NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2024.

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.

NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021.

Over the past few years, the NCCN Guidelines for Melanoma: Cutaneous have been expanded to include pathways for treatment of microscopic satellitosis (added in v2.2020), and the following Principles sections: Molecular Testing (added in v2.2019), Systemic Therapy Considerations (added in v2.2020), and Brain Metastases Management (added in v3.2020). The v1.2021 update included additional modifications of these sections and notable revisions to Principles of: Pathology, Surgical Margins for Wide Excision of Primary Melanoma, Sentinel Lymph Node Biopsy, Completion/Therapeutic Lymph Node Dissection, and Radiation Therapy. These NCCN Guidelines Insights discuss the important changes to pathology and surgery recommendations, as well as additions to systemic therapy options for patients with advanced disease.

NCCN Guidelines Insights: Uveal Melanoma, Version 1.2019.

The NCCN Guidelines for Uveal Melanoma include recommendations for staging, treatment, and follow-up of patients diagnosed with uveal melanoma of the choroid or ciliary body. In addition, because distinguishing between uveal melanoma and benign uveal nevi is in some cases difficult, these guidelines also contain recommendations for workup of patients with suspicious pigmented uveal lesions, to clarify the tests needed to distinguish between those who should have further workup and treatment for uveal melanoma versus those with uncertain diagnosis and low risk who should to be followed and later reevaluated. These NCCN Guidelines Insights describe recommendations for treatment of newly diagnosed nonmetastatic uveal melanoma in patients who have already undergone a complete workup.

Cutaneous Melanoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.

Comparison of keystone flaps and skin grafts for oncologic reconstruction: A retrospective review.

BACKGROUND AND OBJECTIVES: Two common options for the closure of complex defects are local flaps and skin grafting. The keystone flap, a fasciocutaneous flap based on perforators, has demonstrated compelling ease of use, reproducibility, and low complication rates without requiring a distant donor site. Our objective for this study was to compare postoperative outcomes for keystone flaps and skin grafts in cancer resection. METHODS: A retrospective review was conducted of patients undergoing keystone flap closure or skin grafting for soft tissue defects resulting from cancer resection at a single institution from June 2017 to June 2018. Patient demographics, operative indications, length of stay, time to heal, and complications were reviewed. RESULTS: A total of 34 patients were identified having undergone either keystone reconstruction (n = 16) or skin graft (n = 18) after oncologic resection. Patients undergoing keystone flap reconstruction had significantly shorter mobility restriction and healing times. Length of hospital stay and overall complication rates were not significantly different. CONCLUSION: The keystone flap is an adaptable tool that can safely be used for the coverage of complex defects with faster healing, shorter mobility restriction, and comparable complication rates to skin grafting without the need for a distant donor site.

Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Melanoma focuses on adjuvant therapy and treatment of in-transit disease, because substantial changes were made to the recommendations for the 2016 update. Depending on the stage of the disease, options for adjuvant therapy now include biochemotherapy and high-dose ipilimumab. Treatment options for in-transit disease now include intralesional injection with talimogene laherparepvec (T-VEC), a new immunotherapy. These additions prompted re-assessment of the data supporting older recommended treatment options for adjuvant therapy and in-transit disease, resulting in extensive revisions to the supporting discussion sections.

NCCN Guidelines Insights: Melanoma, Version 3.2016.

The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These NCCN Guidelines Insights summarize the data and rationale supporting extensive changes to the recommendations for systemic therapy in patients with metastatic or unresectable melanoma.

Melanoma, version 4.2014.

The NCCN Guidelines for Melanoma provide multidisciplinary recommendations for the management of patients with melanoma. These NCCN Guidelines Insights highlight notable recent updates. Dabrafenib and trametinib, either as monotherapy (category 1) or combination therapy, have been added as systemic options for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. Controversy continues regarding the value of adjuvant radiation for patients at high risk of nodal relapse. This is reflected in the category 2B designation to consider adjuvant radiation following lymphadenectomy for stage III melanoma with clinically positive nodes or recurrent disease.

Melanoma, version 2.2013: featured updates to the NCCN guidelines.

