Colon to Rectum
N Engl J Med. 2022;386(24):2261–72
Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer
Background: The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival (RFS), whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood.
Methods: The authors conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was RFS at 2 years. A key secondary end point was adjuvant chemotherapy use.
Results: Of the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk = 1.82; 95% confidence interval [CI]: 1.25–2.65). In the evaluation of 2-year RFS, ctDNA-guided management was non-inferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI: -4.1–6.2 [non-inferiority margin, -8.5 percentage points]). Three-year RFS was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not.
Conclusions: A circulating tumor DNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival.