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

Abstract

Introduction

To assess the prognostic value of post-therapy [177Lu]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

In total, 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).

Conclusion

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.