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Immune response predicts improved survival in Merkel cell carcinoma
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HEMONC TODAY Melanoma and Cutaneous Malignancies.
NEW YORK — Merkel cell carcinoma is a relatively rare cancer, with 1,600 new cases per year in the United States. Mortality is high, at about 40% at 5 years, but therapies targeting the immune system have shown promise.
Risk factors include prolonged sun exposure, particularly in those with light skin; immune suppression; and age older than 50 years. The incidence rate is growing, according to Paul Nghiem, MD, PhD, associate professor of the dermatology division at the University of Washington Medical School. “It is exponential; as the population ages, we are likely to see an increase in incidence,” he said here at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.
The disease presents as a nonspecific, firm, rapidly growing non-tender nodule on sun-exposed skin. Most nodules are thought to be benign and may be misdiagnosed as cysts. However, the pathologic evaluation is very specific for disease, and microscopic examination is critical in making the diagnosis. Usually, sentinel node biopsy is indicated, as well as excision or adjuvant radiation for local and regional control.
“Biopsy has therapeutic significance; microscopic node-positive cancers are vastly more likely to recur if they are not treated either by surgical excision of remaining nodes or radiation. Both have excellent regional control rates,” Nghiem said. The addition of radiation tends to improve outcomes, however; Nghiem cited a study by Lewis and colleagues of 1,254 cases that showed a 3.7 times greater likelihood of local recurrence and a 2.9 times greater likelihood of regional recurrence with surgery alone.
Merkel cell polyomavirus is present in up to 80% of cases, but it is not necessary for the disease to occur. “It’s not clearly causal in any other disease, malignant or otherwise, and interestingly, most of us have it on our skin,” Nghiem said. “It’s very common, but only rarely contributes to disease. There’s never been a convincing case ever of one patient having two primary Merkel cell carcinomas.” Viral status only modestly affects outcome, he said.
Immune system response appears to predict improved survival. Genes upregulated in good prognosis cases are associated with CD8+ T-cell responses, Nghiem said, citing a 2011 study by Paulson and colleagues. Nghiem described an independent validation set of 146 patients across the country, in which high intratumoral infiltration of CD8 cells in 26 patients was associated with 100% Merkel cell cancer-specific survival for those patients.
Interferon-beta alone has been shown to be somewhat effective in the immune response to the disease. Adjuvant chemotherapy in high-risk patients is unfeasible at this time, Nghiem said, due to its immunosuppressive effect. – by Carey Cowles
Presented at: HemOnc Today Melanoma and Cutaneous Malignancies Meeting; June 25-26, 2011; New York.
Disclosure: Dr. Nghiem reported no relevant financial disclosures.
The 2012 HemOnc Today Melanoma and Cutaneous Malignancies Meeting will be held April 13-14 at the Grand Hyatt, New York, NY. Learn more at HemOncToday.com/melanoma.
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