Among patients with high-risk, primary cutaneous melanomas, the risk of death from melanoma, at a median follow-up of 8.8 years, was significantly higher among those randomized to surgery with a 1-cm excision margin than among those randomized to surgery with a 3-cm excision margin. Although overall mortality was also higher in patients with a 1-cm excision margin, that difference was not statistically significant.
Reporting the results in The Lancet Oncology, Andrew J. Hayes, PhD, of the Royal Marsden Hospital National Health Foundation Trust, London, and colleagues, noted, “Our study has re-emphasized that the choice of surgical margins taken around a cutaneous melanoma is important and, to our knowledge, for the first time provides evidence to suggest that a narrower excision margin used for thick primary tumors affects melanoma-specific survival. This finding might be pertinent for specific melanomas for which narrow (1 cm) margins are presently advised—ie, melanomas between 1 mm and 2 mm in thickness with other adverse prognostic features (ulceration or high mitotic rate or both).”
The multicenter study randomized 900 patients in 57 hospitals in the United Kingdom and 1 each in Poland and South Africa. All patients were 18 years or older and had one primary localized cutaneous melanoma greater than 2 mm in Breslow thickness on the trunk or limbs (excluding palms or soles). “Patients could not have any previous history of cancer, other than basal cell carcinoma,” the researchers explained. “Elective lymph node dissection and sentinel node biopsy were not part of routine practice at the time the trial was undertaken, and adjuvant chemotherapy was not allowed in the trial protocol.”
Previously published results showed that at a median follow up of 5 years, patients with 1-cm excision margins had a significantly greater risk of locoregional recurrence than those with 3-cm margins. At that time, no significant differences in melanoma-specific or overall survival were apparent.
At a median follow-up of 8.8 years, 494 patients had died, with 359 of these deaths attributed to melanoma. Among the 453 total patients in the 1-cm group, 194 deaths were attributed to melanoma, compared with 165 melanoma deaths among the total of 447 patients in the 3-cm group (unadjusted hazard ratio [HR] = 1.24; 95% confidence interval [CI]: 1.01–1.53; P = .041).
“The estimated absolute difference in melanoma-specific survival at 10 years between the two groups was 5.95% (95% CI: –0.54 to 12.44),” the investigators found. “Although a higher number of deaths overall occurred in the 1-cm group compared with the 3-cm group (253 vs 241), the difference was not significant (unadjusted HR = 1.14; 95% CI: 0.96–1.36; P = 0.14),” the authors wrote.
“Surgical complications were reported in 35 (8%) patients in the 1-cm excision margin group and 65 (15%) patients in the 3-cm group,” the investigators reported. The most common complications were partial or complete graft loss, which occurred in 10 patients (2%) in the 1-cm group vs 20 patients (4%) in the 3-cm group, and wound dehiscence, 7 patients (2%) in the 1-cm group vs 9 patients (2%) in the 3-cm group.
The study was funded by Cancer Research UK, North Thames National Health Service Executive, Northern and Yorkshire National Health Service Executive, British United Provident Association Foundation, British Association of Plastic Surgeons, the Meirion Thomas Cancer Research Fund, and the National Institute for Health and Research Biomedical Research Centre at the Royal Marsden National Health Foundation Foundation Trust. ■
Hayes AJ, et al: Lancet Oncol. January 16, 2016 (early release online).