Key predictors of recurrence and survival for Merkel Cell Carcinoma elucidated

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1. Immunosuppression was associated with a higher likelihood of Merkel Cell Carcinoma (MCC)-specific mortality. Other factors that affected MCC-specific prognosis include tumor site and extent, results of pathologic nodal evaluation, and presence of radiation treatment. 

2. Metastatic MCC of unknown primary sites were associated with significantly improved outcomes. 

Evidence Rating Level: 2 (Good) 

Study Rundown: MCC is an aggressive neuroectodermal tumor of the skin that is associated with a mortality rate triple that of melanoma. MCC is rare with approximately 1500 new diagnoses annually in the US, and thus, the consolidation of diagnostic and treatment data has been challenging.  In this study, the authors utilized the Kaiser Permanente Northern California (KPNC) database to analyze the host, tumor, diagnostic, and treatment variables on tumor recurrence and mortality rate. Most notably for clinicians, the study revealed that chemotherapy has little benefit on MCC outcomes and may be best reserved for palliative care.  One novel finding from this study was that tumors of unknown primary sites were associated with a decreased risk for distant metastasis and overall mortality. Finally, the data also confirmed associative factors that have been well described in the literature, such as the increased mortality rate in MCC patients who are immunosuppressed.  This article’s strength lies in the large sample size that is often challenging to attain for rare diseases.  The difficulty in controlling confounding factors, such as other co-morbidities, is a major limitation that should be considered when drawing conclusions from mortality data.

Click to read the study in JAMA Dermatology

Relevant reading: Relationships among primary tumor size, number of involved nodes, and survival for 8044 cases of Merkel cell carcinoma

In-Depth [retrospective cohort]: The computerized record system from KPNC was screened for all patients with an initial diagnosis of MCC from January 1, 1995 through December 31, 2009. A total of 220 patients were identified and were assessed for 4 major covariates (host, tumor, diagnostic, and treatment variables) as well as 2 outcomes of interest (disease recurrence and survival). The data was analyzed using univariate and multivariate Cox regression models to estimate adjusted hazard ratios (AHR) and 95% CI for outcomes.  Host variables were significant for an association between immunosuppression and MCC-specific mortality (AHR, 4.9 [95% CI, 1.7-14.4]).  Patients who received sentinel lymph node biopsy without lymphadenectomy experienced a reduction in overall mortality (AHR, 0.4 [95% CI, 0.2-0.7]). Among the treatment variables, both surgery and chemotherapy had no statistically significant effect on outcomes, but radiation therapy was associated with a protective effect on local tumor reoccurrence (AHR, 0.3 [95% CI, 0.1-0.6]).

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