Adjuvant Therapy Tied to Better Survival in High-Risk Merkel Cell Carcinoma

By Will Boggs MD

NEW YORK (Reuters Health) - Adjuvant chemoradiotherapy (CRT) is associated with improved survival in patients with high-risk Merkel cell carcinoma of the head and neck, according to a new retrospective study.

Surgery, either surgical excision or Mohs surgery, is the primary treatment for Merkel cell carcinoma of the head and neck, but there is controversy regarding the role of concurrent chemotherapy in patients who are receiving postoperative radiotherapy.

Dr. Benjamin L. Judson from Yale University School of Medicine in New Haven, Connecticut, and colleagues used the National Cancer Data Base from 1998 to 2011 to evaluate the association between CRT and overall survival in 4,815 adult patients with head and neck Merkel cell carcinoma.

Most of the patients (92.0%) underwent surgical excision, and the remaining 8.0% underwent Mohs surgery, the team reports in JAMA Otolaryngology - Head & Neck Surgery, online December 4.

Of the 58.6% of patients who received postoperative adjuvant therapy, 82.6% received adjuvant radiotherapy, 13.9% received adjuvant CRT and 3.4% received adjuvant chemotherapy.

Five-year overall survival rates were 38.5% for surgery alone, 42.8% for adjuvant radiotherapy, 47.5% for adjuvant CRT, and 28.7% for adjuvant chemotherapy.

Factors independently associated with decreased overall survival included patient age 75 years or older, increasing tumor size, positive margins, and the presence of metastatic lymph nodes. Adjuvant radiotherapy and adjuvant CRT were associated with a better prognosis than surgery alone, whereas postoperative chemotherapy was associated with reduced overall survival.

Adjuvant CRT tended to provide better survival than adjuvant radiotherapy, but this difference was significant only among patients with positive margins, patients with tumors 3 cm or larger, and male patients.

"Although prior studies have not shown an added survival benefit associated with postoperative CRT over radiotherapy, our results suggest that postoperative CRT may be an important tool to use in the management of high-risk patients with head and neck Merkel cell carcinoma," the investigators conclude. "Further multi-institutional studies are needed to investigate possible systemic treatments and treatment intensification in order to improve outcomes in head and neck Merkel cell carcinoma."

Dr. Brett A. Miles from Mount Sinai School of Medicine in New York, who has studied head and neck Merkel cell carcinoma, said the malignancy "is widely known to exhibit aggressive clinical behavior with advanced lesions, nodal metastasis, and positive margins. I would expect postsurgical adjuvant chemoradiation to provide a survival benefit over surgery alone."

"(B)ased on these results, adjuvant chemoradiation should be considered for any Merkel cell carcinoma patient with nodal metastasis or >3 cm, large extensive tumors," Dr. Miles told Reuters Health by email. "It should also be considered in cases where achieving negative surgical margins is not possible. Mohs surgery should be considered in smaller lesions when feasible, as data indicates more reliable margin control in these lesions. For larger lesions with deep invasion, this principle may not hold true due to the complexity of performing Mohs surgery in these lesions."

"The management of intermediate stage disease remains controversial in terms of adjuvant radiation versus adjuvant chemoradiotherapy," Dr. Miles added. "While the current study clearly shows benefit of chemoradiation in the setting of advanced disease, adjuvant radiation alone may be adequate therapy for intermediate lesions; however, current data does appear to favor chemoradiation in the postoperative setting in terms of overall survival."

"Recent new data regarding the analysis of Merkel cell carcinoma has resulted in a dramatic increase in our knowledge regarding this disease," Dr. Miles said. "Current work in biomarkers and the discovery of the Merkel cell polyomavirus have provided us with new data with which to target this disease. Work in viral detection and protein expression continues to further elucidate the role of the virus in the genesis of Merkel cell carcinoma. The development of viral vaccines and targeted agents for the treatment of Merkel cell carcinoma is ongoing. Targeted therapy for these rare tumors may improve outcomes in the future."

Dr. Judson did not respond to a request for comments.

SOURCE: https://bit.ly/1yDdcJq

JAMA Otolaryngol Head Neck Surg 2014.

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