Background: The 12-gene Oncotype DX Colon Recurrence Score assay is a clinically validated genomic assay that evaluates recurrence risks in stage II and stage III colon cancer patients independent of clinical-pathologic features. Improved colon cancer care has reduced recurrence rates since the late 1990’s. Methods: Pre-specified patient-specific meta-analysis methods were used to estimate 1-, 3- and 5-year recurrence risk combining the 12-gene colon recurrence score (RS) validation studies CALGB 9581, NSABP C-07 and SUNRISE. Cox models had effects for RS result, number of nodes examined (<12 or ≥ 12), T-stage, MMR status, and stage (II, IIIAB or IIIC). Baseline cumulative hazard estimates used the latest two studies to reflect current medical practice. Estimates for surgery, surgery+5FU and surgery+5FU+oxaliplatin treatment were provided by integrating stage-specific 5FU hazard ratios from a meta-analysis of the QUASAR study (2007) and a pooled analysis of NSABP studies (Wilkinson 2010), and oxaliplatin treatment effect estimates from NSABP C-07. Recurrence risk with 5FU alone was not estimated for MMR-deficient patients due to expected lack of 5FU efficacy in these patients (Sargent 2010). Results: In the overall population of 2,179 patients, 55%, 32% and 13% were Stage II, IIIA/B and IIIC, 63% had ≥12 nodes examined, 90% were T3, and 88% were MMR proficient. Median RS result was 31 (IQR 23–39). RS result and each clinical-pathologic factor contributed independent prognostic information (meta-analysis Wald tests, all p<.001). Risk estimates are generally lower than previous RS report risk estimates. For patients with pathological stage II, T3, MMR-proficient tumors with ≥12 nodes examined, approximately 40% are expected to have 5-year recurrence risk ≤10% with surgery alone based on the distribution of RS results. The table shows example 5-year recurrence risk estimates for specific RS results and clinical-pathologic characteristics. Conclusions: The new recurrence risk estimates provide more patient-specific information reflecting more current medical practice than previous reports using RS result, allowing better, more individualized treatment decisions.

56% of patients in the meta-analysis population were T3 with ≥12 nodes examined.