Subtypes of minimal residual disease and outcome for stage II colon cancer treated by surgery alone

Introduction: Twenty-five percent of stage II colon cancer (CC) patients relapse within 5 years due to minimal residual disease (MRD) not eliminated by surgery. We hypothesise that subtypes of MRD, defined by circulating tumour cells (CTCs) and bone marrow micrometastasis (mM), have different types and kinetics of relapse. Methods and patients: One month after surgery, blood and bone marrow samples were taken to detect CTCs and mM using immunocytochemistry with anti-carcinoembryonic antigen (CEA). Follow-up was for up to 5 years or relapse. Disease-free survival curves using Kaplan-Meier (DFS) and restricted mean disease-free survival times (RMST) were calculated for three prognostic groups: A: MRD (-), B: mM (+) CTC (-) MRD and C: CTC (+) MRD. Results: One hundred and eighty-one patients (82 men) have participated, mean age was 68 years and median follow-up was 4.04 years (A (N = 105), B (N = 36) and C (N = 40)). For the whole cohort of 5 years, DFS was 70%, median DFS has not reached (Groups A: 98%, B: 63% and C: 7%) and median DFS for Groups A and B have not reached. RMST for the whole cohort of 4.1 years, Group A was 4.9 years, B was 4.1 years and C was 1.7 years. Serum CEA was significantly higher in Group C. No significant differences for sex, age or high-risk adverse prognostic factors between groups were detected. Conclusions: MRD subtypes define relapse patterns and may be useful to define the risk of relapse in stage II CC patients, in which patients may benefit or not from additional therapy and warrants further studies with a larger number of patients.