The Impact of PSMA PET–Based Eligibility Criteria Used in the Prospective Phase II TheraP Trial in Metastatic Castration-Resistant Prostate Cancer Patients Undergoing Prostate-Specific Membrane Antigen–Targeted Radioligand Therapy

Prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) has shown encouraging results for treatment of metastatic castration-resistant prostate cancer (mCRPC) in the prospective, multicenter, randomized phase II TheraP study. The inclusion criteria for that study comprised a pretherapeutic ⁶⁸Ga-PSMA-11 PET scan showing sufficient tumor uptake using a predefined threshold and the absence of ¹⁸F-FDG–positive, PSMA ligand–negative tumor lesions. However, the prognostic value of these PET-based inclusion criteria remains unclear. Therefore, we evaluated the outcome of mCRPC patients treated with PSMA RLT using TheraP as well as other TheraP-based PET inclusion criteria. Methods: First, patients were dichotomized into 2 groups whose PSMA PET scans did (TheraP contrast-enhanced PSMA [cePSMA] PET–positive) or did not (TheraP cePSMA PET–negative) fulfill the inclusion criteria of TheraP. Notably, unlike in TheraP, ¹⁸F-FDG PET was not performed on our patients. Prostate-specific antigen (PSA) response (PSA decline ≥ 50% from baseline), PSA progression-free survival, and overall survival (OS) were compared. Additionally, patients were further dichotomized according to predefined SUV_max thresholds different from those used in TheraP to analyze their potential impact on outcome as well. Results: In total, 107 mCRPC patients were included in this analysis (TheraP cePSMA PET–positive, n = 77; TheraP cePSMA PET–negative, n = 30). PSA response rates were higher in TheraP cePSMA PET–positive patients than in TheraP cePSMA PET–negative patients (54.5% vs. 20%, respectively; P = 0.0012). The median PSA progression-free survival (P = 0.007) and OS (P = 0.0007) of patients were significantly longer in the TheraP cePSMA PET–positive group than in the TheraP cePSMA PET–negative group. Moreover, being in the TheraP cePSMA PET–positive group was identified as a significant prognosticator of longer OS (P = 0.003). The application of different SUV_max thresholds for a single hottest lesion demonstrated no influence on outcome in patients eligible for PSMA RLT. Conclusion: Patient selection for PSMA RLT according to the inclusion criteria of TheraP led to a better treatment response and outcome in our preselected patient cohort. However, a relevant number of patients not fulfilling these criteria also showed substantial rates of response.