Local Recurrence and Survival in Patients With Melanoma >2 mm in Thickness at Difficult Sites Treated With 1-cm Versus 2-cm Margins

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Andrea Maurichi Melanoma Surgical Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Francesco Barretta Department of Epidemiology and Data Science, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Roberto Patuzzo Melanoma Surgical Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Gianfranco Gallino Melanoma Surgical Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Ilaria Mattavelli Melanoma Surgical Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Michal Shimonovitz-Moore Melanoma Surgical Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
Peritoneal Surface Malignancy and Melanoma Unit, Department of Surgery A, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

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Eran Nizri‏ Melanoma Surgical Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
Peritoneal Surface Malignancy and Melanoma Unit, Department of Surgery A, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

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Matteo Matteucci Melanoma Surgical Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Valeria Summo Plastic and Reconstructive Surgical Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Mara Cossa Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Barbara Valeri Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Umberto Cortinovis Plastic and Reconstructive Surgical Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Rosalba Miceli Department of Epidemiology and Data Science, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Mario Santinami Melanoma Surgical Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Background: Melanoma guidelines recommend surgical excision with 2-cm margins for melanomas >2 mm in thickness. However, this procedure may be problematic at critical anatomic sites. We aimed to compare the outcomes of wide (2 cm) versus narrow (1 cm) excision margins in patients with melanoma >2 mm in thickness near critical structures. Patients and Methods: We retrospectively examined 736 patients undergoing excision with wide versus narrow margins at the National Cancer Institute in Milan, Italy, between 2001 and 2015. Results: A total of 265 (36.0%) patients received a wide local excision—82 (30.9%) with linear repair and 183 (69.1%) with flap or graft reconstruction. A total of 471 (64.0%) patients received a narrow excision—320 (67.9%) with linear repair and 151 (32.1%) with flap or graft reconstruction (P<.001). The 10-year overall survival rate was 69.5% (95% CI, 63.3%–76.2%) in the wide group and 68.7% (95% CI, 63.8%–74.0%) in the narrow group (P=.462); 10-year crude cumulative incidence (CCI) of local recurrence was 5.4% (95% CI, 3.2%–9.2%) in the wide and 8.8% (95% CI, 6.4%–12.1%) in the narrow group (P=.150). Multivariable Fine-Gray modeling of the CCI of local recurrence showed that Breslow thickness (P=.010) was the only statistically significant parameter. Multivariable Cox models for overall survival showed that age (P<.001), Breslow thickness (P<.001), and sentinel lymph node status (P=.019) were statistically significant covariates. Excision margin was not a significant parameter affecting patients’ outcome. Conclusions: Wide local excision with 1-cm margins for melanoma >2 mm in thickness was not associated with an increased risk of local recurrence and did not affect overall survival.

Submitted September 4, 2023; final revision received May 12, 2024; accepted for publication July 8, 2024. Published online November 13, 2024.

A. Maurichi and F. Barretta contributed equally as co–first authors.

R. Miceli and M. Santinami contributed equally as co–last authors.

Author contributions: Concept & design, and/or acquisition of data, and/or data analysis & interpretation: Maurichi, Barretta, Patuzzo, Shimonovitz-Moore, Nizri, Cortinovis, Miceli, Santinami. Writing—original draft: Maurichi, Barretta, Gallino, Mattavelli, Matteucci, Summo, Cossa, Valeri, Miceli, Santinami. Writing—review & editing: Maurichi, Barretta, Gallino, Mattavelli, Matteucci, Summo, Cossa, Valeri, Miceli, Santinami. Final approval: All authors.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: The Emme Rouge Foundation provided financial support for this study.

Correspondence: Andrea Maurichi, MD, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Melanoma Surgical Unit, Via Giacomo Venezian 1, 20133 Milan, Italy. Email: andrea.maurichi@istitutotumori.mi.it
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  • Expand
  • 1.

