Incorporating apical lymph node status into the seventh edition of TNM classification improves prognosis prediction in stage III colon cancer: A multicenter cohort study in Japan

Background: The node classification outlined in the seventh edition of the tumor-node-metastasis (TNM) classification is based solely on the number of metastasized lymph nodes. We examined the prognostic value of apical lymph node metastasis and the additive value of incorporating apical lymph node status into a risk model based on the seventh edition. Methods: Our cohort study involved 1355 patients with Stage III colon cancer who underwent tumor resection with dissection of regional (including apical) lymph node at 71 hospitals across Japan between 2000 and 2002. The main exposure was pathologically confirmed apical lymph node metastasis, and the primary endpoint was cancer-specific death. Results: Apical lymph node metastasis was present in 113 (8.3%) of the patients. During 5,356 patient-years (median 5.0 year) of follow-up, 221 (16.3%) instances of cancer-specific death were observed. After adjustment for tumor and node classification (as described in the seventh edition) and other prognostic factors, apical lymph node metastasis was found to be independently associated with cancer-specific death (hazard ratio, 2.29; 95% confidence interval [CI], 1.49-3.52). Incorporating apical lymph node metastasis into the prognostic model based on the seventh TNM edition significantly improved discriminative performance for cancer-specific death (difference in concordance index, 0.0146; 95% CI, 0.003-0.026) and risk reclassification for cancer-specific death at 5 years (category free net reclassification improvement, 19.4%; 95% CI, 5.0%-33.4%), respectively. Conclusions: Assessment of apical lymph node metastasis provided independent prognostic information beyond that achievable with the seventh TNM edition in patients with Stage III