PSMA PET/CT–guided intensification of salvage radiotherapy versus conventional planning for biochemical recurrence after radical prostatectomy: A GRADE-assessed systematic review and meta-analysis.

e17145 Background: Salvage radiotherapy (SRT) is the standard treatment for biochemical recurrence (BCR) after radical prostatectomy, yet outcomes remain variable. Prostate-specific membrane antigen PET/CT (PSMA-PET/CT) improves detection of recurrent disease and may allow more precise radiotherapy targeting. We conducted a systematic review and meta-analysis to compare oncologic outcomes and toxicity between PSMA-PET/CT–guided and conventionally planned SRT. Methods: PubMed, Embase, and Scopus were searched for randomized trials and comparative cohort studies published through July 2025. Eligible studies included men with BCR after radical prostatectomy treated with PSMA-PET/CT–guided or conventional SRT. The primary endpoint was failure-free survival (FFS). Secondary outcomes included biochemical progression-free survival (bPFS), treatment modification rates, and grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicities. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using random-effects models. Risk of bias was assessed using RoB-2 and the Newcastle-Ottawa Scale. Results: Six studies published between 2021 and 2025 comprising 912 patients were included. PSMA-PET/CT–guided SRT was associated with significantly improved FFS compared with conventional SRT (RR 0.56, 95% CI 0.36–0.86; p = 0.008; I² = 0%), corresponding to an absolute reduction of 178 events per 1,000 treated patients. Treatment modification rates were substantially higher with PSMA-PET/CT guidance (RR 32.03), though heterogeneity was high (I² = 95%); sensitivity analysis eliminated heterogeneity, suggesting interstudy variability as the primary driver. Rates of grade ≥2 acute and late GI and GU toxicities were similar between groups. Grade 3 toxicity was more frequent with PSMA-PET/CT–guided SRT (RR 2.34, 95% CI 1.14–4.78), although absolute event rates were low. Conclusions: PSMA-PET/CT–guided salvage radiotherapy is associated with improved failure-free and biochemical progression-free survival compared with conventional planning, without an increase in grade 2 GI or GU toxicity. While grade 3 adverse events were modestly higher, overall rates remained low. These findings support PSMA-PET/CT–guided SRT as an effective strategy for men with biochemical recurrence after prostatectomy, pending confirmation in prospective randomized studies.