Variation in the Depth of Excision of Melanoma: Title and subTitle BreakA Survey of US Physicians FREE

While evidence supporting the current guidelines for width of excision of melanoma is fairly well established, there is a paucity of data supporting the ideal depth of excision. Handley^{1 - 2} was one of the first physicians to publish recommendations for the surgical treatment of melanoma. His recommendations were based on the autopsy findings from 1 woman who died of metastatic melanoma. Analysis of this isolated autopsy case eventually gave rise to the recommendation to surgically resect melanomas with 5-cm margins of normal skin and to extend the excision down to the level of the fascia. Since Handley's original publications, many researchers have attempted to determine the ideal width of excision for melanoma with the aim of preventing tumor progression. Early researchers were inclined to excise more rather than less tissue, some researchers even promoting the amputation of an entire extremity involved with melanoma. Substantial changes in the surgical approach to melanoma did not occur until the observations correlating tumor depth of penetration with patient prognosis were published by Clark et al³ and Breslow.⁴ Many began to challenge the idea of treating all melanomas with the same 5-cm-wide excision.

While much research has focused on determining the most appropriate lateral margins of excision for melanoma,^{5 - 6} few publications address the most appropriate depth of excision for melanomas of differing thicknesses.^{7 - 9} In 1992, a National Institutes of Health (NIH) consensus panel convened to create guidelines for surgical excision of melanoma in situ and thin invasive melanoma.¹⁰ Recommendations included a 0.5-cm margin of excision to subcutaneous tissue for melanoma in situ and a 1.0-cm margin of excision to fascia for thin invasive melanoma (<1 mm). Although the lateral excision margins recommended by the NIH consensus panel for invasive melanomas were based on results obtained from prospective randomized studies, the recommendations on depth of excision for melanoma appear to have been based only on the personal opinions of the panel members and not on evidence-based study results. To our knowledge, there is currently no sound scientific evidence for or against excision of melanoma to the fascia, and we embarked on this study to determine current practice norms. Our objectives were to assess and compare the current practice patterns of US melanoma specialists and general dermatologists regarding depth of excision performed for melanomas of varying histologic thicknesses.

In July 2007, we assembled a data set of general dermatologists and other specialists who treat melanoma and/or pigmented lesions. The pool of general dermatologists was selected using the Official ABMS [American Board of Medical Specialties] Directory of Board Certified Medical Specialists software, 2006 version (Chicago, Illinois). A random sample of 1000 board-certified dermatologists was selected. To identify melanoma and/or pigmented lesion specialists, we reviewed the Skin Cancer Foundation's online physician database (http://www.skincancer.org/apps/physician-finder/). A total of 184 pigmented lesion specialists were identified, and their contact information was gleaned using Web-based resources. Participants were asked to complete a survey regarding the depth of excision for melanoma. The Memorial Sloan-Kettering institutional review board reviewed this study and deemed it exempt research.

A 2-page survey was developed to assess physicians' opinions on appropriate depth of excision for melanoma. The survey included 13 questions regarding surgical excision depth management issues and physician demographics and clinical practice characteristics. The survey was pilot tested on a group of dermatologists and dermatologic surgeons at Memorial Sloan-Kettering Cancer Center. Based on reviewer comments from the pilot testing, the survey was finalized. The survey and a postage-paid return envelope were mailed to each of the 1184 physicians selected for the study between July and September 2007. Nonresponders were sent a reminder mailing 3 weeks after the first mailing. A third and final reminder mailing that included a replacement survey was sent 3 weeks later.

Results were tabulated, and descriptive frequencies were used to describe demographics and survey responses. Respondents were classified as specialists (dermatologists and nondermatologists) and nonspecialist dermatologists defined by our sampling strategy. Specialists included dermatologists, oncologists, head and neck surgeons, plastic surgeons, general surgeons, and dermatologic surgeons working within a pigmented lesion clinic. Nonspecialists were dermatologists not affiliated with a pigmented lesion clinic.

