Melanoma-specific Mortality Research Articles

Declining invasive and rising insitu melanoma incidence trends in Iceland: A nationwide cohort study.

Melanoma is increasing worldwide, with incidence rates of invasive melanoma and melanoma insitu (MIS) varying by country. To provide updated invasive melanoma and MIS incidence and mortality trends in Iceland and explore differences among sex and rurality. In this whole-population study using the Icelandic Cancer Registry, patients diagnosed with invasive melanoma or MIS between 1957 and 2021 were included. Sex-specific world standardized incidence (WSR) and mortality rates were assessed by rurality. Joinpoint analysis was used to calculate trends using annual per cent change (APC). Invasive melanoma incidence rates increased from 0.66 to 7.0 (men) and 1.6 to 11.0 (women) per 100,000 person-years, and from 0.2 to 4.0 and 0.9 to 9.5 per 100,000 person-years for MIS in men and women, respectively, with a statistically significant linear trend (p = 0.001). WSR peaked in both men and women (10.7, 17.9 per 100,000 person-years) between 2002 and 2006 and has since been trending down. Between 1991 and 2005, the rise in invasive melanoma occurred more frequently in urban regions. Between 2003 and 2005, joinpoint analysis demonstrated a downtrend in invasive melanoma in men and women (-0.29, -0.73; p < 0.05). For MIS, the WSR peaked at 12.4 per 100,000 person-years in women between 1997 and 2001 before down-trending to 4.2. In recent years (2017-2021), the WSR has been steadily increasing in women with an APC of 1.43. Melanoma-specific mortality has decreased since 2012 (-0.07; p < 0.05). Declining invasive melanoma incidence and mortality rates in conjunction with the recent rise in MIS may reflect the impact of Iceland's sun safety and anti-sunbed educational campaigns, federal regulation of sunbeds and earlier melanoma detection in urban areas.

The benefit of sentinel lymph node biopsy in elderly patients with melanoma: A retrospective analysis of SEER Medicare data (2010-2018)

BackgroundSentinel lymph node status is critical for melanoma staging and treatment. However, the factors influencing SLNB and its oncologic benefits in elderly patients are unclear. MethodsWe conducted a retrospective analysis of patients aged ≥65 with clinically node-negative melanoma and Breslow depth ≥1 ​mm, using Surveillance, Epidemiology, and End Results Medicare database (2010–2018). Multivariable logistic regression assessed SLNB likelihood by demographic and clinical factors, and Cox-proportional hazard models evaluated overall and melanoma-specific mortality (MSM) for SLNB recipients versus non-recipients. ResultsOf 13,160 melanoma patients, 62.29 ​% underwent SLNB. SLNB was linked to reduced all-cause mortality (HR: 0.65 [95%CI 0.61–0.70]) and MSM (HR: 0.76 [95%CI 0.67–0.85]). Older age, non-White race, male sex, and unmarried status was associated with decreased SLNB likelihood, while cardiopulmonary, neurologic, and secondary cancer comorbidities were associated with increased SLNB likelihood. ConclusionsThough less frequently performed, SLNB is associated with lower mortality in elderly melanoma patients. Advanced age alone should not contraindicate SLNB.

Melanoma Deaths by Thickness: Most Melanoma Deaths Are Not Attributable to Thin Melanomas

IntroductionPrevious population-based studies have reported that the majority of melanoma mortality is related to patients with thin (≤1 mm Breslow thickness) melanomas. The aim of the present study was to evaluate the relative proportion of melanoma-specific deaths across all stages of melanoma at diagnosis over the past 20 y in the United States. MethodsA review of all cutaneous melanoma cases in the US Surveillance, Epidemiology, and End Results registry from 2004 to 2020 was performed. Breslow thickness was categorized as thin (≤1.0 mm), intermediate (>1-4 mm), or thick (>4 mm). All-cause deaths and melanoma-specific deaths were compared across tumor thickness and stage groups at diagnosis. Survival analysis was performed with nonmelanoma deaths considered as a competing risk to estimate the cumulative incidence of melanoma-specific death. ResultsMost melanoma deaths occurred in patients who initially presented with local disease (53%) compared to regional (36%) or distant (11%) disease (P < 0.001). However, most (66%) of the melanoma-specific deaths in patients who presented with localized disease were in those with intermediate or thick (i.e., Breslow thickness >1.0 mm) primary tumors compared to those with thin melanomas (34%). The cumulative incidence of melanoma-specific death at 10 y in patients with localized thin melanomas at the time of diagnosis was 2.6% (95% confidence intervals 2.5%-2.7%). ConclusionsThe public health burden in terms of melanoma-specific mortality is related to patients with tumors >1 mm Breslow thickness, many of whom have regional and distant metastatic disease at the time of diagnosis, not patients with thin melanomas.

