Survival Outcomes in Lymph Node-Positive Merkel Cell Carcinoma (Stage III): A Comparison Between Known and Unknown Primary Tumors and Their Sun Exposure Sites

Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer, with prognosis influenced by tumor location and primary status. This study evaluated clinicopathological features and survival outcomes in patients with MCC from multiple centers in Israel. Methods: Data on demographics, tumor characteristics, lymph node (LN) involvement, treatment, and survival were collected. Patients were stratified by primary tumor status (known vs. unknown) and tumor location (sun-exposed vs. non-sun-exposed). Disease-free survival (DFS) and overall survival (OS) were estimated using Kaplan–Meier analysis, and multivariate analyses were performed. Results: The cohort included 80 patients diagnosed with stage 3 (with LN involvement) MCC, of whom 52 (65%) had primary MCC with lymph node involvement, and 28 patients (35%) with unknown primary MCC. The majority were male (81.3%), with a median age of 71.2 years (range, 37–92). The median DFS and OS for the entire cohort were 24 and 32 months, respectively. Patients with unknown primary tumors had longer DFS (34 vs. 18 months; p = 0.0503) and OS (43 vs. 28 months; p = 0.0362) compared with those with known primary MCC. Non-sun-exposed tumors were associated with longer median DFS (32 vs. 18.5 months; p = 0.0663) and OS (41 vs. 23 months; p = 0.0353). Five-year survival analysis showed improved outcomes in patients with unknown primary tumors (DFS 54% vs. 35%, p = 0.04; OS 57% vs. 42%, p = 0.03) and in non-sun-exposed tumors (DFS 51% vs. 33%, p = 0.05; OS 57% vs. 40%, p = 0.04). Conclusions: Unknown primary status and non-sun-exposed tumor location are potentially associated with improved long-term survival in patients with MCC. These findings highlight the prognostic importance of tumor origin and anatomical site in MCC management.