Lack of Hierarchical Survival Prognosis in AJCC Staging for Colon and Rectal Cancer—Implications for Future Summary Stage Classification

Background: Current American Joint Committee on Cancer (AJCC) staging for colorectal cancer utilizes TNM framework groups disease based on extent and provides prognostic information, ideally with a hierarchical logic. We sought to evaluate survival as a function of stage within the 8^th edition AJCC staging system for colon and rectal cancer. Methods: Patients with primary colon or rectal cancer diagnosed 2010-2016 were identified from the National Cancer Database (NCDB). Survival curves were used to determine staging hierarchy for colon and rectal cancer. Multivariable modeling was used to identify relative contributions of variables (z-score) to survival, and hazard ratio (HR)-based groupings were constructed. Results: Among 270,584 colon and 53,846 rectal cancer patients, AJCC summary staging was non-hierarchical (e.g. HR IIC=2.92, HR IIIA=0.85-1.31). Multivariable analysis demonstrated high T category (T4a, T4b) confers the greatest mortality (colon: T4a HR 2.76, T4b HR 3.04; rectum: T4a HR 3.29, T4b HR 3.73), while high T category as well as high N category (colon: T4a z=66.9, T4b z=64.6, N2b z=55.7; rectum: T4b z=31.1, N2b z=25.1) contributed substantially to the survival model. HR based TN groupings resulted in hierarchical stage organization. Conclusions: Current AJCC stage groups for colorectal cancer are non-hierarchical. High T category has a greater impact on survival than N category for patients with early N disease, while high N category was more important for patients with early T disease. An organizational framework based on HR groupings is hierarchical and provides more accurate prognostic information.