Evaluation of a Population-Based Targeted Screening Approach for Skin Cancer with Long-Time Follow-Up in Austria including Potential Effects on Melanoma Mortality.

whether screening for skin cancer affects melanoma-specific mortality in a population-based setting remains unclear. in this population-based cohort study, we characterized and evaluated a skin cancer prevention program following a targeted screening approach conducted in 1989-1994 in the Austrian province Vorarlberg, with follow-up until 2019. The general population and attendees of a health examination program served for comparison. in the screening program including full follow-up until 2019, 207 invasive and 187 in situ melanomas were identified in 8997 individuals. Incidences of invasive and in situ melanomas were elevated compared to the general population (IRR 2.92, 95%-CI 2.49-3.41, and IRR 4.13, 95%-CI 3.53-4.83, respectively) and the health examination program (HR 3.02, 95%-CI 2.59-3.52, and HR 3.90, 95%-CI 3.30-4.61, respectively). Breslow thickness and Clark's level at time of invasive diagnosis were significantly lower in 1989-2019, but the tumor characteristics of the melanomas diagnosed during 1989-1994 did not differ from the comparison groups. Moreover, melanoma mortality was significantly elevated in the screening program (IRR 1.66, 95%-CI 1.00-2.75 vs. the general population, HR 2.12, 95%-CI 1.25-3.61 vs. the health examination cohort). Melanoma mortality in Vorarlberg declined until 2004, though statistically non-significantly. given the uncertain effectiveness and high public expenditures of population-wide mass screening programs, primary prevention and targeted risk-based skin cancer screening might be promising alternatives.

Abstract 806: Rural residence as a protective factor in melanoma mortality: Insights from a comprehensive analysis of 3,979 New Mexico cases (2010-2017)

Abstract Purpose: Cutaneous melanoma is a significant public health concern with increasing incidence rates over the past three decades. While survival rates have improved, disparities exist among racial/ethnic groups and socioeconomic factors. Our objective was to explore the connection between survival rates of cutaneous melanoma and demographic/socioeconomic factors in New Mexico's varied population, particularly in rural vs. urban settings. Methods: This retrospective study utilized data from the New Mexico Tumor Registry (NMTR) within the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. A total of 3,979 cases of cutaneous melanoma diagnosed between 2010 and 2017 among New Mexico residents were analyzed based on specific ICDO-3 criteria. The impact of demographic characteristics, socioeconomic factors, and stage at diagnosis on melanoma-specific mortality was investigated. Cases with incomplete data or where melanoma was not the primary cancer were excluded. Survival differences were assessed using Kaplan-Meier methods and the Cox Proportional Hazards Model, with analyses conducted with a significance threshold set at P=0.05. Only histologically confirmed melanoma cases were included in the study. Results: In our analysis of 3,979 melanoma cases spanning 2010 to 2017, non-Hispanic whites (NHW) displayed the highest incidence (n = 3,617, P &amp;lt; 0.001). Conversely, Hispanic Whites (HW) and American Indians (AI) exhibited a higher likelihood of later-stage diagnoses, with 19.2% of American Indians diagnosed at stage 3, in contrast to 3.9% of NHW and 10.3% of Hispanic Whites (P &amp;lt; 0.001). Rural areas showed a propensity for advanced-stage diagnoses (P &amp;lt; 0.001), and diagnosis stage exhibited an inverse relationship with per capita income (P &amp;lt; 0.001). Increased mortality was observed among males, individuals over 50, and American Indians (all P &amp;lt;0.05). Rural American Indian or Hispanic patients had a hazard ratio of mortality at 0.37 (95% CI, 0.15-0.89). An overall decline in melanoma mortality post-2012, with a notable reduction after mid-2015 (P &amp;lt; 0.001), despite a slight increase in diagnoses from 529 in 2010 to 569 in 2017 (P = 0.034) was observed. Sensitivity analyses revealed that rural residence among AI/Hispanic individuals was associated with a lower risk of melanoma-specific mortality (HR 0.37, p = 0.026 in the inclusive analysis; HR 0.36, p = 0.025 in the exclusion of in-situ cases). Conclusions: Our study indicates rural residency is associated with more advanced melanoma diagnoses and lower income correlates with later-stage diagnoses. However, rural living may offer a protective effect against mortality for American Indian/Hispanic populations. Overall mortality has declined since 2012, contrasting with a slight rise in diagnoses. Citation Format: Yeojin Park, Aaron Segura, Lynn Midani, Barbara Gutierrez, Larimar I. Rodriguez, Charles Wiggins, Vernon S. Pankratz, John R. Durkin. Rural residence as a protective factor in melanoma mortality: Insights from a comprehensive analysis of 3,979 New Mexico cases (2010-2017) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 806.

