What is Metastatic Melanoma?
The rate of skin cancer, specifically melanoma, has been on the rise for many years and it’s the most dangerous type of skin cancer. People diagnosed with melanoma at its early stages have a 94% survival rate. However, the types of melanoma that affect the mucus membranes and eyes usually have a poorer prognosis. In the past, melanoma was known to be very aggressive and resisted traditional treatment methods like chemotherapy, radiation, and early versions of targeted therapies. But recent advances in combining targeted therapies and different types of immune therapies have dramatically improved the survival rates and quality of life for people with advanced melanoma.
Interestingly, melanoma is different from other skin cancers because it can spread not just locally, but also to regional and distant parts of the body. How likely a person’s melanoma spreads is directly related to how deep the original cancer invaded and whether it caused an ulcer. When melanoma spreads, it first invades nearby tissue, promotes new blood vessels for growth, moves into the bloodstream or lymphatic system, then spreads and starts growing in other organs – a process known as metastasis. People with melanoma can still have metastasis even if their lymph nodes appear negative for cancer or their sentinel (first) lymph node biopsy comes out negative. Additionally, removing all lymph nodes hasn’t been shown to extend survival for people who have lymph node-positive melanoma.
There have been instances where melanoma spread from a donor to a recipient following an organ transplant, even when the transplant happened years after the donor’s melanoma diagnosis. This scenario represents the possibility of early, hidden, tiny spreading (micrometastasis) of melanoma. According to The American Society of Clinical Oncology, only about 4% of melanomas are already metastatic at diagnosis, indicating the spread of melanoma involves several factors including the tumor’s surrounding environment and the body’s immune system. Despite efforts, finding specific genetic changes that cause melanoma to spread hasn’t been very successful. However, certain genetic alterations and mutations occur more frequently in metastatic melanomas.
Last but not least, melanoma often spreads to the brain, causing high rates of illness and death, as well as making treatment more difficult due to the brain’s protective barrier (the blood-brain barrier).
What Causes Metastatic Melanoma?
Some types of melanoma, a kind of skin cancer, are linked with too much sun exposure over a long time. But in some cases, we’re not sure what causes the melanoma. The 2018 World Health Organization (WHO) groups melanomas into several categories.
Types of melanoma that are often linked with too much sun exposure:
– Pathway I. This is called superficial spreading melanoma or low-sun damage melanoma.
– Pathway II. This is called lentigo maligna melanoma or high-sun damage melanoma.
– Pathway III. This is called desmoplastic melanoma.
Types of melanoma are not always linked with sun damage:
– Pathway IV: This is called Spitz melanomas.
– Pathway V: This is called acral melanoma.
– Pathway VI: These are called mucosal melanomas.
– Pathway VII: These melanomas start in birthmarks.
– Pathway VIII: These melanomas start in blue moles.
– Pathway IX: This is called uveal melanoma.
There’s also a type of melanoma called nodular melanoma that can occur in any of these pathways. We know that four main types of melanoma affect the skin:
– Superficial spreading melanoma is the most common melanoma. It often has an uneven shape, irregular edges, changes in color, and it’s larger than normal. It grows slowly across the top layer of the skin and it does not go deeper into the skin.
– Nodular melanoma can be found in areas that are frequently exposed to the sun, like the head and neck. Under the microscope, it’s seen that it only grows vertically, not horizontally across the skin. It grows quickly and is usually already deep in the skin when it’s found. It makes up 15-20% of melanomas but causes 40% of melanoma deaths.
Lentigo maligna melanoma usually occurs in older people on their face, where the skin has been damaged by the sun. It starts from a sun spot that slowly grows and changes color from brown to black with uneven edges.
Acral lentiginous melanoma also isn’t consistently linked to sun damage, but it tends to affect the palms of the hands, the soles of the feet, or under the nails.
Risk Factors and Frequency for Metastatic Melanoma
According to the National Cancer Institute’s (NCI) data, melanoma is now the fifth most common cancer in both men and women. In 2023, it’s estimated that there will be 97,610 new melanoma cases in the US, possibly causing around 7,990 deaths.
