Comparative outcomes of radical prostatectomy, radiotherapy, and radiotherapy plus androgen deprivation therapy for high-risk and very high-risk prostate cancer: a narrative review.

BACKGROUND AND OBJECTIVE: High-risk and very high-risk prostate cancer (PCa) accounts for approximately 15-20% of newly diagnosed cases and are associated with substantial risk of disease progression, metastasis, and cancerspecific mortality. The comparative effectiveness of radical prostatectomy (RP), external beam radiotherapy (EBRT), and radiotherapy combined with androgen deprivation therapy (RT + ADT) remains uncertain because randomized head-to-head trials are lacking. This narrative review aims to synthesize the comparative effectiveness of RP, EBRT, and RT + ADT in patients with high-risk and very high-risk PCa, with respect to survival outcomes, optimal ADT duration, and toxicity/quality-of-life profiles.

METHODS: Literature searches were conducted across PubMed, Cochrane Library (CENTRAL), and ClinicalTrials.gov through May 2026. Studies comparing RP, EBRT, and/or RT + ADT in patients with high-risk PCa [prostate-specific antigen (PSA) ≥20 ng/mL, Gleason score 8-10/International Society of Urological Pathology (ISUP) grade ≥4, or clinical stage ≥T3a] were included. Primary outcomes were overall survival (OS), prostate cancer-specific survival (PCSS), and biochemical recurrence-free survival (bRFS).

KEY CONTENT AND FINDINGS: Observational studies comparing RP and RT-based strategies have reported conflicting results for OS: some studies reported more favorable outcomes with RP [hazard ratio (HR) 1.60, 95% confidence interval (CI): 1.25-2.05 for EBRT + ADT vs. RP], whereas others reported more favorable outcomes with RT-based strategies (HR 1.22, 95% CI: 1.05-1.43 for RP vs. EBRT plus brachytherapy). For patients with Gleason score 9-10 disease, observational analyses suggested that EBRT with brachytherapy boost was associated with lower prostate cancer-specific mortality compared with RP (HR 0.38, 95% CI: 0.21-0.68). For RT-treated patients, randomized controlled trials (RCTs) support the use of 18-24 months of ADT. Quality-of-life analyses consistently showed worse urinary incontinence and sexual dysfunction after RP, worse bowel symptoms after RT, and compounded toxicity with multimodal therapy.

CONCLUSIONS: For patients with high-risk and very high-risk PCa, radiotherapy combined with 18-24 months of ADT is supported by evidence from randomized trials compared with radiotherapy alone. Comparative survival evidence between RP and RT-based strategies remains conflicting and is limited by observational designs and selection bias. Treatment selection should be individualized according to patient age, comorbidity burden, tumor characteristics, and quality-of-life preferences. Randomized trials directly comparing contemporary RP with modern RT + ADT are urgently needed.