Evaluation of Circulating Tumor DNA for Methylated BCAT1 and IKZF to Detect Recurrence of Stage II/Stage III Colorectal Cancer (CRC)

Benjamin L. Musher, Joshua E. Melson, Gianni Amato, David Chan, Marisa Hill, Iftekhar Khan, Samith T. Kochuparambil, Susan E. Lyons, James Orsini, Susanne K. Pedersen, Bruce Robb, Joel Saltzman, Jennifer Silinsky, Snigdha Gaur, Melissa K. Tuck, Lawrence C. LaPointe, Graeme P. Young

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background: Most recurrences of early-stage colorectal cancer detected with current surveillance measures are widespread and incurable. Circulating tumor DNA (ctDNA) may facilitate earlier diagnosis of recurrent colorectal cancer and improve cancer-related outcomes.Methods: Plasma from patients undergoing standard surveillance after definitive treatment for stage II/III colorectal cancer was assayed with COLVERA and carcinoembryonic antigen (CEA) at a single time point. Results were correlated with radiographic imaging. Assay performance, including sensitivity and specificity for recurrence, were compared. Impact of potentially confounding variables was also explored.Results: 322 patients were included in the final analysis, and 27 recurrences were documented over a median follow-up period of 15 months. Sensitivity for recurrence was 63% [confidence interval (CI), 42.4–80.6] and 48% (CI, 28.7–68.1) for COLVERA and CEA (≥5 ng/mL), respectively (P = 0.046), while specificity was 91.5% (CI, 87.7–94.4) and 96.3% (CI, 93.4–98.1), respectively (P = 0.016). Smoking and age were independent predictors of CEA but not COLVERA positivity.Conclusions: COLVERA was more sensitive but less specific than CEA in detecting recurrent colorectal cancer. Short median follow-up may have been responsible for apparent false positives in COLVERA. Studies with serial sampling and longer follow-up are needed to assess whether earlier detection of colorectal cancer recurrence translates into clinical benefit.Impact: This prospective study showed that COLVERA (a two-gene ctDNA assay) was more sensitive for detection of recurrence in a cohort of patients undergoing surveillance after definitive therapy for stages II and III colorectal cancer.
Original languageEnglish
Pages (from-to)2702-2709
Number of pages8
JournalCancer Epidemiol Biomarkers Prev
Volume29
Issue number12
DOIs
Publication statusPublished - Dec 2020

Keywords

  • circulating tumor DNA (ctDNA)
  • Methylated BCAT1
  • Methylated IKZF1
  • CRC colorectal cancer
  • CEA
  • COLVERA
  • carcinoembryonic antigen

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