A 2-cm resection margin resulted in the same 5-year overall survival and recurrence-free survival as did a 4-cm margin in a randomized controlled trial of more than 900 patients with cutaneous melanoma thicker than 2 mm.
The findings suggest that in patients with thicker melanomas, a 2-cm margin is safe and sufficient, according to Dr. Peter Gillgren of Karolinska Institute, Stockholm, and Stockholm Söder Hospital and his colleagues.
At a median follow-up of 6.7 years, the 5-year overall survival was 65% in 465 patients randomized to treatment with a 2-cm surgical resection margin, as well as in 471 patients randomized to treatment with a 4-cm resection margin. Recurrence-free survival at 5 years was 56% in both groups, and 10-year survival was 50% in both groups, the investigators reported (Lancet 2011 Oct. 24 [doi:10.1016/S0140-6736(11)61546-8]).
"The failure to clear genetically abnormal melanocytes with an adequately wide excision might be the precursor to locoregional recurrence."
Surgical resection margin size in patients with cutaneous melanoma thicker than 2 mm has been a point of controversy, largely due to a paucity of data comparing outcomes based on margin size, but most international guidelines suggest an excision margin of 2-3 cm for thick melanomas, the investigators noted. "A trade-off exists between a wide excision, with consequent surgical difficulties, and the relapse risk with a narrow excision, which could compromise disease-free survival, or worse, overall survival," they wrote.
However, the findings of this study indicate that not only is survival similar with 2-cm and 4-cm margins, but that the smaller margin size also improves the likelihood of skin closure without skin grafting or skin flaps. Primary closure was possible in 69% vs. 37% of patients in the 2-cm and 4-cm groups, respectively, while split skin grafts were used in 12% and 47% of the patients in the two groups. And surgical flaps were used in 4% and 6% of patients in the two groups, noted the investigators.
Patients in this study, which was launched by the Swedish Melanoma Study Group in cooperation with the Danish Melanoma Group, were adults aged 75 years or younger with a primary cutaneous melanoma thicker than 2 mm and with clinically localized disease on the trunk or upper or lower extremities. Patients were enrolled from Jan. 22, 1992, to May 19, 2004. One patient in each group was lost to follow-up but was included in the analysis.
Despite some limitations, such as protocol violations in 15% of cases and the fact that the study was planned as an equivalency trial that was to include 2,000 patients, the investigators noted that the study is the largest randomized controlled trial to date of resection margins for thick melanomas, and that they believe the results provide "the best evidence yet about the size of surgical excision margins."
"We show that with a surgical margin of 2 cm, the skin can be closed without skin grafting or skin flaps in most cases," they wrote, noting that previous data have already shown that hospital stay is longer in patients treated with a 4-cm margin, and that complication rates are higher in patients treated with split skin grafts, compared with primary sutures.
A meta-analysis of all randomized trials of cutaneous melanoma thicker than 2 mm should be conducted, they concluded.
The study was funded by the Swedish Cancer Society and the Stockholm Cancer Society. The authors reported having no relevant financial disclosures.