Better Oncological Outcomes After Prostate-specific Membrane Antigen Positron Emission Tomography-guided Salvage Radiotherapy Following Prostatectomy.

Background And Objective Up to 50% of patients with prostate cancer experience prostate-specific antigen (PSA) relapse following primary radical prostatectomy (RP). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is increasingly being used for staging after RP owing to its high detection rate. Our aim was to compare outcomes for patients who received salvage radiotherapy (sRT) with versus without PSMA PET guidance.Methods In this observational case-control study, the control group consisted of 344 patients from the SAKK09/10 trial (sRT without PSMA PET guidance from 2011 to 2014). The treatment group consisted of 1548 patients from a retrospective multicenter cohort (PSMA PET-guided sRT from July 2013 to 2020). Data were collected up to November 2023. Patients with pN1 status at RP, initial cM1 status, cM1 status on PET, or PSA >0.5 ng/ml were excluded. Patients with detectable PSA after RP who were treated with sRT were eligible. We assessed 3-yr biochemical recurrence-free survival (BRFS) and metastasis-free survival (MFS).Key Findings And Limitations The study population of 717 patients comprised a control group (n = 255) with median follow-up of 75 mo and a PSMA PET group (n = 462) with median follow-up of 31 mo. In the PSMA PET cohort, 103 patients (22.3%) had PSMA-positive pelvic lymph nodes (PLNs), 85 (18.4%) received androgen deprivation therapy (ADT), and 104 (22.5%) underwent PLN irradiation. The BRFS rate at 3 yr was 71% (95% confidence interval [CI] 64-78%) for the control group and 77% (95% CI 72-82%) for the PSMA PET group. The PSMA PET group had favorable BRFS at 18-24 mo after sRT (hazard ratio 0.32, 95% CI 0.0.14-0.75; p = 0.01) and a lower rate of lymph node relapse after sRT (standardized mean difference 0.603). The MFS rate at 3 yr was 89.2% (95% CI 84.6-94.1%) for the control group and 91.2% (95% CI 88.1-94.4%) for the PSMA PET group.Conclusions And Clinical Implications Our results suggest a moderate improvement in short-term BRFS if PSMA PET is used to guide sRT. One possible reason is individualized PLN coverage facilitated by PET. MFS was not improved by PSMA PET guidance for sRT.Patients' Summary For patients who experience recurrence of prostate cancer after surgical removal of their prostate, salvage radiotherapy (sRT) is a further treatment option. We found that a type of scan called PSMA PET (prostate-specific membrane antigen positron emission tomography) to identify recurrence and guide sRT can improve recurrence-free survival because of better targeting of pelvic lymph nodes that may contain cancer cells.