Improved survival for stage IV melanoma from an unknown primary site

Abstract

9031 Background: We and others have observed a survival advantage for nodal metastasis from an unknown versus a known primary melanoma (MUP versus MKP). Although nodal metastasis in the setting of MUP has been attributed to precursor nevus cells in a lymph node, we believe that immune-induced regression of the primary is more likely. To test this hypothesis, we examined the prognostic impact of MUP in patients with melanoma metastatic to distant sites. Methods: We reviewed prospectively acquired data for 2,247 patients diagnosed with AJCC 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 identified known/unknown primary (HR=1.141, P=0.0316) and five other significant covariates: age (HR=1.148, P=0.0069), sex (HR=1.17, P=0.0012), site of metastasis (HR=1.336, P<0.0001), number of different metastatic sites (HR=1.303, P<0.0001), and decade of diagnosis (HR=0.713, P<0.0001). Matching of MUP and MKP by these significant covariates yielded 392 matched pairs. Median and 5-year OS rates were significantly greater for MUP patients than for all matched MKP patients (P=0.0002) or for MKP patients matched by M1 category (for M1b and M1c) or number of metastatic sites (Table). Conclusions: The significant survival advantage for MUP compared to MKP in stage IV melanoma suggests a systemic effect. We hypothesize that the clinical absence of a known primary is the result of a strong and durable endogenous antitumor response that alters disease biology and thereby improves clinical outcome. Immunologic studies to identify the nature of this endogenous response warrant further investigation. Variable N Pairs MKP Median Survival (months) MKP 5-year Survival (%) MUP Median Survival (months) MUP 5-year Survival (%) P Matched Outcome 392 11 10+3 16 18+4 0.0002 M1 Category M1a 26 16 18+15 20 12+12 0.4109 M1b 95 13 9+6 19 21+9 0.0155 M1c 271 10 10+4 15 18+5 0.0009 # Sites 1 170 14 11+5 19 26+7 0.0009 2 222 10 10+4 13 12+5 0.0361 MUP=melanoma of unknown primary; MKP=melanoma of known primary No significant financial relationships to disclose.