We first assessed relative frequencies of survey responses by specialty status. Pearson χ² tests were calculated to assess whether depth of excision was associated with specialty status. We next used logistic regression to assess the relationship between melanoma thickness (categorized into 6 levels ranging from thin [<0.50 mm] to thick [>4.00 mm]) and physician specialty status. All estimates were adjusted for number of melanomas diagnosed per year and practice setting (solo, group, or academic). Tests for linear trend were also estimated to assess whether there was an association between melanoma thickness and depth of excision. Stata software (StataCorp LP, College Station, Texas), version 9, was used for all analyses.

Eighty-seven surveys were returned undeliverable owing to an incorrect mailing address. Of the returned surveys, 22 were considered ineligible because (1) the physician was deceased or indicated that he or she was retired and no longer practicing (n = 21) or (2) the physician was a full-time dermatopathologist and did not see patients (n = 1). The final study analysis included 498 completed surveys. The overall response rate was 45% (498 of 1097 [1184 total respondents − 87 ineligibles]). The response rate for the specialists was 63% (115 of 183 [184 total respondents − 1 ineligible]), and for nonspecialist dermatologists it was 43% (383 of 892 [1000 total respondents − 108 ineligibles]).

Practice characteristics for specialists and nonspecialist dermatologists are summarized in Table 1. Specialists were more likely to practice in an urban setting than were nonspecialist dermatologists (78% vs 46%) (P < .001). Self-reported practice volume varied significantly between the 2 groups, with 58% of nonspecialist dermatologists reporting more than 400 patient visits per month compared with only 16% of specialists reporting a similar volume (P < .001). Although the specialists reported fewer patient visits per month, 51% of specialists reported diagnosing more than 20 melanomas in the previous year, whereas only 11% of nonspecialist dermatologists reported diagnosing a similar volume of melanomas.

Distribution of depth of excision for varying histologic tumor thickness is listed in Table 2. There was no significant difference in excision depth among the specialties for melanoma in situ (P = .15)—most respondents in each group reported excision into subcutaneous tissue, ie, superficial to deep fat: 84% of nonspecialist dermatologists (n = 316); 94% of specialist dermatologists (n = 50); and 76% of specialist nondermatologists (n = 47).

For invasive melanoma, significant differences were observed among treating groups, with the greatest incongruence reported for thin invasive melanoma (Breslow thickness <0.50 mm, P = .02; Breslow thickness 0.50-0.75 mm, P < .001; and Breslow thickness 0.76-1.00 mm, P < .001) (Table 2). As shown in the Figure, specialist nondermatologists consistently reported excising more deeply than specialist dermatologists and nonspecialist dermatologists. For melanoma thinner than 0.50 mm, 59% of specialist nondermatologists reported excising to fascia (n = 16) vs 32% of specialist dermatologists (n = 9) and 29% of nonspecialist dermatologists (n = 55). This increased to 79% of specialist nondermatologists reporting excising to fascia for melanoma of Breslow thickness ranging from 0.76 to 1.00 mm (n = 48) vs 51% of specialist dermatologists (n = 27) and 40% of nonspecialist dermatologists (n = 148). In general, more specialist nondermatologists reported excision to fascia for thin invasive melanoma than both specialist and nonspecialist dermatologists.

For thicker melanomas (>1.00 mm), as demonstrated in the Figure, differences among treating physician groups decreased, with most respondents from each group reporting excision to the fascia (Table 2).

In 1907, Handley,^{1 - 2} a British physician, published 2 articles in the Lancet regarding recommendations for excision margins of melanoma. His observations and recommendations were based on the autopsy of a woman with metastatic melanoma. He specifically studied the metastatic inguinal lymph nodes; the primary tumor had previously been excised. He wrote “permeation of the lymphatics is the principal agent in this local centrifugal spread.”^{1 (p932)}He noted intralymphatic involvement deep to the fascial plane, and based on this finding he recommended a 1-inch surgical excision of the skin surrounding the tumor and an additional 2 inches of subcutaneous tissue, including fascia and underlying muscle.^{1 - 2} He proposed the same surgical approach for involved lymph nodes. These recommendations formed the basis of the surgical approach to melanoma for the next half century.

Expanding on Handley's recommendations, subsequent researchers recommended more extensive surgical excision for melanoma, including removal of the subcutaneous tissue, with or without the fascia, in continuity from the primary site and complete dissection of the regional nodal basin(s).^{11 - 12} At times, amputation was undertaken as treatment for melanoma of the extremity, and radical mastectomy was performed for melanoma of the breast.^{12 - 13} Despite aggressive procedures to obtain a surgical cure, many patients went on to develop distant metastases with poor prognoses.

