Merkel Cell Carcinoma of the Skin: Deducing the Pattern of Spread from an International Aggregated Database of 949 Patients.

(1) Background: It is controversial if Merkel cell carcinomas (MCCs) spread to lymph nodes or distant metastases (LNM/DM) first. (2) Methods: A total of 303 patients from six institutions (March 1982-February 2015) were combined with individual patient data from a PubMed search, totaling 949 patients. The primary outcome was recurrence patterns. (3) Results: (a) More patients presented with lymph node metastases (LNMs) than DMs at diagnosis: 17.9% (166 among the 929 patients with known staging) vs. 1.9% (18/929); (b) 310/929 (33.4%) developed lifetime DM, of whom 220/310 also developed LNM. The majority (133 patients) of patients were documented to have developed LNM before DM. (c) A shorter median time of 1.5 months (range: 0-47.0) from initial diagnosis to LNM, versus 8 months (range: 0-107.8) to DM, was also found. Another observation was that 2.4% (23/949) of patients with primary tumors ≤1 cm developed lifetime DM, with the smallest being 0.2 cm. (4) Conclusions: Three observations support the idea that prior LNM gives rise to subsequent DM as the main pathway of dissemination in MCC. This implies that patients with nodal metastases should be considered for adjuvant systemic therapy studies as an enriched population. Participation in clinical trials is strongly encouraged.