Treatment Outcomes for Metastatic Melanoma of Unknown Primary in the New Era: A Single-Institution Study and Review of the Literature

Abstract

Background: Metastatic melanoma of unknown primary (MUP) is uncommon, biologically ill defined, and clinically understudied. MUP outcomes are seldom reported in clinical trials. In this study, we analyze responses of MUP patients treated with systemic therapy in an attempt to inform treatment guidelines for this unique population. Methods: New York University (NYU)'s prospective melanoma database was searched for MUP patients treated with systemic therapy. PubMed and Google Scholar were searched for MUP patients treated with immunotherapy or targeted therapy reported in the literature, and their response and survival data were compared to the MUP patient data from NYU. Both groups' response data were compared to those reported for melanoma of known primary (MKP). Results: The MUP patients treated at NYU had better outcomes on immunotherapy but worse on targeted therapy than the MUP patients in the literature. The NYU MUP patients and those in the literature had worse outcomes than the majority-MKP populations in 10 clinical trial reports. Conclusions: Our study suggests that MUP patients might have poorer outcomes on systemic therapy as compared to MKP patients. Our cohort was small and limited data were available, highlighting the need for increased reporting of MUP outcomes and multi-institutional efforts to understand the mechanism behind the observed differences.

Treatment of melanoma of unknown primary in the era of immunotherapy and targeted therapy: A Dutch population‐based study

“…In this large population‐based study, we reported the OS for patients with MUP since the introduction of immunotherapy and targeted therapy. A recent small, single‐center study has also evaluated survival in patients with MUP who received novel therapy and showed that 23 patients had a median OS of 9 months after initiating immunotherapy . In an accompanying systematic review, the authors only identified three other papers reporting on patients with MUP who received immunotherapy (a phase II study, a retrospective cohort study, and one case report) and seven papers concerning targeted therapy (six case reports and one small prospective observational study reporting on one patient).…”

“…While clinical trials of novel therapy have included patients with MUP, the outcomes in these patients have not been reported specifically . Given the potential difference in biology compared to MKP, knowing the outcomes during novel therapy for patients with MUP could aid clinical decision‐making.…”

“…13 While clinical trials of novel therapy have included patients with MUP, the outcomes in these patients have not been reported specifically. 14 Given the potential difference in biology compared to MKP, knowing the outcomes during novel therapy for patients with MUP could aid clinical decision-making. In the current study, we aimed to investigate the incidence, presentation, and treatment of MUP in the Netherlands and to assess overall survival (OS) associated with MUP in the era of novel therapy.…”

Patients with melanoma of unknown primary show better outcome under immune checkpoint inhibitor therapy than patients with known primary: preliminary results

“…1,2 Once melanoma has spread into the lymph nodes, or even visceral organs and the brain, it remains a life-threatening disease despite the advent of molecular targeted or immunotherapies. 1,2 Melanoma of unknown primary (MUP) [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] represents an unusual subtype of melanoma which was reported to be about 2-9% of melanoma of known primary (MKP) at all stages. 3 Some of the literature in the different geographic regions demonstrated better overall survival of MUP than of MKP.…”

“…15 Other publications, however, reported an equal or even worse clinical outcome for patients with MUP when compared to MKP with comparable stage of disease. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Hence, the prognosis of patients with MUP compared to MKP patients is still unclear and likely depends on the clinical scenario investigated. A 5-year overall survival rate of MUP before the era of the immune checkpoint inhibitor was reported to range from 8% to 18% with the most common metastatic sites in lymph nodes and gastrointestinal tract.…”