    Swetter SM, Johnson D, Albertini MR, et al. NCCN Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous. Version 2.2024. Accessed August 30, 2024. To view the most recent version, visit https://www.nccn.org

    • PubMed
    • Export Citation
  • 2.

    Michielin O, van Akkooi ACJ, Ascierto PA, et al. Cutaneous melanoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019;30:18841901.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Garbe C, Amaral T, Peris K, et al. European consensus-based interdisciplinary guideline for melanoma. Part 2: treatment - update 2019. Eur J Cancer 2020;126:159177.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Sladden MJ, Nieweg OE, Howle J, et al. Updated evidence-based clinical practice guidelines for the diagnosis and management of melanoma: definitive excision margins for primary cutaneous melanoma. Med J Aust 2018;208:137142.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Balch CM, Soong SJ, Smith T, et al. Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1–4 mm melanomas. Ann Surg Oncol 2001;8:101108.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Gillgren P, Drzewiecki KT, Niin M, et al. 2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial. Lancet 2011;378:16351642.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Thomas JM, Newton-Bishop J, A’Hern R, et al. Excision margins in high-risk malignant melanoma. N Engl J Med 2004;350:757766.

  • 8.

    Hayes AJ, Maynard L, Coombes G, et al. Wide versus narrow excision margins for high-risk, primary cutaneous melanomas: long-term follow-up of survival in a randomised trial. Lancet Oncol 2016;17:184192.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Utjés D, Malmstedt J, Teras J, et al. 2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: long-term follow-up of a multicentre, randomised trial. Lancet 2019;394:471477.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Kelly JW, Sagebiel RW, Calderon W, et al. The frequency of local recurrence and microsatellites as a guide to reexcision margins for cutaneous malignant melanoma. Ann Surg 1984;200:759763.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Niebling MG, Haydu LE, Lo SN, et al. The prognostic significance of microsatellites in cutaneous melanoma. Mod Pathol 2020;33:13691379.

  • 12.

    Kimsey TF, Cohen T, Patel A, et al. Microscopic satellitosis in patients with primary cutaneous melanoma: implications for nodal basin staging. Ann Surg Oncol 2009;16:11761183.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Ascierto PA, Del Vecchio M, Mandalá M, et al. Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial. Lancet Oncol 2020;21:14651477.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Eggermont AMM, Kicinski M, Blank CU, et al. Association between immune-related adverse events and recurrence-free survival among patients with stage III melanoma randomized to receive pembrolizumab or placebo: a secondary analysis of a randomized clinical trial. JAMA Oncol 2020;6:519527.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Dummer R, Hauschild A, Santinami M, et al. Five-year analysis of adjuvant dabrafenib plus trametinib in stage III melanoma. N Engl J Med 2020;383:11391148.

  • 16.

    Dummer R, Brase JC, Garrett J, et al. Adjuvant dabrafenib plus trametinib versus placebo in patients with resected, BRAFV600-mutant, stage III melanoma (COMBI-AD): exploratory biomarker analyses from a randomised, phase 3 trial. Lancet Oncol 2020;21:358372.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. CheckMate 067: 6.5-year outcomes in patients (pts) with advanced melanoma. J Clin Oncol 2021;39(Suppl):Abstract 9506.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Robert C, Ribas A, Schachter J, et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol 2019;20:12391251.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Robert C, Grob JJ, Stroyakovskiy D, et al. Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med 2019;381:626636.

  • 20.

    Gutzmer R, Stroyakovskiy D, Gogas H, et al. Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2020;395:18351844.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Seth R, Messersmith H, Kaur V, et al. Systemic therapy for melanoma: ASCO guideline. J Clin Oncol 2020;38:39473970.

  • 22.

    Luke JJ, Ascierto PA, Carlino MS, et al. KEYNOTE-716: phase III study of adjuvant pembrolizumab versus placebo in resected high-risk stage II melanoma. Future Oncol 2020;16:44294438.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Zijlker LP, Eggermont AMM, van Akkooi ACJ. The end of wide local excision (WLE) margins for melanoma? Eur J Cancer 2023;178:8287.

