Survival paradox between stage IIB/C (T4N0) and stage IIIA (T1-2N1) colon cancer

The survival paradox between stage IIB/C (T4N0) and stage IIIA (T1-2N1) colon cancer remains in the 7th edition of the American Joint Committee on Cancer staging system. This multicenter study aimed to compare the oncologic outcomes of T4N0 and T1-2N1 colon cancers and to investigate the presumptive prognostic factors that might influence the survival paradox.

Patients who underwent curative surgery for pT4N0 (n = 224) and pT1-2N1 (n = 135) primary colon cancer between January 1999 and December 2010 at five tertiary referral cancer centers were included for analysis. The clinicopathologic, treatment-related factors, and oncologic outcomes in terms of the 5-year overall survival (5-OS) and 5-year disease-free survival (5-DFS) were compared.

The T4N0 group had significantly worse 5-OS and 5-DFS rates than the T1-2N1 group (5-OS: 84.0 vs. 92.3 %, p = 0.012; 5-DFS: 73.6 vs. 88.0 %, p = 0.001). T4N0 cancers more frequently showed elevated preoperative carcinoembryonic antigen, lower grade of differentiation, larger tumor size, and higher proportions of perineural invasion, microsatellite instability, obstruction, and perforation than T1-2N1 cancers. Peritoneal seeding and liver metastasis were the predominant recurrence pattern in the T4N0 and T1-2N1 groups, respectively (p = 0.042). The T4N0 group showed inferior survival to the T1-2N1 group in postoperative adjuvant chemotherapy (5-OS: 87.1 vs. 93.2 %, p = 0.045; 5-DFS: 76.1 vs. 89.0 %, p = 0.001).

T4N0 colon cancer had significantly worse oncologic outcomes than T1-2N1 cancer regardless of adjuvant chemotherapy. The survival paradox may result from the biologic aggressiveness of T4N0 colon carcinomas.