Lymphatic expression of the proliferation marker Ki67 is linked to sentinel node positivity, recurrence and mortality in primary cutaneous melanoma.

Lymphangiogenesis is a precursor to lymphovascular invasion, and may therefore signal a higher risk of metastasis and mortality in primary cutaneous melanoma. This retrospective longitudinal study aimed to evaluate whether emergent lymphangiogenesis, as measured through co-expression of endothelial proteins with the proliferation marker Ki67, was associated with poorer prognosis in a cohort of patients with single primary cutaneous melanoma. We screened all patients with a single locally invasive primary cutaneous melanoma who received sentinel lymph node biopsy at a tertiary dermatology centre in Brisbane, Australia between 1994 and 2007. Primary melanoma sections were stained via Opal multiplex immunofluorescence, and categorized according to the presence of Ki67 within either CD31+ or D2-40+ endothelial cells. Multivariate Cox regression modelling was used to evaluate associations between endothelial Ki67 positivity and clinical outcomes, with adjustment for age, sex, Breslow depth, ulceration, and anatomical location. Overall, 264 patients were available for analysis, with a median follow-up duration of 7.1 years. The presence of D2-40+ /Ki67+ co-expression was associated with greater melanoma-specific mortality (adjusted hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.33-3.10; p = 0.001) and recurrence (adjusted HR: 1.70; 95% CI: 1.33-3.10; p = 0.001) relative to absence. CD31+ /Ki67+ co-expression was not prognostic in this cohort. Lymphatic proliferation, as measured through D2-40+ /Ki67+ co-expression, predicted greater melanoma-specific mortality and recurrence in this cohort of primary cutaneous melanoma.

Persistent poverty and incidence-based melanoma mortality in Texas.

Previous studies have shown that individuals living in areas with persistent poverty (PP) experience worse cancer outcomes compared to those living in areas with transient or no persistent poverty (nPP). The association between PP and melanoma outcomes remains unexplored. We hypothesized that melanoma patients living in PP counties (defined as counties with ≥ 20% of residents living at or below the federal poverty level for the past two decennial censuses) would exhibit higher rates of incidence-based melanoma mortality (IMM). We used Texas Cancer Registry data to identify the patients diagnosed with invasive melanoma or melanoma in situ (stages 0 through 4) between 2000 and 2018 (n = 82,458). Each patient's PP status was determined by their county of residence at the time of diagnosis. After adjusting for demographic variables, logistic regression analyses revealed that melanoma patients in PP counties had statistically significant higher IMM compared to those in nPP counties (17.4% versus 11.3%) with an adjusted odds ratio of 1.35 (95% CI 1.25-1.47). These findings highlight the relationship between persistent poverty and incidence-based melanoma mortality rates, revealing that melanoma patients residing in counties with persistent poverty have higher melanoma-specific mortality compared to those residing in counties with transient or no poverty. This study further emphasizes the importance of considering area-specific socioeconomic characteristics when implementing place-based interventions to facilitate early melanoma diagnosis and improve melanoma treatment outcomes.

Association between dermatology follow-up and melanoma survival: A population-based cohort study

BackgroundGuidelines recommend that patients with melanoma undergo dermatologic examination at least annually. Adherence to follow-up and its impact on survival are unclear. ObjectiveTo determine the level of adherence to annual dermatologic follow-up in patients with primary cutaneous melanoma, identify predictors for better adherence, and evaluate whether adherence was associated with melanoma-related mortality. MethodsRetrospective inception cohort analysis of adults with primary invasive melanoma in Ontario, Canada from 2010-2013 with follow-up until December 31, 2018 ResultsAdherence to dermatologic follow-up was variable with only 28.0% of patients seeing a dermatologist at least annually (median follow-up 5.0 years). Younger age, female sex, higher income, greater access to dermatology care, stage 2/3 melanoma, prior keratinocyte carcinoma, fewer comorbidities, and any outpatient visit in the 12 months prior to melanoma diagnosis were predictors for adherence. Greater adherence to annual dermatology visits was associated with reduced melanoma-specific mortality compared with lower levels of adherence (adjusted hazard ratio 0.64, 95% CI 0.52-0.78). LimitationsObservational study design and inability to identify skin examinations performed by non-dermatologists ConclusionAdherence to annual dermatology visits after melanoma diagnosis was low. Greater adherence may promote better patient survival but warrants confirmation in further research including randomized trials.