  • 24.

    Frishberg DP, Balch C, Balzer BL, et al. Protocol for the examination of specimens from patients with melanoma of the skin. Arch Pathol Lab Med 2009;133:15601567.

  • 25.

    Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma of the skin. In: Amin MB, Edge SB, Greene FL, et al., eds. AJCC Cancer Staging Manual, 8th ed. Springer; 2017:563585.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Houghton AN, Bloomer WD, Chu D, et al. NCCN Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous. Version 1.2000. To view the most recent version, visit https://www.nccn.org

    • PubMed
    • Export Citation
  • 27.

    Houghton AN, Bloomer WD, Chu D, et al. NCCN Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous. Version 1.2002. To view the most recent version, visit https://www.nccn.org

    • PubMed
    • Export Citation
  • 28.

    Coit DG, Andtbacka R, Bichakjian CK, et al. NCCN Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous. Version 2.2009. To view the most recent version, visit https://www.nccn.org

    • PubMed
    • Export Citation
  • 29.

    Coit DG, Thompson JA, Albertini MR, et al. NCCN Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous. Version 3.2018. To view the most recent version, visit https://www.nccn.org

    • PubMed
    • Export Citation
  • 30.

    Flury BK, Riedwyl H. Standard distance in univariate and multivariate analysis. Am Stat 1986;40:249251.

  • 31.

    Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med 2015;34:36613679.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials 1996;17:343346.

  • 33.

    Durrleman S, Simon R. Flexible regression models with cubic splines. Stat Med 1989;8:551561.

  • 34.

    Jackett LA, Satgunaseelan L, Roper E, et al. Residual melanoma in wide local excision specimens after 'complete' excision of primary cutaneous in situ and invasive melanomas. Pathology 2022;54:7178.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Namin AW, Welby L, Baker AT, Dooley LM. Positive margins in cutaneous melanoma of the head and neck: implications for timing of reconstruction. Otolaryngol Head Neck Surg 2021;164:10521057.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Rawlani R, Rawlani V, Qureshi HA, et al. Reducing margins of wide local excision in head and neck melanoma for function and cosmesis: 5-year local recurrence-free survival. J Surg Oncol 2015;111:795799.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Hunger RE, Angermeier S, Seyed Jafari SM, et al. A retrospective study of 1- versus 2-cm excision margins for cutaneous malignant melanomas thicker than 2 mm. J Am Acad Dermatol 2015;72:10541059.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Pasquali S, Haydu LE, Scolyer RA, et al. The importance of adequate primary tumor excision margins and sentinel node biopsy in achieving optimal locoregional control for patients with thick primary melanomas. Ann Surg 2013;258:152157.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Hanna S, Lo SN, Saw RP. Surgical excision margins in primary cutaneous melanoma: a systematic review and meta-analysis. Eur J Surg Oncol 2021;47:15581574.

  • 40.

    Pandya R, Basra M, Twohig E, et al. Can we reduce excision margins for head and neck melanoma? A 12-year retrospective study. Br J Oral Maxillofac Surg 2022;60:134139.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Ruskin O, Sanelli A, Herschtal A, et al. Excision margins and sentinel lymph node status as prognostic factors in thick melanoma of the head and neck: a retrospective analysis. Head Neck 2016;38:13731379.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Moncrieff MD, Gyorki D, Saw R, et al. 1 versus 2-cm excision margins for pT2-pT4 primary cutaneous melanoma (MelMarT): a feasibility study. Ann Surg Oncol 2018;25:25412549.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Rossi AJ, Verbus EA, Faries MB, et al. A phase III, multicenter, randomized controlled trial investigating 1-cm versus 2-cm surgical excision margins for stage II primary cutaneous melanoma (MelMarT-II). Ann Surg Oncol. Published online April 22, 2022. doi:10.1245/s10434-022-11766-z

    • PubMed
    • Search Google Scholar
    • Export Citation

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