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Contemporary Surgical Management of Melanoma

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

Deadline for manuscript submissions: 15 March 2025 | Viewed by 16610

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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 are 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. These topics include clinical characteristics and surgical treatment of rare melanoma subtypes; margins in primary melanoma surgery; preoperative and intraoperative identification of sentinel lymph nodes in melanoma surgery; when to use sentinel node biopsy in melanoma, with trends and future directions; clinical and imaging follow-up for high-risk melanoma; gene expression profiling and biomarkers for predicting melanoma recurrence and response to surgical and systemic treatment; adjuvant therapy for high-risk stage II melanoma; neoadjuvant therapy for metastatic melanoma; intralesional and infusional updates for metastatic melanoma; and the role of surgery for stage IV melanoma.

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.

Thank you.

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 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

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Published Papers (10 papers)

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19 pages, 4401 KiB

Open AccessArticle

Preoperative and Intraoperative Identification of Sentinel Lymph Nodes in Melanoma Surgery

by Stanley P. Leong, Mehdi Nosrati, Max C. Wu, Donald M. Torre, Ted F. Bartley, Kevin B. Kim, Christopher Soon, John Moretto and Mohammed Kashani-Sabet

Cancers 2024, 16(15), 2767; https://doi.org/10.3390/cancers16152767 - 5 Aug 2024

Viewed by 1072

Abstract

According to the American Joint Commission on Cancer (AJCC) 8th edition guidelines, SLN biopsy is recommended for primary melanomas with a Breslow thickness of at least 1 mm. Additionally, the National Comprehensive Cancer Network (NCCN) recommends that a SLN biopsy may be considered for melanoma patients with T1b lesions, which are 0.8–1 mm thick or less than 0.8 mm thick with ulceration. It can also be considered for T1a lesions that are less than 0.8 mm thick but have other adverse features, such as a high mitotic rate, lymphovascular invasion, or a positive deep margin. To reduce the false negative rate of melanoma SLN biopsy, we have introduced the intraoperative use of Sentinella, a gamma camera, to enhance the identification rate of SLNs beyond that of the traditional gamma hand-held probe. At the Center for Melanoma Research and Treatment at the California Pacific Medical Center, a multidisciplinary approach has been established to treat melanoma patients when the diagnosis of primary melanoma is made with a referral to our melanoma center. This comprehensive approach at the melanoma tumor board, including the efforts of pathologists, radiologists, dermatologists, surgical, medical and radiation oncologists, results in a consensus to deliver personalized and high-quality care for our melanoma patients. This multidisciplinary program for the management of melanoma can be duplicated for other types of cancer. This article consists of current knowledge to document the published methods of identification of sentinel lymph nodes. In addition, we have included new data as developed in our melanoma center as newly published materials in this article to demonstrate the utility of these methods in melanoma sentinel lymph node surgery. Informed consent has been waived by our IRB regarding the acquisition of clinical data as presented in this study. Full article

(This article belongs to the Special Issue Contemporary Surgical Management of Melanoma)

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12 pages, 1039 KiB

Open AccessReview

Selective Sentinel Node Dissection in Melanoma with Trends and Future Directions

by Eric Pletcher and Mark B. Faries

Cancers 2024, 16(21), 3625; https://doi.org/10.3390/cancers16213625 - 27 Oct 2024

Viewed by 682

Abstract

Starting with its earliest descriptions, melanoma has been recognized as a tumor with a predilection for metastasis to regional lymph nodes. This tendency led to initial recommendations for very aggressive early surgical management of the regional nodal basin. However, those recommendations were the source of much controversy over nearly a century, until the minimally invasive surgical technique of sentinel lymph node (SLN) biopsy was developed by Morton, Cochran and colleagues. This technique has been evaluated in a series of prospective clinical trials, which have clarified its role and the management of lymph nodes in this disease. Current controversies relating to SLN biopsy include optimal selection of patients for the procedure, the role of gene expression profiling in initial melanoma management, and the potential therapeutic effects of SLN biopsy-based management. In addition, the SLN appears to be a rich source of data relating to the host–tumor interface and the immune microenvironment, which may advance our understanding of the biology of melanoma. Finally, although the surgical technique is well developed at this point, there may be additional technical improvements that are possible as well. Full article

(This article belongs to the Special Issue Contemporary Surgical Management of Melanoma)

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24 pages, 1360 KiB

Open AccessReview

Therapeutic Treatment Options for In-Transit Metastases from Melanoma

by Francesco Russano, Marco Rastrelli, Luigi Dall’Olmo, Paolo Del Fiore, Carlomaria Gianesini, Antonella Vecchiato, Marcodomenico Mazza, Saveria Tropea and Simone Mocellin

