Melanoma/sandbox

Lymphadenectomy

Lymphadenectomy is the surgical removal of one or multiple lymph nodes. This procedure is performed for melanoma patients in order to gather valuable prognostic information on the metastases of an identified melanoma. Another goal is to discover any clinically hidden sites of melanoma metastasis that could potentially lead to clinically evident tumors if not removed. Surgical lymph node removal for melanoma patients involves one or several lymph nodes nearest to the melanoma site being dissected and analyzed for the presence of cancer cells. The closest lymph node to the melanoma site is referred to as the sentinel lymph node (SLN); nearby lymph nodes are referred to as regional lymph nodes. The removal of the SLN is termed sentinel lymph node dissection (SLND) whereas the removal of all regional lymph nodes is termed complete lymph node dissection (CLND). The presence and maturity of cancer cells in the lymph nodes of melanoma patients provide prognostic information used by physicians to determine the most effective treatment method which can include further surgery and/or adjuvant therapy (treatment of cancer by pharmaceuticals).[1][2] Another, more ambitious, goal of regional lymph node dissection is to surgically treat and/or cure melanoma metastases.[2][3][4] This goal is ideal and stems from the fact that prompt SLND slows the progression of cancerous cells. This function of lymph node dissection is based on the hypothesis that melanoma spreads in a linear manner, from its primary site, through the local lymphatics, to the regional lymph node, before spreading to distant sites.[2][6]

Adjuvant Therapy

Adjuvant therapy is the use of pharmaceuticals, non-specific immunostimulatory agents, and chemotherapy to treat cancer patients. Chemotherapy has been shown to be least effective amongst these alternatives and is no longer used in melanoma treatment due to its toxicity. Usage of non-specific immunostimulatory agents also failed to provide successful results in melanoma treatment. Usage of the pharmaceutical interferon-α has produced the most promising results in terms of non-surgical management of melanoma. Treatment with interferon is less invasive than lymph node dissections but its side effects result in a decrease in quality of life for its recipients. [2][5][7] A lack of conclusive research on interferon treatment correlating with improved survival rates has prevented the drug from becoming a part of the melanoma standard of care. [7] Additionally, conflicting opinions in the medical and research communities over which patients stand to benefit the most from interferon treatment has further complicated its path to becoming a part of the standard of care for melanoma. [2][5][7]

Controversy

There is disagreement and conflicting opinion amongst physicians and researchers regarding the most appropriate treatment plan for patients diagnosed with melanoma. This incongruity amongst research professionals is the result of a combination of factors including questionable effectiveness of all melanoma treatment methods and conflicting hypotheses regarding the mechanism by which melanoma metastasizes. The most effective treatment that can be provided is early detection of possible melanomas and utilization of the current treatment methods.

Lack of Effective Results

There has been no clinical trials that provide any evidence of an increase in patient survival after surgical treatment of melanoma has been administered.[7] Equally troubling is the lack of conclusive evidence for interferon’s effectiveness. Because there is no cure for melanoma, researchers usually define patient survival in two ways: as overall survival (OS) and disease-free survival (DFS), defined as the total amount of time a patient lives for after diagnosis and the amount of time a patient lives free of cancer symptoms, respectively.

Researchers opposed to lymph node dissection as a standard treatment method argue that many patients that undergo this procedure will not benefit from the information obtained.[2] For example, patients with cutaneous melanomas having a Breslow thickness of >4mm have over a 60% chance that cancerous cells have spread to their regional lymph nodes and over a 70% chance that they have spread to some distant site.[4] Because of this high likelihood of cancer metastasis in patients with thick melanomas, researchers argue that an invasive lymph node dissection is unnecessary for these patients. For patients with ulcerated (inflamed due to dead skin tissue) melanoma sites, research has shown that treatment by interferon results in an increase of DFS.[8] While some researchers use this as evidence of interferon’s effectiveness, others consider its side-effects and inability to improve OS just as ineffective and damaging to a patients quality of life as treatment by surgery.

Theory behind Different Treatment Options

A fundamental difference between researchers in support of surgical treatment of melanoma and researches in support of adjuvant therapy is the understanding of the means by which melanoma spreads in the body. Researchers in favor of lymph node removal use the traditional, linear, hypothesis. Following this hypothesis, lymph node removal is way of removing one of the locations that melanoma is known to use for metastasis. By removing this stop along the cancer’s metastatic path, researchers believe the melanoma can be effectively stopped and contained/treated.[2][6] A more recently developed hypothesis incorporates the process of micrometastasis to support a pharmaceutical treatment method.[5] Micrometastasis is the process of microscopic amounts of cancer cells traveling to distant sites early on in tumor development, a process that would render the removal of lymph nodes virtually ineffective in terms of OS.[5] The prognosis for untreated distant site metastasis is a 6-9 month survival period. [7] The hypothesis of melanoma cancer cell metastasis dealing with mircometastasis does not follow a linear path of cancer progression. Instead, the hypothesis is that melanoma travels simultaneously through local and regional lymphatics as well as local blood vessels to distant sites where they may remain dormant for years before forming tumors and producing symptoms in a patient.[2][6]

Difficulty of Treatment Evaluation

Due to the long amount of time a micrometastasized cancer cell can remain dormant for, measuring the success of melanoma treatment options is a process that requires close attention and a long period of time. Thus, results that support the effectiveness of a treatment method, such as surgery or adjuvant therapy, are not yet definitive but must be measured in the conventional method of OS and DFS percentages.[8]

References

1 Piotr Rutkowski MD, PHD, Zbigniew I. Nowecki MD, PHD, Wirginiusz Dziewirski MD, Marcin Zdzienicki MD, PHD, Andrzej Pienkowski MD, PHD, Maciej Salamacha MD, Wanda Michej MD, Slawomir Trepka MD, Elzbieta Bylina BSC, Wlodzimierz Ruka MD, PHD, et al. “Melanoma without a Detectable Primary Site with Metastases to Lymph Nodes.” Dermatologic Surgury 2010; 36: 868 – 876

2 van Akkooi, Alexander CJ; Voit, Christiane; Verhoef, Cornelis; Eggermont, Alexander MM, et al. “New developments in sentinel node staging in melanoma: controversies and alternatives.” Current opinion in oncology 2010; 22: 169 – 177

3 Csaba Gajdos MD, Kent A. Griffith MPH, MS, Sandra L. Wong MD, Timothy M. Johnson MD, Alfred E. Chang MD, Vincent M. Cimmino MD, Lori Lowe MD, Carol R. Bradford MD, Riley S. Rees MD, Michael S. Sabel MD et al. “Is there a benefit to sentinel lymph node biopsy in patients with T4 melanoma?” Cancer 2010; 115: 5752 – 5760

4 Charles M. Balch et al. “The Role of Elective Lymph Node Dissection in Melanoma: Rationale, Results, and Controversies.” Journal of Clinical Oncology 1988; 6: 163-72. Print.

5 Mays, Michael P., Robert C.G. Martin, Alison Burton, Brooke Ginter, Michael J. Edwards, Douglas S. Reintgen, Merrick I. Ross, Marshall M. Urist, Arnold J. Stromberg, Kelly M. McMasters, and Charles R. Scoggins et al. “Should All Patients with Melanoma between 1 and 2mm Breslow Thickness Undergo Sentinel Lymph Node Biopsy?” Cancer 2010; 116: 1535-544. Print.