Refining prognostic stratification in salvage radiotherapy for prostate cancer: a retrospective multicenter cohort study using PSMA-PET and machine learning.

Abstract

Salvage radiotherapy (SRT) is the standard treatment for biochemical recurrence (bREC) after radical prostatectomy (RP), yet optimal radiation dose, field size, and the role of advanced imaging like PSMA-PET remain unclear. This study assessed the impact of SRT dose and the prognostic role of PSMA-PET on 2-year biochemical relapse-free survival (bRFS) in patients with localized disease. In this retrospective multicenter study, 255 patients treated with SRT across 11 centers were selected from a database of 1,201 cases. Inclusion criteria included PSA persistence/recurrence (≥0.1 ng/mL) post-RP and negative PSMA-PET for nodal or distant metastases. Patients receiving androgen deprivation therapy or with PSA > 0.5 ng/mL pre-SRT were excluded. Prognostic factors were identified using LASSO analysis and modeled with CART analysis. The primary endpoint was 2-year bRFS. With a median follow-up of 33 months, 2-year bRFS was 88.2 %. Lower pre-SRT PSA (<0.2 ng/mL), PSMA-PET negativity, longer PSA doubling time, older age, favorable ISUP grades (1-2), and shorter intervals from surgery to bREC were associated with improved bRFS. CART analysis demonstrated that PSMA-PET findings significantly influenced prognosis in patients with PSA levels below 0.2 ng/mL, while PSA-doubling time was predictive in patients with PSA 0.2-0.5 ng/mL. SRT dose and elective nodal irradiation did not significantly affect bRFS. This study underscores the complexity of prognostic modeling in SRT for prostate cancer, highlighting the value of PSMA-PET and CART for refined risk stratification.