A cohort study of 188,862 cases of all-stage melanomas of the trunk and extremities found no differences in overall survival between patients treated with Mohs micrographic surgery or with wide local excision.¹ “These findings add to the existing body of evidence demonstrating that wide local excision is not associated with a greater survival benefit than Mohs micrographic surgery for treatment of cutaneous melanoma,” wrote Addison Demer, MD, Senior Associate Consultant, Department of Dermatology and Assistant Professor at Mayo Clinic, Rochester, Minnesota, and colleagues in JAMA Dermatology.

That body of evidence includes a recently published study by the same group, demonstrating that Mohs surgery is associated with improved overall survival for patients with melanomas of the head and neck.² In addition, a study by researchers at Yale University found that Mohs surgery “was associated with a modest improvement in overall survival relative to wide margin excision” for stage I melanomas across all anatomic sites.³ The contribution from this study was that it included all-stage in situ and invasive melanomas but was limited to the trunk and upper and lower extremities.

Addison Demer, MD

Clinical Implications

In an interview with The ASCO Post, Dr. Demer explained that he and his colleagues looked first at head and neck cancers. “We felt those tumors were most likely to benefit the most. They are the ones that are more commonly receiving Mohs surgery in our practices as well as in practices across the country. So, it was a good starting place.”

“We had data showing survival benefits for head and neck melanoma,” Dr. Demer added. The Yale researchers “presented data for early-stage melanoma of all sites demonstrating a survival benefit, and that left us in a position to clinically wonder how to counsel our patients. That is what prompted this latest study. It was to better determine whether the survival benefit for Mohs surgery, at least as observed in the National Cancer Database for head and neck melanomas, is seen for trunk and extremity tumors or whether the survival benefit seen in the Yale study was really from the improved survival in head and neck tumors. The latter ended up being the case, based on the data presented” in this most recent study.

“These studies have shed positive light on results that you can obtain with Mohs surgery,” Dr. Demer noted. “None of them have shown a survival disadvantage, and most have shown equal or improved local recurrence rates.”

Most Had Wide Excision

Among the 188,862 cases of all-stage in situ and invasive melanomas identified in the National Cancer Database, the mean age of the patients was 58.8 years; 97.7% were treated with wide local excision, and just 2.3% were treated with Mohs surgery. That low percentage reflects “the current state of guidelines, where Mohs isn’t recognized by the National Comprehensive Cancer Network (NCCN^®) for invasive tumors of any location,” Dr. Demer said. Rather, the NCCN “recommends wide local excision universally for all cutaneous melanomas,” he noted.

In addition, “tumors that meet the criteria most surgeons are looking for to do Mohs surgery on a melanoma are fairly infrequent on the trunk and extremities,” Dr. Demer noted. When Mohs surgery is used, it is usually for melanomas “of the head and neck or special sites and those that tend to be lentigo maligna, lentigo maligna subtypes, where there is a tendency for them to be larger tumors in a background of sun-damaged skin. In general, those tumors have a higher predilection for subclinical spread, which makes obtaining clear margins challenging.”

The authors acknowledged, however, “that it is possible, due to the small number of patients in the Mohs micrographic surgery treatment group, the study was not powered sufficiently to identify a statistically significant survival difference, if one exists.”

Kaplan-Meier estimates showed Mohs surgery was associated with increased 5-year overall survival for all trunk and extremity tumors, 86.1% vs 82.9% for wide local excision (P = .001). Multivariate Cox analysis, however, “showed no overall difference in all-cause mortality” for melanomas treated with wide local excision or Mohs surgery; the hazard rates with wide local excision were 1.097 for melanomas of the trunk, 1.013 for melanomas of the upper extremity (including the shoulders), 0.934 for melanomas of the lower extremity (including the hips), and 1.031 for combined trunk and extremity sites. “No statistically significant difference in overall survival was observed at any site when invasive tumors alone were included,” the authors wrote.

“Tumors on the head and neck and special sites are more likely to have subclinical tumor spread, making it challenging to obtain negative margins.”

