Merkel Cell Carcinoma Treatments

Treatment of Merkel cell carcinoma (MCC) is based mainly on the stage of the disease and the overall health of the patient. The core treatments for MCC, along with surgical excision, have been radiation and chemotherapy, but some revolutionary therapies have recently moved into the forefront.  

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. MCC is especially responsive to radiation.

If the cancer has reached the local lymph node basin (stage III), doctors generally also excise and/or irradiate all the nodes in the basin, thereby reducing the risk of recurrence and possibly preventing spread (metastasis) to distant sites beyond the lymph nodes, including organs (stage IV).  

Sentinel Node Biopsy

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 enlarged nodes are 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.) 

In a sentinel node biopsy, a surgeon removes and checks one or two nodes (the “sentinel nodes”) closest to the tumor, on the premise that metastatic cells from the tumor will first reach these nodes. 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 do a course of radiation on the basin itself after all the lymph nodes are removed.  If further testing shows that the cancer has metastasized beyond the lymph nodes (stage IV), other treatments come into play, including immunotherapy and a variety of chemotherapies.  

The Checkpoint Blockade Immunotherapies

Recently, researchers achieved the first significant successes ever in treatment of stage IV Merkel cell carcinoma, with an intravenous form of immunotherapy called “checkpoint blockade therapy.” In March, 2017, the US Food and Drug Administration (FDA) approved the checkpoint blockade therapy drug avelumab (brand name Bavencio), for the treatment of adults and pediatric patients 12 years and older with MCC. The FDA based its approval, the first ever for advanced MCC, on data from a clinical trial in which 33 percent of the patients experienced complete or partial shrinkage of their tumors.

Checkpoint blockade immunotherapies block certain molecules that inhibit or “check” T cell production to prevent excessive and potentially dangerous inflammatory and autoimmune reactions under normal conditions. By blocking these inhibiting molecules, the drugs release waves of T cells to attack the MCC cells. 

Avelumab blocks programmed death-ligand 1 (PD-L1), a molecule that binds to another molecule called PD-1 (programmed death-1) on tumor cells, forming the complex that inhibits T cell activation. By blocking PD-L1, avelumab prevents it from binding with PD-1, thereby releasing T cells to fight MCC. In the avelumab trial, the responses lasted more than six months in 86 percent of responding patients and more than 12 months in 45 percent of responding patients.

In December 2018, the FDA granted accelerated approval to a second checkpoint blockade therapy, pembrolizumab (brand name Keytruda), for adult and pediatric patients with recurrent locally advanced or metastatic MCC. The FDA based its approval on a multicenter clinical trial of 50 adult and pediatric patients with recurrent or advanced disease who had not received prior systemic therapy. Fifty-six percent of patients responded to the drug, with 24 percent going into complete remission. Among the 28 patients who responded, 96 percent had response durations of greater than six months and 54 percent had response durations of greater than 12 months. Median progression-free survival was 16.8 months.

Pembrolizumab was previously approved for treatment of advanced melanoma patients, whose lives it has sometimes extended by many years, sending the disease into long-term remission.

Pembrolizumab blocks the immune-inhibiting molecule PD-1, thereby releasing waves of T cells to attack the cancer cells. Sixty-four percent of the responding patients in this study had the Merkel cell polyomavirus, suggesting that antigens from the virus may have enhanced therapeutic response. Future studies will investigate whether pembrolizumab and other treatments can indeed target the polyomavirus. [See Merkel Cell Carcinoma – Causes]

On May 30, 2017, a team of researchers from Fred Hutchison University and the University of Washington in Seattle reported the successful results of a small study combining avelumab with two other treatments (autologous T-cell transfer therapy and either radiation or another immunotherapy called interferon). Three out of four stage IV metastatic MCC patients treated with this experimental combination are in complete remission following the treatment, with no sign of the cancer remaining. In autologous T-cell transfer therapy, the researchers extract T cells that recognize the MCC from the patient’s blood, multiply them in the lab and then reinject them into the patient to boost their attack on the MCC cells. When they add the avelumab, it appears to kick the enhanced T cells into high gear.   

A previous study of four patients combining the T-cell transfer therapy with radiation or interferon, but not including avelumab, was not as successful, with disease progressing in three of the patients, two of whom have since died.    


To date, standard chemotherapy has never been tremendously beneficial for MCC patients.

Doctors usually recommend it 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.

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, 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 they are hard to detect 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.

Medical Reviewer:

Deborah S. Sarnoff, MD

Last Medical Review: June 9, 2017
Last Revised: July 13, 2018

Causes of Merkel
Cell Carcinoma
Risk Factors and
Warning Signs

Stages of Merkel
Cell Carcinoma