A novel TNtdM staging system integrating tumor deposits into N staging and reweighting T staging for nonmetastatic colorectal cancer.

BACKGROUND

We aim to develop an updated, parsimonious pathologic tumor, lymph node, and metastasis staging system with ideal hierarchical outcomes for nonmetastatic colorectal cancer.

METHODS

Available individual patient data from 161,208 patients with nonmetastatic colorectal cancer were collected from the Surveillance, Epidemiology, and End Results database (2010-2020, training data set) and the Zhejiang Cancer Hospital (2010-2024, validation data set). The TNtdM framework was proposed by integrating the tumor deposit counts into N staging and reweighting T staging.

RESULTS

Tumor deposit was significantly associated with poor prognosis in patients with nonmetastatic colorectal cancer (hazard ratio, 1.39; P < .001), and its count was found to be negatively linearly correlated with cancer-specific survival (tumor deposit 1: 1-3; hazard ratio, 1.31;  tumor deposit 2: ≥4; hazard ratio, 1.77; P < .001). The novel NTD staging system (NTD0-4), integrating N and tumor deposit categories, robustly stratified patients into 5 groups with monotonically declining 5-year cancer-specific survival rates from 87.2% (NTD0) to 38.9% (NTD4) (P < .001). By incorporating this NTD system and increasing the weighting of T staging, the TNtdM staging system, comprising 7 substages (stages IA, IB, IIA, IIB, IIIA, IIIB, and IIIC), was established and successfully resolved the survival paradox (eg, the 5-year cancer-specific survival rates: 79.6% in stage IIA, 70.5% in stage IIB, and 57.6% in stage IIIA). The survival curves stratified by the TNtdM classification demonstrated excellent separation and stepwise deterioration of cancer-specific survival with increased substages. Compared with the eighth edition of the American Joint Committee on Cancer tumor, lymph node, and metastasis staging system, the TNtdM exhibited higher discrimination power and better goodness of fit. The above results were further externally validated in the Zhejiang Cancer Hospital cohort.

CONCLUSION

The TNtdM staging system provided superior risk stratification and more accurate prognostic information than the current American Joint Committee on Cancer staging, thereby supporting its implementation in guiding precise clinical decision-making for nonmetastatic colorectal cancer.