Patient-Reported Outcomes Through 5 Years for Active Surveillance, Surgery, Brachytherapy, or External Beam Radiation With or Without Androgen Deprivation Therapy for Localized Prostate Cancer

Abstract

Importance: Understanding adverse effects of contemporary treatment approaches for men with favorable-risk and unfavorable-risk localized prostate cancer could inform treatment selection.

Objective: To compare functional outcomes associated with prostate cancer treatments over 5 years after treatment.

Design, setting, and participants: Prospective, population-based cohort study of 1386 men with favorable-risk (clinical stage cT1 to cT2bN0M0, prostate-specific antigen [PSA] ≤20 ng/mL, and Grade Group 1-2) prostate cancer and 619 men with unfavorable-risk (clinical stage cT2cN0M0, PSA of 20-50 ng/mL, or Grade Group 3-5) prostate cancer diagnosed in 2011 through 2012, accrued from 5 Surveillance, Epidemiology and End Results Program sites and a US prostate cancer registry, with surveys through September 2017.

Exposures: Treatment with active surveillance (n = 363), nerve-sparing prostatectomy (n = 675), external beam radiation therapy (EBRT; n = 261), or low-dose-rate brachytherapy (n = 87) for men with favorable-risk disease and treatment with prostatectomy (n = 402) or EBRT with androgen deprivation therapy (n = 217) for men with unfavorable-risk disease.

Main outcomes and measures: Patient-reported function, based on the 26-item Expanded Prostate Index Composite (range, 0-100), 5 years after treatment. Regression models were adjusted for baseline function and patient and tumor characteristics. Minimum clinically important difference was 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritative symptoms, and 4 to 6 for bowel and hormonal function.

Results: A total of 2005 men met inclusion criteria and completed the baseline and at least 1 postbaseline survey (median [interquartile range] age, 64 [59-70] years; 1529 of 1993 participants [77%] were non-Hispanic white). For men with favorable-risk prostate cancer, nerve-sparing prostatectomy was associated with worse urinary incontinence at 5 years (adjusted mean difference, -10.9 [95% CI, -14.2 to -7.6]) and sexual function at 3 years (adjusted mean difference, -15.2 [95% CI, -18.8 to -11.5]) compared with active surveillance. Low-dose-rate brachytherapy was associated with worse urinary irritative (adjusted mean difference, -7.0 [95% CI, -10.1 to -3.9]), sexual (adjusted mean difference, -10.1 [95% CI, -14.6 to -5.7]), and bowel (adjusted mean difference, -5.0 [95% CI, -7.6 to -2.4]) function at 1 year compared with active surveillance. EBRT was associated with urinary, sexual, and bowel function changes not clinically different from active surveillance at any time point through 5 years. For men with unfavorable-risk disease, EBRT with ADT was associated with lower hormonal function at 6 months (adjusted mean difference, -5.3 [95% CI, -8.2 to -2.4]) and bowel function at 1 year (adjusted mean difference, -4.1 [95% CI, -6.3 to -1.9]), but better sexual function at 5 years (adjusted mean difference, 12.5 [95% CI, 6.2-18.7]) and incontinence at each time point through 5 years (adjusted mean difference, 23.2 [95% CI, 17.7-28.7]), than prostatectomy.

Conclusions and relevance: In this cohort of men with localized prostate cancer, most functional differences associated with contemporary management options attenuated by 5 years. However, men undergoing prostatectomy reported clinically meaningful worse incontinence through 5 years compared with all other options, and men undergoing prostatectomy for unfavorable-risk disease reported worse sexual function at 5 years compared with men who underwent EBRT with ADT.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Penson reported receiving grants from the Agency for Healthcare Research and Quality (AHRQ) and the Patient-Centered Outcomes Research Institute (PCORI) during the conduct of the study. Dr Goodman reported receiving grants from the National Institutes of Health (NIH) and PCORI during the conduct of the study. Dr Hamilton reported receiving grants from Vanderbilt and NIH during the conduct of the study. Dr Cooperberg reported receiving personal fees from Dendreon, Astellas, Bayer, AstraZeneca, and MDx Health outside the submitted work. Dr Hashibe reported receiving grants from AHRQ during the conduct of the study. Dr Koyama reported receiving grants from AHRQ and PCORI during the conduct of the study. Dr Barocas reported receiving grants from the AHRQ, PCORI, and the National Center for Advancing Translational Sciences during the conduct of the study and personal fees from Clovis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Flow of Participants in the Comparative Effectiveness Analyses of Surgery and Radiation (CEASAR) Study of the Association Between Contemporary Treatments for Localized Prostate Cancer Through 5 Years

