Sidedness Determines Clinical Characteristics and Survival Outcomes in Medullary Adenocarcinoma of the Colon

Colon medullary adenocarcinoma (MAC) is a rare histologic subtype. Clinical presentation and cancer outcomes of MAC, compared to colon adenocarcinoma (AC), remain incompletely described. Annual age-adjusted incidence rates were computed using Surveillance, Epidemiology, and End Results (2002-2017). A cohort analysis using the National Cancer Database (2010-2016) compared patient characteristics in an unmatched dataset and prognostic characteristics in a 1:1 matched subset. Reported annual age-adjusted incidence of MAC has significantly increased, with an average annual percent change (APC) increase of 23.8% (95% CI: 19.2-28.6); concurrent AC incidence declined (APC: - 2.8, 95% CI: - 3.1 to - 2.8). Analyses of 1018 MAC and 210,784 AC unmatched patients showed that MAC patients were more often older, female, and white, with higher disease stage, poorly-differentiated tumors, right-sided laterality, and lymphovascular invasion (all p < 0.0001). Among those with known microsatellite status, instability was more prevalent among MAC than AC patients (82% vs. 24%, p < 0.0001). Multivariate analyses of the matched dataset revealed that MAC histology was not independently associated with overall survival. However, when stratifying by laterality, left-sided MAC was associated with shorter survival when compared to right-sided MAC (HR 1.66, 95% CI 1.16-2.38) and right-sided AC (HR 1.54, 95% CI 1.12-2.12). The reported incidence of MAC is increasing, in contrast to the declining incidence of AC. MAC clinical and molecular features are distinct from AC and likely account for outcome differences. Overall, left-sided MAC was associated with the shortest OS. Molecular profiling may improve treatment guidelines for MAC.