Prognostic Impact of the Number of Examined Lymph Nodes in Stage II Colorectal Adenocarcinoma: A Retrospective Study

BACKGROUND: Evaluation of lymph node status is critical in colorectal carcinoma (CRC) treatment. However, as patients with node involvement may be incorrectly classified into earlier stages if the examined lymph node (ELN) number is too small and escape adjuvant therapy, especially for stage II CRC. The aims of this study were to assess the impact of the ELN on the survival of patients with stage II colorectal cancer and to determine the optimal number. METHODS: Data from the US Surveillance, Epidemiology, and End Results (SEER) database on stage II resected CRC (1988-2013) were extracted for mathematical modeling as ELN was available since 1988. Relationship between ELN count and stage migration and disease-specific survival was analyzed by using multivariable models. The series of the mean positive LNs, odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS (Locally Weighted Scatterplot Smoothing) smoother, and the structural break points were determined by the Chow test. An independent cohort of cases from 2014 was retrieved for validation in 5-year disease-specific survival (DSS). RESULTS: An increased ELN count was associated with a higher possibility of metastasis LN detection (OR 1.010, CI 1.009-1.011, p < 0.001) and better DSS in LN negative patients (OR 0.976, CI 0.975-0.977, p < 0.001). The cut-off point analysis showed a threshold ELN count of 21 nodes (HR 0.692, CI 0.667-0.719, p < 0.001) and was validated with significantly better DSS in the SEER 2009 cohort CRC (OR 0.657, CI 0.522-0.827, p < 0.001). The cut-off value of the ELN count in site-specific surgeries was analyzed as 20 nodes in the right hemicolectomy (HR 0.674, CI 0.638-0.713, p < 0.001), 19 nodes in left hemicolectomy (HR 0.691, CI 0.639-0.749, p < 0.001), and 20 nodes in rectal resection patients (HR 0.671, CI 0.604-0.746, p < 0.001), respectively. CONCLUSIONS: A higher number of ELNs are associated with more-accurate node staging and better prognosis in stage II CRCs. We recommend that at least 21 lymph nodes be examined for accurate diagnosis of stage II colorectal cancer.