The NCCN Guidelines for Melanoma provide multidisciplinary recommendations on the clinical management of patients with melanoma. This NCCN Guidelines Insights report highlights notable recent updates. Foremost of these is the exciting addition of the novel agents ipilimumab and vemurafenib for treatment of advanced melanoma. The NCCN panel also included imatinib as a treatment for KIT-mutated tumors and pegylated interferon alfa-2b as an option for adjuvant therapy. Also important are revisions to the initial stratification of early-stage lesions based on the risk of sentinel lymph node metastases, and revised recommendations on the use of sentinel lymph node biopsy for low-risk groups. Finally, the NCCN panel reached clinical consensus on clarifying the role of imaging in the workup of patients with melanoma.

Comparison of the use and results of sentinel lymph node biopsy in children and young adults with melanoma.

BACKGROUND: Data on sentinel lymph node (SLN) biopsy in children with melanoma are limited. In this study, the authors compared the factors associated with SLN biopsy use and metastases in pediatric and young adult patients with melanoma. METHODS: The 2008 Surveillance, Epidemiology, and End Results (SEER) databases were used to examine melanoma cases from 2003 to 2008. Data extracted include age, sex, race, stage, tumor thickness, ulceration, lymph node status, surgical treatment, and survival. Logistic regression models were used for adjusted analyses. RESULTS: In total, 717 children (age <20 years) and 1368 young adults (age 20-24 years) were identified who were diagnosed with melanoma. Factors that were associated with SLN biopsy use included tumor ulceration (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.4-4.3) and greater thickness (OR, 17; 95% CI, 12-24 for >1 mm vs ≤1 mm), but not younger age (OR, 1.3; 95% CI, 0.94-1.8) in adjusted analyses. SLN metastasis was correlated with ulceration (OR, 3.0; 95% CI, 1.6-5.8), increased thickness (OR, 6.8; 95% CI, 3.1-15 for 2.01-4.0 mm vs ≤1 mm), and for the interaction between age <20 years and thickness 1.01 to 2.00 mm (OR, 6.5; 95% CI, 1.7-25) in adjusted analyses. Children with nonulcerated melanomas that measured 1.01 to 2.00 mm in thickness were significantly more likely to have SLN metastases than young adults (24% vs 4%; P < .001). CONCLUSIONS: Thickness and ulceration were strong predictors of both the use of SLN biopsy and positive SLN biopsy results in children and young adults with melanoma. Compared with young adults, children were more likely to have SLN metastases despite having similar rates of SLN biopsy use.

Surgical treatment of melanoma patients with early sentinel node involvement.

Sentinel lymph node biopsy (SLNB) is a standard staging procedure for many patients with clinically node negative, invasive melanoma, providing excellent prognostic information in appropriately selected patients. The broad acceptance of SLNB into clinical practice has resulted in substantial numbers of patients found to have microscopic nodal metastases. For patients with a positive sentinel node, a completion lymph node dissection (CLND) is the current standard of care. The majority of patients who undergo CLND are found to have histologically negative non-sentinel nodes, and yet are exposed to the potential morbidity of CLND, including infection, wound complications, and lymphedema. We do not yet know if there is a survival benefit from CLND that justifies its morbidity and we are currently unable to identify clinical and pathologic factors that may be associated with the likelihood of benefit from CLND. Controversy regarding the management of melanoma patients with a positive sentinel node highlights the need for continued investigation in melanoma biology, treatment, and outcomes. Patients with minimal tumor burden in their regional nodes would especially benefit from a better understanding of the appropriate management strategies. Ongoing clinical trials are aimed at determining whether CLND is superior to nodal observation and surveillance in patients with positive sentinel nodes, and at determining the outcome of patients with minimal disease in their sentinel node who forego CLND. These studies may help to resolve the uncertainties of the management in these patients. Until we have further information, CLND for melanoma patients with positive sentinel nodes remains the preferred, standard management strategy.

Promoter hypermethylation in sentinel lymph nodes as a marker for breast cancer recurrence.

PURPOSE: Promoter methylation of tumor suppressor genes in histologically negative sentinel lymph nodes (HNSN) of early stage breast cancer patients has not been extensively studied. This study evaluates the methylation frequency and pattern in HNSN to determine if detection of hypermethylation of one or more genes is associated with an increased recurrence risk in node negative breast cancer. EXPERIMENTAL DESIGN: In 1998, a prospective study of patients with early stage breast cancer and HNSN was initiated in order to correlate sentinel node analysis with clinical outcome. Nodal tissue was selected from 120 HNSN patients for methylation analysis in at least one and up to six sentinel nodes using a panel of nine genes. Corresponding primary breast tumors from 79 patients were also evaluated for hypermethylation. Methylation analysis was performed using nested Methylation Sensitive PCR (n-MSP). Logistical regression was used to evaluate the relationship between clinical recurrence and methylation status. RESULTS: Over a median follow-up of 79 months, 13 of the 120 patients had clinical recurrence. Hypermethylation of genes was frequently observed in HNSN, but there was no correlation of methylation pattern and clinical recurrence. However, increased frequency of gene methylation of the primary tumor correlated with clinical recurrence. CONCLUSIONS: Although hypermethylation of multiple genes occurs frequently in HNSN of breast cancer patients, it is not associated with breast cancer recurrence in the first 7 years of clinical follow-up.

