Background Prostate-specific membrane antigen (PSMA) PET is used to guide postprostatectomy salvage radiotherapy (SRT) and enable intensification through dose escalation and target modification. The oncologic benefit and safety profile of PSMA PET–guided intensification remain uncertain. We aimed to synthesize comparative and single-arm evidence on oncologic outcomes and toxicity of PSMA PET–guided intensification of postprostatectomy SRT. Methods We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, Embase and Cochrane Library were searched from inception to 26 December 2025. Comparative and single-arm studies evaluating PSMA PET–guided intensification of postprostatectomy SRT were included. We included clinical studies using PSMA PET/CT or PET/MRI to guide radiotherapy intensification and excluded preclinical studies and non-original reports. Primary outcomes were failure-free survival (FFS) and biochemical recurrence–free survival (bRFS). Secondary outcomes included metastasis- and survival-related endpoints, treatment escalation, and toxicity. Meta-analysis was conducted only when sufficient comparative data were available. Hazard ratios were pooled in RevMan 5.4.1 using fixed- or random-effects models according to heterogeneity. Risk of bias was assessed with the Newcastle–Ottawa Scale. Statistical significance was set at two-sided P0.05. Results Fifteen studies met inclusion criteria, including five comparative and ten single-arm studies. Two studies reported FFS-type endpoints; because only two studies were available and endpoint definitions differed substantially, these findings were summarized descriptively. Four comparative studies involving 692 patients contributed to bRFS meta-analysis. PSMA PET–guided SRT showed numerically improved bRFS versus standard SRT, but the difference was not statistically significant (pooled HR 0.61, 95% CI 0.33–1.13; P = 0.12; I²=55%). Other secondary oncologic outcomes were variably reported with limited events and were synthesized descriptively. Severe genitourinary or gastrointestinal toxicity was uncommon, and some studies suggested delayed treatment escalation. Conclusions PSMA PET–guided intensification of postprostatectomy SRT may improve biochemical control without an increase in severe toxicity; however, a statistically significant bRFS benefit was not demonstrated and evidence for other oncologic outcomes remains limited. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420261277044.
Liu et al. (2026) studied this question.