Long-term clinical outcomes and genomic predictors of PSMA-PET/CT-guided cytoreductive progression-directed therapy in patients with oligoprogressive castration-resistant prostate cancer.

Abstract

190 Background: The long-term effect of cytoreductive progression-directed therapy (PDT) based on prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) in oligoprogressive castrate-resistant prostate cancer (opCRPC) remains unclear. In this study, we aimed to evaluate the long-term clinical outcomes of PSMA-PET/CT-guided PDT and identify the genomic predictors associated with clinical effect in opCRPC. Methods: This study included 87 consecutive opCRPC patients who received PDT to the lesions identified by PSMA-PET/CT. Among them, 81 patients underwent targeted next-generation sequencing to characterize genomic alterations. Progression-free survival (PFS), local failure-free survival (LFFS), and overall survival (OS) were estimated using the Kaplan-Meier method, and potential predictors were assessed through Cox proportional hazards regression. Prostate-specific antigen (PSA) response was also evaluated. Results: Median follow-up was 56 months. PSA decline was observed in 83 cases (95.4%), with 77 cases (88.5%) achieving a PSA 50 response and 58 cases (66.6%) achieving a PSA 90 response. The median PFS was 14 months. The median LFFS and median OS were not reached. The rates for 5-year PFS, LFFS and OS were 27%, 66% and 62%, respectively. High-risk alterations (HRA) were defined as any pathogenic alteration in AR, TP53, RB1, or PTEN. Multivariate Cox regression analysis revealed that PDT coverage and HRA signature were independent predictors of PFS, LFFS, and OS. Conclusions: The cytoreductive PDT to opCRPC lesions detected by PSMA-PET/CT had encouraging PSA responses and favorable long-term outcomes in opCRPC patients. Complete coverage PDT and the absence of HRA signature were significantly associated with improved PFS, LFFS, and OS following PSMA-PET/CT-guided PDT. These findings highlight the potential value of integrating genomic signatures with PSMA-PET/CT-guided treatment.