Sentinel lymph node biopsy is unreliable in predicting melanoma mortality for both younger and older patients.

Melanoma disease patterns vary with patient age. To evaluate sentinel lymph node biopsy (SLNB) in managing melanoma at differing patient ages. Online prediction tools were applied to compare SLNB positivity (SLNB+) and survival risk at patient ages 20-80. Tübingen melanoma data were used to determine variations in the hazard ratio of SLNB+ for mortality at different patient ages. Regardless of tumour thickness, predicted SLNB+ rates were markedly higher than mortality rates for 20-year-old patients. For 80-year-old patients, it is the opposite. If 1000 20-year-olds with a 0.4 mm thickness non-ulcerated melanoma underwent SLNB, 100 would likely be positive. If all 100 were to be offered adjuvant drug therapy (ADT), fewer than three more melanoma deaths in those 1000 patients would be avoided. In total, 97 patients would have received medication they may never have needed. If 1000 80-year-olds with a 3 mm thickness non-ulcerated melanoma underwent SLNB, only 40 would likely be positive. In total, 274 patients would be predicted to die of melanoma, 245 being SLNB negative and 29 SLNB+. ADT linked to SLNB+ could deny treatment to 89% of these high-risk patients. The authors relied on published risk data. SLNB has poor specificity at predicting mortality in young melanoma patients and poor sensitivity in older patients. SLNB is not indicated in managing cutaneous melanoma for patients under 40 or over 60 years of age. Many such patients could be managed with wide local excision alone in their clinician's office-based practice. For all cutaneous melanoma patients at all ages, linking ADT to BAUSSS biomarker, (an algorithm of Breslow thickness, age, ulceration, subtype, sex and Site) rather than SLNB+ is likely more appropriate. BAUSSS provides a more accurate melanoma-specific mortality risk assessment for patients without burdening them with added surgery, hospitalization, costs or morbidity risk.

Rural Melanoma Patients Have Less Surgery and Higher Melanoma-Specific Mortality.

Melanoma causes most skin cancer-related deaths, and disparities in mortality persist. Rural communities, compared to urban, face higher levels of poverty and more barriers to care, leading to higher stage at presentation and shorter survival in melanoma. To further evaluate these disparities, we sought to assess the association between rurality and melanoma cause-specific mortality and receipt of recommended surgery in a national cohort. Patients with primary non-ocular, cutaneous melanoma from the SEER database, 2000-2017, were included. Outcomes included melanoma-specific survival and receipt of recommended surgery. Rurality was based on Rural-Urban Continuum Codes. Variables included age, sex, race, ethnicity, income, and stage. Multivariate regression models assessed the effect of rurality on survival and receipt of recommended surgery. 103,606 patients diagnosed with non-ocular cutaneous primary melanoma met criteria during this period. 93.3% (n = 96620) were in urban areas and 6.7% (n = 6986) were in rural areas. On multivariate regression controlling for age, sex, race, ethnicity, and stage patients living in a rural area were less likely to receive recommended surgery (aOR .52, 95% CI: .29-.90, P = .02) and had increased hazard of melanoma-specific mortality (aHR 1.19, 95% CI: 1.02-1.40, P = .03) even after additionally controlling for surgery receipt. Using a large national cohort, our study found that rural patients were less likely to receive recommended surgery and had shorter melanoma cause-specific survival. Our findings highlight the importance of access to cancer care in rural areas and how this ultimately effects survival for these patients.

