Change in circulating tumor DNA after hepatic resection for metastatic colorectal cancer

Background: Hepatic resection can be curative in well-selected, metastatic colorectal cancer (mCRC) patients. Circulating tumor DNA (ctDNA) has shown promise in predicting response and early recurrence. This prospective study assessed the prognostic ability of ctDNA from blood drawn pre and post-resection. Methods: Between November 2014 and November 2015, patients with radiologically detected, biopsy-confirmed mCRC were enrolled. Blood was obtained intraoperatively from the hepatic vein (HV), portal vein (PV), and a peripheral vein pre-resection and postoperatively from a peripheral vein within 2–4 weeks. The presence of commonly mutated, targetable genes in ctDNA was analyzed and the agreement was assessed with Cohen’s kappa and percent agreement (PA). Disease-specific survival (DSS) in all patients and disease-free survival (DFS) after complete resection was assessed from surgery with Kaplan-Meier methods. Results: Fifty-nine patients were enrolled and 23 had their primary tumor removed at hepatic resection. Agreement was high between preoperative peripheral vein and HV and PV ctDNA containing mutated APC (n = 4, k = 0.78–0.88, PA = 95.9–98.0%) or TP53 (n = 7–8, k = 0.73–0.80, PA = 91.8–93.9%) pre-resection. No difference was seen between pre and postoperative mutated APC (P = 0.45), but postoperative mutated TP53 was significantly less common than before resection (P = 0.008), as was ctDNA overall (P = 0.002). DSS and DFS at 1 year were 97% (95% CI: 87–99%) and 53% (95% CI: 38–66%), respectively. In patients with ctDNA with an APC mutation, 1 year DFS was 80% (95% CI: 20–97%) compared to 50% (95% CI: 35–64%) in APC-absent patients (P = 0.06). Conclusion: ctDNA detected before and after hepatic resection varied significantly but was not prognostic of DFS or DSS. APC mutations in patients with mCRC showed a possible trend toward better DFS.