BACKGROUND & AIMS: This study investigated whether a circulating tumor DNA (ctDNA) assay using digital PCR (dPCR) could provide early relapse detection and disease-free corroboration at molecular level during postoperative surveillance of colorectal cancer (CRC). METHODS: The ctDNA dynamics of 52 patients with CRC measured by dPCR targeting 87 individual tumor-specific mutations (1-5 per patient) were compared with results for conventional surveillance using serum tumor markers and computed tomography scanning (CTS). The data were collected between March 2016 and June 2018. RESULTS: A total of 1,526 prospectively collected plasma samples from 867 timepoints were analyzed. The average number of ctDNA assays per patient was 16.4 and the median follow-up was 1,503 days (range 322-1,951 days). Among patients with Stage II or higher disease who underwent curative resection as their initial surgery (n=47), patients who were ctDNA-positive during the postoperative period (n= 9) showed a higher risk of relapse than those who had sustained ctDNA-negative results (n=38) (hazard ratio 56.3, 95%CI 7.8-407.0, P < 0.0001). Elevated ctDNA levels were observed in nine of 10 clinical-relapse patients (11 of 13 events) with an average lead time from a ctDNA-positive time-point to clinical relapse of 191.9 days (range 0-376 days). Given periodic CTS surveillance with ctDNA, 218 (57.1%) CTSs were presumed to be unnecessary for clinical relapse detection and a ctDNA assay would still provide a lead time of 307 days (range 45-582 days). CONCLUSION: Our findings suggest that the ctDNA assay can reduce the frequency of CTS for relapse diagnosis during postoperative surveillance of CRC.

The authors have declared no competing interest.

UMIN Clinical Trial Registry number, UMIN000045114

This work was supported by a Grant-in-Aid for Scientific Research KAKENHI [16K19951, 16K19952, 16H06279, 17K10605, 19K09224, 20K09064, 20K08966, and 21K07223], Keiryokai Collaborative Research Grant [#136 and #145], and Iwate Prefectural Research Grants [H30, R2, and R3]

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