Investigators examine benefit of level 3 dissection in melanoma

September 1, 2013

Results of a retrospective chart review revealed patients with melanoma who present with bulky axillary disease develop distant metastases very quickly, prompting the plan for a prospective study to examine the preoperative impact of shrinking tumors through the use of systemic therapy.

 

QuickRead: Level 3 nodes bear metastases more often in patients with palpable disease and in patients with bulky disease compared to sentinel lymph node positive patients.

Banff, Alberta - Results of a retrospective chart review revealed patients with melanoma who present with bulky axillary disease develop distant metastases very quickly, prompting the plan for a prospective study to examine the preoperative impact of shrinking tumors through the use of systemic therapy.

The retrospective investigation aimed to look at the extent of surgery necessary for patients who presented in one of three ways, says Frances Wright, M.D., M.Ed., F.R.C.S.C., associate professor of surgery, University of Toronto, and director of surgical oncology fellowship program, University of Toronto.

Dr. Wright spoke here about how level 3 nodes, that is nodes medial to the insertion of pectoralis minor to the clavicular head, bear melanoma metastases and the effect on patient outcome at the annual Canadian melanoma conference.

“These were patients with melanoma who had either sentinel-positive disease, or disease that you can palpate, or a very amount of disease or bulky amounts of disease,” says Dr. Wright, noting limited data exist on the need to resect level 3 nodes as part of an axillary dissection for melanoma.

Lymphadectomy benefits unknown

Currently, in patients who have sentinel lymph node positive disease, complete lymphadectomy is controversial and the clinical benefit is not known. This question is being addressed in the Multicenter Lymphadenectomy Trial Part 2 (MSLT 2).

There is also little evidence for benefit of level 3 dissection compared to a level 1/2 dissection. A study published in 2012 concluded that a level 3 dissection offered minimal benefit in melanoma patients with a positive axillary sentinel lymph node (Namm JP, Chang AE, Cimmino VM, et al. J Surgl Oncol. 2012;105(3):225-228).

The study involved patients from two centers, Sunnybrook Odette Cancer Center/University of Toronto, and the Tom Baker Cancer Center/University of Calgary. All of the patients included in the review had undergone level 3 dissection for melanoma, with a goal to cure disease, between 2005 and 2011.

A total of 117 patients were included. A total of 65 patients were sentinel lymph node positive and had median age of 54, 44 had palpable disease and a median age of 61.5, and eight had palpable disease and a median age of 50.5.

The investigators found the median number of nodes of all three levels was 24, the median number of sentinel lymph nodes was three, and the median number of level 3 nodes was five.

Researchers found level 3 nodes bear metastases infrequently (3 percent) in sentinel lymph node positive patients, that they bear metastases more often (18 percent) in patients with palpable disease, and all level 3 nodes bear metastases in patients with bulky disease.

SLN positivity and level 3 dissection

“Based on our findings, patients who are sentinel lymph node positive don’t need to have a formal level 3 dissection,” says Dr. Wright, noting a level 1/2 dissection appears to be sufficient in patients with sentinel lymph node positive patients. “When you undergo a formal level 3 dissection, there is likely a small amount of additional morbidity and pain which, it looks like, we can avoid.”

However, 20 percent of patients with palpable disease had level 3 disease and consequently a level 3 dissection is appropriate in these patients, according to Dr. Wright. In patients with bulky disease, level 3 is most commonly palliative as patients develop distant disease quickly.

Dr. Wright says investigators found different survival and outcomes in terms of when the patient develops metastases.

Distant recurrence occurred with greater rapidity a with greater degree of disease: the median time to distant metastases was 13.6 months in patients with palpable disease and 2.1 months in patients with bulky disease. Patients with level 3 disease had a poorer overall survival than those who did not, 15.2 percent versus 61.1 percent, a difference that was statistically significant.

“It was a really surprising finding in terms of the rapidity with which patients develop distant metastases,” Dr. Wright says. “It was much faster than we had anticipated. Even the median time for patients with palpable disease to develop distant metastases was fast at 13 months.”

Dr. Wright and colleagues also measured the loco-regional recurrence rate and systemic recurrence rate, finding greater disease correlated with higher rates of both.

Dr. Wright and other investigators are launching a pilot study to assess the impact of preoperative administration of systemic therapy in patients with palpable and bulky disease.

“The goal is that we would shrink disease preoperatively to change outcomes,” she says, noting vemurafenib would be administered to patients who are BRAF positive.

Disclosures: Dr. Wright reports no relevant financial interests.