Assessing Response to ¹⁷⁷Lu-PSMA Radioligand Therapy Using Modified PSMA PET Progression Criteria

PET/CT targeting the prostate-specific membrane antigen (PSMA) plays a key role in staging of patients with prostate cancer. Moreover, it is used not only for the assessment of adequate PSMA expression of prostate cancer cells before PSMA-targeting radioligand therapy (RLT) but also for restaging during the course of therapy to evaluate response to treatment. Whereas no established criteria exist for systematic response evaluation so far, recently proposed PSMA PET Progression (PPP) criteria might fill this gap. The aim of this study was to assess the feasibility of PPP criteria in patients undergoing PSMA RLT and their prognostic implications. Methods: In this retrospective analysis, PSMA PET/CT scans of 46 patients before and after completion of PSMA RLT were analyzed separately by 2 readers using modified PPP criteria. After interobserver agreement assessment, consensus results (progressive vs. nonprogressive disease) were compared in a multivariate Cox regression model (endpoint, overall survival [OS]). Results: Interobserver agreement using the modified PPP criteria was substantial (Cohen κ = 0.73), with a concordance in 87% of patients. The median OS of all patients after PSMA RLT (n = 46) was 9.0 mo (95% CI, 7.8-10.2 mo). Progression according to the modified PPP criteria was found in 32 patients and was a significant (P ≤ 0.001) prognostic marker for OS, with a hazard ratio of 15.5 (95% CI, 3.4-70.2). Conclusion: Response assessment in patients undergoing PSMA RLT using modified PPP criteria are reproducible and highly prognostic for OS. The modified PPP criteria should be validated in future prospective trials.