Long-term research that was initiated at UCLA’s Jonsson Comprehensive Cancer Center on lymphatic mapping and sentinel-node biopsy, techniques for detecting the earliest spread (metastasis) of melanoma, the deadliest form of skin cancer, has confirmed that these techniques significantly prolong patients’ disease-free and melanoma-specific survival over the traditional observational “watch and wait” techniques.
This affirms a new standard for detecting melanoma metastasis to the lymph nodes by allowing doctors to quickly determine which patients actually have nodal metastasis and may benefit from having their non-sentinel lymph nodes removed (approximately 20% of patients), while sparing the surgery and its associated complications and substantial cost for the many patients who it cannot benefit (approximately 80% of patients).
Led by the late Dr. Donald L. Morton, former UCLA professor of surgery and director of the John Wayne Cancer Institute in Santa Monica and Dr. Alistair J. Cochran, professor in the departments of surgery and pathology and laboratory medicine at the David Geffen School of Medicine at UCLA, the study was published in the New England Journal of Medicine, and evaluated outcomes of 2001 melanoma patients at 10 years of follow-up. The results confirm that lymphatic mapping and sentinel-node biopsy represent an advantageous change in practice for doctors treating melanoma patients.
One important long-term finding was that the thickness of the initial melanoma tumor relates to the effectiveness of these treatments in managing nodal and other metastases. Patients with primary melanoma tumors of intermediate thickness (1.20 to 3.5 millimeters thick) who had sentinel-node biopsies with immediate complete removal of the lymph nodes if the sentinel node contained cancer cells had an overall disease-free survival of 71.3% compared with 64.7% for those whose nodes were observed without sentinel biopsy. The research also found that sentinel-node biopsy prolonged distant disease-free survival (survival without disease spread to distant organs such as brain, lungs, or liver) and melanoma-specific survival (survival without development of additional metastases) for patients with lymph node metastasis from primary melanomas of intermediate thickness.
20% of patients with melanoma have disease spread to nearby (regional) lymph nodes at initial diagnosis. Traditional treatment of these patients was surgical removal of the primary tumor and a rim of “normal” tissue around it, then observation of the lymph nodes. If the nodes developed signs of metastasis over time they were then surgically removed. This spared 80% of patients unnecessary surgery, but was possibly too late to stop disease spread in the 20% who had metastasis. The alternative treatment was to remove all patients’ lymph nodes, since every patient was potentially at risk of metastasis, which would subject 80% of patients to unnecessary surgery and its considerable complications. Drs. Morton and Cochran and their colleagues in the division of surgical oncology (later the John Wayne Cancer Clinic) at UCLA sought and eventually perfected a method to specifically identify the 20% of patients whose tumors had already spread to the lymph nodes.
Before cancer cells spread throughout the lymph nodes, they track through the lymphatic system, first entering the lymph node most directly connected to the tumor – the sentinel lymph node. A mixture of blue dye and radioactive tracer is injected into the tissues around the primary tumor to find the lymphatic channels that lead to the first tumor-draining lymph node. The dye – isotope mixture follows the same lymphatic path used by the melanoma cells to spread to the sentinel node. The sentinel node is removed and minutely examined by microscopy, using sensitive probes that can detect even single melanoma cells. If tumor cells are not found in the sentinel node it is highly unlikely that there will be tumor in other non-sentinel nodes and further nodal surgery is considered unnecessary. If cancer cells are found in the sentinel node, all other lymph nodes in the nodal group are immediately removed.
“Ever since the advantages of lymphatic mapping and sentinel-node biopsy were recognized by the cancer treatment community, the technique has become widely used and is viewed as a practice-changing development,” Cochran said, “which is a very gratifying for all who worked on developing and testing the approach at UCLA and The John Wayne Cancer Clinic and in centers around the world.”
These study results confirm that for patients with intermediate thickness melanomas, early sentinel biopsy decreases the risk of cancer recurring in the lymph nodes, and decreases patients’ chances of dying from the disease. Although some patients with thick primary tumors benefit from having their lymph nodes removed, the findings suggest that the timing of the intervention is not as crucial for them as it is for patients with intermediate thickness primary tumors. Not enough patients with thin melanomas were in this trial to permit conclusions on their benefit from the technique, thus the effect of lymphatic mapping and sentinel-node biopsy in managing patients with thin primary melanomas remains for later study.
This research was supported by the National Cancer Institute of the National Institutes of Health and the Australian and New Zealand Melanoma Trials Group.
Final Trial Report of Sentinel-Node Biopsy versus Nodal Observation in Melanoma, Authors: Donald L. Morton, M.D., John F. Thompson, M.D., Alistair J. Cochran, M.D., Nicola Mozzillo, M.D., Omgo E. Nieweg, M.D., Ph.D., Daniel F. Roses, M.D., Harold J. Hoekstra, M.D., Ph.D., Constantine P. Karakousis, M.D., Ph.D., Christopher A. Puleo, P.A.-C., Brendon J. Coventry, B.M., B.S., Ph.D., Mohammed Kashani-Sabet, M.D., B. Mark Smithers, M.B., B.S., Eberhard Paul, M.D., William G. Kraybill, M.D., J. Gregory McKinnon, M.D., He-Jing Wang, M.D., Robert Elashoff, Ph.D., and Mark B. Faries, M.D. for the MSLT Group, N Engl J Med February 13, 2014 DOI: 10.1056/NEJMoa1310460