Abstract 16756: Trends of Cardiovascular Deaths in Patients With Melanoma From 2005 to 2019: An Analysis Based on SEER Program Database

Introduction: Melanoma is the fifth most common cancer diagnosis in the United States. With recent advances in treatment modalities, including immune checkpoint inhibitors (ICIs), targeted therapies, there has been improvement in survival among melanoma patients. However, increasing resistance and treatment related adverse effects (TrAEs) are being reported including cardiovascular side effects. Objectives: To evaluate the trend of cardiovascular specific death rate among patients with melanoma. Methods: We used Surveillance, Epidemiology, and End Results (SEER) Program database 17 registries from 2000 to 2019 and SEER*Stat Version 8.4.1 software to analyze the data using the rate session. Joinpoint software, version 4.7.1.0 was used to create log-linear time trends annually. Results: Our study included 301,632 patients with melanoma from 2005 to 2019. The annual percentage change (APC) of melanoma was 0.46% (95% CI -1.45 to 1.07, p&gt;0.05) annually from 2005 to 2011 and 3.33% (95% CI 1.79 to 4.27, p&lt;0.05) annually from 2011 to 2014 and the incidence rate decreased by 0.06% (95% CI -1.44 to 0.5, p&gt;0.05) annually from 2014 to 2019. Melanoma specific mortality rate increased annually by 2.03 % (95% CI 0.78 to 3.94, P &lt;0.05) from 2005 to 2013 and decreased by 5.49% annually (95% CI -8.65 to -3.65, P &lt;0.05) from 2013 to 2019. Cardiovascular disease specific mortality rate increased by 7.08% annually (95% CI 4.66 to 9.64, P &lt;0.05) from 2005 to 2019. (Figure 1) Conclusion: Our study shows that there has been an annual increase in cardiovascular specific mortality rate from 2005 to 2019, while there was annual decrease in melanoma specific mortality rate from 2013 to 2019. Increase in cardiovascular specific death rates could be due to the direct toxicity of newer therapies and prolonged survival, which further could be due to advancement in diagnostics and newer therapies.

Stage-Specific Risk of Recurrence and Death From Melanoma in Denmark, 2008-2021

To ensure optimal treatment and surveillance of patients with melanoma, knowledge of the clinical stage-specific risk of recurrence, mortality, and recurrence patterns across the American Joint Committee on Cancer Eighth Edition (AJCC8) substages is needed. To estimate stage-specific recurrence and melanoma-specific mortality rates, assess absolute stage-specific risks of recurrence and mortality, and describe stage-specific recurrence patterns, including conditional rates. Retrospective cohort study of prospectively collected nationwide population-based registry data. Nationwide, population-based cohort study. The 25 720 Danish patients, 18 years or older, diagnosed with first-time stage IA to IV cutaneous melanoma between January 1, 2008, and December 31, 2019, were included and followed up from time of primary treatment until December 31, 2021. First diagnosis of stage IA to IV cutaneous melanoma. Stage-specific cumulative incidence of recurrence and melanoma-specific mortality, melanoma-specific recurrence-free survival, and assessed absolute stage-specific risks of recurrence and melanoma-specific mortality. Secondary outcomes were stage-specific recurrence patterns, including conditional rates, and melanoma-specific survival. We followed up 25 720 patients for a median of 5.9 years (95% CI, 58.9-59.3 years). Mean age was 59.1 years (95% CI, 58.9-59.3 years). Patients with stage IIB to IIC melanoma were older, had more comorbidities at diagnosis, and had the lowest rate of pathologic staging by sentinel node biopsy (81.6%-87.4%). A total of 10.6% of patients developed recurrence; first recurrence included distant recurrence, alone or with synchronous locoregional recurrence, in 56.6% of patients. We found a comparable risk of recurrence in stages IIIA and IIB (29.7% vs 33.2%) and in stages IIIB and IIC (35.9% vs 36.8%), respectively. Melanoma-specific mortality was comparable between stages IIIA and IIA (13.0% vs 13.6%) and between stages IIIB and IIB (18.4% vs 22.0%), respectively. These risk patterns persisted in cause-specific hazards models. This nationwide, population-based cohort study found that the increasing stages of the current AJCC8 staging system do not accurately reflect an increasing risk of recurrence and mortality in melanoma. The high proportion of distant recurrences suggests that hematogenous spread is a more common metastatic pathway than previously assumed, and surveillance with routine functional/cross-sectional imaging should be considered for stages IIB to IV. Future efforts should be put toward developing new tools for risk stratification and determining the survival effect of routine imaging in surveillance.

