Clinical protocols to monitor efficacy of [ ¹⁷⁷ Lu]Lu-PSMA radiopharmaceutical therapy in metastatic castration-resistant prostate cancer.

Abstract

39 Background: To assess the prognostic value of post-therapy [ 177 Lu]Lu-PSMA (LuPSMA)-SPECT/CT by visual RECIP 1.0 during LuPSMA radioligand therapy and to develop an evidence-based clinical protocol to monitor efficacy to LuPSMA. Methods: Patients who received LuPSMA between April 2019 and November 2023 and who underwent at least two LuPSMA-SPECT/CT (SPECT) were included. Three independent readers interpreted pairs of baseline and interim LuPSMA-SPECT/CT after 2 cycles of therapy for visual Response Evaluation Criteria In PSMA-imaging (RECIP) 1.0. The primary outcome was the prognostic value of post-therapeutic SPECT by RECIP 1.0 for overall survival after LuPSMA. The secondary outcome was the agreement between SPECT and PSMA-PET/CT (PET) performed after 2 cycles of LuPSMA. Results: 105 patients were included. In SPECT PD was associated with shorter OS compared to SD (HR=2.51;95%;CI:1.19-5.28;p=0.015) and to PR (HR=6.48;95%;CI:2.67-15.70;p<0.001). 73/105 (69.5%) had a PET after 2 cycles. 7/73 (10%), 30/73 41%), 22/73 (30%), and 30/73 (41%) patients had a tumor progression by SPECT, PET, SPECT+PSA, and PET+PSA, respectively. All 7/73 (10%) patients with PD by SPECT had PD by PET. The C-index for SPECT was inferior to the one of SPECT+PSA (0.54 vs 0.62; p=0.03) and PET (0.54 vs 0.66; p<0.001) while SPECT+PSA did not differ significantly from PET (0.62 vs 0.66; p=0.07). Conclusions: Post-therapeutic SPECT/CT by RECIP 1.0 after 2 cycles of LuPSMA therapy is prognostic for overall survival and can be used for treatment response evaluation purposes. PSMA-PET/CT identified significantly higher number of patients with progressive disease compared to LuPSMA-SPECT/CT. A composite classification system of LuPSMA-SPECT/CT+PSA was not significantly different from interim PSMA-PET/CT for response evaluation to LuPSMA.