PROSTATE 

Patient-Reported Outcomes through Five Years for Active Surveillance, Surgery, Brachytherapy, or External Beam Radiation With or Without Androgen Deprivation Therapy for Localised Prostate Cancer - PDF Version
Hoffman KE, Penson DF, Zhao Z, Huang LC, Conwill R, Laviana AA, Joyce DD, Luckenbaugh AN, Goodman M, Hamilton AS, Wu XC, Paddock LE, Stroup A, Cooperberg MR, Hashibe M, O'Neil BB, Kaplan SH, Greenfield S, Koyama T, Barocas DA.
JAMA. 2020 Jan 14;323(2):149-163 

­­­Importance: 
Understanding adverse effects of contemporary treatment approaches for men with favourable-risk and unfavourable-risk localised prostate cancer could inform treatment selection. 

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

Design, Setting, and Participants: 
A prospective, population-based cohort study of 1386 men with favourable-risk (clinical stage cT1 to cT2bN0M0, prostate-specific antigen [PSA] ≤20 ng/ml, and Grade Group 1-2) prostate cancer and 619 men with unfavourable-risk (clinical stage cT2cN0M0, PSA of 20-50 ng/ml, or Grade Group 3-5) prostate cancer diagnosed in 2011 through 2012, accrued from five Surveillance, Epidemiology and End Results Programme sites and a US prostate cancer registry, with surveys through to 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 favourable-risk disease and treatment with prostatectomy (n = 402) or EBRT with androgen deprivation therapy (n = 217) for men with unfavourable-risk disease. 

Main Outcomes and Measures: 
Patient-reported function, based on the 26-item Expanded Prostate Index Composite (range, 0-100), five years after treatment. Regression models were adjusted for baseline function and patient and tumour characteristics. Minimum clinically important differences were 10 to 12 for sexual function, six to nine for urinary incontinence, five to seven for urinary irritative symptoms, and four to six for bowel and hormonal function. 

Results: 
A total of 2005 men met inclusion criteria and completed the baseline and at least one post-baseline survey (median [interquartile range] age, 64 [59-70] years; 1529 of 1993 participants [77%] were non-Hispanic white). For men with favourable-risk prostate cancer, nerve-sparing prostatectomy was associated with worse urinary incontinence at five years (adjusted mean difference, -10.9 [95% CI, -14.2 to -7.6]) and sexual function at three 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 one 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 five years. For men with unfavourable-risk disease, EBRT with ADT was associated with lower hormonal function at six months (adjusted mean difference, -5.3 [95% CI, -8.2 to -2.4]) and bowel function at one year (adjusted mean difference, -4.1 [95% CI, -6.3 to -1.9]), but better sexual function at five years (adjusted mean difference, 12.5 [95% CI, 6.2-18.7]) and incontinence at each time point through five years (adjusted mean difference, 23.2 [95% CI, 17.7-28.7]), than prostatectomy. 

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