About Melanoma

Melanoma is a personal journey, different for every patient and every friend or family member. It’s a personal disease, with different causes, symptoms, courses of progression, treatments and prognosis. It’s useful to know about the disease as you make your own personal journey with melanoma.

What Is Melanoma?

Melanoma is a type of skin cancer most commonly caused by damage to the DNA in a certain type of skin cells called melanocytes, often due to exposure to ultraviolet light.

This damage can cause skin cells to form cancerous tumours, but if caught early it is almost always curable. However, if left untreated, melanoma can spread, or metastasize, to other parts of the body – such as the brain, bones, liver, and lungs.

When melanoma cannot be fully removed by surgery (stage III unresectable), or has metastasized (stage IV), it is known as advanced melanoma and is the most serious form of skin cancer. Until recently, advanced melanoma was a disease with limited treatment options and a poor prognosis. In the last few years, however, significant advances in the molecular understanding of this disease have allowed the development of novel and promising treatments. However, advanced melanoma can still be much more difficult to treat than melanoma that remains localized.

Canadian Facts and Figures

• Melanoma is one of the top 10 cancers diagnosed in Canada, accounting for 3% of all new cancer diagnoses.
  
• It was estimated that 6,800 Canadians were diagnosed with melanoma in 2015. That’s an average of more than 18 Canadians diagnosed with melanoma every day.
• It is estimated that in 2015, 1,150 Canadians died from their melanoma.
  
• In Canada, the incidence of melanoma has been increasing significantly over the past several decades. From 2001 to 2010, the incidence of melanoma increased 2.3% per year for men and 2.9% per year for women.
  

The Stages of Melanoma

Dr. Mihalcioiu explains the different stages of melanoma.

Melanoma, like many cancers, is characterized into 4 main cancer stages Melanoma staging is based on the thickness of the cancerous tumour in the skin and whether and how far it has spread. Determining the stage of melanoma can include physical exams and biopsies, as well as imaging tests such as CT or MRI scans. The 4 main stages of melanoma are:

The cancerous tumour has formed within the skin but is small and localized and is growing at a slow rate.

The cancerous tumour, though localized, is considered intermediate melanoma as it is larger (generally over 1-millimeter thick) and/or growing at a faster rate than a stage I tumour. It has not been found in lymph vessels, lymph nodes, or distant organs.

Resectable (removable) melanomas are cancerous tumours that have spread to lymph nodes, but can still be removed by surgery. There is no distant spread.

Unresectable (unremovable) melanomas are cancerous tumours that have spread beyond the skin to the lymph nodes, and surgery may not be able to remove all of the cancer. There is no distant spread.

Also known as metastatic melanoma, it means the melanoma has metastasized, or spread, to lymph nodes that are distant from the primary cancerous tumour, or to organs, such as the lungs, liver, brain, or bones.

• Stage I – The cancerous tumour has formed within the skin but is small and localized and is growing at a slow rate.^xiii
• Stage II – The cancerous tumour, though localized, is considered intermediate melanoma as it is larger (generally over 1-millimeter thick) and/or growing at a faster rate than a stage I tumour. It has not been found in lymph vessels, lymph nodes, or distant organs.^xiv
• Stage III Resectable (removable) melanomas are cancerous tumours that have spread to lymph nodes, but can still be removed by surgery. There is no distant spread.
• Unresectable (unremovable) melanomas are cancerous tumours that have spread beyond the skin to the lymph nodes, and surgery may not be able to remove all of the cancer. There is no distant spread.^xv
• Stage IV – Also known as metastatic melanoma, it means the melanoma has metastasized, or spread, to lymph nodes that are distant from the primary cancerous tumour, or to organs, such as the lungs, liver, brain, or bones.^xvi

Patients with unresectable Stage III melanoma and Stage IV (metastatic) melanoma are considered to have advanced melanoma.

Despite these staging definitions, not all melanoma cases are the same. Patients may have different genetic changes present in their tumour, also called mutations, making their disease uniquely personal.

Mutations in Advanced Melanoma : Not A “One Size Fits All” Disease

Advanced melanoma (unresectable or metastatic melanoma) varies from person to person due to changes in the genes that are unique to each person with the disease.

In fact, melanoma is one of the cancers with the highest frequency of mutations. There are several melanoma mutations that you can be tested for, and identifying your form may influence the choice of treatment to help you control this disease.

Mutations in Advanced Melanoma (Unresectable or Metastatic)

BRAF+ – This mutation is found in nearly 50% of all advanced melanomas and is the most common type of genetic mutation associated with the disease. There are several forms of BRAF mutations, including V600E, V600K, V600D, V600G, and V600R. BRAF mutation is most common in patients whose tumours are not caused by chronic sun-induced damage.

NRAS – The second most common mutation found in advanced melanoma is NRAS. These mutations have been found in 15%-20% of melanomas. These tumours tend to be thicker and grow faster.

c-KIT –The c-KIT mutation can vary based on ethnicity. These mutations have been found in about 6%-7% of advanced melanoma in Caucasians, but are more common in Asian populations. c-KIT mutations are more likely to be found in melanomas that start on the palms of the hands, soles of the feet, under the nails, inside the mouth or nose or other mucosal areas and in areas that get regular sun exposure.

If a gene test was conducted, and no mutation was detected, the tumor may be referred to as "wild-type." Wild-type means that no specific gene mutation was identified in the melanoma tumor.

When it comes to advanced melanoma (unresectable or metastatic), knowledge is powerful. A genetic test can help identify if the tumour has a mutation. Genetic tests are performed on a sample of the tumour that has been removed by your doctor (also known as a biopsy).