Eventually, the notions of depth of excision of melanoma began to change. In 1964, Olsen¹⁴ observed that patients in whom the fascia was left intact had a lower rate of subsequent metastatic disease, and she postulated that the fascial plane might offer protection against lymphatic spread. Based on this theory, she recommended leaving the fascia intact. In 1982, Kenady et al¹⁵ reported no statistical difference in incidence of recurrence, site of recurrence, or survival rate between patients from whom the fascia had been removed vs those who had it left intact. Depth of excision was recommended to include subcutaneous tissue to the fascia.

While there have been a number of studies assessing lateral excision margins for the surgical management of melanoma, to our knowledge there is no clinical evidence to support or refute our current depth of excision recommendations. Current guidelines, including those of the National Comprehensive Cancer Network (NCCN) Melanoma Panel,¹⁶ the British Association of Dermatologists,¹⁷ and the American Academy of Dermatology (AAD) Guidelines/Outcomes Committee,¹⁸ do not make direct recommendations with regard to depth of excision. The AAD guidelines state that “Excising to fascia may not be necessary for melanoma tumors confined to the upper levels of the skin,”^{18 (p584)} but they do not elaborate.

The results of the present survey demonstrate considerable variation among different treating groups of physicians. A consistent excision depth was only demonstrated for the treatment of melanoma in situ. For all thicknesses of invasive melanoma, specialist nondermatologists reported excising to a greater depth than specialist and nonspecialist dermatologists, with the greatest discrepancies reported for thin invasive melanoma.

Differences in surgical training or comfort level with surgical technique may be contributors to the observed differences between dermatologists and nondermatologists assessed. Anatomic location of the primary melanoma may also account for differences in technique: Some anatomic sites have a more readily definable fascial plane, and different sites vary considerably in adipose tissue distribution.

In a 1995 editorial article, the following explanation was given for current depth of excision recommendations for invasive melanoma^{19 (p533)}:

“The National Institutes of Health Consensus Panel and every randomized trial still recommend excision to the underlying fascia. The recommendation is based on the anatomic understanding that the lymphatics drain to the regional lymph nodes in the subcutaneous tissue extending to the underlying muscle fascia. Therefore, excision of melanoma should extend to the muscle fascia.”

This would imply that the purpose of removing subcutaneous tissue to the fascia is to capture intralymphatic melanoma cells. Given our current understanding of the rapid movement of the lymphatic system, demonstrated by our use of lymphoscintigraphy and sentinel node biopsy, it would seem unlikely that intralymphatic melanoma cells could be captured at the time of excision. However, the movement of melanoma cells along the external surface of a vessel, a process called extravascular migratory metastasis (EVMM), should be considered.^{20 - 21} In EVMM, the melanoma cell is believed to travel in close proximity to the vessel wall in the pericyte location, which may represent a mechanism of development for “in transit” epidermotropic and regional lymph node metastases.²¹ If this mechanism of spread exists in melanoma, then the rate of migration of these cells may play an important role in determining optimal depth of excision.

Given the current variation in depth of excision practices and lack of clinical data, studies assessing depth of excision and patient outcomes are needed to better define the surgical management of melanoma.

Correspondence: Jennifer L. DeFazio, MD, Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 800 Veteran's Hwy, Second Floor, Hauppauge, NY 11788 (defazioj@mskcc.org)

Accepted for Publication: March 9, 2010.

Published Online: July 19, 2010. doi:10.1001/archdermatol.2010.156

Author Contributions: Drs DeFazio, Marghoob, Pan, Dusza, and Halpern had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Marghoob, Pan, and Halpern. Acquisition of data: DeFazio, Pan, Dusza, and Khokhar. Analysis and interpretation of data: Marghoob and Dusza. Drafting of the manuscript: DeFazio and Dusza. Critical revision of the manuscript for important intellectual content: Marghoob, Pan, Dusza, and Halpern. Statistical analysis: Dusza. Administrative, technical, and material support: DeFazio, Marghoob, Pan, Dusza, and Khokhar. Study supervision: Marghoob, Dusza, and Halpern.

Financial Disclosure: None reported.