In Comparison to PSA, Interim Ga-68-PSMA PET/CT Response Evaluation Based on Modified RECIST 1.1 After 2^nd Cycle Is Better Predictor of Overall Survival of Prostate Cancer Patients Treated With ¹⁷⁷Lu-PSMA

Background: Prostate-specific membrane antigen (PSMA) targeting radioligands have transformed treatment of prostate cancer. Radioligand therapy (RLT) with ¹⁷⁷Lu-PSMA in metastasized castration resistant prostate cancer (mCRPC) achieves objective response and disease stabilization in roughly two third of patients, whereas one third of patients progress. This study was performed to assess the role of interim PSMA PET/CT after the 2^nd cycle of RLT for early prediction of overall survival in patients undergoing RLT with ¹⁷⁷Lu-PSMA. Methods: 38 mCRPC patients (68.9 ± 8.1 y) treated with at least two cycles of RLT at 8 week intervals and interim ⁶⁸Ga-PSMA PET/CT (PET) at 8–10 weeks after the 2^nd cycle of RLT were included in this study. Prostate-specific antigen (PSA) response was evaluated according to the Prostate Cancer Working Group 3 criteria. Radiographic response assessment of soft tissue, lymph node, and bone lesions was performed according to RECIST 1.1 including the PET component. Patients’ data were collected for follow-up from the local Comprehensive Cancer Center Register. Results: Median follow-up was 19.7 months (4.7–45.3). PSA response after the 2^nd therapy cycle showed partial remission (PR) in 23.7%, stable disease (SD) in 50%, and progressive disease (PD) in 26.3% of patients. In comparison, 52.6, 23.7, and 23.7% of patients showed PR, SD, and PD respectively on PET/CT. The strength of agreement between PSA response and PET/CT response criteria was only fair (kappa 0.346). Median overall survival (OS) was 22.5 months (95% CI: 15.8–29.2). Median OS stratified to PSA/PET response was 25.6/25.6 months for PR, 21.7/30.6 months for SD and 19.4/13.1 months for PD (p = 0.496 for PSA and 0.013 for PET/CT response). Conclusions: Interim PSMA PET/CT based response evaluation at 8–10 weeks after the 2^nd cycle of RLT is predictive of overall survival and PD in patients treated with ¹⁷⁷Lu-PSMA. On the contrary, PSA appears to have only limited predictive value.