Liquid Biopsy Biomarkers in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Prostate-Specific Membrane Antigen Radioligand Therapy: Protocol for a Prospective, Longitudinal Multicenter Observational Study

Abstract BackgroundProstate cancer is the second leading cause of cancer-related mortality in men worldwide. Prostate-specific membrane antigen (PSMA)–targeted radioligand therapy (RLT) has emerged as a theranostic strategy for metastatic castration-resistant prostate cancer (mCRPC), with [177 ObjectiveThe LOOPS (Liquid Biopsy as a Biomarker in Patients Treated with PSMA Radioligand Therapy) study aims to prospectively investigate the prognostic and predictive value of ctDNA in patients undergoing PSMA RLT. MethodsLOOPS is a prospective, multicenter observational biomarker trial recruiting 100 patients with mCRPC eligible for PSMA RLT across 3 Bavarian cancer research centers in Germany. Patients will undergo up to 6 cycles of [177 ResultsThe study has been funded by the German Research Foundation (Deutsche Forschungsgemeinschaft) since July 2025. Patient recruitment has already commenced, and in January 2026, a total of 63 patients have been enrolled. Analysis of LBx samples was initiated in January 2026, while recruitment and data collection are ongoing. ConclusionsThe LOOPS study will provide the first prospective, systematic evaluation of ctDNA as a biomarker in PSMA RLT. By integrating molecular, imaging, and clinical data, it aims to clarify the role of LBx in response monitoring and the early identification of resistance. The results could pave the way toward personalized therapeutic strategies in mCRPC.