Validation of the Melanoma Institute of Australia's Sentinel Lymph Node Biopsy Risk Prediction Tool for Cutaneous Melanoma.

BACKGROUND: For patients with cutaneous melanoma, sentinel lymph node biopsy (SLNB) is used to stage regional lymph nodes pathologically and inform prognosis, treatment, and surveillance. To reduce unnecessary surgeries, predictive tools aim to identify those at lowest risk for node-positive disease. The Melanoma Institute of Australia (MIA)'s Prediction Tool for Sentinel Node Metastasis Risk estimates risk of a positive SLNB using patient age and primary melanoma Breslow depth, histologic subtype, ulceration, mitotic rate, and lymphovascular invasion. METHODS: A single-institution validation was performed of the MIA Calculator with 982 cutaneous melanoma patients that included all relevant clinicopathologic factors and SLNB pathology outcomes. The study evaluated discrimination via receiver operating characteristic (ROC) curves, calibration via calibration plots, and clinical utility via decision curve analysis of the MIA model in various subgroups. The data were fit to MIA model parameters via a generalized linear model to assess the odds ratio of parameters in our dataset. RESULTS: The Calculator demonstrated limited discrimination based on ROC curves (C-statistic, 0.709) and consistently underestimated risk of SLN positivity. It did not provide a net benefit over SLNB performed on all patients or reduce unnecessary procedures in the risk domain of 0% to 16%. Compared with the original development and validation cohorts, the current study cohort had thinner tumors and a larger proportion of acral melanomas. CONCLUSIONS: The Calculator generally underestimated SLN positivity risk, including assessment in patients who would be counseled to forego SLNB based on a predicted risk lower than 5%. Recognition of the tool's current limitations emphasizes the need to refine it further for use in medical decision-making.

Estimating remaining life expectancy in veterans with basal cell carcinoma using an automated electronic health record scoring system: A retrospective cohort study.

BACKGROUND: Active surveillance may be considered for low-risk basal cell carcinomas (BCCs) in patients with limited life expectancy; however, estimates of life expectancy are not readily available. Veterans Health Administration's Care Assessment Need (CAN) score may address this problem. OBJECTIVE: We examined the CAN score's performance in predicting 1-, 3-, and 5-year mortality in US veterans with BCC. METHODS: This retrospective cohort study used national Veterans Health Administration's electronic medical record data. The CAN score's performance in the prediction of mortality in veterans with BCC was evaluated based on tests of goodness-of-fit, discrimination, and calibration. RESULTS: For 54,744 veterans with BCC treatment encounters between 2013 and 2018, the CAN score performed well in the prediction of mortality based on multiple tests. A threshold CAN score of 90 had a positive predictive value of 55% for 3-year mortality, clinically useful in identifying patients with intermediate-term survival. LIMITATIONS: The study relied upon the combination of diagnosis codes and procedure codes to identify BCC cases. CONCLUSION: The CAN score has the potential to improve the quality of cancer care for veterans by providing clinicians with an estimate of life expectancy and facilitating conversations in cases where active surveillance can be considered.

Cutaneous melanoma.

Cutaneous melanoma is a malignancy arising from melanocytes of the skin. Incidence rates are rising, particularly in White populations. Cutaneous melanoma is typically driven by exposure to ultraviolet radiation from natural sunlight and indoor tanning, although there are several subtypes that are not related to ultraviolet radiation exposure. Primary melanomas are often darkly pigmented, but can be amelanotic, with diagnosis based on a combination of clinical and histopathological findings. Primary melanoma is treated with wide excision, with margins determined by tumour thickness. Further treatment depends on the disease stage (following histopathological examination and, where appropriate, sentinel lymph node biopsy) and can include surgery, checkpoint immunotherapy, targeted therapy, or radiotherapy. Systemic drug therapies are recommended as an adjunct to surgery in patients with resectable locoregional metastases and are the mainstay of treatment in advanced melanoma. Management of advanced melanoma is complex, particularly in those with cerebral metastasis. Multidisciplinary care is essential. Systemic drug therapies, particularly immune checkpoint inhibitors, have substantially increased melanoma survival following a series of landmark approvals from 2011 onward.

Advances in cutaneous squamous cell carcinoma.