Disease-specific survival of malignant melanoma after Mohs micrographic surgery is not impacted by initial margins: A systematic review and meta-analysis

During Mohs surgery for melanoma, evidence has demonstrated that many surgeons opt for smaller initial margins than traditionally recommended (0.5cm for in situ and 1cm for invasive). Literature regarding surgical outcomes based on initial margin is sparse. To determine differences in disease-specific survival of melanoma after Mohs micrographic surgery for varied initial surgical margins. A literature search was conducted on February 14, 2022, from MEDLINE via PubMed (1946-present), Embase (1974-present), Central (1991-present), and Scopus (1960-present). The primary outcome was disease-specific mortality. Nineteen studies were included for final analysis. The overall disease-specific mortality rate of melanoma in all included studies was 0.5% (CI, 0.1-0.8; P, .010). Disease-specific mortality for 1 to 5, 5, and 6 to 10mm categories were 0.4% (CI, 0.0-0.9; P, .074), 0.7% (CI, 0.2-1.3; P, .2-1.3), and 0.4% (CI, -0.9 to 1.8; P, .524), respectively. None of the variances across initial margin categories were statistically significant. Early-stage melanomas have low overall mortality rates. In our associated article, initial margins of 5 to 10mm were shown to have the lowest rates of local recurrence. In this systematic review and meta-analysis, melanoma-specific mortality was not significantly impacted by the initial surgical margin taken during Mohs micrographic surgery.

Risk of Mortality After a Diagnosis of Melanoma In Situ

The incidence of melanoma in situ (MIS) is increasing more rapidly than any invasive or in situ cancer in the US. Although more than half of melanomas diagnosed are MIS, information about long-term prognosis following a diagnosis of MIS remains unknown. To evaluate mortality and factors associated with mortality after a diagnosis of MIS. This population-based cohort study of adults with a diagnosis of first primary MIS from 2000 to 2018 included data from the US Surveillance, Epidemiology, and End Results Program, which were analyzed from July to September 2022. Mortality after a diagnosis of MIS was evaluated using 15-year melanoma-specific survival, 15-year relative survival (ie, compared with similar individuals without MIS), and standardized mortality ratios (SMRs). Cox regression was used to estimate hazard ratios (HRs) for death by demographic and clinical characteristics. Among 137 872 patients with a first-and-only MIS, the mean (SD) age at diagnosis was 61.9 (16.5) years (64 027 women [46.4%]; 239 [0.2%] American Indian or Alaska Native, 606 [0.4%] Asian, 344 [0.2%] Black, 3348 [2.4%] Hispanic, and 133 335 [96.7%] White individuals). Mean (range) follow-up was 6.6 (0-18.9) years. The 15-year melanoma-specific survival was 98.4% (95% CI, 98.3%-98.5%), whereas the 15-year relative survival was 112.4% (95% CI, 112.0%-112.8%). The melanoma-specific SMR was 1.89 (95% CI, 1.77-2.02); however, the all-cause SMR was 0.68 (95% CI, 0.67-0.7). Risk of melanoma-specific mortality was higher for older patients (7.4% for those 80 years or older vs 1.4% for those aged 60-69 years; adjusted HR, 8.2; 95% CI, 6.7-10.0) and patients with acral lentiginous histology results (3.3% for acral lentiginous vs 0.9% for superficial spreading; HR, 5.3; 95% CI, 2.3-12.3). Of patients with primary MIS, 6751 (4.3%) experienced a second primary invasive melanoma and 11 628 (7.4%) experienced a second primary MIS. Compared with patients without a subsequent melanoma, the risk of melanoma-specific mortality was increased for those with a second primary invasive melanoma (adjusted HR, 4.1; 95% CI, 3.6-4.6) and was decreased for those with a second primary MIS (adjusted HR, 0.7; 95% CI, 0.6-0.9). The results of this cohort study suggest that patients with a diagnosis of MIS have an increased but low risk of melanoma-specific mortality and live longer than people in the general population, suggesting that there is significant detection of low-risk disease among health-seeking individuals. Factors associated with death following MIS include older age (≥80 years) and subsequent primary invasive melanoma.

Association of Excision Margin Size With Local Recurrence and Survival in Patients With T1a Melanoma at Critical Structures

