Cost-Effectiveness of Proton Therapy Compared With Photon Therapy in Breast Cancer

Proton therapy reduces radiation exposure to the heart, lungs, and contralateral breast compared with conventional photon-based breast radiotherapy. However, its clinical benefit-particularly relative to photon deep inspiration breath-hold (DIBH)-remains uncertain, and its high cost raises questions about cost-effectiveness.

To evaluate the cost-effectiveness of proton therapy compared with photon-based radiotherapy, including DIBH and free breathing (FB), among patients with breast cancer in Belgium.

This economic evaluation using state-transition microsimulation cost-effectiveness analysis was conducted between December 2024 and February 2025 from the Belgian health care payer perspective. The model incorporated patient-specific probabilities of complications, including cardiovascular disease, secondary malignant tumors, and radiation pneumonitis, derived from normal tissue complication probability models and representative national data. Deterministic and probabilistic sensitivity analyses were conducted. Participants were a simulated cohort of Belgian women with breast cancer, reflecting national incidence and survival data, stratified by baseline cardiovascular risk, smoking status, and age.

Comparison of proton therapy vs photon therapy delivered via DIBH or FB. Scenarios were analyzed based on tumor laterality, regional nodal irradiation, and varying cost assumptions for proton therapy.

The primary outcome was incremental cost-effectiveness ratio (ICER), expressed in euros per quality-adjusted life-year (QALY) gained. Cost-effectiveness defined by a willingness-to-pay threshold of €45 000 per QALY.

The simulated cohort included 1 million patients (310 000 aged 60 to 69 years [31.0%]). Proton therapy was not cost-effective in any scenario under base case assumptions. The greatest potential benefit was observed in patients with moderate to high baseline cardiovascular risk receiving left-sided irradiation with regional nodal irradiation, with an ICER of €292 438 (95% CI, €290 598-294 299) per QALY for proton therapy compared with photon free breathing. Under the most optimistic cost scenario (full treatment capacity and a 15% reduction in proton therapy costs), proton therapy was cost-effective compared with photon free breathing in approximately 36 000 of 1 000 000 simulated patients (3.6%), but it was not cost-effective compared with photon deep inspiration breath-hold in any subgroup, with ICERs exceeding €700 000 per QALY across all comparisons.

Findings from this economic evaluation of proton therapy for breast cancer suggest that proton therapy is unlikely to be cost-effective for most Belgian patients under current cost conditions, except for a small subset of high-risk patients, especially when DIBH is available.