Development of a Risk Score and Nomogram to Predict Individual Benefit Attained from the Addition of Adjuvant Chemotherapy in the Treatment of Stage II Colon Cancer.

Background: Current guidelines recommend considering adjuvant chemotherapy (AC) for stage II colon cancer (CC) with poor prognostic clinicopathologic and molecular features. However, the relative impact of individual or constellations of high-risk features remains undefined. We developed an individualized point-of-care tool to predict survival benefit attained from the addition of AC.

Methods: The National Cancer Database was queried for all patients with resected stage II CC from 2004 to 2015. A prognostic risk score and nomogram were constructed using twelve clinicopathologic and molecular prognostic factors associated with outcomes for CC. Overall survival (OS) was compared between surgery alone and AC groups. The nomogram was validated for discrimination and calibration using bootstrap-adjusted Harrell's concordance index (C-index). For population-level estimation, OS was compared based on quartiles.

Results: Of 132,666 patients with stage II CC, 16.8% received AC. The calibration curve of the constructed nomogram showed a good agreement between predicted and observed median and 3-, 5-, and 10-year survival (bootstrap-adjusted C-index 0.699, CI: 0.698-0.703). Population-level risk score analysis (median [Q1, Q3]; 4.9 [4.6, 5.5]) demonstrated that patients with scores > 3.34 had significantly decreased risk of death with the addition of AC (all p < 0.001). No survival advantage was associated with AC among patients with low risk scores (risk score < 3.34: HR: 0.94, 95% CI: 0.80-1.11, p = 0.47).

Discussion: A composite weighted risk score is critical to individualizing AC in select high-risk patients. Our nomogram provides individualized prognostication and estimation of benefit attained from AC. This may better inform treatment decisions and aid future trial design.