PSMA PET/CT for Response Assessment and Overall Survival Prediction in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Androgen Receptor Pathway Inhibitors
Qaid Ahmed Shagera, Ioannis Karfis, Paulus Kristanto, Spyridon Sideris, Romain Diamand, A. Santapau, Alexandre Peltier, Thierry Roumeguère, Patrick Flamen, Carlos Artigas
Abstract
We aimed to evaluate the role of prostate-specific membrane antigen (PSMA) PET/CT for response assessment and outcome prediction in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor pathway inhibitors (ARPIs), including abiraterone acetate or enzalutamide. <b>Methods:</b> We retrospectively analyzed 30 ARPI-treated mCRPC patients who underwent <sup>68</sup>Ga-PSMA-11 PET/CT within 8 wk before (baseline) and 12 ± 4 wk after treatment initiation. Total PSMA tumor volume was calculated using the fixed threshold method (SUV ≥ 3). Patients were categorized as PSMA responders (PSMA-Rs) or PSMA nonresponders (PSMA-NRs) on the basis of both European Association of Urology/European Association of Nuclear Medicine (EAU/EANM) criteria and Response Evaluation Criteria in PSMA PET/CT (RECIP) 1.0. PSMA-R included patients with a complete response, a partial response, or stable disease, and PSMA-NR included those with progressive disease. On the basis of prostate-specific antigen (PSA), patients were classified as biochemical responders if PSA decreased by at least 50% and as nonresponders if it did not. The Φ-coefficient was used to evaluate the correlation of PSMA- and PSA-based responses. Survival analysis was performed using the Cox regression hazard model and the Kaplan–Meier method. Predictive accuracy was tested for both response criteria. <b>Results:</b> On the basis of PSMA PET/CT, 13 (43%) patients were PSMA-NR according to the EAU/EANM criteria and 11 (37%) patients were PSMA-NR according to RECIP 1.0. Significant correlations were observed between PSMA- and PSA-based responses for both criteria (Φ = 0.79 and 0.66, respectively). After a median follow-up of 25 mo (interquartile range, 21–43 mo), the median overall survival was significantly longer for PSMA-R than PSMA-NR (54 vs. 22 mo) for both the EAU/EANM criteria and RECIP 1.0, with hazard ratios of 6.9 (95% CI, 1.9–26; <i>P</i> = 0.004) and 5.6 (95% CI, 1.69–18.26, <i>P</i> = 0.005), respectively. No significant difference in predictive accuracy was found between the 2 criteria (C-index, 0.79 vs. 0.76, respectively, <i>P</i> = 0.54). Flare phenomena at the second PSMA PET study were not observed in our cohort. <b>Conclusion:</b> Our results demonstrate that PSMA PET/CT is a valuable imaging biomarker for response assessment and overall survival prediction when performed at 3 mo after ARPI treatment initiation in mCRPC patients. Both proposed PSMA response criteria (EAU/EANM and RECIP 1.0) seem to perform equally well. No PSMA flare was observed. Prospective validation of these findings is strongly needed.