Study Disputes Lymph Node Removal Standard in Melanoma

Claus Garbe, MD

Patients with melanoma who are found to have micrometastases after an initial positive sentinel node biopsy can safely forgo a complete lymph node dissection (CLND), thus avoiding the risk of debilitating adverse events from the surgery, according to a study reported at the 2015 ASCO Annual Meeting.¹

The study found no differences in several key survival outcomes among 483 patients with stage III melanoma and a positive sentinel lymph node biopsy who were randomized to observation only versus CLND. The study did detect a higher 14.6% rate of lymph node regional metastases among the observation group, compared with 8.3% in the CLND group.

“This is the first study which tested the general recommendation of complete lymphadenectomy in patients with positive nodes,” lead author Claus Garbe, MD, a professor of dermatology at the University of Tübingen in Germany, said during an ASCO press briefing. “We cannot confirm this recommendation, and we expect that the practice will change.”

The study focused on patients with micrometastases; the researchers would continue to recommend CLND for patients with larger, clinically detectable macrometastases.

Lynn M. Schuchter, MD, FASCO, a melanoma specialist who served as an expert ASCO commentator at the briefing, said the trial is an important study that helps elucidate how to manage patients with a lower risk of recurrence but that more evidence is needed for a broad change in current practice.

She said the standard of care currently is to perform CLND if positive sentinel lymph nodes are found through mapping but that clinicians are increasingly questioning whether the second procedure is needed, “especially if there is microscopic lymph node involvement.”

“It’s a relatively small study and I don’t think we would make a complete change in our recommendations yet based upon this study,” Schuchter said.

“I think we’ll wait in terms of making definitive changes in our management with the results of another larger study.”

For patients, the questions the trial posed have significant implications. The risks of CLND include infection and nerve damage. Lymphedema can occur in more than 20% of patients and persist long term in 5% to 10% of patients, ASCO said in a statement.

Garbe and colleagues, who conducted their study through the Dermatologic Cooperative Oncology Group in Germany, sought to determine whether there would be a ≥10% survival difference between CLND and observation among patients who had positive sentinel node biopsies. Participants in the observation group were monitored with a lymph node ultrasound every 3 months and additional imaging tests every 6 months. Patients in the CLND cohort were monitored on the same schedule after their surgery.

Garbe said investigators initially planned to conduct the study over a 6-year period with 558 enrolled patients, for which they had expected to screen more than 4000 people. “Recruitment was more difficult than expected and we needed 9 years to recruit 483 patients,” he explained.

Researchers said the two groups did not differ significantly in age, gender, localization, ulceration, tumor thickness (median 2.4 mm for both cohorts), number of positive nodes, or sentinel node tumor burden. Patients had been diagnosed with cutaneous melanoma of the trunk and extremities.

After a median follow-up of 35 months, the study found no statistically significant differences between the two groups in terms of 5-year recurrence-free survival (P = .72), distant metastases-free survival (P = .76), and melanoma-specific survival (P = .86).

Another analysis is planned in 3 years, but Garbe said in a statement that he does not believe the overall findings would change because prior research has indicated that approximately 80% of melanoma recurrences surface within 3 years of initial diagnosis.

Meanwhile, the John Wayne Cancer Institute in Santa Monica, California, is continuing to investigate the same research questions in the ongoing MSLT-II trial.²

The study is evaluating nodal ultrasound observation versus CLND in 1925 patients who have had a positive sentinel node biopsy that fits into one of these categories: Breslow thickness of ≥1.20 mm and Clark level III; Clark level IV or V, regardless of Breslow thickness; or ulceration, regardless of Breslow thickness or Clark level.

The trial, which is designed to detect a 5% difference in survival between the two management strategies, will follow patients for 10 years. Results are expected in 2022.

References

1. Leiter U, Stadler R, Mauch C, et al. Survival of SLNB-positive melanoma patients with and without complete lymph node dissection; a multicenter, randomized DECOG trial. J Clin Oncol. 2015;33 (suppl; abstr LBA9002).

2. NIH Clinical Trials Registry. www.ClinicalTrials.gov. Identifier: NCT00297895.

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