Lymph-node dissection increases rates of regional disease control

Brian Gastman, M.D., who specializes in treating melanoma patients, says it’s hard to argue against the results of a herculean effort - a multi-institutional, prospective, randomized phase 3 study that shows lymph node dissection isn’t the only, nor possibly the best option for melanoma patients with sentinel lymph node metastasis.

In fact, patients will likely fare as well, while avoiding the surgical complications of lymph node dissection, with the less invasive sentinel node biopsy, says Dr. Gastman, a Cleveland Clinic surgeon. It’s a finding that can be counterintuitive to many patients and their doctors, he said in response to a study that was recently published in the New England Journal of Medicine.

The study, referred to as MSLT-II, showed no added benefit to the removal of the other lymph nodes. However, sentinel-lymph-node biopsy was found to be associated with increased melanoma-specific survival among patients with node-positive intermediate thickness melanomas (1.2 to 3.5 mm). The study’s lead author Mark B. Faries, M.D., of The Angeles Clinic and Research Institute in Los Angeles, said the new study clarifies information patients need if they have a sentinel lymph node metastasis.

“Up to this point, there was less certainty about the pros and cons of a completion lymph node dissection in that situation. [But now we know] having a positive sentinel node does not automatically lead to a complete dissection. Most patients who have melanoma in the sentinel node will have had all of their disease removed with the biopsy procedure,” he said in an interview with Dermatology Times.

The research is important because it might alleviate concerns dermatologists may have for the morbidity of node dissection. Since the sentinel node procedure is significantly less morbid and carries most of the prognostic and therapeutic value of early nodal intervention, for many or most patients, the toxicity of a node dissection can be avoided, Dr. Faries says.

“We now know the advantages and disadvantages of completion node dissection. Advantages of having the surgery include gaining more prognostic information and decreasing the overall risk of recurrence. Disadvantages are an increased risk of complications, specifically lymphedema, which occurred in 24 percent of patients in the [completion lymph-node dissection] arm and 6 percent of those in the observation arm,” he said.

The study

This was an international trial in which patients with sentinel-node metastases were randomized into one of three groups:  standard pathological assessment or a multi-marker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end-point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of non-sentinel-node metastasis.

Dr. Faries and colleagues found that the immediate completion lymph-node dissection was not associated with increased melanoma specific survival among 1,934 patients in the intent-to-treat group and 1,755 patients in the per-protocol analysis group in which the three-year rate of melanoma survival was similar amongst both the dissection group and the observation group (86±1.3% and 86±1.2%) at 43-month follow-up.

The dissection group experienced a slightly higher rate of disease-free survival as compared to the observation group (68±1.7% and 63±1.7%) at three years, based on an increased rate of disease control in the regional nodes.

“These results must be interpreted with caution,” Dr. Faries and colleagues wrote in the study. They noted that non-sentinel-node metastases, which were present in 11.5% of patients in the dissection group, are a “strong independent prognostic factor for recurrence.

Cancer assessment

“The sentinel node biopsy used commonly for breast and melanoma cancer is an exquisitely sensitive way to assess whether a cancer has spread to a regional lymph node. As little as one cancer cell metastasizing can be identified, way before many millions of cells would have to metastasize to be seen on something like a CAT scan,” Dr. Gastman explains.

“In the case of melanoma, it tells you that the cancer is spreading into the lymph nodes as opposed to going into the blood system, and it shows that the tumor is more aggressive versus a sentinel node biopsy tumor that is negative. However, if you know that a lymph node harbors cancer and that tumors tend to spread from lymph node to lymph node before disseminating all over the body, it is intuitive to then remove the other lymph nodes,” he said.

Complete node dissection remains a reasonable option for patients.

“Our subgroup analyses did not show a particular group that would benefit from a survival standpoint, though more analysis of that question is needed over time,” Dr. Faries says. “Patients who want more information … to help them decide whether to pursue adjuvant medical therapy or clinical trials may choose to have the surgery done. Those who want to decrease their risk for recurrence, particularly in the lymph nodes, might also choose the surgery. Finally, those who are not able to have close follow up with lymph node ultrasounds should probably have immediate dissection, since our study cannot verify the safety of observation in that situation.”

“Only 13 percent of the study included head and neck melanomas, which are known to have a more variable metastatic pattern. [So,] should these be included in practice management changes? … in that vein, I reserve some judgment,” Dr. Gastman says. “However, like the MSLT-I study, which shows the importance of a sentinel node biopsy, we cannot ignore this important paper. And for me, until proven otherwise, the use of what we call a completion lymphadenectomy in patients with micro metastatic disease identified by sentinel node biopsy should be discussed with patients, but not made mandatory.”

The study provides broadly definitive information for what might be the last major question in the initial surgical management of melanoma, Dr. Faries says.

“More information will be helpful in determining whether the prognostic information currently obtained from non-sentinel nodes can be derived by other means and how much added value nodal ultrasound provides in follow up. The study remains active as we gather more follow up information to help answer those questions,” Dr. Faries says.

“For the patient type described in this paper, we will continue to offer the completion lymphadenectomy surgery, as it was shown to reduce recurrence in those non-sentinel node biopsy lymph nodes and adds prognostic information,” he said.

Dr. Gastman says that in discussions with patients, he’ll address long-term survival and risks, such as lymphedema, that should be considered.

“A patient always makes the final decision to have or not have a surgery, but the information I will impart to these patients will now change, and they may make different decisions than patients I treated before this paper,” he said.

Reference

Mark B. Faries, M.D., John F. Thompson, M.D., Alistair J. Cochran, M.D., et al. "Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma," NEJM. June 8, 2017. DOI: 10.1056/NEJMoa1613210