177Lutetium-PSMA-I&T therapy for metastatic castration-resistant prostate cancer (mCRPC): the first multicenter real-world study of 177Lu-PSMA-I&T in Brazil

PURPOSE: Despite the approval of 177Lu-PSMA-617 as standard treatment for patients with mCRPC, at least 50% of patients do not respond to the therapy, especially those with visceral disease. This study analyzes real-world outcomes of 177Lu-PSMA-I&T used in heavily pretreated patients in Brazil. METHODS: Retrospective analysis of patients with mCRPC previously treated with at least one androgen receptor pathway inhibitor (ARPI) who underwent 177Lu-PSMA-I&T between 2020 and 2025 in two large oncology centers. Our primary endpoint was prostate-specific antigen (PSA) response rate of 50% or more (PSA50). Secondary endpoints included overall survival (OS) and time to next sequential therapies (TNST). Statistical analyses were performed in JAMOVI and RStudio. RESULTS: Forty-three patients were included, with median age 74 years and median baseline PSA 41 ng/mL. Prior to 177Lu-PSMA-I&T, 86% received more than one ARPI line and 23.3% underwent more than one taxane-based chemotherapy. Visceral disease was present in 41.9%. The overall PSA50 response for all patients was 44.2% and for patients with visceral disease was 33.3%. Median OS was 13.9 months [95% confidence interval (CI) 10.9-19.2] and 12-month survival was 55.5% [95% CI 42.1%-73.3%]. Out of the 24 patients who received subsequent therapies, median TNST was 2.9 months [95% CI 1.6-5.4]. CONCLUSIONS: Our results showed that 177Lu-PSMA-I&T achieved a PSA response comparable to those treated with 177Lu-PSMA-617 in randomized trials, despite our heavily treated patients' characteristics. A significant number of patients had visceral disease with expected lower PSA response, highlighting the need for more active combinations in this subgroup.