Early detection of prostate carcinoma using trajectories of circulating epithelial tumor cell (CETCs/CTCs) numbers

Background: Prostate cancer is a leading cause of mortality in elderly men, underscoring the need for early and effective detection strategies. PSA-based screening remains controversial due to uncertain benefits in reducing mortality and associated risks, such as invasiveness, comorbidities, and overdiagnosis. Overdiagnosis can lead to unnecessary treatments and complications for indolent disease. In clinical practice, patients often retain limited information after consultations, and inconsistent risk communication by physicians can hinder informed shared decision-making. Therefore, a minimally invasive screening approach using serial circulating epithelial tumor cells (CETCs/CTCs) in patients at increased risk of prostate cancer may enhance informed decision-making. Methods: CETCs/CTCs were quantified in peripheral blood from men aged 50-85 years in a screening cohort (n=35) and in patients undergoing PSMA-PET for suspected prostate cancer (n=49). PSA levels were measured at the time of PSMA-PET, and serial CETC/CTC counts were correlated with PSMA-PET findings. Results: Serum PSA levels did not differ significantly between patients with positive (n=27) and negative (n=24) PSMA-PET scans (p=0.94). However, CETC/CTC counts were significantly higher in PSMA-PET-positive patients compared to those in the screening cohort (p<0.001). ROC analysis identified an optimal threshold of 450 CETCs/CTCs per mL blood, with a specificity of 0.7 and a sensitivity of 0.6. Serial monitoring revealed distinct trajectories: increasing CETC/CTC counts were observed in 11 of 13 (90%) patients who later developed PSMA-PET-positive findings, while only 2 of 21 (8%) patients with decreasing CETC/CTC counts were PSMA-PET positive. Kaplan-Meier analysis demonstrated a highly significant difference in PSMA-PET-free survival between the two groups (p<0.001; hazard ratio 9.48). Conclusions: Serial monitoring of CETCs/CTCs provides dynamic, non-invasive insights into prostate cancer activity. Rising CETC/CTC counts were strongly associated with PSMA-PET positivity, suggesting their potential as early biomarkers for prostate cancer progression and treatment monitoring.