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

Abstract

Background: Larger tumor size and lymph node involvement are traditionally associated with increased colon cancer-specific mortality.

Objective: 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.

Design: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results database.

Setting: Geographic areas included in one of the 18 Surveillance, Epidemiology, and End Results registries were used.

Patients: We identified 99,594 patients with nonmetastatic colon adenocarcinoma treated with surgery between 1988 and 2001.

Main outcome measures: 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.

Results: 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).

Limitations: The main limitations are the retrospective design and information available in the study database.

Conclusion: 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.