Human malignancies arise predominantly in tissues of epithelial origin, where the stepwise transformation from healthy epithelium to premalignant dysplasia to invasive neoplasia involves sequential dysregulation of biological networks that govern essential functions of epithelial homeostasis. Cutaneous squamous cell carcinoma (cSCC) is a prototype epithelial malignancy, often with a high tumour mutational burden. A plethora of risk genes, dominated by UV-induced sun damage, drive disease progression in conjunction with stromal interactions and local immunomodulation, enabling continuous tumour growth. Recent studies have identified subpopulations of SCC cells that specifically interact with the tumour microenvironment. These advances, along with increased knowledge of the impact of germline genetics and somatic mutations on cSCC development, have led to a greater appreciation of the complexity of skin cancer pathogenesis and have enabled progress in neoadjuvant immunotherapy, which has improved pathological complete response rates. Although measures for the prevention and therapeutic management of cSCC are associated with clinical benefit, the prognosis remains poor for advanced disease. Elucidating how the genetic mechanisms that drive cSCC interact with the tumour microenvironment is a current focus in efforts to understand, prevent and treat cSCC.

Early Detection and Prognostic Assessment of Cutaneous Melanoma: Consensus on Optimal Practice and the Role of Gene Expression Profile Testing.

Importance: Therapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined. Objective: To provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM. Evidence Review: Case scenarios were interrogated using a modified Delphi consensus method. Melanoma panelists (n = 60) were invited to vote on hypothetical scenarios via an emailed survey (n = 42), which was followed by a consensus conference (n = 51) that reviewed the literature and the rationale for survey answers. Panelists participated in a follow-up survey for final recommendations on the scenarios (n = 45). Findings: The panelists reached consensus (≥70% agreement) in supporting a risk-stratified approach to melanoma screening in clinical settings and public screening events, screening personnel recommendations (self/partner, primary care provider, general dermatologist, and pigmented lesion expert), screening intervals, and acceptable appointment wait times. Participants also reached consensus that visual and dermoscopic examination are sufficient for evaluation and follow-up of melanocytic skin lesions deemed innocuous. The panelists reached consensus on interpreting reflectance confocal microscopy and some but not all results from epidermal tape stripping, but they did not reach consensus on use of certain pigmented lesion evaluation tools, such as electrical impedance spectroscopy. Regarding GEP scores, the panelists reached consensus that a low-risk prognostic GEP score should not outweigh concerning histologic features when selecting patients to undergo sentinel lymph node biopsy but did not reach consensus on imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status. Conclusions and Relevance: For this consensus statement, panelists reached consensus on aspects of a risk-stratified approach to melanoma screening and follow-up as well as use of visual examination and dermoscopy. These findings support a practical approach to diagnosing and evaluating CM. Panelists did not reach consensus on a clearly defined role for GEP testing in clinical decision-making, citing the need for additional studies to establish the clinical use of existing GEP assays.

What Is Melanoma?

This JAMA Patient Page describes melanoma, its risk factors, diagnosis, treatment, and prognosis.

Association of multiple primary melanomas with malignancy risk: A population-based analysis of entries from the Surveillance, Epidemiology, and End Results program database during 1973-2014.

BACKGROUND: Genetic and environmental risk factors have been associated with the development of multiple primary melanomas (MPMs). We hypothesized that individuals with MPMs might have an increased incidence of internal malignancies. OBJECTIVE: To identify the risk for subsequent malignancies in MPM patients. METHODS: Multiple primary standardized incidence ratios were analyzed for individuals with ≥1, ≥2 and ≥3 primary melanomas (PMs) recorded in the Surveillance, Epidemiology, and End Results database during 1973-2014. RESULTS: We identified 223,799 individuals with ≥1 PM, 19,709 with ≥2 PMs, and 3,995 with ≥3 PMs. Risks of subsequent internal malignancy increased with number of PMs, with observed:expected ratios of 0.99, 1.14, and 1.23 (P < .05) for patients with ≥1 PM, ≥2 PMs, and ≥3 PMs, respectively. Internal malignancy was higher in younger MPM patients and those with superficial spreading melanoma. The most common malignancies among MPM patients included breast, prostate, thyroid, soft tissue, brain, kidney, non-Hodgkin lymphoma, and chronic lymphocytic leukemia. Risk for subsequent cutaneous melanoma increased with observed:expected ratios of 8.09, 22.52, 41.03 (P < .05) for patients with ≥1 PM, ≥2 PMs, and ≥3 PMs, respectively. LIMITATIONS: Surveillance, Epidemiology, and End Results records limited information about pigmentation phenotypes, histology, and treatments. CONCLUSION: Patients with MPMs have an increased risk for subsequent internal and cutaneous malignancies and might benefit from tight adherence to age-specific cancer screening.

