Cost-Effectiveness Analysis of Ultra-Short Whole Breast Radiation Therapy Alone vs. Endocrine Only or Combined Treatment for Low-Risk ER-Positive Early-Stage Breast Cancer in Women Age 70 and Older

Abstract

<h3>Purpose/Objective(s)</h3> The optimal management of early-stage, low-risk, hormone-positive breast cancer in women age 70 and older remains controversial. Recent trials have shown whole-breast radiation courses of only 5 fractions have similar outcome as longer courses, reducing the cost and inconvenience of treatment. We therefore performed a cost-utility analysis to compare ultra-short whole breast irradiation (U-WBI) to endocrine therapy (ET) alone and to combined ET and U-WBI. <h3>Materials/Methods</h3> We simulated the cost-effectiveness and acute and late effects of different treatment approaches for women age 70 years or older with pT1-2N0 ER-positive invasive ductal carcinoma treated with lumpectomy with negative margins using a Markov microsimulation model. The strategies were: U-WBI performed with a 3D technique over 5 fractions without a boost ("RT Alone"), adjuvant ET (anastrozole for 5 years) without RT ("AI Alone"), or the combination of the two. The FAST-Forward trial served as the basis for this analysis. The combination strategy was calibrated to match the trial results. The relative effectiveness of the RT Alone and AI Alone strategies were inferred from historical randomized trials. Costs were obtained from 2022 Medicare rates. Utilities and other costs were obtained from the literature. The primary endpoint was the cost-effectiveness of the 3 strategies over a 10-year horizon as measured by the incremental cost-effectiveness ratio (ICER), with a value of $100,000/QALY deemed "cost-effective". Deterministic and probabilistic sensitivity analyses were performed to evaluate parameter uncertainty. <h3>Results</h3> The model was validated using 500,000 simulated patients, each treated with the 3 strategies. The model results agreed well with the pre-specified target outcomes. On average, RT Alone was the least expensive strategy ($15,200), with AI Alone slightly more expensive, ($16,761), and combination therapy the most costly ($20,416). The most effective strategy was the combination (9.497 QALY), with small differences between RT Alone (9.453) and AI Alone (9.420). Therefore, the AI Alone strategy was more costly and less effective than RT Alone (dominated), and the combination therapy was slightly more expensive than the usual definition of "cost-effective" (ICER $117,721 relative to RT Alone). Probabilistic sensitivity analysis demonstrated RT Alone to be cost-effective in 52% of trials, with combination in 35% and AI Alone in 13%. <h3>Conclusion</h3> U-WBI without ET represents a cost-effective strategy for low-risk women in the United States, with slightly higher QALY outcome compared to AI Alone. Combination therapy improves outcome very modestly. Hence, many patients may prefer RT Alone in order to avoid the possible side effects of ET. Discussion of these options must account for patients' weighing of these issues.