Immune response predicts improved survival in Merkel cell carcinoma
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.