Abstract
Background: Current TNM staging system has been used the same category definitions for both rectal cancer patients with and without neoadjuvant chemoradiotherapy (NCRT). However, ypTNM stage, especially ypN stage does not well predict patients' survival after NCRT. Whether tumor regression in lymph nodes (LRG) may improve the prediction has not been well studied. Methods: In total, 358 patients with rectal cancer and received NCRT followed by radical resection were recruited from 2004 to 2015, and the median follow-up time was 57.5 months. Main outcome measures was patients' disease-free survival (DFS). Findings: 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 of 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 a multivariate Cox regression analysis, MTTRG and M-NLRG (P<0.001 and P=0.030) were significantly associated with DFS. The estimated 5-year DFS was 86.6%，60.3% and 36.4% for patients with M-NLRG-0, M-NLRG-1, M-NLRG-2 respectively (P<0.001). Significant difference was obtained among patients with NCRT after incorporating TRG and LRG simultaneously into the current ypTNM staging system (P<0.001). Interpretation: LRG was an important prognostic factor in rectal cancer patients treated with NCRT and could refine ypTNM staging system. The modified ypTNM staging system in combination with LRGmax, LNR and TRG could improve DFS prediction in each subset of patients. Funding Statement: This work was supported by the CAMS Initiative for Innovative Medicine (2016-12M-1-007). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The Institutional Review Board of the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) approved this study.
Highlights
Neoadjuvant chemoradiotherapy (NCRT) has become the standard of care for locally advanced mid-low rectal cancer.[1]
The treatment response is evaluated by tumor regression grade (TRG) in primary tumor, which has been reported to have a significant impact on prognosis in a number of studies.[3,5,6,7]
We reported that the treatment response of primary tumors had prognostic significance and could refine the TNM staging system
Summary
Neoadjuvant chemoradiotherapy (NCRT) has become the standard of care for locally advanced mid-low rectal cancer.[1]. Lymph node metastasis is the most important prognostic factor in rectal cancer.[9] Despite the downstaging effect of NCRT, lymph node status has been found to be significantly correlated with prognosis and clinical outcomes. Several studies suggested that the number of negative lymph nodes and lymph node ratio (LNR) had significant prognostic value.[14,15,16] In this study, we evaluated the prognostic significance of LRG, and combined LRGmax and LNR into a new prognostic factor (M-NLRG) that could predict disease-free survival (DFS) better than ypN stage. We incorporated TRG and LRG into the current ypTNM staging system for cancer survival
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