Obstruction predicts worse long-term outcomes in stage III colon cancer: A secondary analysis of the N0147 trial

Abstract

Background: Patients with colon cancer often present with obstruction. Large series have reported obstruction among the high-risk features, yet prospective data on its specific prognostic influence are lacking. We hypothesized that obstruction is an independent risk factor for poor prognosis in patients with stage III colon cancer.

Methods: N0147 was a trial conducted between 2004 and 2009 that randomly assigned patients with stage III colon cancer to adjuvant regimens of folinic acid (leucovorin calcium), fluorouracil, and oxaliplatin or fluorouracil, leucovorin, and irinotecan, with or without cetuximab. Patient-level data from the control chemotherapy-only arms were obtained. Patient, tumor, and treatment characteristics were abstracted. Disease-free survival and overall survival were estimated by the Kaplan-Meier method. Proportions were compared by χ² and Fisher exact tests. Univariable and multivariable survival analyses were performed using Cox proportional hazards models.

Results: Of 1,543 patients with stage III colon cancer, 250 (16.2%) presented with obstruction. Patients with obstruction were equally likely to complete 12 cycles of adjuvant chemotherapy (75.9% vs 77.1%, P = .6). With median follow-up time of 30.9 months among survivors, five-year overall survival and disease-free survival were worse among patients with obstruction (overall survival 67.7% vs 78.0%, P < .001; disease-free survival 53.9% vs 67.0%, P < .0001). On multivariable analysis, obstruction remained significantly associated with worse survival after adjusting for T stage, N stage, performance status, age, sex, histologic grade, and body mass index (overall survival hazard ratio 1.57, 95% confidence interval 1.12-2.20, P = .001; disease-free survival 1.52, 95% confidence interval 1.18-1.95, P < .001).

Conclusion: In this prospectively followed cohort of patients with stage III colon cancer treated with adjuvant chemotherapy, obstruction was associated with recurrence and worse survival. Moreover, this effect was independent of T and N stage and histologic grade. These results suggest that obstruction should be incorporated into novel risk-stratification models.