Clinical-pathological differences in colorectal cancer: Rectum, left colon, and microsatellite instability—ABDON study.

Abstract

e15653 Background: Colorectal cancer (CRC) is a heterogeneous disease and shows distinct clinical-pathological features based on tumor location and molecular characteristics, particularly microsatellite instability (MSI). This result of defective DNA mismatch repair (MMR) is associated with unique tumor profiles. Although differences in the laterality of CRC are acknowledged, the impact of the MMR status between the left colon and rectum remains poorly explored. This study aims to elucidate these disparities and provide insights into how tumor site and MMR status influence the varied profiles of CRC. Methods: We performed an observational and retrospective single-center study of a comparative cohort of patients with localized or locally advanced left colon or rectum cancer. Patients' characteristics and outcomes were compared according to MSI versus microsatellite stability (MSS) status, in ratio 1:2. The primary endpoints were to assess the clinical, pathological, and molecular characteristics of this population. The second endpoint included overall survival (OS) and disease-free survival (DFS). Statistical analyses were conducted using descriptive statistics, Kaplan-Meier methods, and Cox proportional hazards models. Results: From January 2014 to December 2023, a total of 102 patients were included; 34 (33.3%) had MSI and 68 (66.7%) had MSS; 30 (29.4%) had rectal cancer and 72 (70.6%) had left colon cancer. The most common MSI subtype detected 15 (14.7%) was in the MSH2/MSH6 genes. While only 8 (23.5%) MSI patients developed metastasis during follow-up, 42 (65.6%) MSS patients progressed in the same way ( p < .001) . The median follow up was 48 months and the median OS was 81 months (95% confidence interval [CI]: 66.28-95.72) for MSS patients ( p = 0.001) versus unachieved for MSI patients (HR 0.146; 95% CI 0.034-0.630; p = 0.010 ). The median DFS time was 27 months (95% CI 18.54-35.451) for the MSS group, while it was not reached for the MSI cohort (HR 0.293; 95% CI 0.136-0.631; p = 0.002 ). The multivariate Cox regression indicated that individuals with MSS are approximately 2.4 times (CI 95% 1.089–5.300; p = 0.03 ) more likely to experience progression compared to those with MSI. Conclusions: The MSI group showed significantly better survival, despite unmet DFS and OS medians. This study reiterates that microsatellite status is a critical marker for prognosis and therapeutic decision-making. However, these results highlight the need for further investigation, through enhanced data integrity, to validate and expand these findings.