Comparative effectiveness of primary tumor resection in metastatic colon cancer: An instrumental variable analysis.

674 Background: Although the safety of chemotherapy without primary tumor resection (PTR) has been established, questions remain regarding potential survival benefit with PTR. The purpose of this study was to compare mortality with and without PTR among patients with unresectable metastatic colon cancer using nationwide hospital based cancer registry data. Methods: An observational study was conducted of patients with stage 4 colon cancer identified from the National Cancer Data Base (2003-2005). Patients who underwent metastectomy were excluded. Patient, treatment, and hospital data were analyzed. Multivariate Cox regression stratified by receipt of chemotherapy was performed to compare survival with and without PTR. To account for treatment selection bias, Propensity Score Weighting (PSW) and Instrumental Variable (IV) analyses, using hospital-level PTR rate as the instrument, were performed. In order to account for the potential bias associated with early comorbidity or disease burden associated deaths (survivor treatment bias), 1 year landmark analysis was performed. Results: A total of 14,399 patients met inclusion criteria and 6,735 patients were eligible for landmark analysis. PTR was performed in 38.2% of the total cohort and 73.8% of those at landmark. Using multivariate Cox regression analysis, PTR was associated with a significant reduction in mortality (HR 0.39; 95% CI, 0.38-0.41). This effect persisted with PSW (HR 0.4; 95% CI, 0.38-0.43). However, IV analysis showed a much smaller effect, (RR 0.88; 95% CI, 0.83-0.93). While a smaller benefit was seen on landmark analysis using multivariate Cox regression (HR 0.6; 95% CI, 0.55-0.64) and PSW (HR 0.59; 95% CI, 0.54-0.64), IV analysis showed no improvement in survival with PTR (RR 0.97; 95% CI, 0.87-1.06). Stratification by chemotherapy did not alter the results. Conclusions: Among patients with stage IV colon cancer, PTR offered no survival benefit over systemic chemotherapy alone when the IV method was applied at the 1 year landmark. Subject to selection and survivor treatment bias, standard regression analysis may overestimate the benefit of PTR. Future study should focus on identifying patients most likely to benefit from PTR.