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Cancers
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Contemporary Surgical Management of Melanoma
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Contemporary Surgical Management of Melanoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 15 November 2024 | Viewed by 5632

Special Issue Editors

Prof. Dr. Stanley P. Leong

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Guest Editor
Department of Surgery and Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, 2340 Clay Street, 2nd floor, San Francisco, CA 94115, USA
Interests: melanoma; sentinel nodes; cancer metastasis
Prof. Dr. Jonathan S. Zager

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Guest Editor
1. Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA
2. Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
Interests: melanoma; metastatic melanoma; regional chemotherapy; in-transit melanoma; intralesional; perfusional
Prof. Dr. Giorgos Karakousis

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Guest Editor
Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA
Interests: melanoma; sentinel lymph node biopsy; prognostic factors

Special Issue Information

Dear Colleagues,

With the recent developments in checkpoint inhibition and targeted therapy against melanoma, along with the multicenter randomized study of lymphadenectomy following a positive sentinel lymph node biopsy, surgery for melanoma has continued to evolve. This Special Issue on surgery for melanoma is focused on its evolving role in the current therapeutic landscape.

Traditionally, surgery was the mainstay of treatment for locally advanced melanoma and regional metastatic melanoma. With advancements in surgical techniques, such as sentinel lymph node biopsy for nodal staging and the advent of systemic therapies with checkpoint inhibitors/immunotherapy and targeted therapy for the treatment of metastatic melanoma and in the adjuvant setting, there has been a significant de-escalation in the extensiveness of melanoma surgery. As medical treatment is evolving, so too is the surgical treatment for melanoma. In this Special Issue, we define the changing surgical approaches to melanoma in the context of the current landscape of medical treatment for this disease.

A series of articles is presented in this Special Issue by an international team of surgical oncologists with expertise in their respective topics on the role of surgery for melanoma, with topics including: clinical characteristics and surgical treatment of rare melanoma subtypes; margins in primary melanoma surgery; preoperative and intraoperative sentinel node identification in melanoma surgery; when to use sentinel node biopsy in melanoma, with trends and future directions; neoadjuvant therapy for metastatic melanoma; adjuvant therapy for high-risk stage II melanoma; perioperative considerations for tumor tissue procurement to obtain tumor-infiltrating lymphocytes for adoptive cell therapy; intralesional and infusional updates for metastatic melanoma; the role of surgery for stage IV melanoma; and gene expression profiling and biomarkers for predicting melanoma recurrence and response to surgical and systemic treatment.

We are grateful to the Editorial Board of Cancers for the opportunity to publish ‘Contemporary Surgical Management of Melanoma’ in this Special Issue. We are especially indebted to all the expert authors who have contributed their time and expertise to the numerous articles presented in this work.

Prof. Dr. Stanley P. Leong
Prof. Dr. Jonathan S. Zager
Prof. Dr. Giorgos Karakousis
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • surgery
  • primary melanoma
  • metastatic melanoma
  • surgical treatment
  • checkpoint inhibition

Published Papers (5 papers)

