Study tracks distant metastatic patterns of Merkel cell carcinoma

SCOTTSDALE, ARIZ. – Distant metastatic sites of Merkel cell carcinoma most often involved the supraclavicular, retroperitoneal, and iliac lymph nodes, in a single center retrospective study of 305 patients.

Merkel cell carcinoma metastases “clearly favored distant nodes, but the distribution of other metastatic sites was distinct from other cancers, such as melanoma,” Jamiluddin Qazi, an undergraduate student at the University of Washington, Seattle, said at the annual meeting of the Society for Investigative Dermatology. The findings could help guide imaging and other surveillance of patients after they develop a primary Merkel cell tumor, he added.

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About 2,000 individuals in the United States are diagnosed with Merkel cell carcinoma every year. About 40% of these patients develop metastatic disease, which has a 5-year survival rate of less than 25%, Mr. Qazi noted. Indeed, median survival after diagnosis of metastatic Merkel cell carcinoma was only 9.5 months in one recent study (J Cutan Pathol. 2010;37:20-7). Programmed death 1 (PD-1) blockade with pembrolizumab (Keytruda) can potentially improve survival (N Engl J Med. 2016; 374:2542-52), “but there is no consensus regarding follow-up for Merkel cell carcinoma. The 2016 National Comprehensive Cancer Network (NCCN) guidelines recommend ‘follow up as clinically indicated,’ and a lack of data has led to ambiguity,” Mr. Qazi said.

Working with oncologists and radiologists at the Seattle Cancer Care Alliance, he analyzed a tissue and clinical database of 442 initial distant Merkel cell carcinoma metastases among 305 patients. Initial distant metastases were defined as the first lesions detected beyond the regional lymph nodes of the primary tumor. A total of 69% of patients had one initial distant metastasis, 19% had two concurrently identified lesions, 9% had three lesions, and 4% had at least four lesions, Mr. Qazi reported.

“Merkel cell carcinoma seemed to metastasize to unusual places, but clearly preferred the distant lymph nodes. In all, 26% of metastases localized there, most commonly to the supraclavicular, retroperitoneal, and iliac nodes,” he said. The next most common site of distant metastasis was the liver (15% of lesions), followed by the skin and bone (13% of lesions each), lung (6%), and pancreas (5%). Less common sites included the heart, spleen, abdominal muscle, brain, kidneys, adrenal glands, gonad, chest wall, and stomach.

Comparing these findings with a similar study in melanoma (J Oncol 2012. doi: 10.1155/2012/647684) showed that both cancers have about the same chances of metastasizing to the liver, bone, kidneys, adrenal glands, and stomach, Mr. Qazi said. However, Merkel cell carcinoma was less likely to metastasize to the brain (3% of lesions, vs. 12% for melanoma) and lung (6% vs. 14%), and was more likely to metastasize to the pancreas (5% vs. 1%).

Now the investigators are working to link metastatic sites with factors such as the location of the primary tumor, the presence or absence of lymphovascular invasion, and the status of the immune system and Merkel polyomavirus infection, said Mr. Qazi. They also are analyzing time from diagnosis or treatment to metastasis to help guide decisions about when to order follow-up imaging. Ultimately, they hope to create an online tool that enables clinicians to describe a primary Merkel cell carcinoma and rapidly receive automated information about the most likely timing and location of metastasis.

The National Institutes of Health supported the study. Mr. Qazi had no conflicts of interest.