Clinical Development of PSMA-Targeted Imaging and Radioligand Therapies in Cancer: A ClinicalTrials.gov-Based Analysis of Completed Studies

Abstract

Background: Prostate-specific membrane antigen (PSMA) has emerged as one of the most important molecular targets in oncology, enabling both highly sensitive diagnostic imaging and targeted radioligand therapy. Over the past decade, PSMA-directed agents have transformed the management of prostate cancer and are increasingly being explored in other malignancies.
Objective: To characterize completed clinical trials investigating PSMA-targeted imaging and therapeutic interventions registered on ClinicalTrials.gov, with emphasis on study design, clinical phases, enrolment characteristics, disease indications, and therapeutic strategies.
Methods: A registry-based cross-sectional analysis was conducted using ClinicalTrials.gov. The search term “PSMA” was applied with the filter “Completed Studies.” Data were retrieved on study title, condition, intervention, phase, enrolment, study design, study type, and primary outcomes. Descriptive analyses were performed to summarize the characteristics and trends of completed PSMA-related clinical trials.
Results: A total of 175 completed studies were identified. Interventional studies accounted for 147 trials (84.0%), while 28 (16.0%) were observational. The cumulative enrolment across all studies was 15,625 participants. Phase II studies represented the largest proportion of trials (n=40), followed by Phase I studies (n=36), Early Phase I studies (n=17), and Phase III studies (n=10). Prostate cancer was the predominant disease indication, appearing in 88 studies. Diagnostic imaging using 68Ga-PSMA PET/CT and 18F-PSMA PET/CT constituted a major area of investigation, whereas therapeutic studies increasingly evaluated radioligand therapies including 177Lu-PSMA. Most studies focused on diagnostic accuracy, lesion detection, staging, treatment response assessment, and safety evaluation. Despite substantial growth in PSMA-directed research, relatively few completed studies reported posted results on the registry.
Conclusion: Completed PSMA-related clinical trials demonstrate rapid expansion of both diagnostic and therapeutic applications of PSMA-targeted technologies. The field remains heavily focused on prostate cancer, although emerging investigations in other solid tumours are increasing. Continued development of radioligand therapies and theranostic approaches is expected to further advance precision oncology.