Original article
Metastatic melanomas of unknown primary show better prognosis than those of known primary: A systematic review and meta-analysis of observational studies

https://doi.org/10.1016/j.jaad.2014.09.029Get rights and content

Background

Melanoma of unknown primary (MUP) is a condition of metastatic melanoma without a primary lesion.

Objective

We sought to identify the prognosis of MUP compared with melanoma of known primary (MKP).

Methods

We searched for observational studies containing at least 10 patients with MUP from MEDLINE and EMBASE from inception to December 22, 2012. The outcomes of interest were overall and disease-free survival; meta-analyses of hazard ratio stratified by stage using a random effects model were performed. In addition, second systematic review identified risk factors influencing the survival of patients with MUP.

Results

Eighteen studies including 2084 patients with MUP and 5894 with MKP were included. MUP had a better overall survival compared with MKP in stage III (15 studies; hazard ratio 0.83, 95% confidence interval 0.73-0.96, P = .010) and stage IV (6 studies; hazard ratio 0.85, 95% confidence interval 0.75-0.96, P = .008). Secondly, 22 studies including 3312 patients with MUP were reviewed, and increased stage and old age were the risk factors in patients with MUP.

Limitations

Diverse observational studies were reviewed, and selection and reporting biases are possible.

Conclusions

The current meta-analyses suggest better survival outcomes in patients with MUP than those in patients with MKP with the same corresponding tumor stage.

Section snippets

Methods

This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.8 Firstly, a quantitative synthesis of all relevant studies that compared the prognosis of MUP with that of MKP was planned. The primary outcome of interest was overall survival (OS), which was defined as time from melanoma diagnosis to death or last follow-up. Secondary outcome was disease-free survival (DFS), defined as time from melanoma diagnosis to local or

Search results

Of the 1594 records initially identified after removing duplicates, 1500 studies were discarded because–after reviewing the titles and abstracts–it appeared that these articles clearly did not meet the prescribed criteria. A total of 94 studies were assessed in full text for eligibility (Fig 1), of which 76 were excluded for the following reasons: not about MUP (n = 9), duplicated data (n = 2), review articles (n = 4), case series or less than 10 cases (n = 14), autopsy study (n = 1),

Discussion

The condition of MUP is not rare. In this review, the proportion of MUP ranged from 1.4% to 5.6% among all patients with melanoma. MUP could be classified into 3 categories of subcutaneous, nodal, and visceral diseases, and nodal MUP was the most commonly encountered subtype ranging between 0.7% and 8.8%. However, the entity of MUP has not been fully understood, and the features of survival could be a key to delineate the condition.

This meta-analysis provides evidence that MUP has better

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      Although more than 90% of melanomas have a cutaneous origin, occasionally it is discovered first as a secondary deposit, lymph node or visceral, without evident primary site. This entity of melanoma of unknown primary was initially characterized by Das Gupta in 1963 who was the first to describe the criteria for MUP [1,3]. Metastatic melanoma of unknown primary is a melanocytic lesion in distant sites in the absence of apparent skin involvement and is rare, accounting for up to 3,2% of all incident melanomas as well as being yet poorly understood in terms of pathogenesis.

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      Moreover, it is anticipated that there are survival differences between nodal and visceral MUP patients (Pfeil et al., 2011; Muchmore et al., 1986; Anbari et al., 1997; Katz et al., 2005; Reintgen et al., 1983; Velez et al., 1991; Schlagenhauff et al., 1997; Chang et al., 1998; De Waal et al., 2013). The favorable survival of MUP compared to MKP has also been highlighted in the meta-analysis by Bae et al. (Bae et al., 2015). The authors reported better OS for both stage III (HR 0.83, 95 % CI 0.73–0.96, p = 0.01) and stage IV MUP patients (HR 0.85, 95 % CI 0.75–0.96, p = 0.08), compared to MKP cohorts, respectively.

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    Drs Bae and Choi contributed equally to this work.

    This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2013R1A2A2A04015894).

    Conflicts of interest: None declared.

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