Ann Surg Oncol DOI 10.1245/s10434-016-5167-6 ORIGINAL ARTICLE – MELANOMAS Is a Wider Margin (2 cm vs. 1 cm) for a 1.01–2.0 mm Melanoma Necessary? Matthew P. Doepker, MD1, Zachary J. Thompson, PhD2, Kate J. Fisher, MA2, Maki Yamamoto, MD3, Kevin W. Nethers, MS1, Jennifer N. Harb, MD1, Matthew A. Applebaum, MS1, Ricardo J. Gonzalez, MD1, Amod A. Sarnaik, MD1, Jane L. Messina, MD4, Vernon K. Sondak, MD1, and Jonathan S. Zager, MD, FACS1 1Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL; 2Department of Biostatistics, Moffitt Cancer Center, Tampa, FL; 3Department of Surgical Oncology, University of California, Irvine Medical Center, Orange, CA; 4Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL ABSTRACT Wider margins were associated with more frequent graft or Background. The current NCCN recommendation for flap use only on the head and neck (p = 0.025). resection margins in patients with melanomas between 1.01 Conclusions. Our data show that selectively using a nar- and 2 mm deep is a 1–2 cm radial margin. We sought to rower margin of 1 cm did not increase the risk of LR or determine whether margin width had an impact on local decrease DSS. Avoiding a 2 cm margin may decrease the recurrence (LR), disease-specific survival (DSS), and type need for graft/flap use on the head and neck. of wound closure. Methods. Melanomas measuring 1.01–2.0 mm were evaluated at a single institution between 2008 and 2013. The incidence of melanoma in the United States con- All patients had a 1 or 2 cm margin. tinues to increase with an estimated annual percentage Results. We identified 965 patients who had a 1 cm increase ranging from 1.5 to 4.1 % in 2015.1 Newer (n = 302, 31.3 %) or 2 cm margin (n = 663, 68.7 %). modalities of treatment for advanced metastatic disease, Median age was 64 years, and 592 (61.3 %) were male; including immunotherapy and targeted therapies, have 32.5 and 48.7 % of head and neck and extremity patients been introduced, whereas the surgical treatment of mela- had a 1 cm margin versus 18.9 % of trunk patients noma has undergone minimal change. The ‘‘gold (p \ 0.001). LR was 2.0 and 2.1 % for a 1 and 2 cm standard’’ of treatment for localized melanoma is wide margin, respectively (p = not significant). Five-year DSS excision (WE) of the lesion with a 1 or 2 cm radial was 87 % for a 1 cm margin and 85 % for a 2 cm margin margin based on the thickness of melanoma. Several (p = not significant). Breslow thickness, melanoma on the large, prospective trials have studied resection margins in head and neck, lymphovascular invasion, and sentinel melanomas ranging from 0.8 to 4 mm in thickness lymph node biopsy (SLNB) status significantly predicted (summarized in Table 1).2–7 These studies were unable to LR on univariate analysis; however, only location and demonstrate a significant difference in overall survival SLNB status were associated with LR on multivariate (OS), disease-specific survival (DSS), or local recurrence analysis. Margin width was not significant for LR or DSS. (LR) when a wide margin of 4 or 5 cm was compared to narrow margin of 2 cm.8 One of the earliest studies to report on margins of resection and recurrence was done by Veronesi et al. The authors showed a higher rate of recurrence when a 1 cm margin was used compared with This paper was presented as a poster presentation at the Society of \ Surgical Oncology Annual Cancer Symposium in March 2015. a 3 cm margin for melanomas 2 mm in thickness, although this was not statistically significant. In addition, they reported no difference in OS.9 The data produced Ó Society of Surgical Oncology 2016 from the aforementioned studies helped form the foun- First Received: 11 January 2016 dation for the National Comprehensive Cancer Network J. S. Zager, MD, FACS (NCCN) recommendations for a 1.01–2 mm melanoma.10 e-mail: Jonathan.zager@moffitt.org M. P. Doepker et al. TABLE 1 Summary of clinical studies assessing Breslow thickness and resection margin width Study Year No. of Breslow Margin Median Local recurrence 5-year OS patients thickness width follow-up rate (mm) (cm) (mo) Prospective studies Cascinelli 1998 612 \2 1 versus 3 90 No difference No differencea Cohn-Cedermark et al. 2000 989 0.8–2 2 versus 5 132 No difference No difference Balch et al. 2001 740 1–4 2 versus 4 120 No difference No difference Khayat et al. 2003 337 \2.1 2 versus 5 192 No difference No difference Thomas et al. 2004 774 C3 1 versus 3 60 No differenceb No difference Gillgren et al. 2011 936 [2 2 versus 4 80.4 No difference No difference Retrospective studies Hudson et al. 2012 576 1–2 1 versus 2 38 Increased with No difference 1 cm marginsc Doepker et al. 2015 1024 1–2 1 versus 2 14.8 No difference No difference OS overall survival a No statistical difference was seen in OS