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Melanoma

Introduction

The word 'melanoma' comes from the ancient Greek word for 'black', and describes tumours that can appear in the skin due to the abnormal and malignant (i.e. cancerous) growth of melanocytes - pigment cells in the skin that produce melanin. Melanin ordinarily protects the skin from sun damage caused by ultraviolet (UV) radiation.

There are in fact three types of skin cancer - melanoma, squamous cell carcinoma and basal cell carcinoma, but melanoma is considered the most dangerous of the three as it can spread from the skin to other parts of the body.

As the human body grows, melanocytes sometimes group together and form moles - moles are not themselves cancerous, however if the melanocytes in them begin to grow more rapidly than normal, melanoma can form, which then grows either up above the skin, or down into the layer of skin underneath (the 'dermis'). If not caught at this stage, a melanoma growing down into the dermis can spread to other areas via the lymphatic system or the bloodstream.

Causes

The main cause of melanoma is exposure to any form of UV radiation, for example natural sunlight or artificial UV light from sunbeds or solariums. Melanoma can form anywhere on the surface of the skin, not just in those areas that are exposed to sunlight. Men and women often develop melanoma on different parts of the body - for example melanoma formation on the back is common in men, and on the legs is more common in women.

Statistics from the Cancer Council of Australia indicate that men stand a 7% chance, and women a 4% chance of developing melanoma by the age of 85. Melanoma is the fourth commonest cancer diagnosis in Australia (which, with New Zealand, is the highest diagnosis rate in the world). It is also the sixth commonest cause of death from cancer in men, and the tenth in women.

Risk Factors

There are a number of factors which increase the risk of developing melanoma:

  • Overexposure to UV light – repeated sunburn (especially at a young age i.e. under 15), use of sunbeds / solariums.
  • Age – most diagnoses are in people who are 50+ (but it is also the most commonly diagnosed type of cancer in the 15-44 age bracket).
  • Lowered immune response.
  • Hereditary factors – e.g. family history of melanoma in a close relative; fair skin, light hair / eye colour, freckles.
  • Large number of moles on the skin – particularly a specific type called 'Dyplastic Neavi'.
  • Previous skin cancers.

The danger of sunbed / solarium use is shown in studies which indicate that people under 35 using sunbeds / solariums regularly are at an 87% greater risk of developing melanoma than the general population.

Symptoms

The only noticeable symptom is where there has been a change in the appearance of a mole on the skin. The assessment of these changes uses a system known as 'ABCDE' referring to these changes. ABCDE stands for: Asymmetry (where the mole is no longer round but becomes an irregular shape); Border (where uneven rather than smooth); Colour (where uneven); Diameter (over 6mm may indicate the presence of melanoma) and Evolving (where it is changing or growing).

Diagnosis / Tests

The most important test is to have any unusual looking moles checked by a medical specialist, and to book in for regular examination of your skin and any moles.

Once a melanoma is diagnosed, the ‘stage’ of the cancer is determined, and this depends on tumour thickness, ulceration, spread to nearby skin or lymph nodes, or spread to other sites in the body.

A diagnosis of melanoma is often made after a suspicious skin lesion is identified, then this is removed (excised) and examined by a pathologist under the microscope. This enables additional details about the melanoma such as thickness to be determined. Sometimes the first diagnosis of melanoma is made when a lymph node or a mass is identified, either by noticing a new lump, or a lesion is seen on a scan done for another reason. This lesion is then tested by using a needle (e.g. a fine-needle aspirate, or FNA) to obtain some cells to be examined by a pathologist. In some cases, the primary melanoma is not identified and there is no history of a previous melanoma (unknown primary).

Depending on the features of the primary melanoma, your doctor may advise that you need to have a body scan such as CT (computed tomography) or PET (positron emission tomography). A PET scan is a special scan that uses very small amounts of a radioactive chemical called FDG (which is like a sugar), to produce images of areas in the body where there is more activity within cells that takes up the FDG. These ‘hot spots’ can help indicate whether a cancer may have spread outside to other parts of the body (metastases), and can sometime be used to monitor response to treatment. Your doctor will advise you how often scans should be performed, if any, after the initial diagnosis, depending on risk of recurrence and other factors.

Approximately half of melanomas have an alteration (mutation) within a gene called BRAF. These mutations often enable the melanoma to grow and survive, and there are now drugs that can target this mutation (BRAF inhibitors) and can be very effective in shrinking advanced melanoma. These mutations are not hereditary, so there is no risk of ‘passing on’ the BRAF gene to your family. Testing for the mutation is often done on one of the biopsy samples from an area where the melanoma has spread.

