Purpose: Circulating tumor DNA (ctDNA) has been suggested as a major prognostic factor in resected stage III colon cancer. We analyzed ctDNA of patients randomized in the phase III IDEA-France trial.
Experimental design: ctDNA was tested for WIF1 and NPY by droplet digital PCR with method developed and validated for colorectal cancer. Disease-free survival (DFS) and overall survival (OS) were analyzed via multivariable analysis in patients with ctDNA samples and in sub-groups according to treatment duration (3/6 months) and disease stage (high/low-risk stage III).
Results: Of 2010 randomized patients, 1345 had available ctDNA samples (1017 collected both post-surgery and pre-chemotherapy). More ECOG PS of 0 (78% versus 69%) and T4 and/or N2 (40% versus 36%) were observed in patients studied (n=1017) versus not analyzed (n=993). There were 877 ctDNA-negative (86.2%) and 140 ctDNA-positive (13.8%) patients; their baseline characteristics were similar. With a median follow-up of 6.6 years, the 3-year DFS rate was 66.39% for ctDNA-positive patients and 76.71% for ctDNA-negative patients (P=0.015). ctDNA was confirmed as an independent prognostic marker for DFS (adjusted HR=1.55, 95% CI 1.13-2.12, P=0.006) and OS (HR=1.65, 95% CI 1.12-2.43, P=0.011). ctDNA was prognostic in patients treated for 3 months and with T4 and/or N2 tumors, but not in those treated for 6 months and with T1-3/N1 tumors.
Conclusions: In this first ctDNA assessment of a large series of stage III colon cancer patients enrolled in phase III trial, post-surgery ctDNA was found in 13.8% of them and was confirmed as an independent prognostic marker.