Exploration of exact significance of lymph node ratio and construction of a novel stage in colon cancer with no distant metastasis.

Aim: Lymph node ratio (LNR) seems to be more precise than classic N stage in classifying cancer stage. Thus, we aim to construct a modified classification system based on LNR for colon cancer without distant metastasis.

Methods: This study enrolled two independent cohorts of patients. The primary cohort enrolled 2,152 patients from 2008 to 2013 in Zhongshan Hospital, Fudan University. The validation cohort consisted of 77,406 patients from the Surveillance, Epidemiology, and End Results (SEER) registry from 2004 to 2014. The inclusion criteria were: pathologically confirmed colon cancer, and American Joint Committee on Cancer (AJCC) stage I/II/III. The exclusion criteria included: incomplete follow-up information, rectal cancer, and multiple primary sites. The prognostic value of LNR for overall survival was evaluated. The cutoff value of LNR was determined by the X-tile. Predictive performance of modified classification was determined by the concordance index.

Results: After analysis, 0.05 and 0.50 were determined as the best threshold values of LNR. A value of <0.05, 0.05-0.50 and >0.50 was reclassified as the mN0, mN1 and mN2 stage. A modified classification based on mN0, mN1, and mN2 was further constructed for stage I/II/III colon cancer. C-index of the modified classification was statistically more precise than AJCC classification (0.687 versus 0.605, <0.001). The same results can also be determined in the validation cohort (0.715 versus 0.640, <0.001). Furthermore, a prognostic nomogram including independent factors was constructed. The constructed nomogram showed good performance according to the calibration curve.

Conclusion: The clinical value of LNR level was preferable to classic N stage in colon cancer patients. Our proposed classification based on LNR and AJCC T category can effectively differentiate patients with varied survival outcomes.