Patient-specific meta-analysis of 12-gene colon cancer recurrence score validation studies for recurrence risk assessment after surgery with or without 5FU and oxaliplatin

Individualized estimates of the risk of recurrence in colon cancer patients are needed that reflect current medical practice and available treatment options. Three validation studies of the 12-gene colon recurrence score assay were used with pre-specified patient-specific meta-analysis (PSMA) methods to integrate the 12-gene Oncotype DX Colon Recurrence Score result (RS) with the clinical and pathology risk factors stage, T-stage, mis-match repair (MMR) status, and number of nodes examined to calculate individualized recurrence risk estimates. Baseline risk estimation used the most recent studies, so the risk estimates reflect current medical practice. The effect of fluorouracil (5FU) was estimated with a meta-analysis of two studies. The effect of oxaliplatin was estimated using one of the RS assay validation studies, in which patients were randomized to 5FU with or without oxaliplatin. The RS result and each of the clinical-pathologic factors provided independent prognostic information for recurrence. Among stage II, T3, MMR-proficient patients with ≥12 nodes examined (the most common scenario), patients with RS ≤30 (approximately 48%) have estimated 5-year recurrence risk ≤10% with surgery alone. Among stage IIIA/B, T3, MMR-deficient patients with ≥12 nodes examined, patients with RS ≤19 (approximately 14%) have an estimated 5-year recurrence risk ≤10% with surgery alone. Among stage IIIA/B, T3, MMR-proficient patients with ≥12 nodes examined, those with RS ≤14 (approximately 6%) have estimated 5-year recurrence risk ≤10% with 5FU alone. The PSMA integrates the 12-gene colon RS result with clinical and pathology factors to provide individualized recurrence risk estimates that reflect current medical practice. The risk estimates are in a range that may help inform treatment decisions for a substantial number of stage II and stage III patients.