Treatment

Treatment

Merkel Cell Carcinoma has the potential to be lethal and appropriate management often should involve several types of therapy such as surgery, radiation, and sometimes systemic medications. Multidisciplinary evaluation of patients with this cancer is critical to determine and carry out a proper treatment plan. The treatment will often differ depending on what stage of the cancer the patient has. 

Due to the rarity of this disease, recruitment of enough participants to clinical trials to explore effective treatments is difficult. There is not enough evidence to know the best way to treat Merkel Cell Carcinoma at its different stages. Therefore, Merkel Cell Carcinoma researchers and doctors tries to involve patients in Merkel Cell Carcinoma clinical trials to improve knowledge of treatments for Merkel Cell Carcinoma.

See Research for more information on clinical trials and how to be involved.

Treatment decisions depend on many issues that are highly variable between patients. It is best to obtain care from a multi-disciplinary team of physicians with significant Merkel Cell Carcinoma experience who take into consideration many clinical factors.

Australian Merkel Cell Carcinoma Treatment Guidelines are currently in development.

 

What are my treatment options?

The treatment options for Merkel Cell Carcinoma may vary for different patients and may include a single therapy such as surgery, or a combination of therapies, such as surgery followed by radiotherapy or drug therapy.

Surgery
The goal of surgical excision is to remove the Merkel cell carcinoma so that it does not recur near the primary site or in the nearby lymph nodes. The primary MCC tumour should ideally be removed with clear margins (no microscopic tumour at edge of excision) as judged by pathology examination. Even with margins >2 cm, surgery alone can have a high recurrence rate near the primary MCC site of up to 42%. The chance of local recurrence after surgical excision of the primary tumour is higher for MCC than for the more common types of skin cancer (basal cell carcinoma, squamous cell carcinoma or even melanoma) because MCC more often “jumps” discontinuously to adjacent normal-appearing skin, with recurrences happening quite commonly up to several centimetres away from the edge of the primary tumour. The local recurrence rate can be as high as 20-40% and can typically be reduced to less than 5% by additional local radiation therapy. Merkel cell carcinoma is a highly radiation sensitive cancer in most cases.
Importantly, if radiation is used at the primary site, it is not required for the surgeon to obtain clear margins because radiation kills isolated tumour cells in the radiation field which usually extends at least 5 cm beyond where the tumour was.

Depending on your general health and the location and size of the MCC, surgery may not be possible. In such cases, radiation therapy is sometimes used alone. Several studies suggest that radiation therapy alone may be nearly as effective as both radiation therapy and surgery.

Side effects

Surgical excision side effects are highly dependent on the location and size of the tumour and they mostly relate to how much skin needs to be excised near the tumour.

Radiation Therapy
Radiation therapy, also referred to as radiotherapy or XRT, is the treatment of cancer with penetrating beams of energy waves or streams of particles that can destroy cancer cells. Radiation therapy is delivered to the cancer cells and a margin of surrounding apparently normal tissue, referred to as the radiation field. Radiation therapy damages the genetic material of cancer cells making them unable to grow.  Adjuvant radiation therapy is radiotherapy that is used to destroy any cancer cells that may remain after surgery has removed all of the tumour that is visible. Radiotherapy is associated with a statistically significant improvement in local and nodal recurrence.

Side effects

Common side-effects of radiation therapy in the area being treated include loss of hair, skin irritation (like a sunburn), and changes in the colour and texture of the skin. Radiation to a draining lymph node basin may cause swelling of the arm or leg on the same side that may be long-lasting, and is more likely if extensive nodal surgery has also been carried out. A frequent side effect is fatigue, which usually resolves within a month or two after the radiotherapy is stopped. Accordingly, it is important to eat a well-balanced diet and get plenty of rest. A radiation oncologist may adjust the dose or schedule of radiation therapy based on the side effects. Localized radiation therapy typically does not lead to nausea, vomiting, or hair loss outside of the irradiated area.