— Addison Demer, MD

Tweet this quote

Mohs Surgery Remains Controversial in Cutaneous Melanoma

“The use of Mohs micrographic surgery for the treatment of cutaneous melanoma remains controversial,” the authors wrote. “Despite recent guidelines that have de-emphasized its use, the use of Mohs micrographic surgery for treatment of melanoma in the United States continues to increase. This trend may be explained by the robust and expanding body of data supporting its safety and efficacy for both in situ and invasive disease.”

“Over time, we have had more and more studies come out, database and large retrospective case series, that have time and time again demonstrated an absence of a survival disadvantage with Mohs surgery,” Dr. Demer noted. The data presented in the latest study does not suggest that Mohs surgery should be done for the majority of trunk and extremity tumors, according to Dr. Demer. “In fact, in my practice, very few trunk and extremity melanomas meet the criteria for Mohs surgery,” he noted. Rather, “the data suggest that Mohs treatment of truck and extremity melanomas, including invasive melanomas of all stages, are at the very least safe. Controlling for all normal confounding covariates, we don’t see a survival disadvantage,” Dr. Demer commented.

Mohs micrographic surgery “is a reasonable treatment option based on its safety profile, but we are by no means advocating broad utilization of Mohs for all trunk and extremity tumors,” Dr. Demer emphasized. “I would argue that our standards of care for surgical excision, as outlined by the NCCN, deliver great outcomes for most lower-stage melanomas, and there is not necessarily a statistically significant benefit for Mohs for the majority of those tumors.” For guideline changes to even be considered, he said, would require evidence from well-designed prospective randomized controlled studies.

Findings Support U.S. Practice Patterns

Melanomas and nonmelanomas treated with Mohs surgery “tend to be larger tumors, ones with indistinct borders, and those on challenging anatomic sites, places with high-value real estate—the eyelids, central face, hands, feet, genitalia—where you don’t have a lot of extra tissue,” Dr. Demer explained.

“There are several features of cutaneous head and neck melanoma that may explain why Mohs micrographic surgery is associated with improved survival at this site but not the trunk and extremities,” according to the study report. These features include subclinical tumor spread and narrower-than-recommended margins for melanomas of the head and neck and specialty sites, making it “unsurprising that a significant survival benefit has been observed for tumors treated with Mohs micrographic surgery on the head and neck but not the trunk and extremities.”

“If you look at current practice patterns for head and neck melanoma, surgeons tend to take less than standard guideline recommended margins, due to anatomic considerations, being close to an eyelid or going from the cheek onto the nose, for example,” Dr. Demer noted. In addition, “tumors on the head and neck and special sites are more likely to have subclinical tumor spread, making it challenging to obtain negative margins.” When these two factors are combined, “you can get the elevated rates of recurrence (around 9% to 10%) for wide local excision of head and neck, “whereas the recurrence rates in the majority of the series for head and neck melanoma excised with Mohs are less than 1% to 2%.”

For local recurrence after a standard margin with wide local excision of melanoma on the truck and extremities, “the literature suggests a recurrence rate of less than about 2%,” Dr. Demer added. “So, there is not as much benefit for the average tumor of the trunk and extremities, for a technique that gives complete circumferential peripheral and deep margin assessment,” as does Mohs micrographic surgery.

“The absence of a survival benefit for Mohs micrographic surgery,” according to the study report, “supports current U.S. practice patterns, where wide local excision is the predominant treatment for trunk and extremity melanomas.” 

DISCLOSURE: Dr. Demer reported no conflicts of interest.

REFERENCES

1. Demer AM, Hanson JL, Maher IA, et al: Association of Mohs micrographic surgery vs wide local excision with overall survival outcomes for patients with melanoma of the trunk and extremities. JAMA Dermatol. October 21, 2020 (early release online).

2. Hanson J, Demer A, Liszewski W, et al: Improved overall survival of melanoma of the head and neck treated with Mohs micrographic surgery vs wide local excision. J Am Acad Dermatol 82:149-155, 2020.

3. Cheraghlou S, Christensen SR, Agogo GO, et al: Comparison of survival after Mohs micrographic surgery vs wide margin excision for early-stage invasive melanoma. JAMA Dermatol 155:1252-1259, 2019.