Melanoma is caused by a range of factors, such as your environment, genes, and your immune system. Some studies have especially focused on improving the immune system and understanding cancer pathways. This has helped in developing successful treatments which can target and improve the immune system directly.
- Several specific genes have been linked to an increased risk of melanoma, including CDKN2A, CDK4, and MC1R.
- There’s also a genetic disorder called xeroderma pigmentosum (XP) that can increase your risk. This condition causes the body to improperly repair damage from UV rays, leading to a higher mutation rate.
Signs and Symptoms of Metastatic Melanoma
Melanoma, a type of skin cancer, can be identified early by remembering the ABCDE rule. Each letter represents a different characteristic of melanoma:
- “A” is for Asymmetry: the two halves of the area may differ in shape
- “B” is for Border: the edges may be irregular or blurred
- “C” is for Color: the color may not be the same all over the area and could include shades of black, brown, pink, red, white, or blue
- “D” is for Diameter: it is larger than 6mm, about the size of a pencil eraser
- “E” is for Evolving: the mole is changing in size, shape, or color
An examination tool called a dermoscope can also be useful to help tell if a skin change is benign (not cancer) or malignant (cancer). Once a melanoma diagnosis is confirmed, doctors use the American Joint Committee on Cancer (AJCC) guidelines to decide on the best treatment plan and to predict the patient’s prognosis (outlook).
Testing for Metastatic Melanoma
Metastatic melanoma is a serious skin cancer that can spread to different parts of the body. According to the American Cancer Society, the five-year survival rate for metastatic melanoma that has spread to distant areas of the body is about 32%. However, if the cancer is only spread regionally, which means it’s still relatively close to where it started, the survival rate goes up to 71%. The location of the spread can also impact the overall prognosis.
Your doctor can use a skin tissue sample, also known as a biopsy, to help identify if you have melanoma. This biopsy allows a skin cancer specialist (dermatopathologist) to fully assess the melanoma and confirm the diagnosis. It also helps them understand the stage of your disease and plan your treatment.
If you’ve been diagnosed with more than one melanoma, it might suggest that the disease has spread. Once the diagnosis of melanoma is confirmed through biopsy and laboratory tests, the cancer’s stage is determined. The stage of cancer describes how much cancer is in the body and where it has spread. The American Joint Committee on Cancer (AJCC) uses a system to classify melanoma into five stages (0, I, II, III, and IV); the higher the stage number, the more serious the disease. Stage 0 is a very early-stage melanoma, while stage IV is metastatic melanoma, which means the cancer has spread to distant parts of the body.
There is a specific test for a gene mutation called BRAF, which is found in approximately 40% to 50% of melanomas. This gene can be targeted for treatment in advanced stages of melanoma. The test involves extracting DNA from the tumor and checking for the presence of the BRAF mutation.
The AJCC has established a set of criteria for staging melanoma, which include measuring the size and ulceration status of the tumor (T), checking for the involvement of lymph nodes (N), and identifying the presence of metastasis (M) or spread to other parts of the body.
Screening for metastasis or spread of melanoma can involve various imaging tests such as a Computed Tomography (CT) scan and Positron-Emission Tomography (PET) scan. These can help identify the presence of melanoma in the subcutaneous tissue (under your skin), lymph nodes, lungs, brain, and liver. In some cases, a biopsy of the sentinel lymph node (the first lymph node to which cancer cells are likely to spread from a primary tumor) may be performed to help determine the cancer stage and plan treatment.
Follow-up care and surveillance include regular medical checkups, imaging tests, and laboratory studies. The specific tests and frequency depend on the stage of your melanoma, risk of spread, and overall health status. This helps in monitoring your response to treatment and detecting any new signs of cancer early.
Treatment Options for Metastatic Melanoma
Early-stage melanoma, which is a type of skin cancer, is usually treated by surgically removing the growth and potentially some surrounding skin for safety. If the melanoma is at a more advanced stage and is found in more than one place in the body (known as metastatic melanoma), treatment is more complicated.
In recent years, we have better understood how different genetic changes can lead to melanoma. This knowledge has helped us develop more targeted treatments that can specifically attack cancer cells with these genetic changes. There are several approved treatments now available for metastatic melanoma that either help the immune system to recognize and destroy cancer cells (immunotherapies) or interfere with the way cancer cells grow and divide (targeted therapies).
