On television’s popular “Grey’s Anatomy,” Dr. Izzie Stevens faces a grim diagnosis: stage IV metastatic melanoma. As the drama unfolds, viewers get a glimpse at why patients with the deadliest form of skin cancer ? in the most advanced stage of diagnosis ? face a mere 10-month median survival rate.
In real life, this type of prognosis is devastating and leaves melanoma patients with few options for beating this disease that claims the life of one American almost every hour (every 62 minutes). But dermatologists agree that when melanoma is diagnosed in its earliest, most treatable stages, time is on your side.
Dermatologist Gary S. Rogers, MD, FAAD, professor of dermatology and surgery at Tufts University School of Medicine in Boston, and dermatologist Jason K. Rivers, MD, FAAD, clinical professor of dermatology at the University of British Columbia in Vancouver, reviewed the most common treatments for the different stages of melanoma and offered suggestions for melanoma patients aiming for their five-year survival mark.
When detected in its earliest stages (stage 0 ? stage I), melanoma is highly curable. In fact, the American Cancer Society estimates that the average five-year survival rate for individuals whose melanoma is localized and has not spread beyond the outer layers of the skin is 99 percent. Dr. Rogers explained that for patients diagnosed with a stage 0 or stage I melanoma, a routine, typically office-based surgical procedure to remove the tumor and a margin of normal-looking skin around it is performed and neither chemotherapy nor radiation is required.
In special circumstances where a melanoma occurs on a cosmetically or functionally critical site, such as the lip, nose, eyelid or finger, Dr. Rogers noted that a new technology based on a variation of Mohs surgery is being used successfully. The procedure uses an anti-melanoma targeted antibody known as MART-1 (Melanoma Antigen Recognized by T cells), which improves the speed and accuracy of the procedure. The technique allows the surgeon to microscopically identify and remove the melanoma cells with minimal sacrifice of healthy tissues in real-time (16-20 minutes). The ability to successfully resect (or surgically remove) the cancer with potentially an 1/8 inch margin rather than an inch margin is critical when working on delicate structures such as an eyelid, said Rogers.
For stage II melanomas, surgery is performed to remove the tumor and surrounding tissue. In addition, the dermatologic surgeon often tests the lymph nodes to determine if the cancer has spread. If the melanoma is going to spread, Dr. Rogers noted that 57 percent of the time the first place the cancer goes is to the local draining lymph nodes. A procedure known as a sentinel lymph node biopsy tests the first lymph nodes into which the melanoma drains. If the lymph nodes are free of cancer cells, then the melanoma is considered in stage II with an average five-year survival rate of 70 percent. In this stage, Dr. Rogers explained that interferon may be given as an adjuvant (or drug-enhancing agent) to boost the patient’s immune system.
However, if the lymph nodes are determined to be involved, then the melanoma is classified as stage III. In this stage, the cancer has spread to one or more nearby lymph nodes and the average five-year survival rate drops to 50 percent or less. Once a melanoma has spread beyond the skin growth, a more extensive treatment plan ? which may include surgical removal of the tumor with wide margins, usually including the affected regional lymph nodes; chemotherapy; immunotherapy or radiation therapy ? is often indicated.
When the tumor has spread to a distant site, such as the lung, brain or other organ, this is considered a stage IV melanoma with an average survival rate of only 10 months. One drug being used to treat patients with advanced melanoma is known as dacarbazine or DTIC. However, the remission rate with this drug is only 10 percent.
“No studies to date show that chemotherapy or any treatment regimens are effective when melanoma has spread to other organs,” said Dr. Rogers. “The silver lining is that given the explosion in our understanding of the molecular biology of melanoma, there are a number of drugs and therapies in the pipeline that are being studied to treat the more advanced stage melanomas.”
One potential therapy involves targeting specific drugs to specific genes that are known to go awry in the development of melanoma. There are multiple genes involved in melanoma progression from local tumor to disseminated disease. And, on a molecular level, there are many differences between melanomas that form in chronically sun-exposed areas versus areas of the body that are not sun-exposed, such as the soles or palms. The goal is to find a drug that will target a specific type of gene defect responsible for certain types of melanoma. “Just as one shoe does not fit all sizes, we are on the verge of being able to tailor therapy to a particular patient,” added Dr. Rogers.
Clinical trials also are underway to test a vaccine known as the MAGE-A (melanoma antigen ? family A) vaccine that would be used as an adjuvant to treat certain types of stage III and IV melanoma. MAGE is an antigen that exists in every cell in the body, but it is not expressed (or made apparent as an observable inherited characteristic) except in cancer. The gene that produces the MAGE protein lies dormant but becomes activated on the surface of melanoma cells and other cancers. Now, this vaccine is being tested to target cells that express or produce inherited characteristics of the MAGE antigen. Dr. Rogers estimated that 60 to 70 percent of melanoma patients express the MAGE antigen, and he believes the vaccine could hold tremendous promise in treating more advanced melanomas in the future.
Source: American Academy of Dermatology, USA