More than 17 years ago, I published an article that was largely ignored, predicating that patient benefit from the sentinel node biopsy procedure was unlikely.
I asserted that the lymph nodes are not a reliable filter for melanoma cells, lymphatic drainage is capricious, and many individuals (especially younger ones) have benign neval rests in their lymph nodes that cannot be distinguished from melanoma deposits, since they are both positive for the S100 protein ( Int J Dermatol. 2000 Nov;39[11]:807-11 ). In addition, multiple uncontrolled studies had shown that locating sentinel nodes, followed by a complete lymph node dissection, had no survival benefit. At the time, I argued that sentinel node biopsy should be performed only if the patient was going to be enrolled in a clinical study.
The sentinel node biopsy train roared on, justified by adjunctive interferon therapy. But after 15 years of studies, theadverse effects of interferon, and the lack of benefit from biopsy for melanoma patients have become apparent. A few months ago, it was definitively shown that completion lymph node dissection after a positive sentinel node finding added no survival benefit ( N Engl J Med. 2017 Jun 8;376[23]:2211-22 ).
Many surgical oncologists have built their careers around the flawed premise that removing the draining nodes would cure melanoma. It doesn’t. It is past time to admit it and move on.
So, if completion node dissection does not save lives, why do a sentinel node biopsy? I recently asked a dermatologist friend, who is a committed acolyte of the sentinel node biopsy school, why he continues to recommend sentinel node biopsy if there is no benefit from complete node dissection. His quick response was that patients want to know if they are at higher risk of metastatic disease so that they can be followed closelywith high-resolution ultrasound at a major cancer center and can be eligible for clinical trials. His reply gave me pause, so I asked why completion node dissection was still being recommended. I was told that some patients with positive sentinel nodes lived far away, and if they would not make regular follow-up visits for high-resolution ultrasound, the surgical oncologists do completion node dissection to ensure “local nodal control.” Yipes! You’re going to rip my groin out because I like quiet county living?
I doubt that patients would be enthusiastic if told beforehand that sentinel node biopsies costs $14,000-$18,000, and has a 9% complication rate, and one-third of those patients who have complications end up with permanent lymphedema. I wondered if the patients were told they could have a genetic test done on their already excised melanoma tissue that would tell them if they were in a high-risk group without having an additional invasive surgical procedure. I wondered if they were told that 10%-30% of people with negative sentinel nodes go on to develop metastatic disease. I also wondered if they had been told they would have to walk around with their melanoma, which could spread at any time, for several additional weeks, while waiting for the results of their sentinel node biopsy, instead of having the melanoma immediately removed by their dermatologist. I also wondered if they had been told that high-resolution ultrasound has not definitively been shown to be superior to clinical palpation of the lymph nodes.
I looked into the possibility of clinical trials for patients with positive sentinel nodes, as well. Basedon my search of clinical trials.gov in January, there are 33 trials in the United States studying patients with stage 3 (positive sentinel node) or greater disease. If I had a positive sentinel node, I would look for a study in which I had a chance of getting nivolumab, which recently has been shown to be superior to ipilimumab in the phase 3 Checkmate 238 trial published in 2017 (N Engl J Med 2017 Nov 9; 377:1824-35).
But I am getting ahead of myself.
As a thinking man, if I had a thick melanoma (that was less than 2 mm), I would opt for a genetic test of my already excised melanoma tissue. If the results of that genetic test (which has near identical sensitivity and specificity for developing metastatic disease as a sentinel node) put me in the low-risk group, I would pass on the sentinel node biopsy. This would eliminate a lot of unnecessary surgery. If I fell into the high-risk group, I would consider a sentinel node biopsy so I could get into a study, or determine if I needed to find a way to get my insurance to pay, or if I could personally afford nivolumab. Even if I opted not to take the drug, because of the potential risk of high-grade side effects, the high-risk genetic profile tells me I would still need more frequent follow-up.
These are exciting times. I am looking forward to clinical trials that allow a patient with a high-risk genetic profile to go directly into a trial. We are moving into the realm of individualized genomic medicine in which metastatic melanoma truly becomes a curable disease.
Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Dr. Coldiron has no financial or other conflicts of interest with Castle Biosciences, the manufacturer of the DecisionDx-Melanoma genetic expression profile test. Email him at dermnews@frontlinemedcom.com .
