New level 1 evidence may mark the beginning of the end of complete lymphadenectomy in stage III melanomas with micrometastasis to the sentinel nodes. According to results from a randomized, phase III, noninferiority trial conducted in Germany, patients with a positive sentinel lymph node biopsy (SLNB) attained no survival benefit after undergoing complete lymph node dissection compared with observation (Abstract LBA9002).
“Based on our findings to date, complete lymphadenectomy cannot be recommended in [patients with] melanoma with micrometastases in the sentinel nodes,” Ulrike Leiter, MD, of the University of Tuebingen, Germany, concluded. Dr. Leiter presented the study findings during the Melanoma/Skin Cancers Oral Abstract Session on Saturday, May 30.
Discussant Daniel G. Coit, MD, FACS, of Memorial Sloan Kettering Cancer Center, tended to agree, but was more moderate in his position. “I think it will be very hard to defend not discussing [observation as an] alternative in the face of these data,” he said.
Radical lymphadenectomy currently represents standard practice for patients with a positive SLNB, despite a lack of robust clinical data supporting this approach and the pronounced morbidity of the procedure. At least 20% of patients with melanoma who undergo a complete lymphadenectomy experience grade 3/4 lymphedema that can take months to years to resolve. Wound infection and nerve damage pose additional concerns, along with the added cost of more extensive surgery.
To clearly define the potential benefits of complete lymphadenectomy in patients with melanoma and a positive SLNB, the German Dermatologic Cooperative Oncology Group (DeCOG) devised a long-term trial focused on distant metastasis-free survival (DMFS) as the primary outcome. From January 2006-December 2014, 483 adult patients with cutaneous melanoma of the trunk and extremities measuring at least 1.0 mm thick who had micrometastases in the sentinel lymph nodes joined the study and underwent random assignment to observation or complete lymphadenectomy. Thereafter, patients in both arms were carefully followed with lymph node sonography every 3 months and whole-body imaging every 6 months to monitor for disease recurrence, in agreement with German guidelines.
Although patients who underwent radical lymphadenectomy experienced better disease control in the regional lymph node basin compared with patients followed with close observation (regional lymph node recurrence rate: 8.3% vs. 14.6%, respectively; p = 0.029), this did not translate into enhanced survival outcomes after a median follow-up period of approximately 3 years. In fact, the findings showed nearly identical Kaplan-Meier estimates for DMFS (hazard ratio [HR] 1.02, 95% CI [0.67, 1.56]; p = 0.92), melanoma-specific survival (HR 1.01, 95% CI [0.64, 1.59]; p = 0.98), and recurrence-free survival (HR 0.89, 95% CI [0.63, 1.27]; p = 0.52).
The study design featured the ability to detect a 10% difference in DMFS between groups with 75% power, and currently the difference between arms is 0.3%. A second evaluation of the data is planned in 3 years.
Key data missing from the DeCOG report involved recurrence rates in the nonsentinel nodes. “Proponents of this operation will cite fear of loss of control of the regional nodal basin,” Dr. Coit said, which makes these data important to tease out.
A critical study that will validate or contradict the DeCOG results is the ongoing Multicenter Selective Lymphadenectomy Trial II evaluating complete lymphadenectomy versus ultrasound observation in more than 1,900 patients with SLNB-positive melanoma (NCT00297895). However, the wait will be long, as the final 10-year follow-up results are not anticipated until 2022.
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