up to 12 years b Statistical difference was seen in locoregional recurrence between the 1- and 3 cm margin groups c Local recurrence was 3.6 and 0.9 % in the 1- and 2 cm margin groups, respectively (p = 0.04). This difference was seen on univariate analysis Currently, the NCCN guidelines recommend either a 1 or database of patients from 2002 to 2013. All patients had a WE 2 cm margin width based on evidence extrapolated from the with a 1 or 2 cm radial margin from the clinically visible edge trials summarized in Table 1. No prospective trial has directly of any remaining pigmented lesion or biopsy scar. Demo- compared a 1 or 2 cm margin width for a 1.01–2 mm mela- graphic and clinicopathologic characteristics (sex, age at noma. Typically, a surgeon will use their best discretion in diagnosis, histologic subtype, location of primary tumor, choosing margin widths when treating melanomas 1.01–2 mm Breslow thickness, and sentinel lymph node biopsy (SLNB) in thickness. Best discretion referstothesurgeonusinganarrow status) along with outcomes data were retrieved. Ulceration, margin to preserve functionality and cosmesis or to avoid a lymphovascular invasion (LVI), and mitotic rate (MR) also potential need for skin graft or flap reconstruction. A more recent were evaluated, although these features were not uniformly single-center, retrospective series directly compared outcomes recorded for all patients on final pathology (Table 2). Satel- for a 1 to 2 mm melanoma using a 1 or 2 cm margin width.11 litosis, vertical growth phase, and regression were not Hudson et al. retrospectively reviewed 576 patients with 224 included in the final analysis due to the high number of (38.9 %) having a 1 cm margin and 352 (61.1 %) having a 2 cm unavailable data points. Patients who had reexcision for margin width. The distribution of LR was significant between melanoma in situ or residual disease at the margins after the two groups; the 1 cm group had a recurrence rate of 3.6 % undergoing a 1 or 2 cm margin were also excluded. compared with only 0.9 % in the 2 cm group (p = 0.044). All cases were reviewed and confirmed by a board-certified Interestingly, only head and neck location was associated with dermatopathologist. All available original tissue biopsies LR on multivariate analysis (MVA). The authors demonstrated performed at an outside institution were reexamined before no difference in OS between the two margin groups on MVA.11 clinical evaluation or surgery. Not all patients had SLNB, We sought to add to the literature by directly comparing which was due to patient preference, comorbid conditions the use of a 1 or 2 cm margin width of resection for a 1.01- to preventing the use of general anesthesia, or failure to map on 2 mm melanoma in a large, single institution, retrospective preoperative lymphosctinigraphy. All patients with SLN study. The goal of the study was to determine whether using metastases were offered completion lymph node dissection a narrow margin had an impact on the need for a skin graft or (CLND) as standard of care. Recurrence during follow-up was flap reconstruction, local recurrence, or DSS in patients categorized as local, regional nodal/in-transit, or distant. LR diagnosed with melanomas 1.01–2 mm in thickness. was defined as recurrence within 2 cm of the scar or graft. METHODS Statistical Analysis After obtaining Institutional Review Board approval, a Chi square tests were performed on categorical variables. retrospective series of consecutive patients diagnosed with Wilcoxon rank-sum tests or analysis of variance tests were melanoma 1.01–2 mm was identified from a single-institution used for continuous variables to test for differences between Is a Wider Margin (2 cm vs. 1 cm) for a 1.01–2.0 mm Melanoma Necessary? TABLE 2 Patient demographics and tumor characteristics stratified by resection margin Variable All patients 1 cm 2 cm p value N = 965 n = 302 (31.3 %) n = 663 (68.7 %) Gender (%) Male 592 (61.3) 177 (58.6) 415 (62.6) 0.263 Female 373 (38.7) 125 (41.4) 248 (37.4) Age (years) Median (range) 64 (15–96) 67 (15–96) 63 (15–90) 0.004 Histologic type (%)a Superficial spreading 562 (58.2) 182 (60.3) 380 (57.3) 0.017 Nodular 218 (22.6) 52 (17.2) 166 (25) Acral lentiginous 22 (2.3) 12 (4.0) 10 (1.5) Lentigo maligna 44 (4.6) 21 (7.0) 23 (3.5) Pure desmoplastic 14 (1.5) 5 (1.7) 9 (1.4) Mixed desmoplastic 8 (0.8) 2 (0.7) 6 (0.9) Desmoplastic (NOS) 2 (0.2) 1 (0.3) 1 (0.2) Other 18 (1.9) 5 (1.7) 13 (2.0) Location of primary (%) Head/neck 195 (20.2) 98 (32.5) 97 (14.6) \0.001 Trunk 330 (34.2) 57 (18.9) 273 (41.2) Extremities UE 275 (28.5) 93 (30.8) 182 (27.5) LE 165 (17.1) 54 (17.9) 111 (16.7) Breslow thickness (mm) Median 1.4 1.3 1.4 \0.001 Ulceration (%)a Present 195 (20.2) 64 (21.2) 131 (19.8) 0.679 Absent