F. S. Dahdaleh1, S. Sherman1, A. Benjamin1, E. Poli1, K. K. Turaga1 1The University Of Chicago Medicine,Section Of General Surgery/Surgical Oncology,Chicago, IL, USA
Introduction: Presentation with obstruction is frequent in patients with colon (non-rectal) cancer (CC). Large series have reported obstruction among “high-risk” features, yet data from prospective cohorts on its specific prognostic influence are lacking. We hypothesized that obstruction is an independent risk factor for poor prognosis in patients with stage III CC.
Methods: N0147 was a randomized trial conducted between 2004-09 including patients with Stage III CC randomized to adjuvant FOLFOX/FOLFIRI regimens with or without cetuximab. We obtained patient-level data for those in the control chemotherapy-only arms. Patient, tumor and treatment characteristics were abstracted. Disease-free and overall survival (DFS and OS) were estimated by the Kaplan-Meier method. Proportions were compared by Chi-square and Fisher-exact tests. Uni- and Multivariate survival analyses were performed using Cox-proportional hazards models.
Results: Of 1,543 patients with stage-III CC, 250 (16.2%) presented with obstruction. Obstructive tumors were more likely to be K-ras mutant (35% vs. 30%, p=0.07) and poorly differentiated (28.8% vs. 24.6% vs. p=0.17) but these did not reach statistical significance. Obstructed patients were no less likely to complete 12 cycles of adjuvant chemotherapy (75.6% vs. 77.0% p=0.62). With median follow-up time of 30.1 months among survivors, 5-year overall and disease-free survival was significantly worse among obstructed patients (OS 67.7% vs. 78.0%, p<0.001; DFS 53.9% vs. 67.0%, p<0.0001, Figure). After adjusting for conventional AJCC staging variables including T and N-stage, high-grade histology, and host characteristics, obstruction remained significantly associated with worse survival (OS HR 1.61, 95% CI 1.16-2.24, p=0.005; DFS 1.54, 95% CI 1.21-1.98, p<0.001). This difference was more pronounced in the cohort receiving FOLFOX (HR 2.13, 95% CI 1.46-3.11, p<0.001).
Conclusion: In this prospectively-followed cohort of Stage-III CC patients treated with standard-of-care adjuvant chemotherapy, obstruction was significantly associated with worse survival. Moreover, this effect was independent of T- and N-stage, and histology. Conclusions from this secondary analysis of a randomized trial are less likely to be biased by diagnostic and therapeutic factors, and by disparities in access to care than retrospective series. Inclusion of obstruction in the AJCC staging system might help better stratify these patients at high risk of recurrence and death.