Treatment

The most effective form of treatment is prevention of overexposure to UV radiation - avoiding the use of sunbeds and solariums, and keeping out of the sun, particularly when UV radiation is at its highest in the middle of the day, and using sunscreen and wearing clothes and a hat when outside during the day. This also applies on a cloudy day.

Surgery

Where melanoma is detected early, treatment can be very effective. Surgical removal of a mole and a 'margin' of the surrounding skin is the most effective treatment for melanoma, and is often the only treatment needed for early stage disease. If the melanoma has spread to surrounding skin or lymph nodes, or recurs in these areas after previous treatment, then surgical removal may also be successful in preventing further recurrences.

Immunotherapy

Over the past few years, there have been significant advances in drug development for treatment of advanced melanoma. Immunotherapy works by encouraging the body's own self-defence mechanism - the immune system - to fight cancer cells more effectively. Often when a cancer has become established in the body, the immune system stops recognising the cancer cells and effectively stops fighting them. A range of different drugs have now been developed to encourage the immune system to work more effectively against cancer cells.

Immunotherapy, either with a single drug or with combination approaches, is most often used in advanced melanoma (stage 4) and when it is effective, the response can be maintained for considerable periods of time, which can be many years in some patients. This is because the immune system has been ‘activated’, and can continue to prevent recurrence of melanoma even after the treatment has been stopped.

More recently, clinical trials have shown that immunotherapy may also reduce the recurrence in stage 3 melanoma after surgical resection. Although the drugs are not yet registered for stage 3 melanoma in Australia, they may be available as part of a clinical trial in some centres. In the future, immunotherapy is likely to become an important standard treatment following surgery for many patients with stage 3 melanoma.

Side effects

Immunotherapy sometimes causes side effects but is generally better tolerated than many conventional chemotherapy drugs. The most common side effects of immunotherapy include fatigue, which is usually mild but can be more severe when multiple drugs are used, dry or itchy skin, and effects on the thyroid gland (under or overactivity).

Targeted therapies

Advanced melanoma where there is a mutation in the BRAF gene is often treated with novel ‘targeted drugs’ called BRAF inhibitors. These are oral tablets that are taken daily, and can be very effective in melanoma with this mutation. BRAF inhibitors are usually combined with another targeted oral drug, a MEK inhibitor, which targets the same pathway as BRAF inhibitors. The combination of BRAF/MEK inhibitors has been shown in trials to be more effective than BRAF inhibitors alone.

Side effects of BRAF/MEK inhibitors include fevers or chills, fatigue, nausea and vomiting, diarrhoea, headaches and joint pains. Most of these side effects can be treated with drugs or other strategies such as short treatment breaks.

Other genes that are sometimes altered in melanoma include NRAS and C-KIT, and ongoing trials are examining the potential for other targeted therapies to provide benefit in melanoma.

Radiation therapy

Radiotherapy uses high-energy ionising radiation (like x-rays or gamma rays) to kill cancer cells. It is sometimes used in melanoma to eliminate remaining cells after surgery in stage 3 disease and reduce the risk of recurrence. The use of radiotherapy has declined in recent years, mainly since the advanced and development of drugs such as immunotherapy or targeted therapies. Radiotherapy may also have a role in treating areas of melanoma spread that are at high risk of causing complications, such as when melanoma spreads to the brain or bones.

Chemotherapy

Chemotherapy are drugs used to fight cancer. They are usually given through a needle in the vein. The use of chemotherapy in melanoma has declined significantly in recent years, following the development of newer more effective treatment. It is occasionally used in advanced melanoma when other treatment have not been effective. Side effects include fatigue, and gut symptoms such as nausea and vomiting. Most side effects related to chemotherapy can be managed with other supportive treatments or drugs and tend to improve once treatment is finished.

Clinical trials

Clinical trials are a type of research studies that may be testing a new treatment approach or new drugs. They are the best way to develop new treatments to treat cancer, and often are comparing a new approach to current standard treatments or testing a new treatment when there is no current beneficial treatment. They also are one way of getting the newest treatment for cancer.

The suitability of a clinical trial for each patient depends on the cancer type and stage, prior treatments given, their other health problems, the overall potential for risks and side effects compared to potential benefits, and their preferences. If you want to know more about clinical trials in your particular circumstances, talk to you doctor or health professional.

Related Information

Immunotherapy

Targeted therapies

Chemotherapy