Testing and Treatment

Over the past 40 years, research has significantly improved our understanding of advanced melanoma regarding the molecular and genetic changes of a person’s tumour. New diagnostic tools and treatment options are now available in the fight against advanced melanoma, but the battle continues.

One major advance has been specific genetic tests, which health care professionals can use to detect mutations and screen patients to assess their likelihood of responding to therapies. Until recently, advanced melanoma was a disease with limited treatment options and a poor prognosis. In the last few years, however, significant advances in the molecular understanding of this disease have allowed the development of novel and promising treatments.

Besides treatments that have generally been given a broad range of patients, there are now some specific therapy options to treat advanced melanoma in patients with certain genetic changes (mutations) in their tumour, but physicians must first identify if a mutation is present and which form it may be.

There are many different types of genetic tests available. Some tests can only detect the most common mutations while others are more sensitive and can detect additional, less common forms. BRAF testing can be done with tissue obtained from a sample, or biopsy, from the tumour.

Melanoma treatment guidelines recommend testing for patients with advanced melanoma in order to identify whether genetic changes (mutations) are present in the tumour. Identifying the form of your advanced melanoma is an important step to developing a personalized treatment plan with your doctor. Treatment selection is based on a range of factors including stage of disease, overall health and lifestyle.

Treatment options may include:

Target proteins that are activated by mutated genes. This slows down or stops the growth of cancer cells. In advanced melanoma, targeted therapies are available for patients with the BRAF mutation. Side effects of targeted therapy can vary depending on the specific treatment and generally go away at the end of treatment. The most common side effects include diarrhea and liver problems. Some adverse events that may sometimes be serious or life-threatening may also occur. These include severe fever, heart problems, blood clots, bleeding problems, eye problems, severe skin reactions, lung complications, liver injury, second cancers, radiation injury, harm to unborn babies and reduced effectiveness of birth control using hormones.

Stimulates a patient’s immune system to fight cancer cells. The most common side effects are pain, redness and swelling around the infusion site, diarrhea, nausea, rash and joint pain. Some adverse events that may sometimes be serious or life-threatening may also occur. These include severe allergic reactions, inflammation in the intestines, liver, kidney, lungs, skin, nerves, hormone glands or the eyes, blood sugar problems, stomach, liver, kidney, lung skin, muscle, nerve or eye problems and problems with the pancreas. As well, patients should not breast feed and should not become pregnant as these therapies can cause harm or death to unborn babies.

Involves oral or injectable drugs to inhibit the growth of cancer cells.  ACS Melanoma Skin Cancer 2015, pg 35, A The most common side effect is fatigue, but because these drugs can also kill healthy cells that divide rapidly they can cause mouth sores, nausea and hair loss. These side effects generally go away after treatment. Other side effects include nausea, vomiting and diarrhea and significant impairment of liver and kidney function can also occur.

Surgery is the main treatment option for most early-stage melanomas and used to remove tumours from the body. Any surgery involves the risks of having pain and infection, as well as bleeding, damage to nearby tissues, and reactions to the anesthesia. There may also be specific risks for the type of surgery you have.

Uses high-energy rays, like getting an X-ray but with much stronger radiation, to kill cancer cells. While not often used to treat the original melanoma, it’s sometimes used following surgery to prevent recurrence or slow its spread. Radiation therapy can result in damage to healthy tissues near the radiation site but this almost always recovers afterwards and doctors try to prevent it by using as low a dose as possible, targeting precisely and spreading treatments out over time. The most common side effect of radiation therapy is fatigue but sometimes late effects can appear some time after the therapy.

• Targeted Therapies – Target tumours that have a specific type of damaged gene by targeting the specific mutation and preventing tumours from growing and spreading.^xxxvii In advanced melanoma, targeted therapies are available for patients with the BRAF mutation.^xxxviii Side effects of targeted therapy can vary depending on the specific treatment and generally go away at the end of treatment. The most common side effects include diarrhea and liver problems but others include problems with blood clotting and wound healing, high blood pressure, fatigue, mouth sores, nail changes, loss of hair colour and skin problems such as a rash or dry skin. A very rare side effect is the development of a hole through the wall of the esophagus, stomach, small intestine, large bowel, rectum, or gallbladder.^xxxix
• Immunotherapy – Stimulates a patient’s immune system to fight cancer cells.^xl Immunotherapy can cause rare but severe or even fatal allergic reactions. The most common side effects are pain, redness and swelling around the injection site. They can also cause swelling, weight gain from fluid retention, heart palpitations, sinus congestion, diarrhea and increased risk of infection.^xli
• Chemotherapy – Involves oral or injectable drugs to inhibit the growth of cancer cells.^xlii The most common side effect is fatigue, but because these drugs can also kill healthy cells that divide rapidly they can cause mouth sores, nausea and hair loss. These side effects generally go away after treatment.^xliii
• Surgery – Surgery is the main treatment option for most early-stage melanomas and used to remove tumours from the body.^xliv Any surgery involves the risks of having pain and infection, as well as bleeding, damage to nearby tissues, and reactions to the anesthesia. There may also be specific risks for the type of surgery you have.^xlv
• Radiation Therapy – Uses high-energy rays, like getting an X-ray but with much stronger radiation, to kill cancer cells.^xlvi While not often used to treat the original melanoma, it’s sometimes used following surgery to prevent recurrence or slow its spread.^xlvii Radiation therapy can result in damage to healthy tissues near the radiation site but this almost always recovers afterwards and doctors try to prevent it by using as low a dose as possible, targeting precisely and spreading treatments out over time. The most common side effect of radiation therapy is fatigue but sometimes late effects can appear some time after the therapy.^xlviii

NOTE: This is not a complete list of side effects associated with the above types of treatment and others may occur. In addition, the side effects discussed may not apply to all treatments.