillance, natural declines in urinary and sexual function symptoms occur over time, and the adverse events of radical therapy will be experienced by patients when they are received.

“These new studies provide a useful addition to the evidence, which will help physicians and patients to make difficult decisions about the management of this ubiquitous disease,” Hamdy and Donovan wrote. – by Melinda Stevens

References:

Barocas DA, et al. JAMA. 2017;doi:10.1001/jama.2017.1704.

Chen RC, et al. JAMA. 2017;doi:10.1001/jama.2017.1652.

Hamdy FC and Donovan JL. JAMA. 2017;doi:10.1001/jama.2017.1703.

Disclosures: Barocas reports no relevant financial disclosures. Chen reports grants and personal fees from Accuray, and personal fees from Astellas and Medivation. Please see the full studies for lists of all other researchers’ relevant financial disclosures. Hamdy and Donovan report no relevant financial disclosures.

    Perspective

    Eric Horwitz

    Eric M. Horwitz

    Choosing the right prostate cancer therapy for an individual patient always involves balancing the benefit of the treatment against the potential toxicity of the treatment. For prostate cancer, this can be particularly difficult as there are many excellent ways to treat somebody with organ-confined prostate cancer — surgery or external beam radiation therapy or brachytherapy — and the treatments are quite different with different side effects. It is, ultimately, up to the patient to decide which treatment is best for them, but it is our responsibility as physicians to provide them with the information to make an informed decision. This study by Barocas and colleagues provides patients and physicians with important new information to help in the decision-making process.

    In this prospective population-based cohort study, 2,550 men treated with surgery (n = 1,523), external beam radiation therapy (n = 598) or active surveillance (n = 429), were recruited from 5 SEER registries in 2011 to 2012, to complete the 26-item EPIC questionnaire at 6, 12 and 36 months’ posttreatment. The EPIC questionnaire looked at urinary, bowel, sexual and hormonal function. The primary outcomes were the 36-month domain scores. In this study, there was a statistically significant decline in sexual function between surgery and radiation; there was no difference between radiation and active surveillance. There was also worse urinary incontinence between surgery and the radiation and active surveillance groups. There were no differences in bowel and hormonal function beyond 12 months between any of the treatments. This study is significant because it describes patient-reported outcomes using a validated measure (EPIC-26), and this information should help patients in making a better informed decision regarding what treatment is best for them.


    Eric M. Horwitz, MD

    Fox Chase Cancer Center

    Disclosure: Horwitz reports no relevant financial disclosures.