Comparative Effectiveness of Laparoscopic versus Open Colectomy on 5-Year Overall Survival in Non-Metastatic Colon Cancer: A Target Trial Emulation Study Using Retrospective Cohort Data from a Cancer Registry.

Abstract

Background: The clinical acceptance of laparoscopic colectomy (LC) as a standard alternative treatment for colon cancer hinges primarily on evidence of favorable long-term oncological outcome. The aim of this study was to compare the 5-year overall survival (OS) between stage I-III colon cancer patients who underwent either LC or open colectomy (OC).

Materials and methods: A target trial emulation (TTE) design was implemented using statewide retrospective cohort data from the Mecklenburg-Western Pomerania Cancer Registry spanning 2008 to 2018. The causal interpretation of TTE relied on the assumptions of consistency, conditional exchangeability, and positivity. The Royston-Parmar parametric survival model was applied to estimate the hazard ratio with bootstrapped 95% confidence interval (95% CI). This was complemented by differences in estimates of restricted mean survival time (RMST). Sensitivity analyses, including the E-value method, were conducted to assess the robustness of the estimated treatment effect. Three traditional (fully adjusted, change-in-estimate, and Directed Acyclic Graph-guided) Cox models were performed for comparison purposes.

Results: We included 1265 patients, of whom 30% (n= 380) received LC. The estimated HR for 5-year OS comparing LC with OC was 0.81 (95% CI: 0.60, 1.08). RMST differences for OS favored LC, but the effects were small: 0.12 months (95% CI: -0.10, 0.34), 0.36 months (95% CI: -0.15, 0.87), and 1.20 months (95% CI: -0.20, 2.60) up to 1-, 3-, and 5-years, respectively. Sensitivity analyses generally confirmed the robustness of the results. Traditional Cox models showed a survival advantage for LC, but all were affected by bias.

Conclusion: This study found comparable 5-year OS between LC and OC. The traditional Cox models spuriously overestimated the survival advantage of LC. TTE can provide useful real-world evidence for comparative effectiveness in surgical oncology, particularly when randomized evidence is limited, but it cannot replace well-conducted RCTs.