Surveillance of resected metastatic colorectal cancer utilizing circulating DNA.

Abstract

214 Background: There is limited data to guide surveillance in patients with metastatic colorectal cancer (CRC) who have had curative resection using circulating tumor DNA (ctDNA) in addition to labs and imaging studies. Minimal residual disease (MRD) assays utilize circulating tumor DNA (ctDNA) for the purposes of monitoring for early recurrence and predicting therapeutic response. In this study, we aim to investigate the utility of ctDNA monitoring in the setting of resected metastatic CRC. Methods: Patients were identified through retrospective search at a tertiary care and several satellite settings to identify patients with metastatic CRC who had undergone curative resection and later had ctDNA monitoring (using Signatera assay). IRB approval was obtained for the study. We recorded demographic information (sex, race, age at diagnosis), disease characteristics (stage at diagnosis, site of primary cancer, site of metastasis), treatment regimens, clinical outcomes (recurrence, survival) and follow-up data. Our primary outcome was to evaluate the rate of recurrence in patients with metastatic CRC who had curative resection in two different population, ctDNA positive or ctDNA negative, post-surgery. Results: We identified 35 patients with a median age of 55 years (range 31 – 82) at the time of metastatic diagnosis. In this study cohort, 20 (57%) were female; 23 (66%) were white, and 10 (29%) were African American. 22 (63%) patients had left-sided primary tumors and the remaining (47%) had right-sided primary tumors. At the time of presentation, 23 (66%) patients had synchronous metastases and 12 (34%) developed metachronous metastases. ctDNA positivity was reported in 21 (60%) pts post-curative therapy. Median time from curative therapy to ctDNA positivity was 62 days. 22 (63%) pts experienced recurrence of disease post-curative resection. Median time to recurrence after ctDNA test was first positive was 6.6 months. Among 21 patients in ctDNA positive group, 19 (86%) developed recurrences and among 14 ctDNA negative patients, only 3 (21%) developed recurrences (p-value <0.01). Recurrence free survival was significantly shorter in patients who were ctDNA positive post surgery (Median RFS: 7.17 months, 95% CI: 4.4-18.0 months) compared to those who were ctDNA negative (Median RFS: 30.8 months; 95% CI: 12.6-NR) (p-value=0.005). Conclusions: In patients with metastatic CRC who underwent curative resection ctDNA may have utility in predicting disease recurrence at both academic and community sites. Larger studies are needed for validation of ctDNA as an adjunct test for surveillance in broader population.