Whole-pelvic Versus Prostate-only Radiotherapy in Clinically Node-negative High-Risk Localised Prostate Cancer: A Systematic Review and Meta-analysis with Reconstructed Individual-patient Data.
SEARCH STRATEGY AND SOURCES OF INFORMATION MEDLINE, Embase and ClinicalTrials.gov were searched from database inception to May 2026 without language restriction, supplemented by hand-searching the proceedings of major oncology and radiation-oncology congress (2020-2026). AIMS Whether elective whole-pelvic radiotherapy (WPRT) improves outcomes over prostate-only radiotherapy (PORT) in high-risk localised prostate cancer remains an open question. We synthesised all phase 3 randomised trials and added a reconstructed individual-patient-data (IPD) analysis. MATERIALS AND METHODS We included phase III randomised trials of WPRT versus PORT. Trial-reported hazard ratios (HRs) were pooled using a random-effects meta-analysis, and individual-patient data were reconstructed (Guyot algorithm) and pooled. Outcomes were overall survival, biochemical/progression-free survival, and metastasis-free survival; risk of bias (RoB 2) and certainty (GRADE) were assessed for each outcome. RESULTS Five trials (5172 patients) were included. WPRT did not improve overall survival (HR, 1.07; 95% confidence interval [CI], 0.94 to 1.21; I2 = 0%; prediction interval, 0.92 to 1.24; reconstructed-IPD HR, 0.98; 0.80 to 1.20). The apparent benefit in biochemical/progression-free survival (HR, 0.84; 0.54 to 1.29) and metastasis-free survival (HR, 0.92; 0.54 to 1.57) was driven entirely by a single prostate-specific membrane antigen (PSMA)-staged, single-centre trial; excluding it, both became null (0.90; 0.77 to 1.06 and 1.00; 0.70 to 1.43). WPRT modestly increased late grade ≥2 genitourinary and gastrointestinal events without a meaningful severe-event excess. Certainty was moderate for overall survival and very low for both biochemical/progression-free and metastasis-free survival. CONCLUSION Current randomised evidence does not demonstrate sufficient benefit to support routine elective pelvic irradiation: WPRT does not improve overall survival, and its apparent benefit in progression-related endpoints is not reproducible across trials. POP-RT identifies a clinically plausible subgroup (patients with very-high nodal-risk who were PSMA-staged) in whom benefit is unproven and requires prospective validation in contemporary randomised trials.