Treatment for Patients with Rectal Cancer and a Clinical Complete Response to Neoadjuvant Therapy

Abstract

A clinical complete response to neoadjuvant therapy occurs in a subset of patients with rectal cancer. Management of these patients is controversial and tension exists between the recurrence risk with observation, and the impact of surgery on quality-of-life. Therefore, the objective was to develop a decision-analytic model to evaluate the relative benefits of surgery vs. observation in rectal cancer patients who achieve clinical complete response after neoadjuvant chemoradiation. Clinically relevant inputs and events, including the ability to identify complete responders, likelihood of relapse and of salvage surgery after relapse, and utilities for each health state, were simulated by use of a Markov state-transition model. Transition probabilities and health-state utilities were derived from the literature and expert consensus. One-way and two-way sensitivity analyses were performed to assess the robustness of model results to assumptions. The primary outcome was quality-adjusted life expectancy. In the base-case analysis, the quality-adjusted life expectancy with surgery exceeded observation (5.63 vs. 5.34 quality-adjusted life-years). Sensitivity analysis demonstrated that observation was preferred to surgery if the ability to correctly identify patients with true complete responses exceeded 58 percent, if quality-of-life after surgery was poor (utility <0.81), or if the relative reduction in recurrence risk with surgery was <43 percent when compared with observation. Our model outlines the issues associated with surgery vs. observation, and suggests that surgery is beneficial for the average patient with rectal cancer with a clinical complete response after neoadjuvant therapy. Current limitations in the clinical assessment of patient response to chemoradiation constitute an important factor influencing our results, and therefore warrant further investigation.