Liquid biopsy for promoter methylation in prostate cancer: a promising non-invasive diagnostic weapon

Prostate-specific antigen (PSA) has served as a screening tool for prostate cancer (PCa) for over 30 years, but its low specificity remains a significant limitation. Liquid biopsy based on promoter methylation, an epigenetic modification, holds significant potential to complement PSA testing and enhance the diagnostic accuracy of PCa. Our objective was to assess the diagnostic accuracy of liquid biopsy for promoter methylation in PCa.

We conducted a comprehensive search to screen clinical studies on the application of liquid biopsy for promoter methylation in PCa diagnosis. Subgroup analyses were performed based on sample type, area, control type, method, timing of prostatectomy or prostate massage, and promoter type. The quality of the included articles was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool.

We included 31 studies with a total of 3,880 participants. The results indicated that the sensitivity of promoter methylation detected via liquid biopsy for PCa was 0.55 (95% confidence interval [CI], 0.42-0.67) and the specificity was 0.87 (95% CI, 0.83-0.89), with an area under the curve (AUC) of 0.87 (95% CI, 0.83-0.89). In the serum sample group, specificity reached 0.97 (95% CI, 0.92-0.98), and both the positive likelihood ratio and AUC demonstrated excellent diagnostic performance.

Liquid biopsy for promoter methylation shows excellent specificity for PCa diagnosis, particularly in serum samples. However, further large-scale studies are required before its superiority over PSA testing can be fully established.