Treatment of Merkel cell carcinoma is largely based on the stage of the disease, as well as the overall health of the patient. To date, the core treatments for MCC have been surgical excision, radiation and chemotherapy.
At all stages of MCC, physicians recommend complete excision of the primary (original) tumor, verified by pathologic examination. After excision, if the risk of recurrence or spread to the local lymph nodes is high (due to factors such as a large primary tumor, incomplete excision or a patient with a suppressed immune system), the doctor will usually recommend that the lesion be treated with a course of radiation. In fact, many physicians recommend a course of radiation for all MCC patients. This may destroy any cancer cells that are not detectable by physical exam and can help prevent recurrence or spread of the cancer to the local lymph nodes or beyond. Merkel cell carcinoma is especially responsive to radiation.
If the cancer has reached the local lymph node basin, doctors generally also excise and/or irradiate all the nodes in the basin, thereby reducing the risk of a recurrence and possibly preventing distant metastasis. In most cases, patients with no obvious lymph node disease should undergo a procedure called sentinel lymph node biopsy (SLNB) to verify whether cancerous cells have reached the local lymph node basin. Unlike other skin cancers, MCCs frequently have spread to the nearby lymph nodes or beyond by the time of diagnosis, whether or not the nodes are enlarged or detectable on physical examination. Even a small MCC has about a 30 percent chance of having spread to the nearby lymph nodes by the time of diagnosis. (In comparison, the chance of an average melanoma having spread to the lymph nodes at diagnosis is only 1 percent.)
The results of the sentinel node biopsy are important in helping the doctor determine a patient’s prognosis and future treatment. If the test is negative, no further treatment may be needed. If the test is positive, doctors most often excise the rest of the nodes in the basin and often also do a course of radiation on the basin itself after all the lymph nodes are removed. Depending on further testing, other treatments may come into play as well.
Doctors usually recommend chemotherapy only for patients whose cancer has spread to distant sites, such as organs like the lungs or liver. A variety of chemotherapies have been used for advanced MCC, with varied (and often limited) success. Unfortunately, they often have significant side effects. No controlled clinical studies have shown that any of them extend survival, though they can often lead to short remissions. Doctors also can use them to eliminate or reduce specific lesions to decrease pain and increase the patient’s comfort and mobility.
The latest research has focused on boosting the immune system’s ability to attack the cancer cells. Early studies have been especially promising with “checkpoint blockade” immunotherapies, which block certain receptors that inhibit or “check” T cell production to prevent excessive and potentially dangerous inflammatory and autoimmune reactions.
One such therapy being studied, already FDA-approved for advanced melanoma, is pembrolizumab (KeytrudaR), an intravenously injected drug that blocks an immune-inhibiting receptor called programmed death-1 (PD-1). By blocking PD-1, pembrolizumab can release waves of T cells to attack cancer cells. Pembrolizumab has had exciting success with melanoma patients, sometimes extending lives by many years and sending the disease into long-term remission. It has shown early promise with advanced MCC. In one small early study of 26 advanced MCC patients, 14 (56 percent) responded to treatment with pembrolizumab, with four patients going into complete remission. The majority of the responding patients had the Merkel cell polyomavirus, suggesting that antigens from the virus may have enhanced therapeutic response. Though the study was not designed specifically to determine whether pembrolizumab could block the MCC polyomavirus, the results showed that the treatment had that effect, and future studies will investigate whether this and other treatments can indeed target the polyomavirus.
Another intravenously injected checkpoint blockade therapy that investigators are testing on MCC patients is avelumab, which blocks programmed death-ligand 1 (PD-L1), the molecule that binds to PD-1 on tumor cells, forming the complex that inhibits T cell activation. Just as pembrolizumab releases T cells by blocking PD-1, avelumab releases T cells by blocking PD-L1.
Based on the results of a Phase II global multicenter trial of 88 patients with metastatic MCC published in Lancet Oncology in October of 2016, in November of 2016 the U.S. Food and Drug Administration (FDA) granted “Priority Review” to avelumab to expedite the approval process. Priority Review status reduces the review time from 10 months to a goal of six months from the day of filing. It is given to drugs that may offer major advances in treatment or may provide a treatment where no adequate therapy exists. The hope is to gain FDA approval and make Avelumab widely available as early as possible.
If you have been treated for an MCC, you and your physician should monitor your skin closely for the rest of your life. Recommended follow-up after treatment is every month for six months, every three months for the next two years and every six months thereafter.
Challenges in Diagnosis and Treatment
Diagnosis and management of Merkel cell carcinoma are challenging. Patients as well as physicians may initially mistake these tumors for benign lesions. In fact, at the time of biopsy, 58 percent of MCCs are believed to be benign on initial physical examination by physicians. The single most common presumed diagnosis is a cyst or folliculitis (swelling from inflamed hair follicles).
In some cases, the Merkel cell tumor arises in locations that elude detection, delaying diagnosis: About 5 percent of MCCs occur in mucosal sites, such as the mouth, nasal cavity and throat, where it is hard to detect them before the disease has advanced. In one study, 14 percent of MCCs were initially discovered in the lymph nodes already, without any primary tumor ever being identified.
Since MCC is an especially aggressive cancer, delays in detection can lead to late diagnosis and treatment, where recurrences are common and successful treatment is more difficult to achieve.
Deborah S. Sarnoff, MD