Four types of treatment are currently available for melanoma. Physicians recommend the type of treatment indicated by a number of factors, including the malignant stage of the tumor, the patient's age and physical condition, and any other conditions the patient may have.

Surgery is the standard treatment for melanoma. (Click on Thickness to learn more about tumor thickness and 5-year survival rates. Click on Margin for an explanation of the relationship between tumor thickness and the amount of tumor-free tissue removed around the tumor site). The extent of surgical removal of tissue largely depends on the thickness of the melanoma and the likelihood that surgery is the optimal treatment (for example, in advanced disease with metastasis to the brain, surgery may not be the optimal choice for treatment). A biopsy is performed to confirm a diagnosis of melanoma and determine the thickness of the melanoma. A wider excision of the skin surrounding the melanoma is then performed with margin determined based on the thickness. If indicated, a Sentinel node biopsy may be performed at the time of wide excision to evaluate the lymph nodes for any evidence of metastasis.

Sentinel Node Biopsy

When a melanoma is thick enough to make metastasis a possibility, excisional biopsy may be accompanied by a recently developed method for identifying the lymph nodes at greatest risk for metastasis. This method is known as "lymphatic mapping and sentinel node biopsy". This method can assess accurately the tumor's spread to lymph nodes. The influence of this procedure on patient 5-year survival has not been determined. The procedure is done only for melanomas that have a significant likelihood of metastasis to lymph nodes.

Lymphatic mapping is done to determine the lymph nodes most likely to receive lymphatic drainage (and cancerous cells) from the melanoma site. The test is done with radioisotopes, and sometimes blue dye, to trace the flow of lymph from the site of the melanoma to local and regional lymph nodes. The purpose of lymphatic mapping is to identify the first lymph node -- the "sentinel node" -- to receive lymph draining from the melanoma site.

The sentinel node is removed surgically and sliced into sections for laboratory analysis. The microscopic and other analysis must be fine enough to identify even a single melanoma cell in the node. If no melanoma cell is found in the sentinel node, it is regarded as very unlikely that any melanoma cells have passed through the sentinel node to the next nodes in the lymph drainage basin. If melanoma is found in the sentinel node, all of the nodes may be excised in an attempt to remove all cancer containing tissue.

Studies are underway to determine how sentinel node biopsy and selective lymph node removal affects overall survival rates of patients with melanoma.

Adjuvant therapy is treatment given in the hope of reducing the risk of metastasis or recurrence after surgery for melanoma clinically confined to the skin or lymph nodes. Currently employed forms of adjuvant therapy include interferon and experimental vaccines. Given the toxic and/or experimental nature of these therapies, their use is restricted to patients at significant risk for metastasis.

Therapies for metastases melanoma:
a) Surgery - many metastases (eg. Those to lymph nodes or skin) are amendable to surgical excision
b) Chemotherapy - is the use of anti-cancer drugs to kill malignant cells that  cannot be reached by surgery. Special types of chemotherapy may be used to reach localized or hard-to-reach tumors (for example, perfusion of chemotherapy to a single limb). Chemotherapy may have unpleasant side effects that should be discussed with physicians providing the treatment

Radiation therapy is the use of ionizing radiation from machines (X-rays, gamma rays) or radioisotopes to kill malignant cells and shrink the size of a tumor. This is a form of therapy usually reserved for patients with advanced, metastatic cancer. 

Biologic therapy is the newest type of treatment, and is sometimes available only in investigational settings. Some biologic medicines are versions of molecules made by the human body (for example, interferon and cytokines). Some are monoclonal antibodies against tumor fractions. Others are vaccines. The purpose of biologic therapy is to improve the body's own defenses against cancer cells.

(* Adjuvant therapy and combination therapy will be discussed in greater detail as treatment options, in upcoming updates.)

People with cancer and other serious diseases have usually heard about clinical trials and wonder if this is a treatment option they should consider. Clinical trials are investigational studies of new therapies, new uses of current therapies, new ways to detect disease, and new approaches to making patients comfortable.

• Clinical trials are medical investigative studies in which human beings are the test subjects.
• Clinical trials are a building-block of science-based medicine.
• Clinical trials are required by the Food and Drug Administration for the approval of a new drug or new uses for an existing drug.
• Clinical trials offer patients the opportunity to (a) participate in clinical investigations of a new therapy before it is approved for general use by physicians, and (2) contribute to the knowledge base of medicine.

