Date of Award

2006

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Lynn Wilson

Abstract

Merkel cell carcinoma (MCC) is a rare form of skin cancer, often described as the most aggressive cutaneous malignancy. Its high propensity for dermal-lymphatic invasion, local recurrence, and rapid lymphatic and distant metastasis poses a significant treatment challenge to clinicians. Combining its highly aggressive nature with its low incidence, merkel cell carcinoma is a particularly difficult cancer to study. Two major staging criteria exist for Merkel cell carcinoma. The purpose of this study is to validate and compare the Memorial Sloan Kettering Cancer Center (MSKCC) staging criteria with the American Joint Committee on Cancer (AJCC) Tumor, Node, Metastasis (TNM) staging criteria for Merkel cell carcinoma (MCC) utilizing the Surveillance, Epidemiology, and End Results (SEER) database. The role of radiation therapy (RT) is also evaluated. 1556 cases of MCC from the SEER database (1988-2002) were identified and evaluated. Tumor size, lymph node status, and metastases were staged according to the MSKCC and AJCC TNM staging criteria respectively (n = 561). The primary outcome was overall survival. Covariates included: age at diagnosis, site of primary, receipt of radiation therapy, and MSKCC or AJCC stage respectively. Kaplan-Meier survival analyses and Cox proportional hazards regressions were analyzed using SAS 9.1. The median age was 75 years (range: 22-98) with 39% of patients being female. The median follow up was 2.2 years with a range of 0.4-14.3 in the staged populations. Under the MSKCC staging criteria: five-year overall survival was 59% for stage I (n=224), 45% for stage II (n=114), 33% for stage III (n=140), and 28% for stage IV (n=83). When compared with stage I, the adjusted mortality HR was 1.44 (95% CI 1.03-2.00) for stage II, 2.14 (95% CI 1.57-2.93) for stage III, and 2.61 (95% CI 1.85-3.67) for stage IV. Under AJCC TNM staging criteria: five-year overall survival was 60% for stage I (n=223), 47% for stage II (n=107), 31% for stage III (n=148), and 28% for stage IV (n=83). When compared with stage I, the adjusted mortality HR was 1.41 (95% CI 0.99-1.99) for stage II, 2.13 (95% CI 1.57-2. 89) for stage III, and 2.62 (95% CI 1.86-3.69) for stage IV. Among 478 patients with local or regional disease, 49% received radiation. After adjusting for MSKCC stage and age, radiation was not associated with survival, mortality HR 0.83 (95% CI 0.63-1.09). The interaction of radiation with stage was not significant (P=0.69). Similarly, in the AJCC TNM staged population, radiation was not associated with survival, mortality HR 0.83 (95% CI 0.63-1.09), with no interaction of radiation with stage (P=0.42). The MSKCC staging criteria appropriately and significantly risk stratified MCC within this SEER population. Alternately, the AJCC staging criteria did not significantly risk stratify MCC within this SEER population. The MSKCC criteria appears to better risk stratify MCC than the AJCC staging criteria, within this SEER population. Radiation does not appear to confer a survival advantage among SEER patients with local or regional disease.

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