The prognostic significance of the treatment response of regional lymph nodes and the refinement of the current TNM staging system in locally advanced rectal cancer after neoadjuvant chemoradiotherapy

The current TNM staging system uses the same category definitions for both rectal cancer patients with and without neoadjuvant chemoradiotherapy (NCRT). However, ypTNM stage, especially ypN stage does not predict patient survival after NCRT well. Whether tumor regression in lymph nodes (LRG) may improve the prediction has not been well studied. In total, 358 patients with rectal cancer who received NCRT followed by radical resection were recruited from 2004 to 2015, and the median follow-up time was 57.5 months. The main outcome measure was disease-free survival (DFS). In univariate analysis, factors associated with DFS were ypT stage, ypN stage, number of negative lymph nodes (NLN), lymph node ratio (LNR), tumor regression grade (TRG), M-TTRG (modified ypT stage by combining ypT stage and TRG), maximum LRG (LRGmax), sum score of LRG (LRGsum), LRG ratio (average value of LRGsum), and M-NLRG (modified ypN stage by combining LRGmax and LNR). In the multivariate Cox regression analysis, M-TTRG and M-NLRG (p < 0.001 and p = 0.030, respectively) were significantly associated with DFS. The estimated 5-year DFS rates were 86.6%, 60.3%, and 36.4% for patients with M-NLRG-0, M-NLRG-1, and M-NLRG-2, respectively (p < 0.001). A significant difference in survival was observed among patients with NCRT after incorporating TRG and LRG simultaneously into the current ypTNM staging system (p < 0.001). LRG was an important prognostic factor in rectal cancer patients treated with NCRT and could refine the ypTNM staging system. The modified ypTNM staging system in combination with LRGmax, LNR, and TRG could improve the DFS prediction in each subset of patients.