Long-term outcomes of PSMA PET/CT-guided radiotherapy in biochemical failure patients post-radical prostatectomy: a 5-year follow-up analysis

Purpose: To evaluate the role of PSMA PET/CT-guided salvage radiotherapy (sRT) in improving long-term biochemical recurrence-free survival (bRFS) in patients with biochemical recurrence (BCR) or PSA persistence (PERS) after radical prostatectomy (RP) for localized prostate cancer. Methods: This single-center retrospective study included 100 patients with BCR or PERS after RP who underwent [⁶⁸Ga]Ga-PSMA-11 PET/CT and sRT according to EAU guidelines. The primary endpoint was bRFS (PSA ≤ 0.2 ng/ml). Results: Sixty-three patients had BCR and 37 had PERS. Fifteen patients had PSA pre-RT < 0.5 ng/ml, while 75 had PSA pre-RT ≥ 0.5 ng/ml. [⁶⁸Ga]Ga-PSMA-11 PET/CT was positive in 52 patients, with BCR patients more frequently exhibiting local recurrence while PERS patients showed more nodal involvement. Patients with PERS received sRT and androgen deprivation therapy (ADT) in 57% of cases. The hazard ratio (HR) of treatment failure for patients with PSA pre-RT ≥ 0.5 ng/ml vs. < 0.5 ng/ml was 2.2 (p < 0.039). With a median follow-up of 59 months, treatment failure occurred in 36% of patients, with no difference between BCR and PERS groups. Among those with treatment failure, 64% were [⁶⁸Ga]Ga-PSMA-11 PET/CT positive at recurrence, and 39% received a new PSMA PET/CT-based RT. All patients were alive at the last analysis. Conclusion: [⁶⁸Ga]Ga-PSMA-11 PET/CT-guided sRT demonstrates significant long-term efficacy in patients with BCR or PERS after RP, leading to durable PSA response and guiding further treatment decisions. Trial registration: 244/2016/O/Oss8 November 2016 retrospectively registered.