When it comes to the early stages of the disease, the future is bright. Most people with thin, localized melanomas are cured by appropriate surgery. Early detection still remains the best weapon in fighting skin cancer.

More treatments are available for more advanced disease. The cure rate continues to rise. Research has produced a greater understanding of melanoma, leading to the development of new drugs.

Surgical Excision: The first step in treatment is the removal of the melanoma, usually by surgical excision (cutting it out). Most surgical excisions, also called resections, are done in a doctor's office or as an outpatient procedure with local anesthesia. Scars are usually small and improve over time. Surgery is less extensive than in the past, so scars are smaller.

Discolorations and areas that are depressed or raised following the surgery can be concealed with cosmetics specially formulated to provide camouflage. If the melanoma is larger and requires more extensive surgery, a better cosmetic appearance can be obtained with flaps made from skin that is near the tumor, or with grafts of skin taken from another part of the body. For grafting, the skin is removed from areas that are normally or easily covered with clothing.

There is now a trend towards performing a sentinel lymph node biopsy and tumor removal at the same time.

Setting the Margins

In today's technique, much less of the normal skin around the tumor is removed. The borders of the entire area to be excised — both tumor and healthy skin — are known as the margins. Margins are much narrower than they ever were before. Most surgeons today are following the guidelines recommended by the National Institutes of Health (NIH) and the American Academy of Dermatology Task Force on Cutaneous Melanoma:

• When there is an in situ melanoma, the surgeon excises 0.5 centimeter of the normal skin surrounding the tumor and takes off the skin layers down to the fat.
• In removing a melanoma that is 1 mm or less in thickness, the margins of surrounding skin are extended to 1 cm, and the excision goes through all skin layers and down to the fascia.
• If the melanoma is equal to or greater than 2 mm in Breslow's thickness, a margin of 2–-3 cm is taken.

The lymph nodes must be evaluated before treatment is selected. To find out whether melanoma cells have spread, the physician starts by feeling the nearby lymph nodes. If the melanoma is on the arm, the nearest nodes are in the armpit; if on the leg, they are in the groin. For a melanoma on the head, the closest lymph nodes are usually on the neck on the same side. For a tumor on the trunk, the nodes in either the armpit or the groin could be involved.

When an enlargement or lump in a lymph node can be recognized by touch, it is called palpable. A palpable lymph node will be surgically removed in a node biopsy.

This node is sent to the pathology laboratory to be tested for the presence of malignant cells. If any are found, the patient usually has the other nodes in that lymph node basin removed. Then, additional, or adjuvant, treatments that stimulate the immune system and/or chemotherapy will be recommended.

Non-Palpable Nodes

Sometimes the lymph nodes are not palpable. When that is the case, one of two approaches will usually be followed:

• Wait-and-See: Some physicians advise a "wait-and-see" policy. No further surgery is done at this time, but the patient is asked to return at regular intervals for checkups.
• Remove nodes. Other physicians believe in removing all the nodes in the region of the tumor on the chance that there are hidden cancer cells. You will hear this procedure described by the technical term of a "radical node dissection." There is no definite proof that non-palpable lymph node removal should be performed as a preventive measure. It is a good idea for a melanoma patient to ask the physician about these options and the reasons why one or the other is recommended.
• Selective removal of lymph nodes. In this approach, only the sentinel node and nodes in the region of the primary tumor are removed. This method is being used with increasing frequency for melanomas that are more than 1.00 mm in depth. The surgery is less extensive than the radical node dissection, and studies have found that patients do well.

Microscopic nodal involvement

Palpable nodes may — or may not — be a sign of melanoma. The diagnosis must be confirmed by microscopic evaluation. This is also the procedure for sentinel nodes that are non-palpable, but may still contain cancerous cells. Research is now going on into special biochemical techniques that can identify those melanoma cells that do not show up under routine microscopic examination.

Local vs. Distant Spread

In local forms of the disease, the metastases can reach skin or subcutaneous tissue more than 2 cm from the primary tumor, but not beyond the regional lymph nodes. Once the disease has advanced to Stage IV, melanoma cells have traveled through the body via the bloodstream or lymph vessels, going far from the original tumor site. They may have reached distant lymph nodes or invaded the internal organs. This can be in addition to or instead of the local spread to the lymph nodes or in-transit metastases.

When distant metastases are suspected, they can be traced by scans of the
chest, head, abdomen and pelvis with a CT scan (computed tomography) in which special x-ray equipment and a computer program show a cross-section of body tissues or organs; an MRI (magnetic resonance imaging) which uses a magnet instead of x-ray to create a map of the patient's body; and by PET (positron emission tomography), an evolving radiographic technique. For PET scanning, radioactive sugar, the basic carbohydrate utilized by the body for energy, is injected intravenously into the patient. This sugar is taken up rapidly by any melanoma cells that are present.

