Five-Year Outcomes After Prostate-Specific Membrane Antigen PET/CT-Guided Salvage Radiotherapy Following Radical Prostatectomy

Background: Salvage radiotherapy (sRT) is the standard of care for biochemical recurrence of prostate cancer following radical prostatectomy (RP). In this context, prostate-specific membrane antigen (PSMA) PET/CT offers superior sensitivity and specificity for the detection of recurrent disease. We aimed to evaluate the impact of PSMA PET/CT–guided management on clinical outcomes following sRT. Patients and Methods: We retrospectively screened 5 prospective PSMA PET/CT studies conducted between 2016 and 2021. Eligible patients underwent PSMA PET/CT for restaging at first biochemical recurrence after RP, received sRT, and had ≥24 months of follow-up. Progression-free survival (PFS), freedom from distant progression, and overall survival (OS) were calculated using the Kaplan-Meier method. Adjusted hazard ratios (aHRs) for PFS were derived using Cox proportional hazards regression, adjusting for age, pre-sRT prostate-specific antigen (PSA) level, use of androgen deprivation therapy (ADT), and receipt of whole-pelvis radiotherapy (WPRT). Results: Of the total cohort, 113 patients met the inclusion criteria. Median follow-up was 59.4 months (IQR, 47.4–69.5). Median PSA was 0.4 ng/mL (IQR, 0.3–1.1), and the median time from RP was 19.9 months (IQR, 5.6–51.8). On PSMA PET/CT, 19 (16.8%) patients were staged as TrN0M0, 32 (28.3%) as N1M0, 16 (14.2%) as M1, and 46 (40.7%) as T0N0M0 (no visible disease). ADT was administered to 76 (67.3%) patients, and 63 (55.8%) patients received WPRT. Disease progression occurred in 57 (50.4%) patients. Median PFS was 49.2 months (95% CI, 24.1–74.3), and median freedom from distant progression was 76.4 months (95% CI, 62.9–89.9). The 5-year OS rate was 97.1% (95% CI, 94.1%–100%). Receipt of WPRT was significantly associated with improved PFS among patients staged as TrN0M0 (aHR, 0.12; P =.035), whereas ADT was significantly associated with improved PFS in patients staged as N1/M1 (aHR, 0.37; P =.024). Conclusions: In this 5-year follow-up study from an institution that was an early adopter of PSMA PET/CT, PSMA PET/CT–guided sRT was associated with favorable oncologic outcomes. Exploratory analyses suggest a potential benefit of WPRT following a positive PSMA PET/CT and of ADT in patients with N1/M1 disease.