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

Kashyap, R; Buteau, JP; Bressel, M; Eifer, M; Bollampally, N; Jackson, P; McIntosh, L; Sandhu, S; Hofman, MS

Author(s): Kashyap, R; Buteau, JP; Bressel, M; Eifer, M; Bollampally, N; Jackson, P; McIntosh, L; Sandhu, S; Hofman, MS;
Details: Publication Year 2025-08-01,Volume 66,Issue #8,Page 1265-1270
Journal Title: Journal of Nuclear Medicine
Publication Type: Research article
Abstract: Data are emerging on the prognostic significance of quantitative changes on posttherapy SPECT/CT in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving [(177)Lu]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 [(177)Lu]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 [(177)Lu]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.
Publisher: Society of Nuclear Medicine and Molecular Imaging
Keywords: Humans; Male; *Dipeptides/therapeutic use; Aged; Prognosis; *Lutetium/therapeutic use; Middle Aged; *Single Photon Emission Computed Tomography Computed Tomography; *Radiopharmaceuticals/therapeutic use; *Prostatic Neoplasms, Castration-Resistant/diagnostic imaging/radiotherapy; *Heterocyclic Compounds, 1-Ring/therapeutic use; Treatment Outcome; Survival Analysis; Aged, 80 and over; Radioisotopes; Prostate-Specific Antigen; Lu-PSMA; imaging biomarker; mCRPC; posttherapy SPECT; prostate cancer; radionuclide therapy
Department(s): Cancer Imaging; Biostatistics and Clinical Trials; Medical Oncology
Publisher's Version: https://doi.org/10.2967/jnumed.125.269640
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-07-31 02:10:12

Last Modified: 2025-08-22 08:45:17