Abstract
BACKGROUND: The aim of this study was to estimate the economic burden of radiotherapy (RT) from the perspectives of payers, the healthcare system, patients, and society, and to assess associated quality-of-life (QoL) outcomes. The analysis examined direct medical and non-medical costs, as well as QoL, before, during, and up to six months after RT. Given the inclusion of multiple cancer types, the study reflects a heterogeneous real-world population. An exploratory comparison across RT techniques was also conducted to provide contextual economic insight. METHODS: This analysis included data from 301 cancer patients undergoing RT using various techniques, including two-dimensional radiotherapy (2D), 3D conformal radiotherapy (3D-CRT), volumetric-modulated arc therapy (VMAT), and intensity-modulated radiotherapy (IMRT), at the University General Hospital of Heraklion, Crete, Greece. Clinical and cost data were collected retrospectively, while QoL data were collected prospectively using validated instruments at baseline, end of treatment, and six months post-treatment. Quality-adjusted life years (QALYs) were estimated. The primary analysis compared RT with a hypothetical "no RT" comparator derived from published evidence, while comparisons across RT techniques were conducted as exploratory analyses. Costs and QALYs were evaluated over a 6-month time horizon; therefore, discounting was not applied. Incremental cost-effectiveness ratios (ICERs) were calculated, and probabilistic sensitivity analysis was performed to account for parameter uncertainty. RESULTS: The cost per QALY gained with RT compared with the hypothetical "no RT" comparator varied substantially across techniques and cancer types. In the primary analysis, 2D radiotherapy yielded the lowest ICER (€13,043.27/QALY), while VMAT demonstrated an ICER of €29,945.12/QALY. In contrast, IMRT was associated with a substantially higher ICER (€135,529.51/QALY), suggesting limited cost-effectiveness under commonly accepted willingness-to-pay thresholds, whereas 3D-CRT was found to be dominant. Subgroup analyses revealed marked heterogeneity, with ICERs ranging from €3234.45 to €30,232.50 per QALY gained across cancer types. In certain subgroups, RT was either cost-saving or dominant, particularly in breast cancer (cost-saving with similar QALYs) and in skin cancer and sarcoma (dominant strategies). Sensitivity analyses highlighted considerable uncertainty, especially for 2D radiotherapy, primarily driven by small sample sizes and variability in QALY estimates. CONCLUSIONS: This study provides short-term, real-world evidence on the cost-effectiveness and quality-of-life outcomes of radiotherapy in a Greek healthcare setting. While simpler techniques such as 2D radiotherapy may appear economically favorable, their limited effectiveness and substantial uncertainty may reduce their overall value. In contrast, advanced techniques-particularly VMAT-demonstrate a more consistent balance between cost and clinical outcomes, supporting their role within value-based, patient-centered oncology care. However, the findings should be interpreted with caution due to population heterogeneity, small subgroup sizes, the short (6-month) time horizon, and the use of a hypothetical comparator. Further research with longer follow-up and disease-specific analyses is warranted.