Nodal Status, Number of Lymph Nodes Examined, and Lymph Node Ratio: What Defines Prognosis after Resection of Colon Adenocarcinoma?

In Brief BACKGROUND: Lymph node ratio (LNR) has been proposed as an optimal staging variable for colorectal cancer. However, the interactive effect of total number of lymph nodes examined (TNLE) and the number of metastatic lymph nodes (NMLN) on survival has not been well characterized. STUDY DESIGN: Patients operated on for colon cancer between 1998 and 2007 were identified from the Surveillance, Epidemiology, and End Results database (n = 154,208) and randomly divided into development (75%) and validation (25%) datasets. The association of the TNLE and NMLN on survival was assessed using the Cox proportional hazards model with terms for interaction and nonlinearity with restricted cubic spline functions. Findings were confirmed in the validation dataset. RESULTS: Both TNLE and NMLN were nonlinearly associated with survival. Patients with no lymph node metastasis had a decrease in the risk of death for each lymph node examined up to approximately 25 lymph nodes, while the effect of TNLE was negligible after approximately 10 negative lymph nodes (NNLN) in those with lymph node metastasis. The hazard ratio varied considerably according to the TNLE for a given LNR when LNR ≥ 0.5, ranging from 2.88 to 7.16 in those with an LNR = 1. The independent effects of NMLN and NNLN on survival were summarized in a model-based score, the N score. When patients in the validation set were categorized according to the N stage, the LNR, and the N score, only the N score was unaffected by differences in the TNLE. CONCLUSIONS: The effect of the TNLE on survival does not have a unique, strong threshold (ie, 12 lymph nodes). The combined effect of NMLN and TNLE is complex and is not appropriately represented by the LNR. The N score may be an alternative to the N stage for prognostication of patients with colon cancer because it accounts for differences in nodal samples. The combined effect of total number of lymph nodes examined and the number of metastatic lymph nodes on survival after colon surgery for cancer is complex and not appropriately represented by the lymph node ratio.