Evidence-Based Clinical Protocols to Monitor Efficacy of [177Lu]Lu-PSMA Radiopharmaceutical Therapy in Metastatic Castration-Resistant Prostate Cancer Using Real-World Data.

Our objectives were to assess the prognostic value of posttherapy [177Lu]Lu-PSMA (LuPSMA) SPECT/CT by visual evaluation using RECIP 1.0 during LuPSMA therapy and develop an evidence-based clinical protocol to monitor the efficacy of LuPSMA. Methods: Patients with metastatic castration-resistant prostate cancer who received at least 2 LuPSMA cycles between April 2019 and November 2023 were retrospectively included in this study. Pairs of baseline and interim LuPSMA SPECT/CT (SPECT) and PSMA PET/CT (PET) images after 2 therapy cycles were analyzed per visual RECIP 1.0. Changes in prostate-specific antigen (PSA) levels at 12 wk were categorized by Prostate Cancer Working Group Criteria 3 guidelines and combined with RECIP 1.0 reads to determine disease progression using a composite classification method (PSA + RECIP). The primary outcome was the prognostic value of posttherapeutic SPECT by RECIP 1.0 for overall survival (OS). The clinical protocol was developed on the basis of the prognostic accuracy (Harrell concordance index, or C-index) of SPECT versus PET and the combination of SPECT plus PSA (SPECT + PSA) versus the combination of PET plus PSA (PET + PSA). Results: Data from 105 patients were evaluated. Progressive disease determined by SPECT was associated with shorter OS compared with stable disease (hazard ratio, 2.5; 95% CI, 1.2-5.3; P = 0.015) and with partial response (hazard ratio, 6.5; 95% CI, 2.7-15.7; P < 0.001). Of the 73 patients who underwent PET after 2 cycles, 7 (10%), 30 (41%), 22 (30%), and 30 (41%) had tumor progression shown by SPECT, PET, SPECT + PSA, and PET + PSA, respectively. The C-index for SPECT was inferior compared with that for PET (0.54 vs. 0.66; P < 0.001), whereas the C-indices for SPECT + PSA and PET + PSA did not differ significantly (0.62 vs. 0.66, respectively; P = 0.07). Conclusion: Posttherapeutic LuPSMA SPECT/CT per RECIP 1.0 after 2 therapy cycles was prognostic for OS. LuPSMA SPECT/CT identified significantly fewer patients with RECIP-classified progressive disease; however, SPECT + PSA achieved similar prognostic accuracy to PET + PSA for LuPSMA response evaluation.