For patients with Stages III and IV disease, surgery may be followed with adjuvant therapy. Ask your physician to explain the possibilities and grounds for selection of one treatment over the other.

Chemotherapy

A number of drugs that are active in fighting cancer cells are being used to treat melanoma, either one at a time or incombinations. Currently, Dacarbazine (DTIC), given by injection, is the only chemotherapy approved by the FDA. DTIC may be combined with carmustin (BCNU) and tamoxifen, or with cisplatin and vinblastine. Another drug, temozolomide, can be given orally. Unfortunately, to date, the response of melanomas to chemotherapy has been limited, but a great deal of research into new drugs and new approaches is being carried out.

Another class of drugs, based on a different principle, has come into use more recently. They are anti-angiogenic, which means that they prevent new blood vessels from forming. The reason this is important is that they cut off the blood supply that would otherwise nourish the cancer cells and enable them to grow. These drugs are still experimental and a good deal of research into improving and combining them with others is going on. Studies are underway with the anti-angiogenic drug, thalidomide, combined with the chemotherapeutic agent, temozolomide. Angiostatin and endostatin are two other drugs in this class that have shown some degree of activity against melanoma in preliminary studies.

The isolation-perfusion method is sometimes used as a palliative (pain-relieving) treatment when the melanoma is on an arm or leg. "Isolation" means that the chemotherapy is "perfused" (added to) the blood flowing through the affected limb, and no other part of the body.

Immunotherapy/Biochemotherapy

This is one of the most exciting and changing fields in medicine, based on drugs that act on the body's immune system. A number of newly-developed treatments are now being tested with some success. Among the immunotherapies, several types of experimental melanoma vaccines are now viewed as promising. Unlike the influenza vaccine, given when you are well to prevent disease, these are given to people who already have melanoma. Clinical trials of various types of vaccine are underway with patients whose disease is in Stages III and IV. The vaccines are intended to stimulate the immune system so that it reacts more strongly against a patient's melanoma cells, destroying the cancer or slowing the progression. These vaccines are not a part of routine treatment at this time, so patients with advanced melanomas may wish to discuss this possibility with their physicians.

Another type of immunotherapy (also known as biologic therapy) makes use of chemicals that occur naturally in the body. The one you are most likely to hear about is interferon-alpha. This is the only systemic drug with FDA approval, and it has been shown to improve five-year survival of Stage III patients. Tumor necrosis factor (tumor-killing) factor is another of these naturally occurring substances. Both of these — especially interferon-alpha — are produced by white cells (lymphocytes) when they come in contact with tumor cells, viruses or other harmful substances, and have been shown to kill a number of tumors, including melanomas. They have some anti-angiogenic properties as well. However, both drugs have significant side effects which can limit their use.

Lymphokines, which are chemicals occurring naturally in small quantities in the body, are being used for Stage IV patients. They may also be produced by white blood cells (lymphocytes) which have been specially stimulated by antigens, a basic part of the immune system, to make them better "killers" of malignant cells. The best known of these therapies uses the lymphokine, interleukin-2, with or without the addition of interferon alpha, which enters and attacks melanoma cells. However, interleukin-2 is associated with very significant side effects when given in high doses. This form of immunotherapy is still in the experimental stage.

Gene therapy

A gene is the basic unit of genetic material. It is the code or "blueprint" by which our body's proteins are made. Alterations in these codes can result in uncontrolled cell growth as in cancer.

On the other hand, selected genes can be altered so as to correct genetic defects or enhance the cancer-fighting potential of cells. There is hope that making changes in genes will lead to successes in treating a wide range of illnesses, so this kind of therapy frequently gets newspaper headlines. However, keep in mind that this treatment is in the very early stages of research, and its effectiveness is yet to be proven.

One form of gene therapy is based on creating alterations in the white blood cells or in the tumor-infiltrating lymphocytes so that they will attack the melanoma. This is achieved by removing these cells from the patient, growing them outside the body and treating them so as to increase their number. The next step is the addition of genetic material that produces one of the many growth factors which make the lymphocytes more aggressive as cancer-fighters. These more aggressive lymphocytes are returned to the patient's body in an effort to stimulate the immune system to kill the melanoma and its metastases.

The focus of current research is the identification of genes for specific melanoma antigens. These are molecules found on the cell wall that stimulate the production of antibodies, which are a part of the body's immune defense system. An antibody attaches itself to only one type of antigen. By injecting the gene for the melanoma antigens, the hope is to increase their number and produce a broad attack by the patient's immune system.

Clinical Trials

Many patients, especially those with advanced disease, are participating in clinical trials in order to get new treatments while they are still experimental and not generally available.

Patients who have Stage III and IV melanoma might consider enrolling in a clinical trial, a new or experimental treatment. There are risks involved in enrolling in a clinical trial, but there can be benefits, as well.