Impact of sensitive circulating tumor DNA monitoring on CT scan intervals during postoperative colorectal cancer surveillance

Abstract

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.