All of us treating patients with melanoma must educate our patients about the importance of participating in clinical trials with these new agents so that we can systematically validate the benefits and risks of these agents in prospectively defined patient settings.
The article by Dr. Martin and colleagues provides a thoughtful overview of the rationale for, and risks and benefits of, lymphadenectomy for regional node metastases in melanoma. Of particular importance for the reader is the concept of estimating risk/benefit ratios when we make recommendations to our patients, and the level of evidence on which we base our recommendations. Certainly, under circumstances in which the risks and potential morbidity are increased, our recommendations must be justified by a stronger weight of evidence. Nowhere is this truer than in the recommendations we make to our patients regarding inguinal lymphadenectomy, especially those we make to “high-risk” individuals who are obese and/or elderly. Dr. Martin and his colleagues at Emory University are to be congratulated on their innovative approaches using the videoscopic inguinal lymphadenectomy (VIL) technique for inguinal lymphadenectomy, and on their systematic deployment of clinical trials methodology to document their results. Without doubt, achieving good outcomes with inguinal surgery-without the “nuisance value” and costs of post-operative morbidity (especially seromas, infections, and skin breakdowns that lead to wound dehiscence)-is a challenge for surgeons. The authors’ VIL surgical technique is a logical sequel to the experience with minimally invasive surgery in other anatomic areas. Of course, their results must be further validated, for the VIL technique requires an extra level of technical skill level on the part of melanoma surgeons, as well as incremental costs for the equipment and operating room time. Whether the additional costs of the VIL procedure sufficiently offset the costs associated with postoperative complications, including lost work time, is currently under study.
Over the past two decades, surgeons from the United States, Europe, and Australia have reshaped the standard surgical management of melanoma through randomized surgical trials involving thousands of patients. We have defined more conservative treatment of primary melanoma (scaled in magnitude by tumor thickness) and reduced the need for radical lymphadenectomy through deployment of the lymphatic mapping and sentinel node biopsy technique, which has improved both the staging of melanoma and survival outcomes via earlier detection of and intervention for nodal metastases. Knowing the status of the sentinel lymph node has additional important implications for patients. For the patient with a negative sentinel node, the prognosis is generally very favorable, and he or she can be spared the costs and morbidity of further surgery and adjuvant treatments. On the other hand, when microscopic nodal metastasis is identified in the sentinel node, the treating physician now has the opportunity to consider and discuss with the patient possible roles for both regional lymphadenectomy and adjuvant systemic therapies.
A clinically useful electronic tool for predicting the probability that a melanoma patient will die of metastatic melanoma over the next 10 years can be found at www.melanomaprognosis.org. This “personalized” predictive tool calculates 5- and 10-year survival rates based on clinical and pathological features of an individual melanoma patient and provides valuable information that allows us to better calibrate our treatment recommendations to the biological aggressiveness of that patient’s tumor (ie, more aggressive treatment may be recommended more frequently when the melanoma has adverse features, and vice versa). When I counsel patients, I use the obverse of the predicted 10-year melanoma-specific survival rate. In other words, for a patient with a 48% 10-year survival, I would communicate that he or she has a 52% probability of dying from metastatic melanoma during the next 10 years. Obviously, the discussion will be different for a 35-year-old healthy patient than it will be for a 75-year-old with comorbidities.
Knowing the status of the sentinel lymph node is a requirement for enrollment in many adjuvant therapy melanoma clinical trials. Not having this critical staging information may exclude some patients from potentially benefiting from innovative therapies under evaluation in trials. Moreover, the results of the first Multicenter Selective Lymphadenectomy Trial (MSLT-I) demonstrated a survival benefit among patients with clinical T2N0M0 and T3N0M0 melanomas who had early intervention with lymphadenectomy compared with those whose clinically detectable nodal metastases were detected later in the course of follow-up. For this reason, I can more strongly justify a completion lymphadenectomy in T2 and T3 patients when the sentinel node contains metastasis-although I may be more conservative in my management of clinical T4N0M0 patients with sentinel node metastasis. My more conservative approach in this latter setting stems from the fact that the justification for completion lymphadenectomy is the achievement of better regional control (but not increased survival) and obtaining staging information that may be useful in recommending aggressive forms of adjuvant systemic therapy if there are additional nodal metastases present among the remaining regional lymph nodes.
We are now entering an exciting new era of multidisciplinary melanoma management because of the recent availability of effective systemic targeted treatments (for patients with BRAF mutations), as well as multiple immunotherapy agents that are being used in stage IV melanoma to prolong life (and that will soon be used in higher-risk stage III and IIC patients, with the goal of increasing cure rates). Another new strategy will be to use these powerful agents as neoadjuvant therapy for metastatic melanoma and then surgically remove the tissues containing residual metastases, to identify the refractory cells remaining behind-which, in turn, will guide the use of different systemic agents postoperatively. However, these systemic agents can have significant side effects that must be taken into account when the goal is increasing cure rates among stage III patients, and the evidence for their use in this setting can be reliably obtained only through well designed clinical trials. All of us treating patients with melanoma must educate our patients about the importance of participating in clinical trials with these new agents so that we can systematically validate the benefits and risks of these agents in prospectively defined patient settings.
The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
1. Martin BM, Master VA, Delman KA. Minimizing morbidity in melanoma surgery. ONCOLOGY (Williston Park). 2013;27:1016-27.