The Margin of the Largest Tumor Predicts Overall Survival After Resection of Multitumor Colorectal Liver Metastases.

Abstract

Resection is a potentially curative treatment for colorectal liver metastasis (CRLM). In multitumor CRLM cases, closest margin of all resected tumors, which is the conventional definition of surgical margin, may not be the best prognosticator for outcomes. Retrospective analysis was performed with a cohort of 1943 patients who underwent curative-intent CRLM resection. Univariable analysis, Classification and Regression Tree (CART) modeling, and multivariable regression were used to evaluate different definitions of surgical margin. The goodness-of-fit of the regression models was assessed using validation set. The training set comprised 1,361 patients, with medians of largest tumor's diameter, largest tumor's margin, and closest margin being 3.3 cm, 8 mm, and 5 mm, respectively. In multitumor CRLM training set, multivariable regression demonstrated that largest tumor's margin was significantly associated with overall survival (OS; hazard ratio [HR] = 0.99, 95% confidence interval [CI] 0.98-1.00, p = 0.008); while closest margin had a borderline significant association (HR = 0.99, 95% CI 0.97-1.00, p = 0.078). These findings suggest that largest tumor's margin, not the closest margin, was independently associated with OS. CART analysis identified the largest tumor's diameter and margin as the most predictive factors for OS, whereas closest margin was not. The withheld multitumor validation set comprised 582 patients and demonstrated comparable predictive discrimination between the largest tumor's margin and the closest margin (c-index of OS: 0.593 vs. 0.593). Largest tumor's margin is a more robust prognosticator for OS in multitumor CRLM compared with the closest margin.