Evaluating response to radium-223 using ⁶⁸Ga-PSMA PET/CT imaging in patients with metastatic castration-resistant...

Conventional imaging techniques and prostate-specific antigen (PSA) values are not useful to follow-up patients during Radium-223 treatment. The study aimed to evaluate the predictive value of prostate-specific membrane antigen PSMA PET/CT-based response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Radium-223 dichloride treatment.

Patients treated with radium-223, having performed two ⁶⁸Ga-PSMA-11 PET/CT scans (baseline 1 month before treatment initiation and follow-up 2 weeks after the third cycle), were retrospectively evaluated. Visual and quantitative PET image analyses were performed, and patients were dichotomized into progressive (PD) and non-PD according to Response Evaluation Criteria in PSMA‑imaging (RECIP1.0) and PSMA-PET Progression criteria (PPP). The primary endpoint was overall survival (OS). Cohen's Kappa (κ) was used to test the agreement between the two criteria. The Cox regression hazard model and Kaplan-Meier method were used for survival analyses.

Twenty-eight mCRPC patients were evaluated. Sixteen (43%) and 18 (64%) patients had PD according to RECIP1.0 and PPP, respectively; κ = 0.85 (95% CI 0.65-1.00). After a median follow-up of 16 months (interquartile IQR 9-33), 20 (71%) patients died. Patients with PSMA PD showed a higher risk of death than non-PD according to RECIP1.0 (HR = 2.9; 95% CI 1.14-7.46; p = 0.029) and PPP (HR = 2.8; 95% CI 1.04-7.64; p = 0.042). For both criteria, the median OS was shorter for PD than non-PD (37 vs. 12 months, Log-rank; p < 0.05). The C-index for RECIP1.0 and PPP were almost equal (0.66 and 0.63; respectively).

This study demonstrated that PSMA-PET/CT imaging is valuable for monitoring radium-223 treatment. Both PSMA PET/CT response criteria (RECIP1.0 and PPP) perform similarly predicting OS at follow-up after three cycles of radium-223. These findings urge further validation in prospective trials.