PurposeThe higher detection efficacy of PSMA PET for oligometastatic recurrence of prostate cancer has promoted new loco-regional treatment options. PSMA-targeted radioguided surgery (PSMA-RGS) was introduced to facilitate salvage surgery of small tumor deposits. The objectives of this retrospective analysis are to describe an independent single-center consecutive cohort of patients undergoing PSMA-RGS and to evaluate its clinical and oncological outcomes.MethodBetween 2018 and 2022, 53 patients were treated with PSMA-RGS and 50 patients were available for final analyses. All patients were initially treated with radical prostatectomy (RP) and presented with biochemical recurrence (BCR) with at least one positive lesion on PSMA-PET imaging. After preparation of 99mTc-PSMA-I&S and intravenous injection, surgery was performed by using a gamma-probe intraoperatively.ResultsMedian age was 70 years (IQR 65–73) and the median PSA at salvage surgery was 1.2 ng/mL (IQR 0.6-3.0). In all patients pathologically positive lesions could be removed during PSMA-RGS. 29 (58%) patients had one pathologically positive lesion, 14 (28%) had two and 7 (14%) had three or more, respectively. The overall complication rate was 26% with 4 (8%), 1 (2%), and 8 (16%) having Clavien-Dindo (CD) type I, II, and IIIb complications, respectively. During the follow-up period 31 (62%) patients experienced BCR and 29 (58%) received further therapy.ConclusionsPSMA-RGS is a promising treatment option to enhance salvage surgery in early biochemical recurrence. However, only 42% of the patients treated with PSMA RGS remain without a biochemical recurrence. Further research is mandatory to identify patients, who profit from PSMA-RGS.