Christopher Puleo, PA-C
A 10-year follow-up study of regional melanoma staging strategies found that patients who underwent sentinelnode biopsies had significantly greater disease-free survival rates (DFSRs) compared with patients monitored through nodal observation.
The final results of the Multicenter Selective Lymphadenectomy Trial (MSLT-1), which began in 1994 and enrolled patients through 2002, also showed that biopsy-based staging provides important prognostic information (N Engl J Med. 2014;370(7):599-609).
During the phase III trial, 2001 patients with primary cutaneous melanomas were randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (40%) or wide excision and sentinel-node biopsy (SNB) with intermediate lymphadenectomy for nodal metastases detected on biopsy (60%).
In the MSLT-1 trial, researchers sought to determine whether the minimally invasive SNB could be used after primary surgery to identify patients with clinically occult nodal metastases, instead of waiting for nodal recurrence. Of the 2001 patients initially involved in the study, 1661 underwent randomization and 1638 were included in the 10-year follow-up. Of the initial patient population, 1347 had intermediate-thickness (1.20 to 3.50 mm) primary melanomas and 314 had thick primary melanomas (>3.50 mm).
Mean (± standard error) 10-year DFSRs, the primary endpoint of the study, were significantly improved in the biopsy group, compared with the observation group, among patients with intermediate- thickness melanomas (71.3 ± 1.8% with SNB vs 64.7 ± 2.3% in the observation group), and among those with thick melanomas (50.7 ± 4.0% vs 40.5 ± 4.7%, respectively).
Although sentinel-node biopsies resulted in better DFSRs, there was no significant treatmentrelated difference in the 10-year melanomaspecific survival rates among those in the biopsy group (81.4 ± 1.5%) and those in the observation group (78.3 ± 2.0%) among patients with intermediate- thickness melanomas.
Similarly, there was no difference among patients with thick melanomas (58.9 ± 4.1 with SNB vs 64.4 ± 4.6 with observation). Researchers said the lack of a survival advantage for patients with intermediate-thickness melanomas was not surprising because the overall event rates were lower than expected. In addition, they said the false-negative rates were higher in the earlier years of the study, possibly clouding therapeutic benefits, because staff members had not yet gained experience with the procedures.
Christopher Puleo, PA-C, a coauthor of the study from Moffitt Cancer Center who worked with the patients throughout the course of the trial, said that there are long-term side effects associated with removing the lymph nodes prematurely.
“The one main long-term side effect associated with a node dissection is lymphedema,” Puleo said. “This phenomenon occurs approximately as often as 5% of the time in the axilla and up to 15% to 20% of the time in the groin with rare effects in neck dissections. Depending upon whose statistics you review, the overall chances of patients developing spread of the melanoma to their lymph nodes was 16% to 25% on average.
If you were to take 100% of your patients and electively remove their lymph nodes, only 16% to 25% of them would be getting a benefit from that procedure, but 100% of your patients would have the potential for developing any and all of the side effects associated with the surgery.”
To test sentinel melanoma lymph nodes, a radioactive tracer and a blue-colored dye are injected at or near the melanoma site on the skin and tracked to the sentinel nodes. “It has made it much easier without doing surgeries that are potentially debilitating,” said Puleo.
Sentinel lymph node biopsies in melanoma patients are based on the location of the primary melanoma. The skin is the largest organ in the body, and lymphatic circulation encompasses the entire surface area of the skin. The primary melanoma may have multiple lymphatic drainage sites that flow to many nodal basins. A patient may, therefore, have multiple sentinel lymph node biopsies in various sites based on the drainage of the melanoma.
A lymph node drainage mapping, known as lymphoscintigraphy, is generally obtained as part of presurgical testing to determine the flow of lymphatic drainage from the primary melanoma. This helps surgeons to identify where and which areas require a sentinel lymph node biopsy. A sentinel node biopsy of the various basins must be completed to properly assess the patient’s melanoma.
Sentinel lymph node biopsies are important in predicting a patient’s risk for recurrence and/or metastatic disease. The size of the metastases in the lymph node also is important, for a micrometastases versus a macrometastases determine staging, prognosis, and possible adjuvant therapy recommendations.
By assessing the patient’s sentinel lymph node, it prevents unnecessary removal of additional lymph nodes. Complete lymph node dissections can lead to lymphedema that may impact the patient’s quality of life without necessarily changing overall survival. Sentinel lymph node biopsy prevents erroneous surgeries and unnecessary side effects or complications.
Although overall survival may not be affected with a sentinel lymph node biopsy versus observation, we are able to have predictive information that helps manage the patient’s risk for recurrence.
As new therapies emerge in melanoma, prognostic factors—including sentinel lymph node biopsies—will become more important in deciding a patient’s course of treatment and surveillance.