Shedding Light on Risk, Detection And Treatment of Melanoma by Gina Shaw All right, hereís the moment of truth. How much time have you spent in the sun so far this summer? And how much of that time were you actually wearing sunblock? Thatís right, itís beach season, barbecue season, swimming pool seasonóand skin cancer season. Melanoma, the most serious form of skin cancer, accounts for about 80 percent of all skin cancer deaths and strikes more than 50,000 Americans each year, killing nearly 8,000. The overall incidence of melanoma is also rising at an alarming rate, according to the American Academy of Dermatology (AAD). If current rates of increase continue, one in 68 Americans will develop invasive melanoma during his or her lifetime, a 2000 percent increase from 1930. And in many cases, melanoma is entirely preventable. Although we often hear mixed messages about the kinds of foods that might cause cancer and whether or not certain prescription medications carry a risk of cancer, thereís no confusion about what causes the lionís share of melanoma cases. ìThe fact that the incidence of melanoma continues to increase dramatically is primarily related to sun exposure,î said Dr. Jeffrey Lee, associate professor of surgical oncology and medical director of the Melanoma and Skin Center at M.D. Anderson Cancer Center in Houston, Texas. Although genetic factors such as fair skin, tendency to develop atypical moles, and a previous family history of skin cancer are important, overexposure to the ultraviolet radiation in sunlight plays a major role in many melanoma cases. According to the AAD, short periods of intense exposure, such as sunbathing, are associated with a twofold increase in melanoma risk. If you insist on remaining a sun-worshiper despite all of the warnings, itís important to pay attention to the moles, freckles and other spots on your skin. Watch them for changes. You can remember the potential warning signs using the simple ìABCD rule.î Look for asymmetry (Does one half of the mole not match the other half?), border irregularity (Are the edges ragged, notched or blurred?), color (Is the pigmentation not uniform? Look for shades of tan, brown, black, or dashes of red, white and blue, creating an overall mottled appearance.), and diameter (Is the width greater than six millimetersóabout the size of a pencil eraseróor has the mole grown since you last looked at it?). If you see any one of these signs, visit a dermatologist as soon as possible because although melanoma can be fatal, it does not have to be, especially if it is caught early. ìEven though the incidence of melanoma is increasing, the survival rates for this type of cancer are also increasing. So although more people are developing it, a smaller percentage of those people are dying from melanomas,î said Lee. ìThis is due in part to better treatments, but also to early detection and diagnosis. Everyone should be aware of what melanoma looks like, so that it can be caught early,î he added. When melanoma is detected at less than a millimeter in thickness, for example, the patient has a better than 90 percent chance of being completely cured. Early Diagnosis and Treatment Once a suspicious mole has been identified as a melanoma, itís vital to know whether or not the cancer has stayed on the skinís surface or moved into the lymph system. ìPatients whose melanoma has not spread to their lymph nodes rarely need additional treatment after the melanoma is removed surgically, and their chances for a complete cure are excellent,î said Lee. But even a small amount of cancerous cells spread into the lymph nodes means a very high chance that the cancer will recur after the primary melanoma is removed. ìIn these cases, the patient will need additional treatment, such as further surgery, drugs such as interferon-alpha, and perhaps an investigative treatment such as a vaccine,î Lee noted. Finding out that key piece of information has become much easier in the last decade thanks to a new kind of surgical analysis called the ìsentinel lymph nodeî (SLN), first conceived of by Dr. Donald Morton, medical director and chief of surgery at the John Wayne Cancer Institute. ìFirst, you inject the site of the melanoma with a small amount of radioactive tracer and blue dye. They travel through the lymphatic channels and are taken up by the lymph nodes closest to the tumor,î said Lee. ìThey collect in areas where there is most likely to have been a spread of the cancer, if there is any spread.î Using what Lee called a ìsort of Geiger counterî called a gamma probe, surgeons can detect the ìsentinel lymph nodesî marked by the tracer and dye and remove them in a relatively minor surgical procedure. Then, they examine the node or a few nodes under a microscope to see if any cells have broken off from the place where the tumor began and traveled to the lymph nodes. If the sentinel lymph node doesnít carry metastasized disease, the patientís chance of survival is 90 percent, compared to 65 percent if cancer lurks in the sentinel node. The sentinel lymph node biopsy, said Lee, ìhas changed the way we approach patients, who we treat and how we treat them.î It is commonly believed that the sentinel lymph node biopsy has led to earlier detection of melanoma, and M.D. Anderson is one of several sites nationwide now testing that belief in a randomized clinical trial. ìBefore the SLN biopsy, we would either leave the lymph nodes alone and risk missing the spread of the disease until it was more advanced and possibly too late, or remove lymph nodes even without the evidence of melanoma spread because of the risk,î said Lee. ìBut that means we were likely treating many patients unnecessarily and subjecting them to the side effects of lymph removal, which arenít insignificant.î One possibility that can occur when a whole region of lymph nodes is removed is lymphedemaóa permanent, disfiguring and disabling swelling in the area where the nodes were removed. ìAlso, we can examine a sentinel lymph node much more carefully than we can look at an entire region of lymph nodes,î Lee added. ìThis allows us to potentially find cancer we mightíve missed if we were doing it in the old-fashioned way.î Vaccines on the Horizon? Cancer vaccines may have sounded like science fiction in the 1980s, but today vaccines are being testedóand showing promiseóon patients with kidney, colon, prostate and breast cancer, as well as many other forms of cancer. Melanoma, in fact, was one of the first cancers to be studied for potential vaccines. However, researchers have yet to fully determine if melanoma patients have benefited from such a vaccine. The first vaccine, developed by SLN pioneer Morton, is now in a phase III multi-center randomized clinical trial. Called Canvaxin, itís an ìallogeneic, whole-cell vaccine,î which means that it attempts to stimulate an immune response in the melanoma patient by treating them with a combination of three melanoma cell lines that have been irradiated. ìIn retrospective studies, itís been very promising. Patients with a high risk of recurrence who have been given Canvaxin have survived longer than those who havenít,î said Lee. Cancer specialists are hopeful that the results of the randomized phase III trial will be as positive. Another allogeneic, whole-cell vaccine made from cancer cells broken up into their constituent pieces rather than whole cells is called Melacine. The results of a recent randomized trial of Melacine were a sort of bad news-good news mix. On the one hand, the trial found no overall benefit to patients who took the vaccine. One subgroup of patients, however, did appear to benefit. ìThese were patients who had certain immune function genes called human leukocyte antigen genes,î noted Lee. About 60 percent of melanoma patients have these genes, and a new trial is now being developed to test Melacine specifically in patients with these immune function genes. Other potential melanoma vaccines are further back in the pipeline. Researchers at the National Cancer Institute and at the University of Virginia are separately investigating peptide vaccinesócompletely laboratory-generated vaccines made of small proteins. The research into peptide vaccines ìis based on scientific studies that have identified peptides from melanoma tumors that are particularly stimulating to the immune system,î explained Lee. ìThe goal is to develop vaccines that are pure and designed to be extremely effective based on laboratory studies, rather than by taking tumors from patients. The thought is that ultimately these vaccines will be more effective and safer.î Gina Shaw is the medical writer for The Washington Diplomat.