Molecular Tumor Boards in Malignant Melanoma: Uncovering Challenges and Opportunities in a Bicenter Retrospective Analysis in Germany

Despite therapeutic advancements, approximately 50% of advanced melanoma patients succumb to metastatic disease. Molecular tumor boards (MTB) aim to identify targetable molecular alterations to guide individualized treatment strategies. Yet, real-world data on patient selection, referral timing, recommendation rates, implementation, and clinical impact remain limited. In this exploratory retrospective bicenter analysis, we evaluated 80 patients with advanced melanoma who presented at institutional MTBs of two comprehensive cancer centers. Clinical and molecular tumor data were analyzed using bioinformatic tools to characterize mutation profiles, treatment recommendations, and their real-world implementation. Most patients (88.3%) had stage IV melanoma at the time of presentation and had received a median of three prior systemic treatment lines. Actionable treatment recommendations were formulated in 77.9% of eligible cases, yet only 33.7% of recommendations were implemented. Non-implementation was most commonly attributable to early patient death or regulatory barriers. Importantly, when recommended therapies were applied, patients experienced significantly improved progression-free survival (7.85 vs. 4.34 months; PFS ratio 1.8) and overall survival (10.64 vs. 5.06 months) compared with patients in whom recommended treatments were not implemented. Among patients with implemented MTB recommendations (n = 26), the median intra-patient PFS ratio was 1.68, and 14 of 26 patients (53.8%) achieved a PFS ratio ≥ 1.3. These findings indicate that MTBs frequently generate clinically actionable recommendations for metastatic melanoma, but late-stage referral substantially limits their real-world implementation. When applied, molecularly guided treatment strategies may confer meaningful clinical benefit, underscoring the importance of earlier integration of MTBs into melanoma care pathways.