Chemotherapy

Chemotherapy is a type of cancer treatment that can kill or slow the growth of cancer cells, but chemotherapy can also target healthy cells. Chemotherapy is mainly used currently to try and treat MCC that has spread and is in the later stages. There may be a role for its use in the adjuvant setting particularly for patients who are perceived to be at high risk of the MCC spreading. MCC can initially be responsive to chemotherapy but can often quickly gain resistance.

Side effects

As chemotherapy also targets healthy cells, side-effects and toxicities involved with this chemotherapy includes hair loss, nausea, vomiting, and infections.

Immunotherapy

Immunotherapy is a type of treatment that uses the body’s own immune system to recognise and destroy cancer cells. Immunotherapy is rapidly replacing chemotherapy as the standard of care for MCC that has spread (metastasised), with favourable progression-free survival rates compared to previous data of patients with MCC receiving chemotherapy.

MCC tumours can hide from the immune system by expressing a protein (PD-L1 or PD-1 are types of these proteins) which can act as a brake on a pathway (called the immune checkpoint pathway) and stop the immune system from recognising and killing the tumour cells.

Therefore the PD1-PDL1 immune-checkpoint pathway is a key therapeutic target for MCC. Immune checkpoint inhibitors are a type of treatment that are currently being investigated, these can block the PD-L1 or PD-1 proteins, allowing the body’s immune system to recognise and kill the tumour cells.

Avelumab (anti-PDL1 antibody) has been approved in Australia for use in patients with advanced-stage MCC. Avelumab and pembrolizumab (anti-PD1 antibody) are both approved in the US for use in patients with advanced-stage MCC. Nivolumab (anti-PD1 antibody) and ipilimumab (CTLA-4 antibody) are also currently under investigation in a number of clinical trials.

However, only around half of patients with advanced-stage MCC respond to immune-checkpoint blockade. Moreover, of those that did respond, a substantial number of patients acquired secondary resistance. More needs to be done to understand the underlying mechanisms of primary and secondary resistance to overcome these issues.

Side effects

Common side effects for immune checkpoint inhibitors include, fatigue, cough, nausea, and itching. These are often seen as an improvement compared to the side-effects caused by traditional chemotherapy. However, in some cases these immunotherapy treatments can cause immune attack against the body. This can lead to colitis (diarrhoea), hepatitis (liver injury), pneumonitis (lung inflammation), hormone changes, or nerve damage. Close clinical supervision is necessary.

Complementary therapies

People who strongly believe in a holistic approach to cancer therapy may benefit from coaching on diet, lifestyle, and exercise. Many people can benefit from more regular exercise, particularly if they can find types of exercise that are enjoyable and if the exercise can mean spending more time with family or friends who can walk, swim, or garden together. Many claims for the benefits of complementary/alternative medicine have not been scientifically verified. Some people already eat healthily and get enough exercise.

Side effects

Certain supplements can have side effects and/or interact with prescription medications, therefore please consult your doctor if you are considering taking any supplements.

Follow Up and Management
During your treatment for Merkel Cell Carcinoma you will attend regular follow up visits to make sure your treatment is working. If the treatment isn’t working, you may be prescribed another treatment after discussion with your doctor.

Following your MCC treatment, you will attend regular follow up visits to make sure your MCC has not returned or spread.

These follow up visits might include;
• Clinic visits with your doctor
• Blood tests
• Imaging scans
• Physical exams
Merkel cell carcinoma
Mailing address:

AMIGOs
C/O Melanoma and Skin Cancer Trials
553 St Kilda Road
Melbourne, VIC 3004, Australia

General enquiries:

Email: amigos@masc.org.au

Melanoma and Skin Cancer Trials
Mailing address:

Melanoma and Skin Cancer Trials
553 St Kilda Road
Melbourne, VIC 3004, Australia

General enquiries:

Email: hello@masc.org.au