How is Merkel cell carcinoma (MCC) treated?

Updated: Oct 07, 2019
  • Author: Guy J Petruzzelli, MD, PhD, MBA, FACS; Chief Editor: Gregory Gary Caputy, MD, PhD, FICS  more...
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Due to the rarity of MCCs, clinical treatment protocols have not undergone extensive comparative trials. Furthermore, no consensus on postsurgical treatment, such as adjuvant chemotherapy versus adjuvant radiation therapy, has been reached in the medical literature.  

Lyhne suggested that treatment and staging for MCC with curative intent should involve (1) CT or positron emission tomography (PET) imaging of the thorax and abdomen, (2) excision of the primary MCC with wide margins, (3) sentinel lymph node biopsy, (4) surgical bed adjuvant radiotherapy, and (5) systemic palliative chemotherapy for patients with advanced-staged metastatic MCC. [43]

Excision of MCC with negative margins is the foundation of surgical treatment. [44]  Surgical resection of the primary tumor entails wide excision with 1-3 cm margins. [39, 45]  Tai and colleagues comprehensively reviewed previously published cases of MCC and concluded that complete excision significantly improved overall survival. [29] In addition, tumor size and location greatly impacted the outcome of surgical excision. A worse prognosis has been associated with primary tumors larger than 2 cm and located in the perianal and vulvar regions.

The high rate of local recurrence even after surgical excision, approximately 50% in some reports, argues strongly for regional lymphadenectomy. [31] In a limited number of cases, Smith and colleagues demonstrated that patients with local and regional control (excision of primary tumor and regional lymphadenectomy) had 50% lower recurrence and mortality rates. [46] However, in one retrospective study, locoregional control did not significantly improve disease-free survival when compared with local control for MCC localized in the neck. [29]  Sentinel node biopsy, which is often used to stage melanoma, does not seem to be useful for staging MCC or for predicting survival. [47]

After surgical excision, adjuvant therapy for MCC is recommended to prevent local recurrence, either via radiation therapy, chemotherapy, or a combination of the two. A 17-patient series supported the use of adjuvant radiotherapy for MCC. [48]

As MCC is radiosensitive, radiation therapy has been shown to decrease the local recurrence rate. [49]  Neck dissection and adjuvant radiotherapy are the foundation for treatment of MCC with positive nodes, while high-risk MCC without positive nodes should also receive adjuvant radiotherapy. [44]  In one retrospective study, Kokoska and colleagues demonstrated that aggressive treatment of MCC with locoregional control (surgical excision and regional lymphadenectomy) in combination with radiation therapy significantly improved survival rates when compared with local excision alone. [50]  A retrospective study by Tai et al demonstrated that the ideal overall radiation dose is 41-50 Gy in MCC therapy. [29]

The role of chemotherapy as adjuvant therapy is not well established in the literature. The basis of chemotherapy is for palliative treatment and advanced-stage MCC. [44]  The chemotherapy regimens used most often for treating MCC are etoposide and cisplatin; cyclophosphamide, doxorubicin, and vincristine; and cyclophosphamide, methotrexate, and 5-fluouracil. In one study, Boyle and colleagues demonstrated carboplatin and etoposide as effective treatment to reduce regional nodal disease in 8 (40%) of 20 patients. However, chemotherapy was less effective than radiation therapy. [51]  In contrast, a small retrospective study by Kokoska et al demonstrated that chemotherapy had no survival benefit. [50]  In another retrospective study, Tai and colleagues obtained similar findings. Chemotherapy was associated with a poorer outcome. These results are confounded by the fact that these patients had more advanced stages of disease. [52]

For metastatic disease, chemotherapy is rarely curative and serves only as palliative treatment. In the literature, no consensus has been reached regarding the ideal chemotherapy regimen. In a retrospective study by Tai and colleagues, the temporary response rate to chemotherapy for distant disease was higher than 50%. However, the disease soon relapses, and the prognosis is poor. Studies have shown no difference in prognosis among the different chemotherapy agents. Furthermore, the response to chemotherapy is usually temporary. [53, 54]

The combination of radiation and chemotherapy seems to be effective for advanced stages of MCC with local and regional involvement. [55]  In a retrospective study of 40 patients, Fenig and colleagues showed that chemotherapy alone was only effective short-term in a regional (lymph node) response, with a 69% partial or complete response. [56]  The addition of radiation significantly improved the efficacy, with a 91% partial or complete response.

Avelumab (Bavencio), an anti–programmed death ligand-1 (anti-PD-L1) immunoglobulin G1 (IgG1) monoclonal antibody, was approved by the US Food and Drug Administration (FDA) in March 2017 for metastatic MCC in adults and pediatric patients aged 12 years or older.

Approval of Avelumab was based on the JAVELIN Merkel 200 open-label, single-arm, multicenter study made up of 88 patients with histologically confirmed metastatic MCC, with progressive disease on or after administration of chemotherapy for distant metastatic disease. The overall response rate reached 33% (29 patients), with partial response in 22% and complete response in 11% of subjects. 86% of subjects with tumor responses had lasting effects for at least 6 months (25 patients), and 45% lasted at least 12 months (13 patients). Response duration lasted from 2.8 to over 23.3 months. [57]

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