A Comprehensive Evaluation of Lymph Node Staging and a Proposal to Subdivide N2b Category in Colorectal Cancer Patients.

Objective: This study aimed to assess the impact of the number of metastatic lymph nodes (LNs) on survival and propose a subdivision of the N2b category in colorectal cancer (CRC) patients. Methods: We retrospectively analyzed from two sources: clinicopathologic data of CRC patients with stage pTxN2bM0 who initially underwent radical surgery at Cancer Hospital, Chinese Academy of Medical Sciences/National Cancer center (NCC), and patients with stage pTxN0-2bM0-1 in the Surveillance, Epidemiology and End Results (SEER) database from January 2010 to December 2015. The optimal cutoff value of the number of positive lymph nodes (PLNs) was determined based on the principle of maximum chi-square value. We constructed survival curves using the Kaplan-Meier method, assessed survival differences with the log-rank test, and conducted univariate and multivariate analyses using the Cox proportional hazard regression model. Results: A total of 68,335 CRC patients were included: 240 from the NCC cohort, and 68,095 from the SEER cohort. Within the SEER cohort, 65,189 patients had M0 stage disease and 2,906 had M1 stage disease. The optimal PLN cutoff value determined by X-tile software (Version 3.6.1) was 13. According to PLN, stage N2b patients were divided into two groups: stage N2b# (7 ≤ PLN < 13) and stage N3 (PLN ≥ 13). In the NCC cohort, the 5-year overall survival (OS) rates of stage N2b# and N3 patients were 66.0% and 45.7%, respectively (p < 0.001). In the SEER cohort, the 5-year cancer-specific survival (CSS) rate was 57.1% for stage N2b# patients compared with 40.2% for stage N3 patients (p < 0.001). The results of multivariate Cox analysis demonstrated that modified stage pN was the independent prognosis factor of OS in the NCC cohort (HR = 1.869, 95%CI:1.253-2.787, p = 0.002); modified stage pN was also the independent prognosis indicator of CSS in the SEER cohort (N3:N0, HR = 8.170, 95%CI: 7.298-9.146, p < 0.001). There was no survival difference between TxN3M0 and TxN0-2b#M0 (5-year CSS rate: 40.2% vs. 30.1%, p = 0.050; 5-year OS rate: 35.3% vs. 27.8%, p = 0.358). Conclusions: The N category served as a strong independent prognostic indicator in CRC patients. Furthermore, PLN emerged as an independent prognostic factor specifically in stage N2b CRC patients. These findings suggest that clinicians may utilize PLN for prognostic stratification and tailor adjuvant therapeutic strategies accordingly for patients diagnosed with stage N2b CRC.