Management of cutaneous melanoma: update on current treatment from surgical perspective
DOI:
https://doi.org/10.18203/2349-2902.isj20232332Keywords:
Melanoma, Sentinel lymph node, Lymph node dissection, Adjuvant therapy, Immunotherapy, BRAF mutationAbstract
Incidence and mortality rate of cutaneous melanoma substantially varies across the globe depending upon early detection and management. Therapeutic developments have revolutionized the treatment. The aim of this paper is to discuss the treatment options for localized and advanced disease in the context of surgery, adjuvant, and neoadjuvant treatment. PubMed, Medline, Guidelines of European Society of Medical Oncology, National Institute of Clinical Excellence, American Joint Committee on Cancer on Melanoma, publications from 2012-2022 were searched. Low risk node negative disease (stage I and IIA) melanoma patients should have curative surgical wide local excision along with SLNB with no adjuvant therapy. High risk node negative disease (stage IIB and IIC) should be treated with curative surgery and SLNB followed by adjuvant immunotherapy. Low risk node positive disease (stage IIIA) surgical resection with SLNB followed by adjuvant systemic therapy, depending upon BRAF mutation status of tumour. High risk node positive microscopic disease (stage IIIB, IIIC, IIID) BRAF V600 mutation, primary resection with SLNB followed by nivolumab or combination of BRAF + MEK inhibitors. For BRAF wild-type tumours, adjuvant immunotherapy with programmed cell death-1 (PD-1) inhibitor. Patient with macroscopic disease that is resectable neoadjuvant combination immunotherapy followed by surgery with lymph node dissection. Metastatic disease (stage IV) regardless, adjuvant combination immunotherapy followed by maintenance nivolumab. Surgical excision is the treatment of choice for most patients with loco regional cutaneous melanoma and is curative in most cases. Checkpoint inhibitors and targeted therapies are important advances in adjuvant, neo adjuvant settings. Despite all the progress, melanoma remains challenging to treat.
Metrics
References
Centre for Disease Control and Prevention. Melanoma incidence & mortality, United States 2012-2016. US Cancer Statistics Data Briefs, No 9. July 2019. Available at: https://www.cdc.gov/ cancer/uscs/about/data-briefs/no9-melanoma-incidence-mortality-UnitedStates-2012-2016.htm. Accessed on 29 March 2023.
Smoller BR. Histological criteria for diagnosing primary cutaneous malignant melanoma. Mod Pathol. 2006;19(2):S34-40.
Madu MF, Franke V, Van de Wiel BA, Klop WMC, Jóźwiak K, van Houdt WJ, et al. External validation of the American Joint Committee on Cancer 8th edition melanoma staging system: who needs adjuvant treatment? Melanoma Res. 2020;30(2):185-92.
Moncrieff MD, Lo SN, Scolyer RA, Heaton MJ, Nobes JP, Snelling AP, et al. Clinical Outcomes and Risk Stratification of Early-Stage Melanoma Micrometastases From an International Multicenter Study: Implications for the Management of American Joint Committee on Cancer IIIA Disease. J Clin Oncol. 2022;40(34):3940-51.
Amaria RN, Menzies AM, Burton EM, Scolyer RA, Tetzlaff MT, Antdbacka R, et al. Neoadjuvant systemic therapy in melanoma: recommendations of the International Neoadjuvant Melanoma Consortium. Lancet Oncol. 2019;20(7):e378-89.
Garbe C, Amaral T, Peris K, Hauschild A, Arenberger P, Bastholt L, et al. European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics - Update 2019. Eur J Cancer. 2020;126:141-58.
Krauthammer M, Kong Y, Bacchiocchi A, Evans P, Pornputtapong N, Wu C, et al. Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas. Nat Genet. 2015;47(9):996-1002.
Cancer Genome Atlas Network. Genomic Classification of Cutaneous Melanoma. Cell. 2015;161:1681.
Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472-92.
Swetter SM, Tsao H, Bichakjian CK, Curiel-Lewandrowski C, Elder DE, Gershenwald JE, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2019;80(1):208-50.