Figure 2.. Unadjusted Disease-Specific Function for Men With Favorable-Risk Disease in a Study of the Association Between Treatments for Localized Prostate Cancer Through 5 Years

Domain scores are from the Expanded Prostate Cancer Index Composite (range, 0-100; higher scores indicate better function). Boxplots illustrate the distribution of scores at 6 months, 3 years, and 5 years. The boxes indicate the lower and upper quartiles and the lines inside the boxes indicate the median. The whiskers extend to the furthest points from the lower and upper quartiles that are still within 1.5 × the interquartile range (upper quartile − lower quartile). All the points beyond 1.5 × interquartile ranges are shown as dots, the intensity of which signifies the relative number of participants with that value.

Figure 3.. Adjusted Disease-Specific Functional Outcomes for Men With Favorable-Risk Disease in a Study of the Association Between Treatments for Localized Prostate Cancer Through 5 Years

Radar plots of adjusted Expanded Prostate Cancer Index Composite functional domain scores. The center of each figure represents worst function (score of 0) and the outermost line represents best function (score of 100). For the sexual function domain, the minimum clinically important difference in score is 10-12; urinary incontinence domain, 6-9; urinary irritative domain, 5-7; and bowel and hormonal function domains, 4-6. The regression models were adjusted for baseline domain score, age, race/ethnicity, comorbidities, cancer characteristics, physical function, social support, depression, medical decision-making style, and accrual site.

Figure 4.. Unadjusted Disease-Specific Function for Men With Unfavorable-Risk Disease in a Study of the Association Between Treatments for Localized Prostate Cancer Through 5 Years

Domain scores are from the Expanded Prostate Cancer Index Composite (range, 0-100; higher score indicate better function). Boxplots illustrate the distribution of scores at 6 months, 3 years, and 5 years. The boxes indicate the lower and upper quartiles and the lines inside the boxes indicate the median. The whiskers extend to the furthest points from the lower and upper quartiles that are still within 1.5 × the interquartile range (upper quartile − lower quartile). All the points beyond 1.5 × interquartile ranges are shown as dots, the intensity of which signifies the relative number of participants with that value.

Figure 5.. Adjusted Disease-Specific Functional Outcomes for Men With Unfavorable-Risk Prostate Cancer in a Study of the Association Between Treatments for Localized Prostate Cancer Through 5 Years

Radar plots of adjusted Expanded Prostate Cancer Index Composite functional domain scores. The center of each figure represents worst function (score of 0) and the outermost line represents best function (score of 100). For the sexual function domain, the minimum clinically important difference in score is 10-12; urinary incontinence domain, 6-9; urinary irritative domain, 5-7; and bowel and hormonal function domains, 4-6. The regression models were adjusted for baseline domain score, age, race/ethnicity, comorbidities, cancer characteristics, physical function, social support, depression, medical decision-making style, and accrual site.

Figure 6.. Unadjusted Health-Related Quality of Life for Men With Favorable- and Unfavorable-Risk Disease in a Study of the Association Between Treatments for Localized Prostate Cancer Through 5 Years

Domain scores are from the Medical Outcomes Study Short Form 36. Domain scores are scaled from 0 to 100, with higher score indicating better function. A minimum clinically important difference in score is 7 on the physical functioning, 6 on the emotional well-being, and 0 on the energy and fatigue domain. The boxes indicate the lower and upper quartiles and the lines inside the boxes indicate the median. The whiskers extend to the furthest points from the lower and upper quartiles that are still within 1.5 × the interquartile range (upper quartile − lower quartile). All the points beyond 1.5 × interquartile ranges are shown as dots, the intensity of which signifies the relative number of participants with that value.