First, let us explain clinical trials in more detail.

The word "clinical" tells you that humans are the subject of an investigative study. "Clinical" pertains to the observation and treatment of human patients, as distinguished from theoretical, laboratory or animal studies.

A clinical study provides information when the study is completed, but that isn’t the end of its usefulness.

The paper or papers that report results of the study are usually referenced in a data bank such as MedLine, the data retrieval system of the National Library of Medicine. At any future time for decades, the papers are available for retrieval by physicians, non-physician scientists and any interested person. If a study was well-designed and its results scientifically and statistically valid, it may be referenced in future studies and future studies may seek to build upon or critically examine its results. Thus, it becomes a building block in a constantly evolving information base.

There are several types of clinical studies, which may be described in an increasing order of complexity.

Case reports are studies of isolated or carefully selected individual patients. A case is usually reported because of some unusually interesting aspect—for example, melanoma in a very young child. Investigators select the cases to report. You cannot volunteer for a case report.

Retrospective studies use case records from hospitals and medical centers to identify trends or patterns over a period of years. For example, a retrospective study might examine patterns of recurrence in melanoma over a 30-year period related to the operative techniques used to remove melanomas from several hundred patients. The study investigators might conclude that one technique was shown to be associated with a lower rate of recurrence. The patients whose records are reviewed for retrospective studies are participants only in the sense that data from their cases was reviewed. Patient identities are never disclosed.

Controlled observational studies of new therapies typically use a group of patients who are the study group, and a control (comparison) group of people who do not receive the treatment under study. The control group may be healthy volunteers, or may be people who have the same disease as the patients but do not receive the treatment under study. The control group may receive a placebo—a nonactive substance with no medicinal effects--or a standard therapy rather than the investigational therapy. The investigator may decide who does or does not receive treatment, or a person other than the investigator may make that decision. The patients and members of the control group are usually "blinded"—that is, they do not know which treatment they are receiving. The principal investigator may also be "blinded" as to which subjects are receiving treatment.

Prospective experimental studies are exemplified by the randomized, double-blind controlled trial (RCT)—the "gold standard" for unbiased study results. In this type of study, patients are randomly assigned to study groups or control groups, and neither investigators nor patients and controls know who is receiving investigational treatment and who is receiving placebo or standard treatment—thus, "double blind". RCTs are the most persuasive study design for proving the effect of a therapy or exposure of a treatment outcome. These studies are expensive and time-consuming, tending to require more study subjects and long periods of follow-up in order to achieve the statistical power necessary to prove or disprove the study hypothesis.

In RCT studies of new drugs and new treatments, volunteers are usually patients who have the disease for which the treatment is being developed. In RCT studies of treatments for metastatic melanoma, volunteers may be randomized to receive the investigational therapy, or a standard therapy which is the best treatment currently available.

Pharmaceutical firms often sponsor RCTs to gather the data necessary to win Food and Drug Administration (FDA) approval for a new drug or new uses of an existing drug. The studies are conducted by investigators in hospitals and medical centers, or by physicians in private offices, independent of any involvement by the sponsoring company.

RCTs are also conducted by large medical centers and by government-supported institutions such as the National Institutes of Health—National Cancer Institute, and Veterans Administration. The hypotheses tested in these trials may involve new therapies, comparison of existing therapies, new applications of existing therapies, new screening methods for earlier detection of disease, or new methods of prevention.

A hypothetical example of a melanoma study conducted by a medical center would be comparison of different combinations of surgery, chemotherapy and radiation in the treatment of advanced metastatic melanoma.

After basic science, laboratory and animal studies have indicated that a drug may be safe and effective for treatment of a specific disease, human clinical trials may be planned as the next step toward FDA approval. Animal studies are important, but the major limitation of animal studies is that animal models are not wholly generalizable to humans due to differences in animal and human biology and other factors.

Clinical studies of a new drug or treatment are usually conducted in three phases.

Phase 1 is the initial study of the drug in humans. The study subjects are usually not more than 20 to 80 volunteers. The purpose of Phase 1 study is to determine the metabolic and pharmacologic actions of the drug in humans, side effects associated with increasing doses, and indications of effectiveness. If Phase 1 studies are completed satisfactorily, Phase 2 trials may be conducted.

