Adherence to guidelines for adjuvant chemotherapy (AC) use in stage II colon cancer (CC).

Abstract

169 Background: Treatment guidelines suggest that AC may be considered inpatients (pts) with "high risk" stage II CC, defined by the presence of >/=1 poor prognostic features, such as obstruction or perforation, T4 stage, <12 lymph nodes retrieved, positive resection margins, and lymphovascular or perineural invasion. However, survival benefits associated with AC use in high risk pts remain largely unproven. Therefore, current recommendations are primarily driven by consensus rather than by evidence. Our aims were to examine population-based concordance with current guidelines for AC use in stage II CC and to explore the relationship between AC use and survival in high- vs. low-risk pts. Methods: All pts diagnosed with stage II CC in British Columbia from 1999 to 2008 and evaluated at 1 of 5 regional cancer centers were reviewed. Kaplan-Meier and Cox regression methods were used to correlate high- vs. low-risk status as well as receipt of AC with relapse-free (RFS), disease specific (DSS), and overall survival (OS). Results: We identified 1,697 stage II CC pts: 1,236 (73%) high risk and 461 (27%) low risk among whom only 363 (29%) and 61 (13%) received AC, respectively. Individuals with high risk features who received guideline-concordant AC were younger (median 62 vs. 72 years, p<0.001) and had better performance status (ECOG 0/1 47% vs. 34%, p=0.02). In the high-risk group, AC was associated with improved 5-year OS, but not with RFS or DSS. After adjusting for confounders, an OS advantage from AC persisted for high-risk pts (HR 0.67, 95 CI 0.52-0.86, p=0.002), but no significant RFS or DSS benefits were seen (HR 0.76, 95 CI 0.58-0.99, p=0.05 and HR 0.75, 95 CI 0.55-1.02, p=0.11, respectively). Subgroup analyses showed that only individuals with T4 lesions had improved RFS (HR 0.63, 95 CI 0.42-0.95, p=0.03), DSS (HR 0.59, 95 CI 0.37-0.93, p=0.02), and OS (HR 0.50, 95 CI 0.33-0.77, p=0.002). Conclusions: In this population-based cohort of stage II CC patients, less than one-third of high risk patients received guideline-concordant AC. Consistent survival benefits were only seen in those with T4 lesions, suggesting a very limited role for AC. Guidelines that are mainly consensus-driven and associated with minimal survival benefits have poor uptake.