Melanoma guidelines recommend surgical excision with 10-mm margins for T1 melanoma. However, this procedure may be problematic at sites close to critical structures such as the scalp, face, external genitalia, acral, periumbilical, and perineal areas. To compare outcomes of wide (10-mm margins) vs narrow (5-mm margins) excision in patients with T1a melanoma near critical structures. This cohort study was a retrospective comparison of 1341 consecutive patients aged 18 years or older from the National Cancer Institute of Milan, Italy, diagnosed between 2001 and 2020 with T1a cutaneous melanoma close to critical structures who accepted wide excision vs narrow excision. Local recurrence and melanoma-specific mortality (MSM) rates with 5-mm vs 10-mm excision margins. The primary aim of the study was to ascertain whether a narrower (5-mm) vs wider (10-mm) excision margin was associated with local recurrence and MSM. The secondary aim was to compare the need for reconstructive surgery in the groups defined by excision margin width. Between April 28 and August 7, 2022, associations were assessed by weighted Cox and Fine-Gray univariable and multivariable models. A total of 1179 patients met the inclusion criteria (median [IQR] age, 50.0 [39.5-63.0] years; female, 610 [51.7%]; male, 569 [49.3%]). Six hundred twenty-six patients (53.1%) received a wide excision (434 [69.3%] with linear repair and 192 [30.7%] with flap or graft reconstruction) and 553 (46.9%) received a narrow excision (491 [88.8%] with linear repair and 62 [11.2%] with flap or graft reconstruction). The weighted 10-year MSM was 1.8% (95% CI, 0.8%-4.2%) in the wide group and 4.2% (95% CI, 2.2%-7.9%) in the narrow group; the weighted 10-year local recurrence rate was 5.7% (95% CI, 3.9%-8.3%) in the wide group and 6.7% (95% CI, 4.7%-9.5%) in the narrow group. Breslow thickness greater than 0.4 mm (subdistribution hazard ratio [sHR] for 0.6 vs 0.4 mm, 2.42; 95% CI, 1.59-3.68; P < .001) and mitotic rate greater than 1/mm2 (sHR for a single increment, 3.35; 95% CI, 2.59-4.32; P < .001) were associated with worse MSM. Multivariable analysis showed that acral lentiginous melanoma, lentigo maligna melanoma, and increasing Breslow thickness were associated with a higher incidence of local recurrence. The study's findings suggest that local excision with 5-mm margins for T1a melanoma may not be associated with an increased risk of local recurrence. Breslow thickness greater than 0.4 mm, mitotic rate greater than 1/mm2, and acral lentiginous melanoma and lentigo maligna melanoma subtypes were associated with a higher risk of recurrence. These findings may be useful for future melanoma treatment guidelines.

Nevus Count, Pigmentary Characteristics, and Melanoma-specific Mortality among Norwegian Women with Melanoma >1.0 mm Thick.

Little is known about if and how nevi and pigmentation are associated with melanoma-specific mortality. However, increased melanoma awareness in people with lighter pigmentation and many nevi may result in earlier diagnosis of thinner less-lethal tumors. The aim of this study was to investigate associations between nevus count (asymmetrical > 5 mm and small symmetrical), pigmentary characteristics (hair colour, eye colour, skin colour, freckling, pigmentary score), and melanoma-specific mortality in subjects with melanomas > 1 mm. Data from the Norwegian Women and Cancer cohort, established in 1991, with complete follow-up of melanoma patients until 2018 through the Cancer Registry of Norway, were used to estimate hazard ratios with 95% confidence intervals for the associations between nevus count, pigmentary characteristics, and melanoma-specific mortality, stratified by tumor thickness using Cox regression. Estimated hazard ratios consistently indicated a higher risk of melanoma death for those with darker vs lighter pigmentary characteristics in patients with tumors > 1.0-2.0 mm and > 2.0 mm thick (e.g. pigmentary score hazard ratio 1.25, 95% confidence interval (0.74-2.13)). Among women with melanomas > 1.0 mm thick, lighter pigmentation and asymmetrical nevi may be associated with lower melanoma-specific mortality, suggesting that factors that increase the risk of melanoma may also be associated with decreased risk of death from melanoma.

Smoking is an Independent Marker of Poor Prognosis in Cutaneous Melanoma.

Previous studies have suggested that persistent tobacco smoking impairs survival in cutaneous melanoma, but the effects of smoking and other prognostic factors have not been described in detail. This study examined the association of smoking (persistent, former, or never) with melanoma-specific (MSS) and overall survival (OS) in patients with cutaneous melanoma treated in Southwest Finland during 2005 to 2019. Clinical characteristics were obtained from electronic health records for 1,980 patients. Smoking status was available for 1,359 patients. Patients were restaged according to the 8th edition of the tumour-node-metastasis (TNM) classification. Smoking remained an independent prognostic factor for inferior melanoma-specific survival regardless of age, sex, stage, and comorbidities. The hazard ratio of death from melanoma was 1.81 (1.27-2.58, p = 0.001) in persistent and 1.75 (1.28-2.40, p = 0.001) in former smokers compared with never smokers. In 351 stage IV patients, smoking was associated with increased melanoma-specific and overall mortality: median MSS 10.4 (6.5-14.3), 14.6 (9.1-20.1), and 14.9 (11.4-18.4) months, p = 0.01 and median OS 10.4 (6.5-14.3), 13.9 (8.6-19.2), and 14.9 (11.7-18.1) months, p = 0.01 in persistent, former, and never smokers, respectively. In conclusion, since smoking represents an independent modifiable poor prognostic factor in patients with cutaneous melanoma, smoking habits should be proactively asked about by healthcare professionals, in order to support smoking cessation.