Cancers 2024, 16(17), 3065; https://doi.org/10.3390/cancers16173065 - 3 Sep 2024

Viewed by 1828

Abstract

In-transit metastases (ITM) in melanoma present a significant therapeutic challenge due to their advanced stage and complex clinical nature. From traditional management with surgical resection, ITM treatment has evolved with the advent of systemic therapies such as immune checkpoint inhibitors and targeted therapies, which have markedly improved survival outcomes. This study aims to review and highlight the efficacy of both systemic and locoregional treatment approaches for ITM. Methods include a comprehensive review of clinical studies examining the impact of treatments like immune checkpoint inhibitors, targeted therapies, Isolated Limb Perfusion, and electrochemotherapy. The results indicate that combining systemic therapies with locoregional treatments enhances both local disease control and overall survival rates. The introduction of modern immunotherapies has not diminished the effectiveness of locoregional therapies but rather improved patient outcomes when used in conjunction. The conclusions emphasize that a multidisciplinary approach integrating systemic and locoregional therapies offers a promising strategy for optimizing the management of ITM in melanoma patients. This integrated treatment model not only improves survival rates but also enhances the quality of life for patients, suggesting a shift in standard care practices toward more comprehensive therapeutic regimens. Full article

(This article belongs to the Special Issue Contemporary Surgical Management of Melanoma)

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16 pages, 531 KiB

Open AccessReview

Adjuvant Therapy for High-Risk Stage II Melanoma: Current Paradigms in Management and Future Directions

by Gracia Maria Vargas, Mohammad Saad Farooq and Giorgos C. Karakousis

Cancers 2024, 16(15), 2690; https://doi.org/10.3390/cancers16152690 - 29 Jul 2024

Viewed by 1343

Abstract

Melanoma is the fifth most common cancer in the United States and accounts for the majority of all skin cancer-related deaths, making it the most lethal cutaneous malignancy. Systemic adjuvant therapy for stage IIB-IV melanoma is now approved for patients who have undergone surgical resection, given the appreciable risk of recurrence and mortality in this patient population. Despite the lower stage, high-risk stage II melanoma (stage IIB/IIC) can often exhibit an even more aggressive course when compared to stage IIIA/IIIB disease, thus justifying consideration of adjuvant therapy in these patients. In this review, we highlight the current standard of practice for the treatment of stage IIB/C melanoma, with a focus on adjuvant therapies supported by published landmark clinical trials, including anti-PD-1 therapy. Notably, adjuvant therapies approved thus far in this patient population have demonstrated an improvement in recurrence-free survival, while their impact on overall survival is pending. Finally, this review highlights currently ongoing trials and future directions for research and treatment possibilities for high-risk clinical stage II melanoma. Full article

(This article belongs to the Special Issue Contemporary Surgical Management of Melanoma)

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13 pages, 247 KiB

Open AccessReview

Clinical and Imaging Follow-Up for High-Risk Cutaneous Melanoma: Current Evidence and Guidelines

by John T. Vetto

Cancers 2024, 16(14), 2572; https://doi.org/10.3390/cancers16142572 - 18 Jul 2024

Viewed by 1384

Abstract

The most recent (eighth) edition of the American Joint Committee on Cancer (AJCC) staging system divides invasive cutaneous melanoma into two broad groups: “low-risk” (stage IA–IIA) and “high-risk” (stage IIB–IV). While surveillance imaging for high-risk melanoma patients makes intuitive sense, supporting data are limited in that they are mostly respective and used varying methods, schedules, and endpoints. As a result, there is a lack of uniformity across different dermatologic and oncologic organizations regarding recommendations for follow-up, especially regarding imaging. That said, the bulk of retrospective and prospective data support imaging follow-up for high-risk patients. Currently, it seems that either positron emission tomography (PET) or whole-body computerized tomography (CT) are reasonable options for follow-up, with brain magnetic resonance imaging (MRI) preferred for the detection of brain metastases in patients who can undergo it. The current era of effective systemic therapies (ESTs), which can improve disease-free survival (DFS) and overall survival (OS) beyond lead-time bias, has emphasized the role of imaging in detecting various patterns of EST response and treatment relapse, as well as the importance of radiologic tumor burden. Full article

(This article belongs to the Special Issue Contemporary Surgical Management of Melanoma)

20 pages, 1311 KiB

Open AccessReview

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 - 28 Jun 2024

Viewed by 1095

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 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)

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17 pages, 775 KiB

Open AccessReview

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

Cited by 2 | Viewed by 1331

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 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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14 pages, 632 KiB

Open AccessReview

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

Cited by 2 | Viewed by 2293

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 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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15 pages, 583 KiB

Open AccessReview

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

Cited by 1 | Viewed by 2169

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 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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14 pages, 272 KiB

Open AccessReview

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

Cited by 3 | Viewed by 2308

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 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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