Melanoma awareness and prevention among latinx and non-latinx white adults in urban and rural California: A qualitative exploration.

BACKGROUND: Melanoma mortality rates in the US are highest among older men, individuals of lower socioeconomic status (SES), and people of color. To better understand these inequities, a qualitative exploratory study was conducted in Northern and Southern California to generate knowledge about barriers and facilitators of awareness, prevention, and early detection of melanoma in lower SES Latinx and non-Latinx White (NLW) individuals living in urban and semi-rural areas. METHODS: Nineteen focus groups were conducted (N = 176 adult participants), stratified by race/ethnicity (Latinx, low-income NLW), geography (semi-rural, urban), and language (English and Spanish). Inductive and deductive thematic analysis was conducted, and the findings were organized using the socioecological model framework: individual, interpersonal, community, and health system/policy levels. RESULTS: Four socioecological themes describe how key factors affect knowledge, perceived risk, preventive behaviors, and melanoma screening. Individual level findings revealed that many participants were not familiar with melanoma, yet were willing to learn through trusted sources. Having brown or darker skin tone was perceived as being associated with lower risk for skin cancer. Interpersonally, social relationships were important influences for skin cancer prevention practice. However, for several Latinx and semi-rural participants, conversations about melanoma prevention did not occur with family and peers. At the community level, semi-rural participants reported distance or lack of transportation to a clinic as challenges for accessing dermatology care. Healthcare systems barriers included burdens of additional healthcare costs for dermatology visits and obtaining referral. CONCLUSIONS: Varying factors influence the awareness levels, beliefs, and behaviors associated with knowledge, prevention, and early detection of melanoma among low-income Latinx and NLW individuals and in semi-rural areas. Results have implications for health education interventions. Navigation strategies that target individuals, families, and health care settings can promote improved prevention and early detection of melanoma in these communities.

Health Care Utilization and Costs in Systemic Therapies for Metastatic Melanoma from 2016 to 2020.

BACKGROUND: Widespread implementation of immune checkpoint inhibitors (ICI) and targeted therapies for metastatic melanoma has led to a decline in melanoma-related mortality but increased healthcare costs. We aimed to determine how healthcare utilization varied by systemic, non-adjuvant melanoma treatment from 2016 to 2020. PATIENTS AND METHODS: Adults with presumed stage IV metastatic melanoma receiving systemic therapy from 2016 to 2020 were identified in Optum, a nationwide commercial claims database. Treatment groups were nivolumab, pembrolizumab, ipilimumab+nivolumab (combination-ICI), or BRAF+MEK inhibitor (BRAFi+MEKi) therapy. Outcomes included hospitalizations, days hospitalized, emergency room (ER) visits, outpatient visits, and healthcare costs per patient per month (pppm). Multivariable regression models were used to analyze whether cost and utilization outcomes varied by treatment group, with nivolumab as reference. RESULTS: Among 2018 adult patients with metastatic melanoma identified, mean (SD) age was 67 (15) years. From 2016 to 2020, nivolumab surpassed pembrolizumab as the most prescribed systemic melanoma therapy while combination-ICI and BRAFi+MEKi therapies remained stable. Relative to nivolumab, all other therapies were associated with increased total healthcare costs (combination-ICI: ß = $47 600 pppm, 95%CI $42 200-$53 100; BRAFi+MEKi: ß = $3810, 95%CI $365-$7260; pembrolizumab: ß = $6450, 95%CI $4420-$8480). Combination-ICI and BRAFi+MEKi therapies were associated with more inpatient hospital days. CONCLUSIONS: Amid the evolving landscape of systemic therapy for advanced melanoma, nivolumab monotherapy emerged as the most used and least costly systemic treatment from 2016 to 2020. Its sharp increase in use in 2018 and lower costs relative to pembrolizumab may in part be due to earlier adoption of less frequent dosing intervals.

Disparities in dermatology AI performance on a diverse, curated clinical image set.

An estimated 3 billion people lack access to dermatological care globally. Artificial intelligence (AI) may aid in triaging skin diseases and identifying malignancies. However, most AI models have not been assessed on images of diverse skin tones or uncommon diseases. Thus, we created the Diverse Dermatology Images (DDI) dataset-the first publicly available, expertly curated, and pathologically confirmed image dataset with diverse skin tones. We show that state-of-the-art dermatology AI models exhibit substantial limitations on the DDI dataset, particularly on dark skin tones and uncommon diseases. We find that dermatologists, who often label AI datasets, also perform worse on images of dark skin tones and uncommon diseases. Fine-tuning AI models on the DDI images closes the performance gap between light and dark skin tones. These findings identify important weaknesses and biases in dermatology AI that should be addressed for reliable application to diverse patients and diseases.

