Epidemiology and survival outcomes of ocular and mucosal melanomas: A population-based analysis Kenneth D. Bishop 1,2 and Adam J. Olszewski 1,3 1 Department of Medicine, Alpert Medical School of Brown University, Providence, RI 2 Division of Hematology/Oncology, Rhode Island Hospital, Providence, RI 3 The Cancer Center at Memorial Hospital of Rhode Island, Pawtucket, RI Extracutaneous melanomas are poorly characterized tumors that include ocular (OM), mucosal (MM) and leptomeningeal mela- nomas, often lacking standardized staging and treatment guidelines. We analyzed cases of cutaneous melanoma (CM, N 5 219,890), OM (N 5 7,069) and MM (N 5 2,755) of different anatomical origins, diagnosed between 1988 and 2010, recorded in the Surveillance Epidemiology and End Results (SEER) database. Relative survival was studied in patients grouped by summary stage classification (localized, regional or distant disease) and in multivariate models adjusting for varying distri- bution of baseline factors. Unlike in CM, the incidence rate in MM increased exponentially with age. Five-year relative survival was significantly worse for OM (78%) and for most mucosal sites (aggregate 34%, range 3–69%) compared with CM (89%). The differences between primary sites were particularly pronounced in localized disease, with a hazard ratio of 5.7 for OM, 4.3–9.0 for external genital or oral cavity MM and 19.8–90.4 for other mucosal locations. Melanomas of the pharynx, gastro- intestinal, urinary tract and vagina had poor outcomes regardless of clinical stage. In contrast to CM, there was no evidence of improved survival in OM and MM during the study period. A substantial proportion of patients with operable OM or MM underwent radical organ resections (13–88% depending on site and stage) or perioperative radiotherapy (0–66%). In conclu- sion, extracutaneous melanomas have a markedly worse survival than CM and aggressive locoregional management appears to be insufficient for their control. Because of poor outcomes in MM, studies of systemic therapy are warranted regardless of the extent of disease at presentation. Extracutaneous melanomas (ECMs) are rare, aggressive can- cers that encompass ocular, mucosal and leptomeningeal mel- anomas. Ocular (OM) and mucosal melanomas (MM) have incidence of less than 1 per 100,000 person-years, making accrual into prospective studies difficult. 1 Consequently, there are no evidence-based management guidelines for these sub- types. ECMs have been reported to occur in older patients, often at an advanced stage, and to have worse prognosis. 2,3 It is possible that mechanisms of carcinogenesis in ECM differ from those in cutaneous melanoma (CM), rendering cur- rently used targeted therapies ineffective. 4 The objective of our study was to examine incidence, survival outcomes and locoregional treatment patterns of CM, OM and MM in the United States over the past two decades using a population- based registry. Patients and Methods Data source The Surveillance Epidemiology and End Results (SEER) pro- gram collects data on cancer incidence, treatment and out- comes from 18 United States (US) registries, currently representing 28% of the total US population. The registry mandates a 98% case ascertainment rate and conducts contin- uous quality assurance programs to secure completeness and consistency of coding. We extracted case listings and inci- dence rates from the November 2012 SEER submission files, covering records and survival follow-up until December 31, 2010. 5 Patients were identified using the International Classifi- cation of Diseases for Oncology, 3rd edition (ICD-O-3) histo- logy codes 8720 through 8790, year of diagnosis 1988–2010 and age of diagnosis 20 years, excluding cases diagnosed at autopsy, on death certificates only or with no recorded sur- vival time. The cutoff year of 1988 was chosen because it marked the beginning of consistent coding of extent of disease classification in SEER. Variables The SEER database contains information on demographic (age, gender, race and ethnicity and marital status), socioe- conomic (using grouped census track-level estimates) and clinicopathologic (histology, primary site, extent of the pri- mary tumor, nodal and metastatic involvement) Key words: melanoma, epidemiology, period survival, mucosal mel- anoma, uveal melanoma, ocular melanoma, SEER, radiotherapy DOI: 10.1002/ijc.28625 History: Received 26 Sep 2013; Accepted 13 Nov 2013; Online 22 Nov 2013 Correspondence to: Adam J. Olszewski, MD, 111 Brewster St., Pawtucket, RI 02860, USA, Tel.: 1401-729-2700, Fax: 1401-633-6550, E-mail: adam_olszewski@brown.edu Epidemiology Int. J. Cancer: 134, 2961–2971 (2014) V C 2013 UICC International Journal of Cancer IJC