Vulvar and Vaginal Melanoma: Real-world Clinical Outcomes and Prognostic Differences From a Single-center Experience

OBJECTIVE: Vulvar and vaginal melanoma are rare gynecologic malignancies with aggressive clinical behavior and poor prognosis. Due to their low incidence and exclusion from most clinical trials, treatment decisions are often extrapolated from cutaneous melanoma data. This study aims to provide real-world insights into the clinical course and outcomes of vulvar and vaginal melanoma in the context of modern systemic therapy. METHODS: We retrospectively analyzed 39 patients with vulvar or vaginal melanoma treated at a single tertiary cancer center between 2011 and 2023. Clinical and pathologic data, including tumor site, stage, treatment modalities, and outcomes, were collected. Systemic therapy regimens included anti-PD-1 antibody monotherapy (either pembrolizumab or nivolumab), anti-PD-1 + anti-CTLA4 combination therapy (ipilimumab and nivolumab), and chemotherapy combined with interleukin-2. Progression-free survival and overall survival were evaluated. RESULTS: Patients frequently presented with locally advanced disease. High rates of multifocality, positive margins, and repeated local recurrence were observed, particularly in vulvar primaries. Among those treated for advanced disease (n = 28), combination immunotherapy yielded the most durable responses. Vulvar melanoma was associated with longer progression-free survival and overall survival compared with vaginal melanoma (median progression-free survival: 33 vs. 5 mo, HR = 3.8; median overall survival: 42 vs. 10 mo, HR = 7.8). CONCLUSIONS: Vulvar and vaginal melanoma present unique diagnostic and therapeutic challenges in gynecologic oncology. Site-specific prognosis and distinct response patterns to immunotherapy underscore the importance of individualized management strategies and multidisciplinary coordination in this rare population.