11089 Background: Short-course radiation therapy (SCRT) has previously been found to be cost-effective compared to long-course chemoradiation (LCRT) for patients with locally advanced rectal cancer undergoing operative management. However, non-operative management protocols have recently become a standard treatment option for patients diagnosed with locally advanced rectal cancer achieving a complete clinical response after total neoadjuvant therapy (TNT) as surgery has significant impacts on quality of life. Recent data suggests higher rates of local regrowth and a correspondingly lower rate of organ preservation with SCRT-TNT compared to LCRT-TNT. With this study, we evaluated the cost-effectiveness of SCRT versus LCRT in the setting of non-operative management for locally advanced rectal cancer. Methods: We built a microsimulation model to simulate 5-year outcomes for 1 million hypothetical patients aged 65 years with locally advanced rectal cancer treated with TNT including either SCRT or LCRT. Patients achieving a complete clinical response with TNT opted for a non-operative management approach, undergoing surgery only with subsequent local progression. Patients not achieving a complete clinical response went directly to surgery. The model incorporated costs, quality of life (measured by health utility), and probabilities of disease progression and death. We extracted probabilities of disease progression and death and health utilities from published literature. We assessed costs from the healthcare payer perspective. We measured cost-effectiveness with incremental cost-effectiveness ratio (ICER), with ICERs under $100,000 per quality-adjusted life-year (QALY) considered cost-effective. One way and probabilistic sensitivity analyses were used to test model uncertainty. Results: We found that compared to SCRT, LCRT increased overall cost by $10,457 and improved effectiveness by 0.16 QALYs resulting in an ICER of $67,200/QALY. The model was most sensitive to assumptions about risks of local recurrence in the non-operative setting, the health utility of non-operative management, and the costs of LCRT and SCRT. The model was not sensitive to assumptions about costs of diagnostic evaluation (i.e. flexible sigmoidoscopy) and probability of distant recurrence. Probabilistic sensitivity analysis demonstrated that LCRT was cost-effective in 91% of iterations. Conclusions: Long-course chemoradiation could represent a cost-effective strategy compared with short-course radiotherapy in the non-operative management of patients with locally advanced rectal cancer. The ongoing ACO/ARO/AIO-18.1 trial testing the hypothesis that LCRT-TNT will increase organ preservation rates relative to SCRT-TNT will help confirm these findings.
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