Over the past 35 years, we have learned a great deal about malignant melanoma. We have recognized that melanoma is a heterogeneous cancer. In other words, the disease may be quite manageable in some patients and yet very aggressive in other patients. We have learned that various outcomes of the disease may be due to different variants of melanoma, which may be related to their unique and different biological behaviors.

The incidence of melanoma has increased significantly over the past 35 years to currently about 1 out 70 Americans, mainly affecting the Caucasian population. About 62,000 melanoma patients are being diagnosed yearly and over 7,000 patients will die of the disease. Whether increasing melanoma incidence is real or due to improved diagnosis still needs to be determined. Although the incidence of melanoma is still increasing rapidly, the overall mortality rate has risen only slightly. This indicates that most of the melanomas being diagnosed are thin primary lesions that can be treated effectively by surgical resection.

In general, when melanoma is diagnosed early with thickness less than 1 mm, the cure rate approaches over 95 percent. If melanoma is not detected until the thickness becomes over 4 mm, the survival rate drops to less than 50 percent. Early diagnosis has been achieved by education, screening and digital dermatoscopy, which can monitor suspicious pigmented lesions serially so that they can be removed earlier for any changes based on the digital pictures recorded in the computer system. When the regional lymph node is involved, the survival is at best around 30 percent. The survival rate drops to single digits when metastasis is found beyond the regional lymph nodes, especially in visceral sites. In the past, the only way to detect metastasis in the regional lymph nodes is to do a complete or radical lymph node dissection, which may be associated with increased morbidity such as lymphadema.

The most important development since 1992 is the demonstration that the regional nodal basin may be best assessed by selectively removing the so called sentinel lymph node, as it is the first lymph node in the regional nodal basin to receive the cancer cells from the primary site before the cancer cells have the ability to progress to other lymph nodes or other body sites. Therefore, at the initial diagnosis of the primary melanoma, it is quite reliable to assess the regional nodal basin by selectively taking out one or a few sentinel lymph nodes to determine whether there are any cancer cells in these lymph nodes. If they are negative, the chance of having additional cancer cells in the nodal basin is less than 5 percent. Thus, over 80 percent of the patients may be spared a more extensive and morbid radical lymph node dissection following the removal of a negative sentinel lymph node.
When patients have metastatic disease in the regional lymph nodes, interferon has been approved by the FDA as an adjuvant therapy with about 15 percent benefit. When patients develop metastatic disease beyond the regional nodal basin, such as lungs, liver and other sites, the prognosis is very poor. The response to chemotherapy is less than 5 percent. Recently, interferon or interleukin-2 have been added to chemotherapy as in biochemotherapy, which results in about 10 percent of the response rate.

Although extensive research in immunotherapy of melanoma has been done with a much better understanding of the immune system against melanoma, the therapeutic benefit is still marginal. Newer immunotherapeutic approaches are being developed. Novel targeting of molecules in the growth pathway of melanoma is being studied to curtail its proliferation. Genetic signatures of different types of melanoma are being determined for profiling melanoma into molecular subgroups so more tailored treatment can be rendered to avoid treatment toxicity to patients who do not need such a treatment.

At the UCSF, we have a multidisplinary melanoma clinic represented by dermatology, dermatopathology, surgical oncology, medical oncology, radiation oncology and other disciplines to offer the best care for melanoma patients in the Bay Area and elsewhere. We are conducting molecular genetic studies to subgroup patients by molecular markers. We have an active sentinel lymph node program to selectively stage patients with primary invasive melanoma so that they can get the appropriate treatments. In our immunotherapy program, we have found that intralesional injection of granulocyte macrophage colony stimulating factor may shrink in-transit melanoma nodules. We are developing novel melanoma vaccines using hybrids of patients’ autologous dentritic cells and melanoma cells to stimulate specific response against their melanoma. Our goal is to bring the latest research findings to the clinic to help the patients.

If community physicians want to seek consultation from the UCSF Melanoma Clinic, they may call the Clinic at 415-353-9900.

In summary, we have learned a lot about malignant melanoma over the past 35 years. Early diagnosis of melanoma is crucial to cure melanoma before it has the ability to metastasize.

—By Stanley P. L. Leong, MD, FACS

Posted on August 1, 2006 06:00 AM