Association Between Very Small Tumor Size and Increased Cancer-Specific Mortality in Node-Positive Colon Cancer.

Abstract

Larger tumor size and lymph node involvement are traditionally associated with increased colon cancer-specific mortality. We sought to determine whether patients with very small tumors associated with lymph node involvement are at paradoxically increased risk of colon cancer-specific mortality in comparison with those who have larger tumors and lymph node involvement. This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results database. Geographic areas included in one of the 18 Surveillance, Epidemiology, and End Results registries were used. We identified 99,594 patients with nonmetastatic colon adenocarcinoma treated with surgery between 1988 and 2001. The primary predictor variables were regional lymph node involvement and primary tumor size by longest dimension, grouped into the following predetermined strata: <5 mm, 5 to 19 mm, 20 to 39 mm, 40 to 59 mm, ≥ 60 mm. We used competing risks regression to determine differences in the risk of colon cancer-specific mortality between strata after controlling for T stage, tumor grade, age, year of diagnosis, race, and number of dissected lymph nodes. Median follow-up among censored patients was 12.9 years. We found a significant interaction between lymph node involvement and tumor size (p < 0.05). Among those with node-negative disease, colon cancer-specific mortality increased monotonically with tumor size. In contrast, among those with node-positive disease, patients with the smallest tumors (<5 mm) were at increased risk of 10-year colon cancer-specific mortality compared with those with tumors sized 5 to 19 mm, 20 to 39 mm, 40 to 59 mm, and ≥60 mm (53.3% vs. 30.1%, 37.5%, 39.2%, and 39.7%; adjusted hazard ratios, 1.63-2.24; p < 0.05 in all cases). The main limitations are the retrospective design and information available in the study database. In the setting of lymph node involvement, very small tumor size may predict for increased colon cancer-specific mortality compared with larger tumors. Smaller tumors associated with lymph node involvement may represent more aggressive malignancies with a distinct biology that merits further investigation.