Functional Outcomes After Localized Prostate Cancer Treatment

Abstract

Importance: Adverse outcomes associated with treatments for localized prostate cancer remain unclear.

Objective: To compare rates of adverse functional outcomes between specific treatments for localized prostate cancer.

Design, setting, and participants: An observational cohort study using data from 5 US Surveillance, Epidemiology, and End Results Program registries. Participants were treated for localized prostate cancer between 2011 and 2012. At baseline, 1877 had favorable-prognosis prostate cancer (defined as cT1-cT2bN0M0, prostate-specific antigen level <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.

Exposures: Radical prostatectomy (n = 1043), external beam radiotherapy (n = 359), brachytherapy (n = 96), or active surveillance (n = 379) for favorable-prognosis disease and radical prostatectomy (n = 362) or external beam radiotherapy with androgen deprivation therapy (n = 206) for unfavorable-prognosis disease.

Main outcomes and measures: Outcomes were patient-reported sexual, urinary, bowel, and hormone function measured using the 26-item Expanded Prostate Cancer Index Composite (range, 0-100; 100 = best). Associations of specific therapies with each outcome were estimated and compared at 10 years after treatment, adjusting for corresponding baseline scores, and patient and tumor characteristics. Minimum clinically important differences were 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritation, and 4 to 6 for bowel and hormone function.

Results: A total of 2445 patients with localized prostate cancer (median age, 64 years; 14% Black, 8% Hispanic) were included and followed up for a median of 9.5 years. Among 1877 patients with favorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -12.1 [95% CI, -16.2 to -8.0]), but not worse sexual function (adjusted mean difference, -7.2 [95% CI, -12.3 to -2.0]), compared with active surveillance. Among 568 patients with unfavorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -26.6 [95% CI, -35.0 to -18.2]), but not worse sexual function (adjusted mean difference, -1.4 [95% CI, -11.1 to 8.3), compared with external beam radiotherapy with androgen deprivation therapy. Among patients with unfavorable prognosis, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel (adjusted mean difference, -4.9 [95% CI, -9.2 to -0.7]) and hormone (adjusted mean difference, -4.9 [95% CI, -9.5 to -0.3]) function compared with radical prostatectomy.

Conclusions and relevance: Among patients treated for localized prostate cancer, radical prostatectomy was associated with worse urinary incontinence but not worse sexual function at 10-year follow-up compared with radiotherapy or surveillance among people with more favorable prognosis and compared with radiotherapy for those with unfavorable prognosis. Among men with unfavorable-prognosis disease, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel and hormone function at 10-year follow-up compared with radical prostatectomy.

Figure 1.. Definition of the Cohort in the CEASAR Study

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 10 years. PSA indicates prostate-specific antigen. ^aPatients from CaPSURE were excluded because they did not receive the 10-year survey.

Figure 2.. Overall and Prostate Cancer–Specific Survival in Patients With Localized Prostate Cancer

Overall and prostate cancer–specific survival probabilities were calculated using the Kaplan-Meier method for men with favorable-prognosis and unfavorable-prognosis prostate cancer through 10 years. Participants were censored at the date of the last registry follow-up. The median time of observation for the favorable-prognosis group was 9.5 years (IQR, 9.2-9.8), and for the unfavorable-prognosis group was 9.4 years (IQR, 9.0-9.8).

Figure 3.. Sexual Function, Urinary Incontinence and Irritation, Bowel Function, and Hormone Function in Favorable-Prognosis PC Through 10 Years

Box plots show unadjusted disease-specific function to 10 years. Crossbars are medians; boxes, IQRs; whiskers extend to the furthest points within 1.5 × IQR; dots, more extreme values with intensity signifying relative number of participants. Curves show adjusted mean EPIC-26 scores starting at unadjusted mean baseline for time zero. Regression models adjusted for baseline domain score, age, race and ethnicity, comorbidities, cancer characteristics, physical function, social support, depression, medical decision-making, and accrual site. Estimated domain scores used mean for continuous variables; mode for categorical variables. Scores and their interpretation are in the Methods. Hormone function assesses symptoms associated with hormone therapy adverse effects. eFigures 1 and 3 in Supplement 1 show more presentations.

Figure 4.. Perceptions of Erectile Insufficiency, Urinary Leakage, Frequent Urination, and Bowel Function in Men With Favorable-Prognosis Prostate Cancer Through 10 Years

The adjusted odds ratios (ORs) of men reporting a moderate or big problem for the individual items are shown on a logarithmic scale relative to active surveillance through 10 years. The line at y = 1 shows active surveillance (reference). The whiskers indicate 95% CIs. The regression models were adjusted for baseline domain score, age, race and ethnicity, comorbidities, cancer characteristics (stage, grade group, and prostate-specific antigen level), physical function, social support, depression, medical decision-making style, and accrual site. The table at the bottom indicates the total number of men who reported whether the individual functional item was a moderate/big problem vs no/very small/small, or erections insufficient for intercourse. eFigure 10 shows the unadjusted probabilities and eFigure 12 shows additional individual functional items in Supplement 1.

Figure 5.. Sexual Function, Urinary Incontinence, Urinary Irritation, Bowel Function, and Hormone Function in Men With Unfavorable-Prognosis Prostate Cancer Through 10 Years

Box plots demonstrate the distribution of unadjusted disease-specific function through 10 years. Crossbars represent medians; boxes, IQRs; whiskers extend to the furthest points within 1.5 × IQR; and more extreme values are shown as dots with intensity signifying the relative number of participants with that value. Curves demonstrate the adjusted-mean Expanded Prostate Cancer Index Composite functional domain scores starting at the unadjusted mean baseline score for time zero. Regression models were adjusted for baseline domain score, age, race and ethnicity, comorbidities, cancer characteristics, physical function, social support, depression, medical decision-making style, and accrual site. Estimated domain scores were calculated using mean for continuous variable and mode for categorical variables. Scores and their interpretation are in the Methods. Shading represents 95% CIs. Hormone function assesses symptoms associated with hormone therapy adverse effects. See eFigure 2 for presentation as radar plots and eFigure 4 for differences between treatments in Supplement 1.

Figure 6.. Perceptions of Erectile Insufficiency, Urinary Leakage, Frequent Urination, and Bowel Function in Men With Unfavorable-Prognosis Prostate Cancer Through 10 Years

The adjusted odds ratios (ORs) of men reporting a moderate or big problem for the individual items are shown on a logarithmic scale relative to radical prostatectomy through 10 years. The line at y = 1 shows radical prostatectomy (reference). The whiskers indicate 95% CIs. The regression models were adjusted for baseline domain score, age, race and ethnicity, comorbidities, cancer characteristics (stage, grade group, and prostate-specific antigen level), physical function, social support, depression, medical decision-making style, and accrual site. The table at the bottom indicates the total number of men who reported whether the individual functional item was a moderate/big problem vs no/very small/small, or erections insufficient for intercourse. eFigure 11 shows unadjusted probabilities and eFigure 13 shows additional individual functional items in Supplement 1.