Therapies for Clinically Localized Prostate Cancer
Authors: Dahm Philipp , Brasure Michelle , Ester Elizabeth , Linskens Eric J. , MacDonald Roderick , Nelson Victoria A. , Ryan Charles , Saha Jayati , Sultan Shahnaz , Ullman Kristen E. , Wilt Timothy J. 
Published: February 2022

Objective. To update findings from previous Agency for Healthcare Research and Quality (AHRQ)- and American Urological Association (AUA) funded reviews evaluating therapies for clinically localized prostate cancer (CLPC). Sources. Bibliographic databases (2013–January 2020); ClinicalTrials.gov; systematic reviews Methods. Controlled studies of CLPC treatments with duration ≥5 years for mortality and metastases and ≥1 year for quality of life and harms. One investigator rated risk of bias (RoB), extracted data, and assessed certainty of evidence; a second checked accuracy. We analyzed English-language studies with low or medium RoB. We incorporated findings from randomized controlled trials (RCTs) identified in the prior reviews if new RCTs provided information on the same intervention comparison. Results. We identified 67 eligible references; 17 were unique RCTs. Among clinically rather than prostate specific antigen (PSA) detected CLPC, Watchful Waiting (WW) may increase mortality and metastases versus Radical Prostatectomy (RP) at 20+ years. Urinary and erectile dysfunction were lower with WW versus RP. WW’s effect on mortality may vary by tumor risk and age but not by race, health status, comorbidities, or PSA. Active Monitoring (AM) probably results in little to no difference in mortality in PSA detected CLPC versus RP or external beam radiation (EBR) plus Androgen Deprivation (AD) regardless of tumor risk. Metastases were slightly higher with AM. Harms were greater with RP than AM and mixed between EBR plus AD versus AM. 3D-conformal EBR and AD plus low-dose-rate brachytherapy (BT) provided a small reduction in all-cause mortality versus three dimensional conformal EBR and AD but little to no difference on metastases. EBR plus AD versus EBR alone may result in a small reduction in mortality and metastases in higher risk disease but may increase sexual harms. EBR plus neoadjuvant AD versus EBR plus concurrent AD may result in little to no difference in mortality and genitourinary toxicity. Conventionally fractionated EBR versus ultrahypofractionated EBR may result in little to no difference in mortality and metastases and urinary and bowel toxicity. Active Surveillance may result in fewer harms than photodynamic therapy and laparoscopic RP may result in more harms than robotic-assisted RP. Little information exists on other treatments. No studies assessed provider or hospital factors of RP comparative effectiveness. Conclusions. RP reduces mortality versus WW in clinically detected CLPC but causes more harms. Effectiveness may be limited to younger men or to those with intermediate risk disease and requires many years to occur. AM results in little to no mortality difference versus RP or EBR plus AD. EBR plus AD reduces mortality versus EBR alone in higher risk CLPC but may worsen sexual function. Adding low-dose-rate BT to 3D-conformal EBR and AD may reduce mortality in higher risk CLPC. RCTs in PSA-detected and MRI staged CLPC are needed.