Perioperative cell-free DNA trends predict recurrence of non-metastatic colorectal cancer significantly earlier than CEA trends over the first 2 years post-operatively in stage II and stage III colon cancer

Purpose: We aimed to compare the diagnostic accuracy of perioperative ΔcfDNA to ΔCEA (over the first 2 years post-operatively) for identifying disease recurrence in colon cancer. Methods: Patients presenting for elective resection for colon cancer with curative intent were screened for inclusion. Perioperative cfDNA levels were measured at seven different times points(pre-operative and post-operative at 3 h, 6 h, 24 h, 48 h, POD3 and POD5). CEA levels were measured on the same patients up to 2 years post-operatively. Change in trend (Δ) was defined as the β coefficient using a logistic regression model. Statistical analysis was performed using SPSS, version 23. Results: Longitudinal data on twenty-two patients were analysed (n = 16 male, n = 6 female) for a median of 29 months (IQR 23 months) during which time three patients developed (distant) recurrence. Perioperative ΔcfDNA at 48Hrs, POD3 and POD5 were significantly associated with early recurrence. ΔCEA was significantly associated with early recurrence at 6 months, 1 year and 2 years post-operatively, only when disease recurrence was macroscopically established. ΔcfDNA was associated with an area under the curve (AUC) of 0.947 (95% CI 0.88–1.0, p < 0.001) and ΔCEA was associated with an AUC of 0.9382 (95%CI 0.88–0.99, p < 0.0001). This translated into a specificity of 97% (95%CI 86.51–99.87%) for ΔcfDNA and 77.5% sensitivity (95%CI 62.5–87.7%) in the immediate perioperative period and an 88.9% specificity (95%CI 56.5–99.4%) and 76.5% sensitivity (95%CI 63.24–86%) for ΔCEA over the first 2 years post-operatively. Conclusions: In this pilot study, following curative resection for colon cancer changing trends in perioperative cfDNA (ΔcfDNA) identify those at risk of recurrent disease before recurrence develops which is at least 6 months earlier than CEA changes (ΔCEA) which are only observed when recurrence is established.