Joshua E. Lane, MD Division of Dermatology, Department of Internal Medicine, and Department of Surgery, Mercer University School of Medicine, Macon, Ga; Division of Dermatology, Department of Medicine, The Medical College of Georgia, Augusta
Rory R. Dalton, MD Department of Pathology, The Medical College of Georgia, Augusta
Omar P. Sangueza, MD Departments of Dermatology and Pathology, Wake Forest School of Medicine, Winston-Salem, NC
The authors have no financial, commercial or proprietary interests to disclose.
Patients with a metastatic melanoma in a sentinel lymph node are advised to have node dissection; but few data address survival
Second, the lymphatic system acts as a drain but not a dam for lymphatic flow. Thus a negative lymph node biopsy does not guarantee that a metastasis has not already occurred.
Third, the increased sensitivity of identification of positive sentinel lymph nodes with more specific tests (ie, immunohistochemistry, PCR, rtPCR) calls a negative result into question. A sentinel lymph node that is “negative” with immunohistochemistry may in fact be positive with gene amplification techniques (PCR, rtPCR).
Fourth, surgeons performing sentinel node biopsies vary in thoroughness when identifying which node or nodes contain the dye. Lymphoscintigraphy is more accurate than using dyes; however, many surgeons use both.44 Thus, while sentinel node biopsy has demonstrated a role in staging, its use and the interpretation of results must be performed with these variables in mind.
Regional lymph node dissection: Does it benefit patients?
Patients found to have metastatic melanoma in a sentinel lymph node are advised to undergo regional lymph node dissection. Unfortunately, few data address survival with this therapy. The role of sentinel lymph node biopsy and elective lymph node dissection in the management of cutaneous malignant melanoma generates debate, much of which focuses on alternate interpretations of the data from the era of elective lymph node dissection for intermediate-thickness melanoma.
The debate over elective lymph node dissection has been summarized by others in detail.47
Proponents of an aggressive strategy correctly point out that data from trials are simply not comparable to what is seen in the current era of sentinel lymph node biopsy.
Opponents of an aggressive strategy, who are numerous and vocal,48-50 correctly observe that no survival benefit has been demonstrated for any treatment strategy based on regional lymph node dissection. However, to be balanced, such long-term outcome data are simply not yet available. Certainly questions will continue to arise regarding the theoretical validity and cost-effectiveness of sentinel lymph node biopsy.48,49,51
How good is adjuvant therapy?
Adjuvant therapy for cutaneous melanoma can include regional external beam radiation, systemic cytotoxic chemotherapy, or immunotherapy. Radiation has a limited role, being used postoperatively to treat regional lymph node dissection beds at high risk of recurrence and to treat locally recurrent and in-transit disease.52
FAST TRACK
Systemic cytotoxin has not been effective as adjuvant therapy
Systemic cytotoxin (often dacarbazine) has not been effective as adjuvant therapy.53 When combined chemo- and immunotherapy is used for metastatic disease, it is with the hope of discovering an effective combination that might also be used in the adjuvant setting.54 However, it has been the initial success with immunotherapy that frames the debate regarding adjuvant systemic therapy for cutaneous malignant melanoma.
High-dose interferon alpha 2b. For thick or node-positive cutaneous malignant melanoma, a statistically significant increase in overall survival with high-dose interferon alpha 2b was demonstrated in a landmark Eastern Cooperative Oncology Group trial.55 Though the results have been confirmed in other trials, the clinical benefit is still debated. The expense and toxicity of the trial, as well as the absence of benefit in a second ECOG trial of high-dose systemic therapy, have contributed to the uncertainty.56
FAST TRACK
Low-dose interferon alpha 2b has been used to reduce toxicity, but it is ineffective
In an effort to reduce toxicity, low-dose systemic interferon alpha 2b has been tested in numerous trials and found to be of no benefit.56 High-dose alpha 2b interferon therapy continues to be a focus of active clinical investigation by national and international cooperative groups. In addition to high-dose systemic interferon, a large number of immunotherapeutic approaches for the systemic treatment of melanoma have been devised and are under active investigation, including non-specific immune adjuvants such as Bacile Calmette-Guerin, levaminsole, vaccines prepared from autologous melanoma cells and vaccines designed against chemically defined antigens (gangliocides).57 Because of the controversies surrounding adjuvant systemic therapy, patients are best served by participating in an ongoing clinical trial if the expense and toxicity of high dose systemic interferon alpha 2b are deemed to be unacceptable.
Acknowledgments
We thank Brian C. Brockway, M.S. (Department of Medical Media, Veterans affairs Medical Center, Augusta, Georgia) for illustrations.
CORRESPONDENCE Joshua E. Lane, MD, 308 Hospital Drive, Suite 200, Macon, GA 31217. E-mail: joshua.lane@lycos.com