Complete lymph node dissection for sentinel node-positive melanoma: assessment of practice patterns in the United States.

BACKGROUND: Currently, complete lymph node dissection (CLND) is recommended after identification of a metastatic lymph node by sentinel lymph node biopsy (SLNB). Guidelines suggest that CLND should be performed as a separate procedure, and a sufficient number of nodes should be examined. Our objective was to examine the utilization, timing, and adequacy of CLND for melanoma in the United States. METHODS: From the National Cancer Data Base, patients diagnosed with stage I to III melanoma during 2004-2005 were identified. Multiple logistic regression was used to assess factors associated with CLND utilization, timing (separate operation from SLNB), and adequacy (examination of > or = 10 nodes). RESULTS: Of the 44,548 patients identified, 47.5% were pathologic stage IA, 23.8% stage IB, 14.1% stage II, and 14.6% stage III. Of the 17% (2942 of 17,524) with nodal metastases on SLNB, only 50% underwent a CLND. Patients were significantly less likely to undergo a CLND after SLNB if > 75 years old or had lower extremity melanomas. Of the patients who underwent a CLND, only 42% underwent the CLND at a separate procedure after the SLNB. Of those who underwent a CLND, 69.2% had > or = 10 nodes examined. Patients were significantly less likely to have > or = 10 nodes examined if they were > 75 years old or had lower extremity melanomas. Patients treated at NCCN/NCI-designated centers were significantly more likely to undergo nodal evaluation in concordance with established guidelines. CONCLUSIONS: Only half of patients with sentinel node-positive melanoma underwent CLND. Quality surveillance measures are needed to monitor, standardize, and improve the care of patients with malignant melanoma.

Sentinel lymph node biopsy in melanoma.

Sentinel lymph node biopsy (SLNB) for patients with newly diagnosed localized invasive melanoma provides excellent prognostic information and results in improved regional disease control. Prior to the common use of SLNB, regional nodal recurrence was the single most common site of melanoma recurrence, with symptomatic, bulky disease that could be disabling and difficult or impossible to control. With the widespread use of SLNB, regional recurrence of melanoma is much less frequent. Even without clear evidence of improvement in overall survival, the significant and reliable prognostic information and the improved regional control make sentinel node biopsy an important procedure that should be offered routinely to many patients with newly diagnosed melanoma.

Screening for cutaneous melanoma.

Current data do not support widespread population-based screening for melanoma. While the incidence of melanoma is high, the overall mortality is low, and thus any potential benefit of screening the general population is hard to demonstrate. No randomized controlled trial showing reduction in mortality has ever been completed and, given the expense and time necessary for such a trial, probably will never be completed. The idea of skin screening remains appealing for this common, visible malignancy which is eminently treatable when detected early. Efforts should be focused on populations at particularly high risk of developing melanoma and on those at high risk of death from melanoma once diagnosed. Persons in kindreds of familial melanoma, and persons who have atypical mole syndrome, those who have a prior diagnosis of melanoma, or those who have diagnosed atypical nevi are all reasonable candidates for routine screening, based on lower-level evidence in the absence of randomized clinical trials targeting these groups. Programs targeting persons of low socioeconomic status and targeting white men over the age of 50 could address groups known to beat especially high risk of melanoma mortality.

Epidemiology, risk factors, prevention, and early detection of melanoma.

The incidence of melanoma has increased over the past several decades. Despite improved case mortality, overall deaths from melanoma have increased because of the large increase in incidence. Although we have a better understanding of the pathogenesis of melanoma and improved early diagnostic capabilities, the burden of disease and societal costs remain high. This article provides an update on the epidemiology of cutaneous melanoma worldwide and the common risk factors including heritable and modifiable risks, emphasizing the importance of education, early detection, and prevention in reducing the disease burden.