Survival outcomes in melanoma of unknown versus known primary receiving immunotherapy: A systemic review and meta-analysis.

Abstract

e21500 Background: Historically, patients with melanoma of unknown primary (MUP) had better survival than those with melanoma of known primary (MKP). However, it remains unclear whether this difference persists among patients treated with immune checkpoint inhibitors (ICIs). Methods: We searched MEDLINE and Embase databases from inception to December 15, 2025, for studies that reported survival outcomes (overall survival, progression-free survival, and/or hazard ratio [HR] with 95% confidence interval [CI]) in patients with MUP and MKP treated with ICIs (anti-CTLA-4 and/or anti-PD-1). When survival outcomes were not reported, we reconstructed individual patient survival data from published Kaplan–Meier curves to derive estimates. We then pooled survival outcomes using a random-effects model based on the generic inverse variance method. Results: A total of seventeen studies published between 2015 and 2025 were included. Among 905 patients with MUP, pooled overall survival rates were 80% at 6 months, 64% at 1 year, 54% at 2 years, and 48% at 3 years. ICI–treated MUP and MKP demonstrated comparable overall survival (672 vs 3,886 patients; HR, 0.99; 95% CI, 0.83–1.18) and progression-free survival (305 vs 1,596 patients; HR, 0.98; 95% CI, 0.54–1.80). Subgroup analyses similarly showed no significant survival differences between MUP and MKP among patients receiving either anti-CTLA-4 or anti-PD-1. Conclusions: Survival outcomes in MUP have improved substantially over the past decade. In contrast to findings from the pre-immunotherapy era, no significant survival differences were observed between MUP and MKP among patients treated with ICIs.