Subtypes of Minimal Residual Disease and Outcome for Stage II Colon Cancer Treated by Surgery Alone

Abstract

Introduction: 25% of stage II colon cancer (CC) patients relapse within 5 years due to minimal residual disease (MRD) not eliminated by surgery. We hypothesize that subtypes of MRD, defined by circulating tumor cells (CTCs) and bone marrow micro-metastasis (mM) have different types and kinetics of relapse. Methods and Patients: One month after curative surgery for stage II CC, blood and bone marrow samples were taken to detect CTCs and mM using immunocytochemistry with anti-CEA. Follow-up was for up to 5 years or relapse, defined as new images detected on CT scan. Survival curves using Kaplan-Meier (KM) and restricted mean survival times (RMST) were calculated for 3 prognostic groups; A: MRD (-); B: mM (+) CTC (-) MRD and C: CTC (+) MRD. Results: 181 patients (82 men) participated, mean age 68 years, median follow up 4.04 years; A: N=105, B: N= 36, C: N=40. For the whole cohort 5yr KM was 70%, median survival not reached, Group A: 98%, B 63%, C 7%, median survivals for Group A and B were not reached. RMST for the whole cohort 4.1 years, Group A 4.9 years, B 4.1 years, C 1.7 years. Serum CEA was significantly higher in Group C. No significant differences for sex or age between groups were detected. Conclusions: MRD subtypes define relapse patterns, Group A MRD (-) had an excellent prognosis, 98% disease free survival at 5 years, Group B had a similar outcome for up to 2 years post-surgery, then increasing relapse occurred (late failure), while Group C had a high risk of early failure. MRD sub-classification may be useful to define risk of relapse in stage II CC patients, which patients may benefit or not from additional therapy and warrants further studies with a larger number of patients. Funding Statement: The study was funded by a Western Metropolitan Health Authority Research Grant. Declaration of Interests: Dr Murray has received consultancy fees from ViatarCTC Solutions, Boston, USA. All other authors reported no conflicts of interest. Ethics Approval Statement: The study was approved by the local ethics committee and fully complied with the Declaration of Helsinki and Chilean law on patient’s rights. All patients provided written informed consent.