Risk Stratification in Patients with Stage II Colon Cancer

Abstract

The decision to receive adjuvant chemotherapy is far from evident and remains controversial in patients with American Joint Committee on Cancer stage II colon cancer. This study analyzes several pathological characteristics in order to assess their (combined) predictive value for outcomes in stage II colon cancer. All stage II patients treated surgically for colon cancer at our tertiary care center (2004-2011) were extracted from a prospectively maintained, Institutional Review Board-approved data repository (n=313). Mortality and metastasis were compared, including multivariable Cox regression adjusted for stage subdivisions (IIA/IIB/IIC) and potential confounders. Colon cancer-specific mortality was substage independently increased in patients with baseline carcinoembryonic antigen (CEA) >5ng/L [hazard ratio (HR)2.88; p=0.022], large vessel invasion (LVI; HR4.59; p<0.001), perineural invasion (HR 3.08; p=0.006), and extramural vascular invasion (EMVI; HR4.96; p<0.001). Overall mortality adjusted for substage, age, and comorbidity was also significantly higher in patients with high-grade disease (HR2.54; p<0.001), LVI (HR1.74; p=0.015), perineural (HR2.42; p<0.001), and EMVI (HR2.79; p<0.001). Metastatic recurrence adjusted for adjuvant chemotherapy status had substage-independent associations with baseline CEA >5ng/L (HR2.37; p=0.046), LVI (HR3.07; p=0.001), perineural invasion (HR2.57; p=0.010), and EMVI (HR2.83; p=0.002). The number of high-risk features (0,1,2-3,4+) was associated with a clear incremental increase in overall and disease-specific mortality and recurrence (p≤0.001). The major inflection point is at two high-risk characteristics or more, whereas 5-year survival is almost halved from 77.4% to 31.7% (p<0.001). The risk score introduced provides a prognostic tool based on readily available data extracted from baseline pathology and preoperative CEA, which provides an easy method to stratify risks of mortality and recurrence and may therefore help in treatment decisions after surgery in stage II patients.