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Merkel Cell Carcinoma Therapeutic Update

  • Skin Cancer (BY Kwong, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Early-stage disease can be cured with surgical resection and radiotherapy (RT). Sentinel lymph node biopsy (SLNB) is an important staging tool, as a microscopic MCC is frequently identified. Adjuvant RT to the primary excision site and regional lymph node bed may improve locoregional control. However, newer studies confirm that patients with biopsy-negative sentinel lymph nodes may not benefit from regional RT. Advanced MCC currently lacks a highly effective treatment as responses to chemotherapy are not durable. Recent work suggests that immunotherapy targeting the programmed cell death receptor 1/programmed cell death ligand 1 (PD-1/PD-L1) checkpoint holds great promise in treating advanced MCC and may provide durable responses in a portion of patients. At the same time, high-throughput sequencing studies have demonstrated significant differences in the mutational profiles of tumors with and without the Merkel cell polyomavirus (MCV). An important secondary endpoint in the ongoing immunotherapy trials for MCC will be determining if there is a response difference between the virus-positive MCC tumors that typically lack a large mutational burden and the virus-negative tumors that have a large number of somatic mutations and predicted tumor neoantigens. Interestingly, sequencing studies have failed to identify a highly recurrent activated driver pathway in the majority of MCC tumors. This may explain why targeted therapies can demonstrate exceptional responses in case reports but fail when treating all comers with MCC. Ultimately, a precision medicine approach may be more appropriate for treating MCC, where identified driver mutations are used to direct targeted therapies. At a minimum, stratifying patients in future clinical trials based on tumor viral status should be considered as virus-negative tumors are more likely to harbor activating driver mutations.

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Authors and Affiliations

  1. Department of Dermatology, Walter Reed National Military Medical Center, Bethesda, MD, USA

    Nicole M. Cassler MD

  2. University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA

    Dean Merrill BA

  3. Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA

    Christopher K. Bichakjian MD

  4. Dermatology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD, 20892-1908, USA

    Isaac Brownell MD, PhD

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  1. Nicole M. Cassler MD
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  2. Dean Merrill BA
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  3. Christopher K. Bichakjian MD
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  4. Isaac Brownell MD, PhD
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Correspondence to Isaac Brownell MD, PhD.

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The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Navy, the Department of Defense, or the National Institutes of Health.

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This article is part of the Topical Collection on Skin Cancer

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Cassler, N.M., Merrill, D., Bichakjian, C.K. et al. Merkel Cell Carcinoma Therapeutic Update. Curr. Treat. Options in Oncol. 17, 36 (2016). https://doi.org/10.1007/s11864-016-0409-1

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