PET-imaging derived prognostic factors for prostate cancer patients with visceral metastases receiving 177LuLu-PSMA radiopharmaceutical therapy (RPT)

Visceral metastases are a significant risk factor and may be the most critical determinant of outcome in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing ¹⁷⁷LuLu-PSMA RPT. In this monocentric real-world study, we evaluated baseline parameters derived from PET scans prior to RPT in order to identify potential prognostic factors in mCRPC patients with visceral metastases. This retrospective study included 320 men with mCRPC treated with in total 1077 cycles of 177 LuLu-PSMA RPT (1–12 cycles/patient). Baseline characteristics, including age, PSA level, Gleason score, metastatic sites, and prior treatments, were evaluated as potential prognostic factors in the overall cohort. 65 patients were diagnosed with visceral metastases. In this subgroup, we analyzed the PET-derived parameters whole body PSMA-positive tumor volume (PSMA-TV), SUVmax, SUVmean, miPSMA expression score and the metastatic pattern of visceral metastases. The estimated median overall survival (OS) for the entire cohort was 15 months. Presence of visceral metastases, Gleason score, and PSA level were significant negative prognostic baseline factors for the entire cohort in the multivariate Cox regression score. The estimated median OS for patients with visceral metastases was 10 months, which was significantly lower than the 16 months observed for patients without visceral metastases. PSMA-TV, miPSMA expression score, and the metastatic pattern were identified as independent prognostic factors in multivariate Cox regression analysis. Patients exhibiting two risk factors or more demonstrated a significantly poorer OS of 4 months compared to patients with a maximum of one risk factor, who showed an OS of 15 months. This study confirmed that visceral metastases represent a major risk factor in patients with mCRPC undergoing 177 LuLu-PSMA RPT. Moreover, PSMA-PET-derived parameters assessed prior to RPT enabled the distinction between high-risk and low-risk subgroups among patients with visceral metastases. These prognostic factors may therefore contribute to improved therapy stratification in mCRPC patients with visceral metastases undergoing 177 LuLu-PSMA RPT.