Real-World Direct Medical Costs and Clinical Outcomes of Immunotherapy and Targeted Therapy for Cutaneous Melanoma: A Bottom-Up Cost-of-Illness Study in a Public Healthcare System

Background/Objectives: Immunotherapy and targeted therapy improve melanoma survival but raise costs. Real-world cost and outcome data are scarce, especially in Central and Eastern Europe. We estimated per-patient costs and outcomes in Serbia’s public healthcare system. Methods: This retrospective, single-centre study assessed costs in 183 patients with cutaneous melanoma who received systemic therapy at a Serbian tertiary centre (2019–2026). Direct medical costs were reconstructed from invoices and discharge letters from the healthcare-sector perspective. Censoring-adjusted mean 24-month costs were estimated from diagnosis (n = 165) and treatment start (n = 179). Outcomes included overall survival (OS), real-world progression-free survival (rwPFS), and time to next treatment or death (TNT-D). Results: Mean 24-month costs per patient were EUR 66,466 (95% CI 58,465–75,334) from diagnosis (EUR 75,388 with the partitioned estimator), 94.7% for systemic therapy, and EUR 107,229 (95% CI 97,405–118,201) from treatment start. At diagnosis, costs were about twice as high in stages III–IV as in stages I–II. By stage at treatment start, costs were similar in stages III and IV (EUR 102,122 vs. 104,535) despite shorter stage IV survival (p < 0.001). Two-year OS was 91.5% for adjuvant and 51.9% for metastatic first-line intent. Conclusions: Systemic therapy drove costs, which were similar in stages III and IV despite poorer stage IV survival. The cost measurement starting point substantially affected estimates and should be reported.