Synergizing Liquid Biopsy and Hybrid PET Imaging for Prognostic Assessment in Prostate Cancer: A Focus Review

Abstract

Positron emission tomography (PET) and liquid biopsy have independently transformed prostate cancer management. This review explores the complementary roles of PET imaging and liquid biopsy in prostate cancer, focusing on their combined diagnostic, monitoring, and prognostic potential. A systematic search of PubMed, Scopus, and Cochrane Library databases was conducted to identify human studies published in English up to January 2025. Seventeen studies met the inclusion criteria and were analyzed according to PRISMA guidelines. Across the included studies, PET-derived imaging metrics, such as metabolic activity and radiotracer uptake, correlated consistently with liquid biopsy biomarkers, including circulating tumor cells and cell-free DNA. Their joint application demonstrated added value in early detection, treatment monitoring, and outcome prediction, particularly in castration-resistant prostate cancer. Independent and synergistic prognostic value was noted for both modalities, including survival outcomes such as overall survival and progression-free survival. Combining PET imaging and liquid biopsy emerges as a promising, non-invasive strategy for improving prostate cancer diagnosis, monitoring, and therapeutic stratification. While preliminary findings are encouraging, large-scale prospective studies are essential to validate their integrated clinical utility.

Keywords: PET/CT; PET/MR; cancer biomarkers; cell free DNA; circulating tumor cells; imaging biomarkers; liquid biopsy; precision medicine; prostate cancer; translational oncology.

Figure 1

PRISMA flow diagram of study selection. The flowchart illustrates the process of study identification, screening, eligibility assessment, and inclusion according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 121 records were retrieved through database searches. After removing duplicates and applying inclusion/exclusion criteria, 17 studies were included in the final qualitative synthesis.

Figure 2

Timeline of publications and radiotracers used. Included studies are plotted by year of publication along the vertical axis. The color-coded dots indicate the primary PET radiotracer employed in each study: PSMA-based (red), FDG (olive), FCH (green), NaF (blue), and other tracers (magenta). This timeline highlights the recent predominance of PSMA-targeted PET imaging in PCa research and its integration with liquid biopsy methodologies.