Accepted for/Published in: JMIR Research Protocols
Date Submitted: Oct 29, 2025
Date Accepted: Feb 26, 2026
Liquid biopsy as a biomarker in patients with metastatic castration-resistant prostate cancer receiving PSMA radioligand therapy: Protocol for a prospective, longitudinal multicenter observational study (LOOPS Study)
ABSTRACT
Background:
Prostate 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 [177Lu]Lu-PSMA-617 demonstrating survival benefits in the VISION trial. However, clinical responses are heterogeneous, and resistance mechanisms remain poorly understood. Liquid biopsy (LBx), particularly circulating tumor DNA (ctDNA), may provide a minimally invasive approach to assess tumor heterogeneity, monitor response, and detect emerging resistance.
Objective:
The 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.
Methods:
LOOPS is a prospective, multicenter observational biomarker trial recruiting 100 mCRPC patients eligible for PSMA RLT across three Bavarian cancer research centers in Germany. Patients will undergo up to six cycles of [177Lu]Lu-PSMA-617. Blood samples for ctDNA analysis will be collected longitudinally (baseline, after cycles 1, 2, 4, and 6) and processed according to standardized protocols. Imaging with PSMA PET/CT and clinical/biochemical data will be systematically collected. Primary aims are to determine the prognostic value of baseline ctDNA and its predictive potential for treatment response. Secondary aims include correlation of ctDNA with clinical, biochemical, and imaging parameters. Exploratory analyses will investigate clonal evolution and resistance mechanisms.
Results:
The 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 for response monitoring and early identification of resistance.
Conclusions:
Results could pave the way toward personalized therapeutic strategies in mCRPC. Clinical Trial: ClinicalTrials.gov NCT07118436; Date of registration 11th August 2025
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