Melanoma Great Debate: Targeted Versus Complete Nodal Dissection Following Neoadjuvant Therapy for Melanoma: Is it Time to Push Forward or Hold Off on Continued De-Escalation of Surgery?

The management of stage III melanoma has undergone profound change with the advent of effective systemic therapies and the growing use of neoadjuvant immunotherapy. This paper highlights the issues raised and points discussed during the Great Debates session at the 2024 SSO Conference in Atlanta, focusing on the necessity of therapeutic lymph node dissection (TLND) after index lymph node (ILN) surgery.

Validation of Invasive Area for Predicting Sentinel Node Status and Survival in Primary Cutaneous Melanoma.

Background: Two-dimensional histologic features have demonstrated independent prognostic value for survival in primary cutaneous melanoma, but their predictive value for sentinel node (SN) status has yet to be validated. We aimed to demonstrate the predictive value of the previously described calculated tumor area (CTA), and the novel Simplified Breslow Area (SBA), for SN metastasis and survival.

Materials And Methods: A total of 177 primary melanomas were assessed for standard histological characteristics, maximum invasive width (IW) of the primary tumor and CTA.

Global Applicability of a Risk Prediction Tool for Sentinel Node Positivity in Patients With Primary Cutaneous Melanoma.

Importance: The Melanoma Institute Australia (MIA) sentinel node (SN) metastasis risk calculator provides estimates of positivity for individual patients based on 6 standard clinicopathological parameters and the full 6-parameter model has been externally validated previously using US data. However, given its geographically widespread use, further validation is required to ensure its applicability to other populations.

Objective: To further externally validate the MIA SN metastasis risk calculator and increase its precision by refinement of the 95% CIs.

Society of Surgical Oncology Consensus Statement: Assessing the Evidence for and Utility of Gene Expression Profiling of Primary Cutaneous Melanoma.

Introduction: Gene expression profiling (GEP) of primary cutaneous melanoma aims to offer prognostic and predictive information to guide clinical care. Despite limited evidence of clinical utility, these tests are increasingly incorporated into clinical care.

Methods: A panel of melanoma experts from the Society of Surgical Oncology convened to develop recommendations regarding the use of GEP to guide management of patients with melanoma.

Clinical outcomes of the management of basal cell carcinomas in individuals aged 90 years and over: a retrospective cohort study.

Background: A retrospective cohort study was undertaken to examine the management of basal cell carcinoma (BCC) in older patients.

Objectives: The aim of this study was to identify subgroups where intervention could be minimized, based on frailty and trends in survival.

Methods: All patients aged ≥ 90 years with histologically confirmed BCC during 2017 and 2018 were included within the study (n = 319).

A Review of Contemporary Guidelines and Evidence for Wide Local Excision in Primary Cutaneous Melanoma Management.

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.

Risk Stratification of Sentinel Node Metastasis Disease Burden and Phenotype in Stage III Melanoma Patients.

Background: Currently, all patients with American Joint Committee on Cancer (AJCC) pT2b-pT4b melanomas and a positive sentinel node biopsy are now considered for adjuvant systemic therapy without consideration of the burden of disease in the metastatic nodes.

Methods: This was a retrospective cohort analysis of 1377 pT1-pT4b melanoma patients treated at an academic cancer center. Standard variables regarding patient, primary tumor, and sentinel node characteristics, in addition to sentinel node metastasis maximum tumor deposit size (MTDS) in millimeters and extracapsular spread (ECS) status, were analyzed for predicting disease-specific survival (DSS).

Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection.

Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers.

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery.

Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases.

Follow-up Schedule for Patients With Sentinel Node-negative Cutaneous Melanoma (The MELFO Study): An International Phase III Randomized Clinical Trial.

Objectives And Design: The MELFO (MELanoma FOllow-up) study is an international phase III randomized controlled trial comparing an experimental low-intensity schedule against current national guidelines.

Background: Evidence-based guidelines for the follow-up of sentinel node-negative melanoma patients are lacking.

Methods: Overall, 388 adult patients diagnosed with sentinel node-negative primary melanoma patients were randomized in cancer centers in the Netherlands and United Kingdom between 2006 and 2016.

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.

Purpose: Indications for offering adjuvant systemic therapy for patients with early-stage melanomas with low disease burden sentinel node (SN) micrometastases, namely, American Joint Committee on Cancer (AJCC; eighth edition) stage IIIA disease, are presently controversial. The current study sought to identify high-risk SN-positive AJCC stage IIIA patients who are more likely to derive benefit from adjuvant systemic therapy.

Methods: Patients were recruited from an intercontinental (Australia/Europe/North America) consortium of nine high-volume cancer centers.

Predictors of Sentinel Lymph Node Metastasis in Patients with Thin Melanoma: An International Multi-institutional Collaboration.

Background: Consideration of sentinel lymph node biopsy (SLNB) is recommended for patients with T1b melanomas and T1a melanomas with high-risk features; however, the proportion of patients with actionable results is low. We aimed to identify factors predicting SLNB positivity in T1 melanomas by examining a multi-institutional international population.

Methods: Data were extracted on patients with T1 cutaneous melanoma who underwent SLNB between 2005 and 2018 at five tertiary centers in Europe and Canada.

Evaluation of the Indications for Sentinel Node Biopsy in Early-Stage Melanoma with the Advent of Adjuvant Systemic Therapy: An International, Multicenter Study.

Background: Patients presenting with early-stage melanoma (AJCC pT1b-pT2a) reportedly have a relatively low risk of a positive SNB (~5-10%). Those patients are usually found to have low-volume metastatic disease after SNB, typically reclassified to AJCC stage IIIA, with an excellent prognosis of ~90% 5-year survival. Currently, adjuvant systemic therapy is not routinely recommended for most patients with AJCC stage IIIA melanoma.

PGC-1α induced mitochondrial biogenesis in stromal cells underpins mitochondrial transfer to melanoma.

Introduction: Progress in the knowledge of metabolic interactions between cancer and its microenvironment is ongoing and may lead to novel therapeutic approaches. Until recently, melanoma was considered a glycolytic tumour due to mutations in mitochondrial-DNA, however, these malignant cells can regain OXPHOS capacity via the transfer of mitochondrial-DNA, a process that supports their proliferation in-vitro and in-vivo. Here we study how melanoma cells acquire mitochondria and how this process is facilitated from the tumour microenvironment.

International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers.

Objective: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma.

Summary Background Data: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization.

MelRisk: Using neutrophil-to-lymphocyte ratio to improve risk prediction models for metastatic cutaneous melanoma in the sentinel lymph node.

Background: Identifying metastatic melanoma in the sentinel lymph node (SLN) is important because 80% of SLN biopsies are negative and 11% of patients develop complications. The neutrophil-to-lymphocyte ratio (NLR), a biomarker of micrometastatic disease, could improve prediction models for SLN status. We externally validated existing models and developed 'MelRisk' prognostic score to better predict SLN metastasis.

Introducing minimally invasive inguinal lymph node dissection in a UK tertiary skin cancer service: Initial experience & outcomes.

Aims: We report the first UK case series of minimally invasive inguinal lymphadenectomy (MILND) for patients with metastatic cutaneous pathology.

Methods: This was a retrospective, single-centre, single-surgeon cohort study. Twenty-one patients who underwent MILND from May 2015 to February 2019 were included.