Prognostic Value of Comprehensive Analysis of Metastatic Prostate Tumor Changes from First to Last [ 177 Lu]Lu-PSMA Therapy Injections Through Serial High-Speed Whole-Body 360° Cadmium–Zinc–Telluride SPECT

Anger SPECT monitoring of [¹⁷⁷Lu]Lu-prostate-specific membrane antigen (PSMA) therapy provides significant prognostic information about patients with metastatic castration-resistant prostate cancer (mCRPC) but with 36- to 90-min recording times and partial body coverage. This study assesses the prognostic information from a comprehensive analysis of tumor changes from the first to the last [¹⁷⁷Lu]Lu-PSMA therapy injections, as provided by whole-body [¹⁷⁷Lu]Lu SPECT recordings from a high-speed 360° cadmium-zinc-telluride (CZT) camera of mCRPC patients. Methods: We included mCRPC patients treated by [¹⁷⁷Lu]Lu-PSMA-617 injections who underwent [⁶⁸Ga]Ga-PSMA-11 PET before treatment, whole-body 360° [¹⁷⁷Lu]Lu CZT SPECT recordings of only 18 min obtained 24 h after each [¹⁷⁷Lu]Lu-PSMA therapy injection, and plasma prostate-specific antigen (PSA) measurements before each injection. We used Cox proportional hazards models to predict overall survival (OS) according to PSA evolution during treatment, as well as tumor SUV_max, SUV_mean, total uptake volume, and total lesion activity (TLA; total uptake volume × SUV_mean) extracted from [⁶⁸Ga]Ga-PSMA-11 PET and the first and last [¹⁷⁷Lu]Lu SPECT scans. Results: We included 72 patients with a median age of 71 y (interquartile range, 64-77 y), treated with up to 6 [¹⁷⁷Lu]Lu-PSMA injections. Among 57 patients with at least 2 [¹⁷⁷Lu]Lu-PSMA treatment cycles, 35 (61%) died during a follow-up of 12.0 mo (range, 4.9-17.5 mo) from the last [¹⁷⁷Lu]Lu-PSMA injection. Most PSA, PET, and SPECT variables were significant univariate predictors of OS. However, only 2 [¹⁷⁷Lu]Lu SPECT variables were selected as multivariate predictors: SPECT detection of new bone lesions during treatment (P < 0.0001) and final SPECT TLA (P = 0.0007). Means of survival times were 19.7 mo (95% CI, 16.6-22.8 mo) in the 19 patients who showed no new bone lesions and final TLA lower than the median of 750 mL·SUV, 14.4 mo (95% CI, 10.9-18.0 mo) in the 19 patients with only 1 of these 2 criteria, and 6.9 mo (95% CI, 4.5-9.6 mo) in the 19 patients with neither criterion. Conclusion: A comprehensive analysis of tumor changes from the first to the last [¹⁷⁷Lu]Lu-PSMA injections, obtained with fast whole-body 360° [¹⁷⁷Lu]Lu CZT SPECT recordings, provides strong prognostic information about mCRPC patients, outperforming conventional OS predictors such as PSA evolution and [⁶⁸Ga]Ga-PSMA-11 PET variables before treatment.