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Original Investigation |

Effect of Host, Tumor, Diagnostic, and Treatment Variables on Outcomes in a Large Cohort With Merkel Cell Carcinoma

Maryam M. Asgari, MD, MPH1,2; Monica M. Sokil, BS1; E. Margaret Warton, MPH1; Jayasri Iyer, MD3; Kelly G. Paulson, MD, PhD3; Paul Nghiem, MD, PhD3,4
[+] Author Affiliations
1Division of Research, Kaiser Permanente Northern California, Oakland
2Department of Dermatology, University of California at San Francisco
3Fred Hutchinson Cancer Research Center, Seattle, Washington
4Division of Dermatology, Department of Medicine, University of Washington, Seattle
JAMA Dermatol. 2014;150(7):716-723. doi:10.1001/jamadermatol.2013.8116.
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Importance  Merkel cell carcinoma (MCC) is a rare, aggressive, neuroendocrine-derived skin cancer with high rates of recurrence and associated mortality. Few published studies have used comprehensive patient data and long-term follow-up to examine factors that predict MCC outcomes.

Objective  To characterize MCC in a large defined-population cohort and analyze predictors of disease recurrence and survival.

Setting, Design, and Participants  Retrospective cohort study of 218 patients with MCC from the cancer registry of Kaiser Permanente Northern California, a large integrated health care delivery system. Patients were diagnosed as having MCC and followed up from January 1, 1995, through December 31, 2009. We examined host (age, sex, race, and immunosuppression), tumor (anatomic site, size, and extent), diagnostic (results of imaging and pathologic nodal evaluation), and treatment (surgery, radiation therapy, and chemotherapy) variables for their association with MCC outcomes.

Exposure  Host, tumor, diagnostic, and treatment factors.

Main Outcomes and Measures  Recurrence (locoregional and distant) of MCC and patient survival (overall and MCC specific).

Results  We estimated adjusted hazard ratios (AHRs) and 95% CIs for outcomes using Cox proportional hazards regression models. After adjustment for host, tumor, diagnostic, and treatment variables, tumor extent (categorized as local, regional, and distant) remained significantly associated with all outcomes. Immunosuppression was associated with higher MCC-specific mortality (AHR, 4.9 [95% CI, 1.7-14.4]), and an unknown primary site was associated with a lower risk for distant metastasis (0.1 [0.0-0.7]) and improved survival (0.4 [0.2-0.9]). Pathological nodal evaluation was associated with a lower risk for metastasis (AHR, 0.2 [95% CI, 0.0-1.0]) and improved survival. Radiation treatment was associated with a decreased risk for locoregional recurrence (AHR, 0.3 [95% CI, 0.1-0.6]), whereas chemotherapy was not associated with any alteration in outcomes.

Conclusions and Relevance  Tumor site and extent, results of pathologic nodal evaluation, and the presence of radiation treatment were associated with MCC recurrence. Immunosuppression, tumor extent, and results of pathologic nodal evaluation were associated with MCC-specific survival, whereas chemotherapy was not associated with any outcomes. Our findings may help to inform diagnostic and therapeutic management of MCCs.

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