Originally published as JCO Early Release 10.1200/JCO.2008.18.9845 on May 18 2009

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Improved Survival for Stage IV Melanoma From an Unknown Primary Site

From the Roy E. Coats Research Laboratories and the Sonya Valley Ghidossi Vaccine Laboratory of the John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA.

Corresponding author: Donald L. Morton, MD, John Wayne Cancer Institute, 2200 Santa Monica Blvd, CA 90404; e-mail: mortond{at}jwci.org.

Purpose We previously demonstrated a survival advantage for nodal metastasis of melanoma from an unknown primary (MUP) versus melanoma from a known primary (MKP). We hypothesized that this survival benefit would extend to MUP patients with distant (stage IV) metastasis.

Patients and Methods We reviewed prospectively acquired data for 2,247 patients diagnosed with American Joint Committee on Cancer stage IV melanoma at our cancer center between 1971 and 2005. Cox regression analysis in a multivariate model identified prognostic factors significant for survival. MUP and MKP patients were then matched by significant covariates. Overall survival (OS) was estimated by Kaplan-Meier method and compared by log-rank analysis.

Results There were 1,849 MKP and 398 MUP patients. Multivariate analysis of patients with complete data sets identified known/unknown primary (hazard ratio [HR], 1.141; P = .032) and five other significant covariates: age (HR, 1.148; P = .007), sex (HR, 1.17; P = .001), site of metastasis (HR, 1.336; P < .001), number of different metastatic sites (HR, 1.303; P < .001), and decade of diagnosis (HR, 0.713; P < .001). Prognostic matching yielded 392 MUP-MKP pairs. Median OS and 5-year OS rate were significantly greater (P < .001) for MUP patients than for all matched MKP patients or for MKP patients matched by M1 category (for M1b and M1c) or number of metastatic sites.

Conclusion The survival advantage previously reported for patients with stage III MUP also applies to patients with stage IV MUP. The mechanism responsible for this improved survival may provide clues for more effective treatment of stage IV melanoma and therefore warrants further investigation. The improved results for MUP suggest that these patients deserve aggressive therapy.

Supported by Grants No. CA29605 and CA12582 from the National Cancer Institute, the Wayne and Gladys Valley Foundation (Oakland, CA), the Harold J. McAlister Charitable Foundation (Los Angeles, CA), the Family of Robert Novick (Los Angeles, CA), the Weil Family Fund (Los Angeles, CA), the Wrather Family Foundation (Los Alamos, CA), the Amyx Foundation Inc (Boise, ID), Berton M. Kirshner (Los Angeles, CA), Todd Kirshner (Los Angeles, CA), Mr. and Mrs. Louis Johnson, (Stanfield, AZ), Heather and Jim Murren (Las Vegas, NV), Mrs. Marianne Reis (Lake Forest, CA), and the Wallis Foundation (Los Angeles, CA).

Presented at the 44th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 30 to June 3, 2008.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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