Pathologic Staging Inconsistency Between ypT4N0 (stage II) and ypT1-2N1 (stage III) After Preoperative Chemoradiotherapy and Total Mesorectal Excision in Rectal Cancer: A Multi-Institutional Study

Abstract Background In the Surveillance, Epidemiology, and End Results population-based data, the survival curves reversed between T4N0 (stages IIB or IIC) and T1-2N1 (stage IIIA) in rectal cancer. However, T4N0 had a higher stage than T1-2N1 in the current colorectal staging system. Patients and Methods We analyzed 1804 patients with rectal cancer who were treated with preoperative chemoradiotherapy and curative surgery. We grouped patients by pathologic stage, and recurrence-free survival (RFS) and overall survival rates were calculated and compared for each stage. We evaluated prognostic factors that influenced recurrence and survival. Results In the recurrence and survival analysis, 3-year RFS rates were 95.9% for ypStage 0, 94.0% for ypStage I, 78.9% for ypStage IIA, 55.8% for ypStage IIB/C, 80.2% for ypStage IIIA, 64.6% for ypStage IIIB, and 44.9% for ypStage IIIC. Patients with ypStage IIB/C showed significantly worse RFS ( P  = .004) than did those with ypStage IIIA. The ypStage IIB/C group showed significantly higher rates of both locoregional recurrence (24.3% vs. 5.5%; P  = .02) and distant metastasis (31.6% vs. 17.1%; P  = .048) than did the ypStage IIIA group. Compared with ypStage IIIA, ypStage IIB/C showed significantly higher pre-chemoradiotherapy carcinoembryonic antigen ( P  = .004), circumferential radial margin involvement ( P  = .001), and positive perineural invasion ( P  = .014). Conclusion Patients with rectal cancer staged ypT4N0 were associated with higher locoregional recurrence and distant metastasis rates than those staged ypT1-2N1 in the current staging system.