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Review

20 pages, 759 KiB  
Review
Clinical Characteristics and Special Considerations in the Management of Rare Melanoma Subtypes
by Adrienne B. Shannon, Jonathan S. Zager and Matthew C. Perez
Cancers 2024, 16(13), 2395; https://doi.org/10.3390/cancers16132395 (registering DOI) - 28 Jun 2024
Viewed by 159
Abstract
Rare histologic subtypes of melanoma, including acral, mucosal, uveal, and desmoplastic melanomas, only make up 5% of all diagnosed melanomas and are often underrepresented in large, randomized trials. Recent advancements in systemic therapy have shown marked improvement in pathologic response rates, improving progression-free [...] Read more.
Rare histologic subtypes of melanoma, including acral, mucosal, uveal, and desmoplastic melanomas, only make up 5% of all diagnosed melanomas and are often underrepresented in large, randomized trials. Recent advancements in systemic therapy have shown marked improvement in pathologic response rates, improving progression-free and overall survival among cutaneous melanoma patients, but there are limited data to demonstrate improved survival among rarer subtypes of melanoma. Acral melanoma has a poor response to immunotherapy and is associated with worse survival. Mucosal melanoma has a large variability in its presentation, a poor prognosis, and a low mutational burden. Uveal melanoma is associated with a high rate of liver metastasis; recent adoption of infusion and perfusion therapies has demonstrated improved survival among these patients. Desmoplastic melanoma, a high-risk cutaneous melanoma, is associated with high locoregional recurrence rates and mutational burden, suggesting this melanoma may have enhanced response to immunotherapy. While these variants of melanoma represent distinct disease entities, this review highlights the clinicopathologic characteristics and treatment recommendations for each of these rare melanomas and highlights the utility of modern therapies for each of them. Full article
(This article belongs to the Special Issue Contemporary Surgical Management of Melanoma)
17 pages, 775 KiB  
Review
Intralesional and Infusional Updates for Metastatic Melanoma
by Michelle M. Dugan, Adrienne B. Shannon, Danielle K. DePalo, Matthew C. Perez and Jonathan S. Zager
Cancers 2024, 16(11), 1957; https://doi.org/10.3390/cancers16111957 - 22 May 2024
Viewed by 629
Abstract
Locoregionally advanced and metastatic melanoma represent a challenging clinical problem, but in the era of immune checkpoint blockade and intralesional and infusional therapies, more options are available for use. Isolated limb infusion (ILI) was first introduced in the 1990s for the management of [...] Read more.
Locoregionally advanced and metastatic melanoma represent a challenging clinical problem, but in the era of immune checkpoint blockade and intralesional and infusional therapies, more options are available for use. Isolated limb infusion (ILI) was first introduced in the 1990s for the management of advanced melanoma, followed by the utilization of isolated extremity perfusion (ILP). Following this, intralesional oncolytic viruses, xanthene dyes, and cytokines were introduced for the management of in-transit metastases as well as unresectable, advanced melanoma. In 2015, the Food and Drug Administration (FDA) approved the first oncolytic intralesional therapy, talimogene laherparepvec (T-VEC), for the treatment of advanced melanoma. Additionally, immune checkpoint inhibition has demonstrated efficacy in the management of advanced melanomas, and this improvement in outcomes has been extrapolated to aid in the management of in-transit metastatic disease. Finally, percutaneous hepatic perfusion (PHP), also approved by the FDA, has been reported to have a significant impact on the treatment of hepatic disease in uveal melanoma. While some of these treatments have less utility due to inferior outcomes as well as higher toxicity profiles, there are selective patient profiles for which these therapies carry a role. This review highlights intralesional and infusional therapies for the management of metastatic melanoma. Full article
(This article belongs to the Special Issue Contemporary Surgical Management of Melanoma)
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Figure 1

14 pages, 632 KiB  
Review
Neo-Adjuvant Therapy for Metastatic Melanoma
by Anke M. J. Kuijpers and Alexander C. J. van Akkooi
Cancers 2024, 16(7), 1247; https://doi.org/10.3390/cancers16071247 - 22 Mar 2024
Viewed by 1354
Abstract
Melanoma treatment is leading the neo-adjuvant systemic (NAS) therapy field. It is hypothesized that having the entire tumor in situ, with all of the heterogeneous tumor antigens, allows the patient’s immune system to have a broader response to the tumor in all its [...] Read more.
Melanoma treatment is leading the neo-adjuvant systemic (NAS) therapy field. It is hypothesized that having the entire tumor in situ, with all of the heterogeneous tumor antigens, allows the patient’s immune system to have a broader response to the tumor in all its shapes and forms. This translates into a higher clinical efficacy. Another benefit of NAS therapy potentially includes identifying patients who have a favorable response, which could offer an opportunity for the de-escalation of the extent of surgery and the need for adjuvant radiotherapy and/or adjuvant systemic therapy, as well as tailoring the follow-up in terms of the frequency of visits and cross-sectional imaging. In this paper, we will review the rationale for NAS therapy in resectable metastatic melanoma and the results obtained so far, both for immunotherapy and for BRAF/MEKi therapy, and discuss the response assessment and interpretation, toxicity and surgical considerations. All the trials that have been reported up to now have been investigator-initiated phase I/II trials with either single-agent anti-PD-1, combination anti-CTLA-4 and anti-PD-1 or BRAF/MEK inhibition. The results have been good but are especially encouraging for immunotherapies, showing high durable recurrence-free survival rates. Combination immunotherapy seems superior, with a higher rate of pathologic responses, particularly in patients with a major pathologic response (MPR = pathologic complete response [pCR] + near-pCR [max 10% viable tumor cells]) of 60% vs. 25–30%. The SWOG S1801 trial has recently shown a 23% improvement in event-free survival (EFS) after 2 years for pembrolizumab when giving 3 doses as NAS therapy and 15 as adjuvant versus 18 as adjuvant only. The community is keen to see the first results (expected in 2024) of the phase 3 NADINA trial (NCT04949113), which randomized patients between surgery + adjuvant anti-PD-1 and two NAS therapy courses of a combination of ipilimumab + nivolumab, followed by surgery and a response-driven adjuvant regimen or follow-up. We are on the eve of neo-adjuvant systemic (NAS) therapy, particularly immunotherapy, becoming the novel standard of care for macroscopic stage III melanoma. Full article
(This article belongs to the Special Issue Contemporary Surgical Management of Melanoma)
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Figure 1

