Narrower excision margins appear to be adequate for high-risk malignant melanoma patients with lesions thicker than two millimeters, according to a study led by researchers at the Karolinska Research Institute in Sweden (Lancet 2011;378:1635–1641).
Peter Gillgren, MD, PhD, of the Department of Oncology and Pathology, together with colleagues at five other research centers in Europe, found excision margins of 2 cm to be as effective as removing 4 cm for stage II-C melanomas thicker than 2 mm, the margin currently used for many high-risk melanomas. And, he said via email, although further research is needed, it is possible that even smaller excision margins could prove effective as well.
"Smaller excisions spare patients from undue suffering and carry as low a risk of complications as wider margins with better cosmetic results, all without compromising safety," he said about the study results.
The researchers compared survival and recurrence in 936 patients randomized to undergo first-line excisions using either a 2 or 4 cm margin. Patients were treated at centers in Sweden, Denmark, Norway, and Estonia. A total of 465 patients underwent smaller excisions, while 471 had 4 cm margins removed, and all patients remained in their respective group regardless of subsequent developments. The study was conducted between 1992 and 2004.
After a median follow-up of about seven years, mortality rates were similar between the two groups. A total of 181 of the 2 cm patients (39%) and 177 in the 4 cm group (38%) died, but the five-year survival rate was the same in both groups at 65 percent, and there was no difference in the recurrence rate between the two groups at 44 percent.
In the Swedish subgroup, patients were followed for an average of 11.8 years, and both survival and recurrence rates were the same regardless of the excision margin used. The recurrence-free survival rate was 55 percent in both groups after five years, and just three percent of patients had a melanoma recurrence in the scar: 20 patients in the 2 cm group and nine in the 4 cm group, a difference that was found not to be statistically significant.
The authors noted that while more patients in the 2 cm group underwent sentinel node biopsy, a sensitivity test did not show any difference in outcome when they were excluded.
Only one previous randomized controlled trial has focused exclusively on patients with malignant melanomas thicker than 2 mm, and that was conducted in 900 patients in 1993 using excision margins between 3 and 4 cm, and it found little difference in survival or recurrence, Gillgren noted.
"Our study had a longer follow-up time than previous studies, and demonstrated that there is no higher risk in performing smaller procedures in patients with high-risk melanoma. We have shown that there is no difference in survival between the groups."
Because malignant melanoma is one of the fastest-growing forms of cancer in Sweden and elsewhere, it is important to draw up guidelines for coordinated therapy and long-term follow-up, he said.
"The most recent international guidelines are to operate on this patient group with a 2–3 cm margin, although this recommendation is based on somewhat scarce evidence. This uncertainty is now less as our study demonstrates that a margin of 2 cm is just as safe as one of 4 cm."
He also called for meta-analysis of all randomized trials of melanoma thicker than 2 mm to further clarify the findings.
Already Widely Used
Melanoma surgical pioneer Charles M. Balch, MD, Professor of Surgery in the Division of Surgical Oncology at the University of Texas Southwestern Medical Center, called the results "the final piece of the puzzle for evidence-based surgery of melanoma."
"These results confirm and extend what we have learned in past randomized studies and have been recommending for some years. The first trial on narrower excision margins was conducted 20 years ago, in thinner melanomas (T1 and T2), while 10 years ago our second study showed the same benefit with excisions of melanomas of 1 mm to 4 mm in thickness. So this trial really gives us the last bit of evidence, especially for thick melanomas that were not part of the earlier surgical trials. Now we have the full story," he said in a telephone interview.
Many oncology surgeons in the United States are already using 2 cm radial margins, based on the early data, he noted.
"While I don't think this new study is going to change surgical practice here in the U.S, since we already are using 2 cm margins for T3 and T4 melanomas, we acknowledge that there is no randomized data for doing so until now. The Scandinavian surgical trial demonstrates that narrower margins are safe, that they spare most patients having to undergo skin grafts and longer hospitalization, and it reduces the risk of disfigurement."
Also asked for his opinion, David W. Ollila, MD, Associate Professor of Surgery and Director of the Multidisciplinary Melanoma Program at the University of North Carolina School of Medicine, said that he has been using narrower margins successfully in patients for around five years.
"The results of the Swedish researchers, as well as those from other trials, confirm that margins greater than 2 cm are unnecessary for any melanoma patient," he said. "I feel these new findings really cement what we have been practicing for about five years, ever since the Swedish group first presented their preliminary results at an international melanoma meeting. This further confirms what we have seen in the clinic."
Important to Have the Confirmation
Donald L. Morton, MD, Chief of the Melanoma Program and Director of the Surgical Oncology Fellowship Program at John Wayne Cancer Institute in Los Angeles, said, "I think the study is pretty straightforward: The findings indicate no difference in locoregional recurrence, distant metastases, or survival when comparing 2 cm vs. 4 cm margins."
He was Chief of Surgical Oncology at UCLA before founding the John Wayne Cancer Institute.
"Most of us had already concluded this, based on earlier studies, but it is always important to have the findings confirmed in another large randomized study," he said.
"The biggest benefit with using smaller margins is that they reduce or eliminate the necessity for skin grafts. With 2 cm margins, it was possible to close the wound in 69 percent of cases compared with just 37 percent of patients undergoing excisions of 4 cm, even though there is not much risk associated with skin grafts."
But there can be scarring with larger excisions. "This is not usually a problem when a lesion is removed from a leg or the torso, but many patients are concerned if the procedure must be done in the facial area."
There is also evidence that even narrower excision margins might be safe for many patients. "It is very clear that 1 cm excisions are safe and effective for lesions that are 1 mm and thinner, but not much study data on melanomas that are 1 to 2 mm," Morton said. "We just do not have good data, but my guess is that 1 cm margins will be equivalent in most patients with melanomas between 1 and 2 mm."© 2012 Lippincott Williams & Wilkins, Inc.
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