International Validation of a Recurrence Risk Model for Stage II Colon Cancer: The SPHERE Study

OBJECTIVE: To validate the utility of recurrence prediction value (RPV) in identifying patients with UICC stage II colon cancer who would benefit from adjuvant chemotherapy (AC).

SUMMARY BACKGROUND DATA: The benefits of AC in Stage II colon cancer remain insufficient.

METHODS: We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer who had undergone surgery. RPV was developed based on the weighting of each high-risk factor. Data from multi-institutional databases in Japan, the United States, and Jordan were used (cohort 1). In addition, nationwide data were obtained from Denmark (Cohort 2). The primary endpoint was recurrence-free survival (RFS).

RESULTS: According to the RPV, a low score was found in 750 (70.2%) patients and high scores in 318 (29.8%) patients in cohort 1. The corresponding numbers were 1031 (70.4%) and 433 (29.6%) patients in cohort 2, respectively. The five-year RFS rates were significantly higher in the group of patients who received AC than in the group who did not in the RPV high sub-group of cohort1 (76.2% vs. 55.6%, P <0.001) and in cohort2 (65.6% vs. 49.8%, P=0.001). Multivariate analyses revealed that AC was an independent prognostic factor for RFS only in the RPV high sub-group of both cohort 1 (hazard ratio (HR) 0.48; 95% confidence interval (CI) 0.29-0.81; P=0.005) and cohort2 (HR 0.69; 95% CI 0.48-0.99; P=0.043).

CONCLUSIONS: This global study validates a readily available clinical data-based algorithm for predicting recurrence in Stage II colon cancer, identifying patients across diverse populations who benefit significantly from AC.