The real‐world outcomes of Lutetium‐177 PSMA‐617 radioligand therapy in metastatic castration‐resistant prostate cancer: Turkish Oncology Group multicenter study

AbstractMetastatic castration‐resistant prostate cancer (mCRPC) remains a challenging condition to treat despite recent advancements. This retrospective study aimed to assess the activity and tolerability of Lutetium‐177 (Lu‐177) PSMA‐617 radioligand therapy (RLT) in mCRPC patients across multiple cancer centers in Turkey. The study included 165 patients who received at least one cycle of Lu‐177 PSMA‐617 RLT, with the majority having bone metastases and undergone prior treatments. Prostate‐specific antigen (PSA) levels were assessed before each treatment cycle, and the biochemical response was evaluated in accordance with the Prostate Cancer Work Group 3 Criteria. The PSA decline of ≥50% was classified as a response, while an increase of ≥25% in PSA levels was indicative of progressive disease. Neither response nor progression was considered as stable disease. The Lu‐177 PSMA‐617 RLT led to a significant PSA response, with 50.6% of patients achieving a >50% decrease in PSA levels. Median overall survival (OS) and progression‐free survival were 13.5 and 8.2 months, respectively. Patients receiving Lu‐177 PSMA‐617 RLT in combination with androgen receptor pathway inhibitors (ARPIs) had a higher OS compared to those receiving Lu‐177 PSMA‐617 RLT alone (18.2 vs 12.3 months, P = .265). The treatment was generally well‐tolerated, with manageable side effects such as anemia and thrombocytopenia. This study provides real‐world evidence supporting the effectiveness and safety of Lu‐177 PSMA‐617 RLT in mCRPC patients, particularly when used in combination with ARPIs. These findings contribute to the growing body of evidence on the potential benefits of PSMA‐targeted therapies in advanced prostate cancer.