A Modified Tumor-Node-Metastasis Classification for Primary Operable Colorectal Cancer

Abstract

Background: The American Joint Committee on Cancer (AJCC) 8th tumor-node-metastasis (TNM) classification for colorectal cancer (CRC) has limited ability to predict prognosis.

Methods: We included 45 379 eligible stage I-III CRC patients from the Surveillance, Epidemiology, and End Results Program. Patients were randomly assigned individually to a training (n = 31 772) or an internal validation cohort (n = 13 607). External validation was performed in 10 902 additional patients. Patients were divided according to T and N stage permutations. Survival analyses were conducted by a Cox proportional hazard model and Kaplan-Meier analysis, with T1N0 as the reference. Area under receiver operating characteristic curve and Akaike information criteria were applied for prognostic discrimination and model fitting, respectively. Clinical benefits were further assessed by decision curve analyses.

Results: We created a modified TNM (mTNM) classification: stages I (T1-2N0-1a); IIA (T1N1b, T2N1b, T3N0); IIB (T1-2N2a-2b, T3N1a-1b, T4aN0); IIC (T3N2a, T4aN1a-2a, T4bN0); IIIA (T3N2b, T4bN1a); IIIB (T4aN2b, T4bN1b); and IIIC (T4bN2a-2b). In the internal validation cohort, compared with the AJCC 8th TNM classification, the mTNM classification showed superior prognostic discrimination (area under receiver operating characteristic curve = 0.675 vs 0.667, respectively; 2-sided P < .001) and better model fitting (Akaike information criteria = 70 937 vs 71 238, respectively). Similar findings were obtained in the external validation cohort. Decision curve analyses revealed that the mTNM had superior net benefits over the AJCC 8th TNM classification in the internal and external validation cohorts.

Conclusions: The mTNM classification provides better prognostic discrimination than AJCC 8th TNM classification, with good applicability in various populations and settings, to help better stratify stage I-III CRC patients into prognostic groups.

Figure 1.

Kaplan-Meier estimates of the proposal modified tumor-node-metastasis (mTNM) classification in the training cohort.

Figure 2.

Details of 2 tumor-node-metastasis (TNM) classifications. (A) AJCC 8th TNM classification; B) mTNM classification.

Figure 3.

Kaplan-Meier estimates of the modified tumor-node-metastasis (mTNM) classification in the internal validation cohort. (A) Colorectal cancer (CRC); B) CRC (+10 152 additional patients); C) Colon cancer; D) Colon cancer (+7956 additional patients); E) Rectal cancer; F) Rectal cancer (+2156 additional patients). Additional patients were those who were older than 72 years or received preoperative treatments. All statistical tests were 2-sided. HR = hazard ratio.