Predictive accuracy of elevated mitotic rate on lymph node positivity and recurrence in thin melanomas.

Mitotic rate (MR) is considered an important prognostic factor for melanoma but is not currently used for staging because its nuanced effect is not yet well-delineated. We sought to determine if T category-specific MR is predictive of sentinel lymph node (SLN) positivity, recurrence, and melanoma-specific mortality (MSM). A retrospective review of patients with primary cutaneous melanoma from 1994 to 2020 at a single academic center was performed. Patient demographics and tumor characteristics were recorded. MR was considered elevated for each AJCC8-defined T category if it was ≥2 mitoses/mm2 for T1, ≥4 mitoses/mm2 for T2, ≥6 mitoses/mm2 for T3, or ≥7 mitoses/mm2 for T4. Statistical analysis was performed to assess the predictive accuracy of MR on selected outcomes while controlling for ulceration. Data from 2,984 patients with complete records were analyzed. Along with Breslow thickness and ulceration, elevated MR was associated with higher risk of MSM (HR 1.816, P=0.0001). There was no difference among patients with ulcerated T1 or T2 tumors regardless of MR, but those with non-ulcerated T1 or T2 tumors and elevated MR were more likely to have positive SLNs (P<0.0001 and P=0.0043, respectively) and recurrence (P=0.0007 and P=0.0004, respectively) compared to counterparts with low MR. There were no notable differences for T3 or T4 tumors based on MR. Elevated MR is associated with SLN positivity and recurrence in thin melanomas, independent of ulceration. SLN biopsy should therefore be strongly considered for patients with non-ulcerated lesions <0.8mm thick if the MR is ≥2 mitoses/mm2.

Disparities in melanoma incidence and mortality in rural versus urban Michigan.

We sought to identifying the possible existence of disparities between rural and urban residents of Michigan for the incidence by stage of disease and disease-specific mortality for cutaneous melanoma (CM). Incidence rates for stage of disease and disease-specific mortality of cutaneous melanoma were calculated and controlled for gender, age, and area of residence from January 1, 2014, to December 31, 2018, from data collected form the Michigan Department of Health and Human Services and the Centers for Disease Control and Prevention. The incidence rates for CM were significantly higher in rural Michigan counties, from 2014-2018, for all patients, both age groups, both genders and all stages. Melanoma-specific mortality rates were also significantly higher for all patients, both age groups and both genders in rural Michigan counties. Using logistic regression analysis, while controlling for age and gender, rural Michigan counties continued to have a higher melanoma-specific morality rate during our study period (OR=1.491; 95% CI, 1.27-1.74; p=<.001). We found significant disparities in the incidence rates and disease specific mortality for cutaneous melanoma in rural compared to urban Michigan from 2014-2018.

Disparities in melanoma-specific mortality by race/ethnicity, socioeconomic status, and health care systems

Despite encouraging trends in survival, sociodemographic inequalities persist among patients with melanoma. We sought to quantify the effect of race/ethnicity, socioeconomic status, and health care systems on melanoma-specific mortality within an insured population of patients. Using a retrospective cohort study, we identified insured adults diagnosed with Stage I to IV melanoma from January 1, 2009, to December 31, 2014, followed through 2017, from the California Cancer Registry. We compared melanoma-specific mortality between insured patients diagnosed within the largest vertically integrated health care system in California, Kaiser Permanente Southern California, and insured patients with other private insurance (OPI). Our cohort included 14,614 adults diagnosed with melanoma. Multivariable analyses demonstrated that race/ethnicity was not associated with survival disparities, while socioeconomic status was a strong predictor of melanoma-specific mortality, particularly for those with OPI. For example, hazard ratios demonstrate that the poorest patients with OPI have a 70% increased risk of dying from their melanoma compared to their wealthiest counterparts, while the poorest patients in Kaiser Permanente Southern California have no increased risk. Our main limitation includes inadequate data for certain racial/ethnic groups, such as Native Americans. Our findings underscore the persistence of socioeconomic disparities within an insured population, specifically among those in non-integrated health care systems.