Targeted treatment for melanoma with one or more tumors in a limited area (known as oligometastatic disease) include surgical removal of the tumors, the targeted use of high-energy x-rays to kill the cancer cells (stereotactic radiation), and a type of genetically engineered virus that can selectively kill cancer cells (talimogene laherparepvec, or T-VEC).
Regular radiation therapy is also used in advanced melanoma, often to help relieve symptoms. For melanoma patients with brain metastases, a type of radiation therapy called stereotactic radiosurgery can be particularly beneficial.
For people with melanoma that has spread to many parts of the body, systemic therapies that work throughout the body are usually the primary treatment approach. In the past, chemotherapy was often used, but newer targeted therapies and immunotherapies have now largely replaced chemotherapy for this purpose.
Targeted therapies are drugs that work by interrupting specific biological processes that cancer cells rely on to survive and grow. For melanoma, targeted therapies have been developed to block the activity of a protein called BRAF, which is mutated in about half of all melanomas and drives uncontrolled cell growth. The BRAF inhibitors dabrafenib, vemurafenib and encorafenib have shown their effectiveness in treating melanoma, but the benefits often do not last because the cancer eventually becomes resistant to these drugs. To delay or prevent this resistance, BRAF inhibitors are often used in combination with drugs that target MEK, another protein involved in the same cell growth pathway.
Immunotherapies are a class of drugs that help the immune system to recognize and attack cancer cells. For melanoma, immunotherapies that target either PD-1 (pembrolizumab and nivolumab) or CTLA-4 (ipilimumab) have been particularly effective. However, these drugs can sometimes cause serious side effects. More recently, a new class of drugs has been developed that target a protein called LAG-3, which also regulates immune responses.
In some cases, other targeted therapies may also be used. For example, about 20% of melanomas have changes in a gene called KIT that make them vulnerable to drugs known as KIT inhibitors. Another small portion of melanomas have changes in a gene called ROS1, which can be targeted with specific drugs.
In summary, the treatment of melanoma has progressed significantly over the last decade, and several effective therapies are now available for metastatic melanoma. While these therapies can often control the disease and even cure some people, there are still challenges to overcome, such as drug resistance and side effects. Thus, research continues to develop better treatments for this disease.
What else can Metastatic Melanoma be?
When trying to diagnose a certain condition, doctors consider some other possible conditions that could be causing the symptoms. These could include:
- Pigmented basal cell carcinoma
- Seborrheic keratosis
- Squamous cell carcinoma (like Bowen disease, pagetoid or pigmented type)
- Dermatofibroma
- Other types of cutaneous metastases
- Paget disease
- Recurrent melanocytic nevi
Each of these has its own unique signs and symptoms, so doctors must perform specific tests to determine the correct diagnosis.
What to expect with Metastatic Melanoma
The future health outlook or prognosis of a cancer called metastatic melanoma largely depends on a few factors such as the stage of cancer, any specific genetic changes in the cancer cells, and the general health of the patient. The survival rate for patients with this cancer, observed from 2012-2018, is around 30% over five years, emphasizing the necessity for effective treatments.
The severity or stage of the disease identified at diagnosis is the most important factor influencing the outlook for individuals with metastatic melanoma. The system used to classify the severity of melanoma is the American Joint Committee on Cancer (AJCC) staging system, which categorizes melanoma based on the depth of the cancer’s penetration, lymph node involvement (cancer spread in the liquid-carrying channels of the body), and how far it has spread to distant areas of the body. People with stage IV melanoma, those with cancer that has spread extensively, usually only survive a median of about 20 months.
In recent times, new treatments have been developed targeting specific genetic changes found in the cancer cells, helping to improve patient survival. A change in the BRAF V600 gene, which is seen in approximately 40-50% of all melanoma cases, has been the focal point of new therapy development. Medicine that inhibit the BRAF gene, such as vemurafenib and dabrafenib, have shown to be effective in treating people with stage IV melanoma that have this gene mutation, with positive response rates in 50-70% of cases.