15 pages, 583 KiB  
Review
A Review of Contemporary Guidelines and Evidence for Wide Local Excision in Primary Cutaneous Melanoma Management
by Sophie E. Orme and Marc D. Moncrieff
Cancers 2024, 16(5), 895; https://doi.org/10.3390/cancers16050895 - 23 Feb 2024
Viewed by 981
Abstract
Surgical wide local excision (WLE) remains the current standard of care for primary cutaneous melanoma. WLE is an elective procedure that aims to achieve locoregional disease control with minimal functional and cosmetic impairment. Despite several prospective randomised trials, the optimal extent of excision [...] Read more.
Surgical wide local excision (WLE) remains the current standard of care for primary cutaneous melanoma. WLE is an elective procedure that aims to achieve locoregional disease control with minimal functional and cosmetic impairment. Despite several prospective randomised trials, the optimal extent of excision margin remains controversial, and this is reflected in the persistent lack of consensus in guidelines globally. Furthermore, there is now the added difficulty of interpreting existing trial data in the context of the evolving role of surgery in the management of melanoma, with our increased understanding of clinicopathologic and genomic prognostic markers leading to the often routine use of sentinel node biopsy (SNB) as a staging procedure, in addition to the development of adjuvant systemic therapies for high-risk disease. An ongoing trial, MelMarT-II, has been designed with the aim of achieving a definitive answer to guide this fundamental surgical decision. Full article
(This article belongs to the Special Issue Contemporary Surgical Management of Melanoma)
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Figure 1

14 pages, 272 KiB  
Review
The Use of Gene Expression Profiling and Biomarkers in Melanoma Diagnosis and Predicting Recurrence: Implications for Surveillance and Treatment
by James Sun, Kameko M. Karasaki and Jeffrey M. Farma
Cancers 2024, 16(3), 583; https://doi.org/10.3390/cancers16030583 - 30 Jan 2024
Viewed by 1690
Abstract
Cutaneous melanoma is becoming more prevalent in the United States and has the highest mortality among cutaneous malignancies. The majority of melanomas are diagnosed at an early stage and, as such, survival is generally favorable. However, there remains prognostic uncertainty among subsets of [...] Read more.
Cutaneous melanoma is becoming more prevalent in the United States and has the highest mortality among cutaneous malignancies. The majority of melanomas are diagnosed at an early stage and, as such, survival is generally favorable. However, there remains prognostic uncertainty among subsets of early- and intermediate-stage melanoma patients, some of whom go on to develop advanced disease while others remain disease-free. Melanoma gene expression profiling (GEP) has evolved with the notion to help bridge this gap and identify higher- or lower-risk patients to better tailor treatment and surveillance protocols. These tests seek to prognosticate melanomas independently of established AJCC 8 cancer staging and clinicopathologic features (sex, age, primary tumor location, thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and/or SLNB status). While there is a significant opportunity to improve the accuracy of melanoma prognostication and diagnosis, it is equally important to understand the current landscape of molecular profiling for melanoma treatment. Society guidelines currently do not recommend molecular testing outside of clinical trials for melanoma clinical decision making, citing insufficient high-quality evidence guiding indications for the testing and interpretation of results. The goal of this chapter is to review the available literature for GEP testing for melanoma diagnosis and prognostication and understand their place in current treatment paradigms. Full article
(This article belongs to the Special Issue Contemporary Surgical Management of Melanoma)
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