Wheatley K, Wilson JS, Gaunt P, Marsden JR. Surgical excision margins in primary cutaneous melanoma: A meta-analysis and Bayesian probability evaluation. Cancer Treat Rev. 2016;42:73.
Melanoma Margins Trial Investigating 1cm v 2cm Wide Excision Margins for Primary Cutaneous Melanoma. Available at: https://clinicaltrials. gov/ct2/show/NCT02385214. Accessed on 10 August 2021.
Nosrati A, Berliner JG, Goel S, McGuire J, Morhenn V, de Souza JR, et al. Outcomes of Melanoma In Situ Treated With Mohs Micrographic Surgery Compared With Wide Local Excision. JAMA Dermatol. 2017;153(5):436-41.
Phan K, Loya A. Mohs micrographic surgery versus wide local excision for melanoma in situ: analysis of a nationwide database. Int J Dermatol. 2019;58:697.
Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, et al. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med. 2017;376:2211.
Michielin O, van Akkooi A, Lorigan P, Ascierto PA, Dummer R, Robert C, et al. ESMO consensus conference recommendations on the management of locoregional melanoma: under the auspices of the ESMO Guidelines Committee. Ann Oncol. 2020;31(11):1449-61.
Melanoma Assessment & management. NICE guidelines no 14, National Institute for Health & Care Excellence. 2022. Available at: https://www.nice.org.uk/guidance/ng14/chapter/Update-information. Accessed on 29 March 2023.
Uhara H, Yamazaki N, Takata M. Applicability of radio colloid, blue dyes and fluorescent indocyanine green to sentinel lymph node biopsy in melanoma. J Dermatol. 2012;39:336-8.
Dinnes J, Ferrante di Ruffano L, Takwoingi Y, Cheung ST, Nathan P, Matin RN, et al. Ultrasound, CT, MRI, or PET-CT for staging and re-staging of adults with cutaneous melanoma. Cochrane Database Syst Rev. 2019;7:CD012806.
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373:23.
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, et al. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2019;381:1535.
Cascinelli N. Margin of resection in the management of primary melanoma. Semin Surg Oncol. 1998;14:272.
Cohn-Cedermark G, Rutqvist LE, Andersson R, Breivald M, Ingvar C, Johansson H, et al. Long term results of a randomized study by the Swedish Melanoma Study Group on 2-cm versus 5-cm resection margins for patients with cutaneous melanoma with a tumor thickness of 0.8-2.0 mm. Cancer. 2000;89(7):1495-501.
Khayat D, Rixe O, Martin G, Soubrane C, Banzet M, Bazex JA, et al. Surgical margins in cutaneous melanoma (2 cm versus 5 cm for lesions measuring less than 2.1-mm thick). Cancer. 2003;97(8):1941-6.
Karakousis CP, Balch CM, Urist MM, Ross MM, Smith TJ, Bartolucci AA. Local recurrence in malignant melanoma: long-term results of the multiinstitutional randomized surgical trial. Ann Surg Oncol. 1996;3(5):446-52.
Thomas JM, Newton-Bishop J, A'Hern R, Coombes G, Timmons M, Evans J, et al. Excision margins in high-risk malignant melanoma. N Engl J Med. 2004;350(8):757-66.
Gillgren P, Drzewiecki KT, Niin M, Gullestad HP, Hellborg H, Månsson-Brahme E, 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(9803):1635-42.
Utjés D, Malmstedt J, Teras J, Drzewiecki K, Gullestad HP, Ingvar C, 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(10197):471-7.
Eroglu Z, Ribas A. Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy. Ther Adv Med Oncol. 2016;8:48.
Eguchi MM, Elder DE, Barnhill RL, Piepkorn MW, Knezevich SR, Elmore JG, et al. Prognostic modeling of cutaneous melanoma stage I patients using cancer registry data identifies subsets with very-low melanoma mortality. Cancer. 2023;129(1):89-97.