Another important factor is the immune status of the person. Our immune system is vital in detecting and eradicating cancer cells, and a new line of treatments called immunotherapies have been presenting hope for individuals with metastatic melanoma. ICIs (Immune Checkpoint Inhibitors), like anti-CTLA-4 and anti-PD-1 antibodies, aid in increasing the body’s immune response to cancer, and have shown to improve treatment response by 20-40%. These can be combined with other treatments, including those targeted on the BRAF mutation or other genetic changes, providing even better results.
In summary, the outlook for metastatic melanoma patients remains tough, with a high death rate and limited treatments available. Nonetheless, the emergence of gene-targeted therapies and new approaches that stimulate the body’s immune response against the cancer have meaningfully improved patient outcomes. Further studies into the biology of this form of cancer, and the creation of new treatment approaches, gives hope for even better outcomes in the future.
Possible Complications When Diagnosed with Metastatic Melanoma
The treatment of metastatic melanoma, a serious skin cancer, often uses a combination of surgery, radiation therapy, immune-boosting treatments, and targeted therapy. Though these treatments can help patients, they come with their own set of complications.
A common issue with metastatic melanoma treatment is inflammation and tissue damage caused by immune-boosting treatments. These treatments empower the immune system to recognize and attack cancer cells. However, this heightened immune response can also lead to inflammation and damage to healthy tissue, causing health issues called immune-related adverse events. These can be serious and demand quick treatment with steroids or other drugs that suppress the immune system, which may affect the success of the initial treatment.
Resistance to targeted therapy is another issue. The treatments, which block specific molecular pathways in cancer cells, can become less effective as cancer cells adapt by mutating or using alternative signaling pathways. If this happens, the disease may progress, and different treatments may become necessary.
There are also potential complications related to surgery, which is often done to remove the initial tumors or metastatic lesions. These complications can include bleeding, infection, and nerve damage. In addition, surgery can cause scarring and functional impairments that may affect quality of life.
Radiation therapy, one of the treatments used in managing metastatic melanoma, comes with its own set of complications, including skin irritation, fatigue, and damage to the tissue surrounding the treated area. It can also increase the risk of developing other types of cancer, particularly in patients who are genetically predisposed to cancer.
Complications of Metastatic melanoma treatment:
- Inflammation and tissue damage from immune-boosting treatments
- Resistance to targeted therapy
- Complications from surgery, such as bleeding, infection, and nerve damage
- Scarring and functional impairments from surgery
- Side effects of radiation therapy, including skin irritation, fatigue, and tissue damage
- Increased risk of other cancers from radiation therapy
The treatment of metastatic melanoma can lead to several complications that could affect the treatment outcomes and the patient’s quality of life. While advances in treatment have improved survival rates, the potential benefits of treatment need to be carefully weighed against the potential complications. Keeping a close watch on these complications and addressing them quickly can help minimize their impact and improve treatment outcomes.
Preventing Metastatic Melanoma
Prevention practices for the spread of melanoma skin cancer include proactively protecting yourself from the sun. This could involve wearing protective clothing and using sunscreen, and having regular skin checks to identify and remove any suspicious marks or blemishes. Recent scientific studies suggest that targeted treatments or immune therapies may lessen the chance of the disease returning in patients at high risk of melanoma. In one clinical trial, the immune therapy drug, pembrolizumab, was shown to extend the period of time without the disease returning in patients who had undergone surgery for serious melanoma.
It is important to support patients in learning about their diagnosis, the treatments available, and potential side effects. Patients need to understand the significance of sticking to their treatment plans and the need for regular checks to catch any adverse reactions early on. It’s also key for patients to know how to deal with symptoms related to treatment, such as fatigue, feelings of nausea, and skin rashes. A number of studies have found that by educating patients it is possible to improve treatment results in individuals with melanoma skin cancer that has spread.
In conclusion, prevention and educating the patient are important components of treating metastatic melanoma effectively. Preventive strategies can help stop the disease from spreading and coming back, while educating patients can enable them to manage their symptoms and make informed decisions about their health. By implementing these strategies, doctors can improve patient outcomes and lessen the difficulties patients face when dealing with melanoma skin cancer that has spread.
