12-Gene Recurrence Score Independently Predicts Recurrence in Patients With Stage II/III Colon Cancer
In a study reported in Journal of Clinical Oncology, Greg Yothers, PhD, of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Biostatistical Center and the University of Pittsburgh Graduate School of Public Health, and colleagues assessed performance of the 12-gene colon cancer recurrence score in patients with stage II or III colon cancer who were treated with fluorouracil (5-FU) with or without oxaliplatin. They found that the recurrence score is an independent predictor of recurrence in this setting and that it provides predictive information beyond standard clinical and pathologic risk factors.
Study Details
The study involved assessment of the 12-gene recurrence score in 892 fixed, paraffin-embedded tumor specimens from patients with stage II or III colon cancer randomly assigned to receive 5-FU or 5-FU plus oxaliplatin in the NSABP C-07 trial; this group represented a randomly selected 50% sample of the patient population with available tissue samples. In total, 449 patients had received 5-FU and 443 5-FU/oxaliplatin, with 29.2% and 29.6% having stage II disease, 46.3% and 45.9% stage IIIA/B disease, and 24.5% and 24.6% stage IIIC disease.
Patients had an average age of 58 years, 88% were white, and 57% were male. In total, 62% of patients with stage II disease and 61% with stage III disease had ≥ 12 nodes examined. Mismatch repair deficiency was more common in stage II disease (18%) than in stage III disease (9%). The recurrence score was analyzed as a continuous score and by predefined high-, intermediate-, and low-risk scores. Data were analyzed by Cox regression adjusting for disease stage and treatment.
Recurrence Score Independently Predicts Recurrence Risk
The continuous recurrence score was significantly associated with recurrence-free interval with a hazard ratio (HR) of 1.96 (P < .001) for each 25-unit increase in score, which was equivalent to a hazard ratio of 1.55 per interquartile range (16-unit increase) after adjustment for stage and treatment. There was no difference in outcomes according to disease stage II, IIIA/B, or IIIC (P = .90 for interaction).
The predefined high-score group (26% of patients) had significantly higher recurrence risk (HR = 2.11, P < .001) vs the low-score group (39% of patients). On multivariate analysis adjusting for stage, mismatch repair status, number of nodes examined, T stage, grade, and treatment, the continuous recurrence score remained a significant predictor of recurrence (HR = 1.57 per 25-unit increase, P = .001). There was no significant interaction between recurrence score and stage (P = .90) or age (P = .76).
No Interaction Between Recurrence Score and Treatment
The average 5-year recurrence rates in 5-FU–treated patients by low-, intermediate-, and high-risk recurrence score groups were: 9%, 13%, and 18% in stage II disease; 21%, 29%, and 38% in stage IIIA/B disease; and 40%, 51%, and 64%, in stage IIIC disease. The relative benefit of oxaliplatin was similar across the range of recurrence scores (P = .48 for interaction), with Cox model estimates suggesting that the absolute oxaliplatin benefit was higher at higher recurrence score values, particularly in patients with stage II and IIIA/B disease.
Kaplan-Meier analysis also showed a greater absolute benefit with oxaliplatin in the high-score group vs the low-score group overall (P = .016) and within each stage. An ad hoc analysis restricted to stage III patients showed that the continuous recurrence score was significantly associated with recurrence-free interval (HR = 1.90 per 25-unit increase, P < .001), with the number of recurrence events in stage II patients being too small to allow a similar analysis.
The continuous recurrence score was also significantly associated with disease-free survival (HR = 1.60 per 25-unit increase 1.60, P < .001) and overall survival (HR = 1.89 per 25-unit increase, P < .001).
The investigators concluded, “The 12-gene Recurrence Score predicts recurrence risk in stage II and stage III colon cancer and provides additional information beyond conventional clinical and pathologic factors. Incorporating Recurrence Score into the clinical context may better inform adjuvant therapy decisions in stage III as well as stage II colon cancer.”
The study was supported by Sanofi-Synthelabo and the National Cancer Institute.
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