When sentinel node biopsy was shown to predict whether early melanoma had spread to regional lymph nodes, it revolutionized care. Before that, dissection of all regional lymph nodes was the norm for most patients. After that, the standard of care became a sentinel node biopsy and then—only if the sentinel node or nodes were positive—a completion lymph node dissection.
Another revolution may now be brewing: A major, current question in melanoma is whether even patients with a positive sentinel node need to undergo a completion lymph node dissection. That question was explored in a formal debate between Daniel G. Coit, MD, a surgical oncologist at Memorial Sloan-Kettering Cancer Center, New York, and Charles M. Balch, MD, Professor of Surgery at The University of Texas Southwestern Medical Center, Dallas, during the Annual Cancer Symposium of the Society of Surgical Oncology (SSO), held recently in Washington, DC.1
Morbidity, Survival Rates
Critics argue that about 80% of patients with a positive sentinel node turn out to have no additional disease. That means completion lymph node dissection puts 80% unnecessarily through a much longer and more costly operation with its risk of complications and morbidities, such as wound infection, lymphedema, and nerve damage.
“We create the potential for significant complications with these operations,” said Dr. Coit, who argued against completion lymph node dissection.
The rate of morbidity associated with completion lymph node dissection is from 5% to 10% according to large studies. But skeptics point to smaller studies and subgroup analyses suggesting the risk may be higher for some patients. Lymphedema, for instance, is more common and severe among overweight patients and those who have had lymph nodes taken from the groin. Thus, overall morbidity rates after completion lymph node dissection are 30% to 40%, and even worse (~60%) after groin dissection.
Dr. Coit also cited evidence from four prospective randomized trials that showed no difference in survival between patients who underwent initial elective lymph node dissection compared to those who underwent delayed therapeutic lymph node dissection if necessary. Dr. Coit also cited two retrospective observational studies that were unable to demonstrate any survival benefit associated with completion lymph node dissection compared to observation after positive sentinel lymph node biopsy. While these studies may reflect patient selection, he indicated that they do support equipoise in the two arms of the ongoing seminal randomized Multicenter Selective Lymphadenectomy Trial 2 (MSLT-2).
Regional Control, Staging
Proponents of completion lymph node dissection point to its value in regional control, regardless of its impact on survival. Dr. Balch, who took the pro side of the debate, cited the Sunbelt Melanoma Trial and others showing that among patients who have immediate completion lymph node dissection, regional recurrence rates are very low compared to those in patients who present later with macroscopic nodal metastases.
“The best evidence we have suggests that [completion lymph node dissection] is effective at achieving regional control,” said Dr. Balch. “I would emphasize that there are many circumstances in which we operate on patients to achieve regional disease control, even if it doesn’t per se increase survival.”
But Dr. Coit questioned the value of the procedure for regional control. He described an observational study suggesting that half of patients with positive sentinel nodes “will recur systemically before it makes any difference whatsoever what we do in the lymph nodes.”
Another argument in favor of completion lymph node dissection is its value in staging, said Dr. Balch. He cited “at least five papers” showing that “it’s not just the number of nodes but that [nonsentinel] nodes have prognosis, and therefore there is a staging value in addition to regional control.”
“I wouldn’t argue with that,” said Dr. Coit. The problem is it’s an expensive test with risks of complications and morbidities, he added.
Critical Trial
One area of agreement among experts is the importance of completing the MSLT-2 trial. Chaired by Donald L. Morton, MD, Chief of the Melanoma Program at John Wayne Cancer Institute, Santa Monica, California, the trial is randomizing sentinel node positive patients into two groups, one to have an immediate completion lymph node dissection, the other to be monitored by nodal ultrasound and have a delayed completion dissection if necessary. The primary endpoint is melanoma-specific survival.
The trial’s accrual goal is 1,926 patients. About 1,680 have been randomly assigned to the two arms, said Mark B. Faries, MD, Director of Melanoma Research at John Wayne Cancer Institute, who gave an update on the trial at the SSO symposium.2 “If we stay at this pace—and the pace actually seems to be picking up—we’ll probably complete accrual early next year.” Analysis of the data, he added, could begin “another couple of years after that.” ■
Disclosure: Dr. Balch has received speaker’s honoraria from Merck. Drs. Coit and Faries reported no potential conflicts of interest.
References
1. Coit DG, Balch CM: Great debates: Completion axillary node dissection is necessary in all melanoma patients with a positive SLN. Society of Surgical Oncology Annual Cancer Symposium. Presented March 9, 2013.
2. Faries MB: MSLT 2: An update. Society of Surgical Oncology Annual Cancer Symposium. Presented March 7, 2013.