Clinically Significant Risk Thresholds in the Management of Primary Cutaneous Melanoma: A Survey of Melanoma Experts.

BACKGROUND: Risk-based thresholds to guide management are undefined in the treatment of primary cutaneous melanoma but are essential to advance the field from traditional stage-based treatment to more individualized care. METHODS: To estimate treatment risk thresholds, hypothetical clinical melanoma scenarios were developed and a stratified random sample was distributed to expert melanoma clinicians via an anonymous web-based survey. Scenarios provided a defined 5-year risk of recurrence and asked for recommendations regarding clinical follow-up, imaging, and adjuvant therapy. Marginal probability of response across the spectrum of 5-year recurrence risk was estimated. The risk at which 50% of respondents recommended a treatment was defined as the risk threshold. RESULTS: The overall response rate was 56% (89/159). Three separate multivariable models were constructed to estimate the recommendations for clinical follow-up more than twice/year, for surveillance cross-sectional imaging at least once/year, and for adjuvant therapy. A 36% 5-year risk of recurrence was identified as the threshold for recommending clinical follow-up more than twice/year. The thresholds for recommending cross-sectional imaging and adjuvant therapy were 30 and 59%, respectively. Thresholds varied with the age of the hypothetical patient: at younger ages they were constant but increased rapidly at ages 60 years and above. CONCLUSIONS: To our knowledge, these data provide the first estimates of clinically significant treatment thresholds for patients with cutaneous melanoma based on risk of recurrence. Future refinement and adoption of thresholds would permit assessment of the clinical utility of novel prognostic tools and represents an early step toward individualizing treatment recommendations.

Differences in Thickness-Specific Incidence and Factors Associated With Cutaneous Melanoma in the US From 2010 to 2018.

Importance: The recent incidence of cutaneous melanoma of different thicknesses in the US is not well described. Objective: To evaluate recent patterns in the incidence of melanoma by tumor thickness and examine associations of sex, race and ethnicity, and socioeconomic status with melanoma thickness-specific incidence. Design, Setting, and Participants: This population-based cohort study analyzed data for 187 487 patients with a new diagnosis of invasive cutaneous melanoma from the Surveillance, Epidemiology, and End Results Registry from January 1, 2010, to December 31, 2018. The study was conducted from May 27 to December 29, 2021. Data were analyzed from June 21 to October 24, 2021. Main Outcomes and Measures: Age-adjusted incidence rates of melanoma were calculated by tumor thickness (categorized by Breslow thickness) and annual percentage change (APC) in incidence rates. Analyses were stratified by sex and race and ethnicity. The associations with socioeconomic status were evaluated in 134 359 patients diagnosed with melanoma from 2010 to 2016. Results: This study included 187 487 patients with a median (IQR) age of 62 (52-72) years and 58.4% men. Melanoma incidence was higher in men compared with women across all tumor thickness groups. Individuals in lower socioeconomic status quintiles and members of minority groups were more likely to be diagnosed with thicker (T4) tumors (20.7% [169 of 816] among non-Hispanic Black patients, 11.2% [674 of 6042] among Hispanic patients, and 6.3% [10 774 of 170 155] among non-Hispanic White patients). Between 2010 and 2018, there was no significant increase in incidence of cutaneous melanoma across the full population (APC, 0.39%; 95% CI, -0.40% to 1.18%). The incidence of the thickest melanomas (T4, >4.0 mm) increased between 2010 and 2018, with an APC of 3.32% (95% CI, 2.06%-4.60%) overall, 2.50% (95% CI, 1.27%-3.73%) in men, and 4.64% (95% CI, 2.56%-6.75%) in women. Conclusions and Relevance: In this population-based cohort study, the incidence of the thickest cutaneous melanoma tumors increased from 2010 to 2018, in contrast with the incidence patterns for thinner melanomas. The findings suggest potential stabilization of overall melanoma incidence rates in the US after nearly a century of continuous increase in incidence. Patients with low socioeconomic status and Hispanic patients were more likely to be diagnosed with thick melanoma. The continued rise in incidence of thick melanoma is unlikely to be attributable to overdiagnosis given the stability of thin melanoma rates.