cfDNA Fragmentation Patterns Correlates with Tumor Burden Measured via PSMA PET/CT Volumetric Parameters in Patients with Biochemical Recurrence of Prostate Cancer

Background Prostate cancer recurrence following primary treatment poses a significant clinical challenge, particularly when detected through biochemical recurrence at low PSA levels. Conventional imaging modalities often fail to localize the disease at this early stage. PSMA PET has demonstrated superior sensitivity in detecting recurrent lesions, even in patients with low PSA. Concurrently, liquid biopsy, through analysis of cell-free DNA (cfDNA), offers a minimally invasive approach for monitoring disease. There is scarce evidence about the association between liquid biopsy and PSMA PET/CT findings. This study aimed to assess the correlation between liquid biopsy and tumor burden assessed by PSMA PET/CT in early recurring prostate cancer patients. Results PSMA PET/CT and liquid biopsies of 32 patients in biochemical recurrence were analyzed. 12 patients (37.5%) had no PSMA PET-measurable disease. Four patients (12.5%) presented local recurrence, seven (21.9%) had recurrence in pelvic lymph nodes, one of whom also had local recurrence. Nine patients (28.1%) presented metastatic recurrence, with or without local or nodal recurrence. PSA levels correlated with molecular imaging data ( p  < 0.05), including wbPSMA-TV40, wbTL-PSMA40, wbSUVmean and wbSUVmax. The mean cfDNA fragment size fraction was inversely correlated with tumour burden measured with wbPSMA-TV, with a Spearman correlation coefficient of -0.451 and a p-value of 0.009. No correlation was found between cfDNA concentration and PET-PSMA data. Conclusion This prospective study demonstrated a statistically significant negative correlation between cfDNA fragmentation patterns and PSMA PET/CT volumetric parameters in localized prostate cancer patients with early biochemical recurrence. These findings underscore the potential of liquid biopsy as a biomarker and a complementary tool to PSMA PET/CT to assess disease progression during the follow-up of these patients.