Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer.

Abstract (PubMed)

IMPORTANCE: Adjuvant chemotherapy in patients with stage III colon cancer prevents recurrence by eradicating minimal residual disease. OBJECTIVE: To determine whether serial postsurgical and postchemotherapy circulating tumor DNA (ctDNA) analysis could provide a real-time indication of adjuvant therapy efficacy. DESIGN: Multicenter, Australian, population-based cohort biomarker study (100 patients, November 2014-May 2017). Median follow-up 28.9 months. Physicians blinded to ctDNA. RESULTS: 96 eligible patients (median age 64). At least 1 somatic mutation identified in all 96 tumors. ctDNA detectable in 20/96 (21%) postsurgical samples (3-year RFI: 47% vs 76% undetectable; HR 3.8, 95% CI 2.4-21.0, P<0.001). ctDNA detectable in 15/88 (17%) postchemotherapy samples (3-year RFI: 30% vs 77%; HR 6.8). Multivariable: postsurgical ctDNA had strongest independent association with RFI (HR 7.5, 95% CI 3.5-16.1). CONCLUSIONS: ctDNA analysis after surgery is a promising prognostic marker in stage III colon cancer.