Prognostic value of PSMA PET–derived tumor volume in metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide

BACKGROUND: In metastatic castration-resistant prostate cancer (mCRPC), clinical outcomes remain highly heterogeneous despite the widespread use of next-generation androgen receptor pathway inhibitors. Reliable imaging-based biomarkers capable of reflecting whole-body tumor burden and predicting prognosis are needed. Prostate-specific membrane antigen (PSMA) PET-derived volumetric parameters have emerged as potential prognostic tools, yet their role in patients treated with abiraterone or enzalutamide remains insufficiently defined. METHODS: We retrospectively analyzed 54 patients with mCRPC treated with abiraterone or enzalutamide between 2013 and 2025. Baseline 68Ga-PSMA PET/CT scans were used to derive quantitative imaging parameters, including PSMA tumor volume (PSMA-TV), total lesion PSMA expression (PSMA-TL), and SUV-based metrics. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier analyses. Receiver operating characteristic analyses identified optimal cut-off values, and Cox proportional hazards models were used to determine independent prognostic factors. RESULTS: Higher baseline PSMA-TV and PSMA-TL were significantly associated with inferior OS and PFS. A PSMA-TV cut-off of ≥ 44.84 demonstrated good discriminatory ability for mortality prediction (AUC = 0.707, p = 0.010). In multivariate analysis, PSMA-TV ≥ 44.84 emerged as an independent predictor of mortality (HR 9.48, 95% CI 1.14-78.97; p = 0.037). Early PSA kinetics provided complementary prognostic information, and a PSA level ≥ 0.20 ng/mL at 6 months was independently associated with disease progression. CONCLUSION: PSMA PET-derived volumetric parameters, particularly PSMA tumor volume, provide robust prognostic information in mCRPC patients treated with abiraterone or enzalutamide. When combined with early PSA kinetics, these imaging biomarkers enable improved risk stratification and may support more individualized treatment strategies. Prospective multicenter studies are warranted to validate these findings.