People with melanoma who test positive for cancer in their sentinel lymph node do not need to have their remaining regional lymph nodes immediately removed to improve their survival.
This is the conclusion of a large, randomized clinical trial, the results of which are published in the New England Journal of Medicine. The study found that melanoma patients who follow a watch-and-wait approach — with later surgery, if necessary — fare equally well in terms of survival compared with those who have their regional lymph nodes immediately removed. That procedure, called a completion lymph node dissection, is currently the standard of care, but it can cause serious side effects.
The results of this study herald an immediate change in practice.
“The main take-home message is that more surgery done in a prophylactic [preventive] fashion is not associated with better outcomes,” says Charlotte Ariyan, a cancer surgeon at Memorial Sloan Kettering and co-author on the new study. “I think nowadays we can be much smarter about selecting the patients who need to have additional procedures.”
Writing in an accompanying editorial, MSK surgical oncologist Daniel Coit calls the study results “definitive” and “unequivocal.” He adds that they should be viewed as practice changing.
A Definitive Trial
The second Multicenter Selective Lymphadenectomy Trial (MSLT-II) included nearly 2,000 patients with melanoma in their sentinel lymph node, the one closest to the tumor. They were divided into two therapy groups. The first group underwent immediate surgical removal of all remaining regional lymph nodes. The second group took a watch-and-wait approach; they had follow-up doctor visits every four months for the first two years, every six months in the following three years, and then annually after that.
For watch-and-wait patients, their remaining lymph nodes were examined by ultrasound during the follow-up visits. If cancer was detected, a completion lymph node dissection was performed. The study was conducted at 63 medical centers around the world.
The results of the decade-long study were clear: There was no significant difference in the rate of deaths due to melanoma between the two groups. In both groups, 86% of the participants were still alive after three years of follow-up.
What’s more, the study echoes the findings of an earlier, somewhat smaller randomized trial conducted in Germany and published last year. “This is the second prospective randomized trial that came to the same conclusion,” Dr. Ariyan says. “There’s a tremendous amount of power in that.”
“It’s rare that we get such a clean, consistent result,” Dr. Coit adds.
Avoiding Unnecessary Side Effects
The finding of similar outcomes between immediate surgery and the watch-and-wait approach is important because removing lymph nodes can have complications. A major one is lymphedema, an uncomfortable and sometimes permanent and disfiguring swelling of the arms or legs. Roughly 24% of patients in the surgery group experienced lymphedema compared with 6% in the watch-and-wait group. (The lymphedema was mild in 64% of the surgery patients, moderate in 33%, and severe in 3%.)
Lymph node dissection can also lead to problems with wound healing, the need for additional time off from work, and chronic pain.
In some instances, Dr. Ariyan notes, the risk of these side effects may be acceptable if there is reason to believe that people will live longer as a result of a treatment or procedure. But in this case, there was no added benefit. “If surgery is not going to affect your survival,” Dr. Ariyan asks, “why subject yourself to all of those risks?”
Less Is More
In his accompanying editorial, Dr. Coit draws a parallel with recent findings obtained in women with sentinel node positive breast cancer. In that group, a completion lymph node dissection did not improve outcomes either.
MSK has a long history in improving treatment options for people with melanoma, including through surgery. It was Dr. Coit who, more than 25 years ago, brought the technique of sentinel lymph node biopsy to MSK. Dr. Coit was a student of Donald Morton, the doctor who pioneered the method and showed that it was an effective way to gauge a patient’s prognosis. Doctors analyze the sentinel lymph node for signs of melanoma cells in order to stage the cancer and determine if it has spread beyond its primary location. Until this study, it was unclear whether someone with melanoma in their sentinel node should have immediate surgery to remove other nodes in the region or not.
Dr. Coit emphasizes that the people in all of these randomized trials deserve a lot of credit for their participation, noting that it takes courage to have your choice of treatment determined randomly by a computer. “The patients are the real heroes here,” he says. “They put themselves on the line so that thousands and thousands of other patients could be spared the morbidity of unnecessary surgery. It’s really extraordinary what they did.”