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In the current study, characteristics and overall survival (OS) of patients with advanced and metastatic MUP and MKP were compared in the era of novel therapy. Patients were selected from the prospective nation-wide Dutch Melanoma Treatment Registry (DMTR). The following criteria were applied: diagnosis of stage IIIc unresectable or IV cutaneous MKP (cMKP) or MUP between July 2012 and July 2017 and treatment with immune checkpoint inhibition and\/or targeted therapy. OS was estimated using the Kaplan\u2013Meier method. The stratified multivariable Cox regression model was used for adjusted analysis. A total of 2706 patients were eligible including 2321 (85.8%) patients with cMKP and 385 (14.2%) with MUP. In comparative analysis, MUP patients more often presented with advanced and metastatic disease at primary diagnosis with poorer performance status, higher LDH, and central nervous system metastases. In crude analysis, median OS of cMKP or MUP patients was 12\u00a0months (interquartile range [IQR] 5 \u2013 44) and 14\u00a0months (IQR 5 \u2013 not reached), respectively (<jats:italic>P<\/jats:italic>\u2009=\u20090.278). In adjusted analysis, OS in MUP patients was superior (hazard rate 0.70, 95% confidence interval 0.58\u20130.85; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). As compared to patients with advanced and metastatic cMKP, MUP patients have superior survival in adjusted analysis, but usually present with poorer prognostic characteristics. In crude analysis, OS was comparable indicating that patients with MUP benefit at least equally from treatment with novel therapies.<\/jats:p>","DOI":"10.1007\/s00262-021-02871-1","type":"journal-article","created":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T17:02:42Z","timestamp":1616864562000},"page":"3123-3135","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Clinical outcome of patients with metastatic melanoma of unknown primary in the era of novel therapy"],"prefix":"10.1007","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0034-3575","authenticated-orcid":false,"given":"Danielle","family":"Verver","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"Gr\u00fcnhagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander C. 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MA has consultancy\/advisory relationships with Pfizer, BMS, MERCK, Sanofi, Astellas, Pierre fabre, and Novartis. AvdE has advisory relationships with Amgen, Bristol-Myers Squibb, Roche, Novartis, MSD, Pierre Fabre. JdG has advisory relationships with Bristol-Myers Squibb, Roche, Pierre Fabre, Servier, MSD, Novartis. JH has advisory relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celsius Therapeutics, GSK, Immunocore, Ipsen, MSD, Merck Serono, Novartis, Neon Therapeutics, Pfizer, Roche\/Genentech, Sanofi, Seattle Genetics and has received research grants not related to this paper from Novartis, Bristol-Myers Squibb, MSD, Neon Therapeutics. GH consultancy\/advisory relationships with Amgen, Bristol-Myers Squibb, Roche, MSD, Pfizer, Novartis and has received research grants not related to this paper from Bristol-Myers Squibb, Seerave. EK has consultancy\/advisory relationships with Bristol-Myers Squibb, Novartis, Merck, Pierre Fabre and received research grants not related to this paper from Bristol-Myers Squibb. KS has advisory relationships with Bristol-Myers Squibb, Roche, Novartis, MSD, Pierre Fabre. AvdV has consultancy relationships with Bristol-Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Pfizer, Sanofi, Ipsen, Eisai. All grants were paid to the institutions and not related to this work. All remaining authors have declared no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Declaration of HELSINKI and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}