Prognostic Value of Posttherapy SPECT/CT for Overall Survival in Patients Undergoing [177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy: Results from 3 Clinical Trials

Data are emerging on the prognostic significance of quantitative changes on posttherapy SPECT/CT in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving [¹⁷⁷Lu]Lu-PSMA-617. Our objective was to assess quantitative and visual changes on posttherapy SPECT/CT as prognostic biomarkers for overall survival (OS) among patients in 3 clinical trials: LuPSMA Phase 2 (ANZCTR12615000912583), LuPARP (NCT03874884), and PRINCE (NCT03658447)]. Methods: We segmented the total tumor burden on posttherapy [¹⁷⁷Lu]Lu-PSMA-617 SPECT/CT using an SUV threshold of 3 to measure SUV_max, SUV_mean, metabolic tumor volume (MTV), and total lesion activity (TLA). We assessed the prognostic value of changes in these quantitative parameters and new lesions identified visually on SPECT/CT after cycle 2 for OS using the Cox proportional hazards model, with age, Gleason score, and change in prostate-specific antigen (PSA) as covariates. Results: Eighty-five patients with mCRPC were analyzed (46 from LuPSMA Phase 2, 25 from PRINCE, and 14 from LuPARP). Patients eligible for inclusion had received at least 2 cycles of [¹⁷⁷Lu]Lu-PSMA-617 with a follow-up time of at least 12 mo. Among these patients, 18 (21.2%) had new metastases visible on cycle 2 SPECT/CT, and this was prognostic for OS in univariate (hazard ratio [HR], 2.38; 95% CI, 1.36-4.18; P = 0.002) and multivariate (HR, 2.85; 95% CI, 1.36-5.98; P = 0.01) analyses. Seven (8.2%) patients with PSA reductions had new lesions on posttherapy SPECT/CT. Reductions in TLA (HR, 0.98; 95% CI, 0.97-1.00; P = 0.016) and MTV (HR, 0.98; 95% CI, 0.96-1.00; P = 0.009) (per 10% increase for both) were associated with OS on univariate analysis but not on multivariate analysis. Changes in SUV_max and SUV_mean were not associated with OS. There was moderate correlation among changes in PSA from cycle 1 to cycle 2 and MTV (correlation coefficient = 0.55; 95% CI, 0.39-0.69; P < 0.001) and TLA (correlation coefficient = 0.56; 95% CI, 0.40-0.69; P < 0.001). Conclusion: The presence of new metastases on posttherapy SPECT/CT after cycle 2 is an independent prognostic biomarker for OS in patients with mCRPC and could guide future prospective research to improve treatment strategies for patients with poor prognoses.