Phase 2 are uncontrolled clinical studies designed to obtain data regarding the effectiveness of the drug for specifically-designated uses (indications), in patients with the disease the drug is designed to treat. Several hundred volunteers may be enrolled in a number of Phase 2 studies, which may be observational studies. Volunteers are selected by criteria outlined by the investigators in the study protocol (study plan). If Phase 2 trials are satisfactorily completed, Phase 3 studies are conducted.

Phase 3 are expanded clinical studies. They are controlled and are often randomized, double-blind controlled trials. In Phase 3 trials the overall benefit-risk value of the investigational treatment is evaluated. Several hundred to several thousand volunteers are enrolled as patients and controls. It is usually at the point of Phase 3 trials that large numbers of patients are sought as volunteers in the trials.

A well-designed, well-conducted clinical trial provides important data for future investigators and for physicians currently treating patients with the disease that was studied.

The results from a single study may be persuasive, but the results will be interpreted in a context of other evidence that links the treatment to health outcomes in patients of different ages, genders, and overall health status. This is the body of evidence a physician will consider when planning treatment for a patient.

The question of eligibility is answered in the protocol (study plan) for each trial. The investigators conducting the trial will have established selection criteria for volunteers who will most effectively test the hypothesis of the trial. Commonly used criteria in a cancer treatment trial are type and stage of cancer, age, gender, and previous treatments.

The type of trial, the study protocol, and the severity of patients’ illness determines where a trial is conducted. When patients are very ill, or when 24-hour monitoring is required, the trial may be conducted at one or more large medical centers and require the volunteers to remain at the centers during the trial. Other trials may have many dispersed locations and accept ambulatory volunteers who are not required to stay at the study locations.

The duration of a clinical trial can be many days to many weeks, depending on the time required to test the study hypothesis adequately. In RCTs, a volunteer may be asked to return for follow-up testing for several weeks or months after the treatment phase is over.

Federal regulations, and the rules of each institution involved in a clinical trial, require that (1) every trial must be approved by an Institutional Review Board (IRB) to assure that volunteer rights and safety are adequately protected, and (2) a volunteer must give informed consent. The process of informed consent requires the study investigators to thoroughly inform volunteers about a study protocol, treatment to be given during the trial, tests that will be carried out, and follow-up procedures after the trial. If the study is blinded and placebo-controlled, the volunteer must be told that he or she may receive placebo or standard treatment rather than the investigational treatment. The volunteer is urged to discuss informed consent with family and physicians before deciding to volunteer to enter a trial. Informed consent means that the volunteer agrees to participate in the trial under conditions explained by the investigators. However, the volunteer is not legally bound to remain in the trial, and may leave at any time without penalty. It is hoped that volunteers will remain in the trial so that study results are not skewed by "drop-outs".

Major risks include side effects of the investigational treatment, and the possibility that the treatment will not be effective. The volunteer may be randomized to receive placebo or standard treatment rather than the investigational treatment—a risk to which the volunteer agrees in informed consent.

Major benefits include having access to a new treatment while it is still under study, being under the care of some of the nation’s top physicians, and contributing to medical knowledge.

Health insurance may not pay for some or all of the costs of treatment received in a clinical trial. Some insurance plans regard clinical trials as "investigational" treatment which they will not cover in cost. Trials underwritten by a pharmaceutical firm pay some, but not all costs of treatment; the volunteer may be liable for costs of some tests, etc. Before entering a clinical trial, a prospective volunteer should gather all information regarding what costs will be covered by the study sponsor, what costs will be covered by health insurance, and what costs may have to be covered by the volunteer.

The easiest ways you can find clinical trials conducted by authoritative sponsors are:

• Talk with your physicians about clinical trials—whether clinical trials are a treatment option you should consider, and which one(s) would be best for you;
• Contact large medical centers and pharmaceutical firms regarding any trials they may be conducting or planning, in the area of your interest; and,
• Search the Internet and World Wide Web for websites of medical centers, pharmaceutical firms, and government-sponsored research centers such as the National Institutes of Health. A good place to start is the National Cancer Institute (NCI) website that lists NCI studies as well as studies conducted by NCI-supported centers: http://cancertrials.nci.nih.gov/