Incidence and mortality trends of primary cutaneous melanoma: A 50-year Rochester Epidemiologic Project study.

Background: National cancer reporting-based registry data, although robust, lacks granularity for incidence trends. Expert opinion remains conflicted regarding the possibility of melanoma overdiagnosis in the context of rising incidence without a corresponding rise in mortality. Objective: To characterize 10- and 50-year trends in melanoma incidence and mortality. Methods: Multicenter, population-based epidemiologic study utilizing the Rochester Epidemiology Project for Olmsted County, Minnesota residents diagnosed with melanoma from 01/01/1970 to 12/21/2020. Age- and sex-adjusted incidence and disease-specific mortality are calculated. Results: Two thousand three hundred ten primary cutaneous melanomas were identified. Current age- and sex-adjusted incidence rates increased 11.1-fold since 1970s (P < .001). Over the last decade, there is an overall 1.21-fold (P < .002) increase, with a 1.36-fold increase (P < .002) among females and no significant increase among males (1.09-fold increase, P < .329). Melanoma-specific mortality decreased from 26.7% in 1970s to 1.5% in 2010s, with a hazard ratio (HR) reduction of 0.73 (P < .001) per 5-year period. Increased mortality was associated with Breslow thickness (HR 1.35, P < .001), age at diagnosis (HR 1.13, P = .001) left anatomic site (HR 1.98, P = .016), and nodular histogenic subtype (HR 3.08, P < .001). Limitations: Retrospective nature and focused geographic investigation. Conclusion: Melanoma incidence has continued to increase over the past decade, most significantly in females aged 40+. Trend variations among age and sex cohorts suggests external factors beyond overdiagnosis may be responsible. Disease-specific mortality of melanoma continues to decrease over the last 50 years.

The Impact of Surgical Delay in Primary Cutaneous Melanoma: A Systematic Review.

BACKGROUND AND OBJECTIVES: The prognosis of patients diagnosed with melanoma is highly dependent on staging, early detection, and early intervention. In this systematic review, the authors aimed to investigate the impact of surgical delay (time between diagnostic biopsy and definitive surgical excision) on melanoma-specific outcomes. MATERIAL AND METHODS: A systematic review was conducted from Embase (1974-present), MEDLINE (1946-present), Cochrane Central Register of Controlled Trials (2005-present), Scopus, and Web of Science. A total of 977 studies were included for review after removal of duplicates. A total of 10 studies were included for final analysis. RESULTS: In total, 70% (7/10) of the studies found that longer wait times between initial biopsy and surgical intervention are correlated with lower overall survival. Among the 9 studies that reported overall survival as a percentage, the median and SD overall survival was 82% ± 5.87. CONCLUSION: There is evidence that prolonged surgical delay in patients diagnosed with Stage I cutaneous melanoma is associated with worsened overall mortality, whereas the effect of surgical delay on overall mortality in Stages II and III melanomas is uncertain. Future prospective studies and randomized clinical trials are needed to better define the appropriate surgical wait times between biopsy and surgical treatment.

Cost-effectiveness analysis of margin-controlled surgery for vulvar Paget's disease.

Objectives: To determine the cost of two surgical treatment approaches for vulvar Paget's disease and model the cost-effectiveness considering differences in recurrence and reoperation over time. Methods: We assessed cost-effectiveness between excision guided by Mohs micrographic surgery (MMS-E) and traditional wide local excision (WLE). We examined billing data from patients with vulvar Paget's disease who underwent MMS-E (cases, n = 24, 2018-2022) or WLE (controls, n = 64, 1990-2020). We created typical treatment bundles incorporating physician-administered services and facility costs standardized to Medicare reimbursements in 2022 United States Dollars (USD). The primary measure of effectiveness was disease-free years of life. A secondary analysis estimated quality-adjusted life years (QALY). A Markov model simulated treatment pathways over a 10-year time horizon. Transition probabilities were based on institutional recurrence rates (3-year RR 6.7 % for MMS-E vs 34.1 % for WLE). We used a willingness-to-pay threshold of 100,000 USD per QALY. Results: The cost of a single surgical episode was 34,664 USD for MMS-E and 14,969 USD for WLE. In the setting of lower recurrence rates with MMS-E, the incremental cost was 12,789 USD per disease-free year gained. A secondary analysis incorporating QALY showed an incremental cost of 72,820 USD per QALY. Conclusions: MMS-E appears to be a cost-effective treatment for vulvar Paget's disease compared to historic standard of care. Our ability to estimate quality of life gained by avoiding disease recurrence was limited by scant data for this rare condition; thus, future studies incorporating health utility values are needed to facilitate a more comprehensive analysis.

Intraoperative Immunohistochemistry During Mohs Micrographic Surgery and Staged Excision Decreases Local Recurrence Rates for Invasive Cutaneous Melanoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Mohs micrographic surgery (MMS) is increasingly used to treat cutaneous melanoma. However, it is unclear whether intraoperative immunohistochemistry (IHC) improves surgical outcomes. OBJECTIVE: To determine whether intraoperative IHC during MMS and staged excision is associated with a decreased risk of poor surgical outcomes. MATERIALS AND METHODS: Search of 6 databases identified comparative and noncomparative studies that reported local recurrence after MMS or staged excision with or without IHC for melanoma. Random-effects meta-analysis was used to estimate pooled local recurrence rates, nodal recurrence, distant recurrence, and disease-specific mortality. RESULTS: Overall, 57 studies representing 12,043 patients with cutaneous melanoma and 12,590 tumors met inclusion criteria. Combined MMS and staged excision with IHC was associated with decreased local recurrence in patients with invasive melanoma (0.3%, 95% CI: 0-0.6) versus hematoxylin and eosin alone (1.8%, 95% CI: 0.8%-2.8%) [ p < .001]. Secondary outcomes including nodal recurrence, distant recurrence, and disease-specific mortality were not significantly different between these 2 groups. Study heterogeneity was moderately-high. CONCLUSION: Local recurrence of invasive melanoma is significantly lower after MMS and staged excision with IHC as opposed to without IHC. These findings suggest that the use of intraoperative IHC during MMS or staged excision should strongly be considered, particularly for invasive melanoma.Trial Registration PROSPERO Identifier: CRD42023435630.

Disease-Specific Mortality of Dermatofibrosarcoma Protuberans After Mohs Surgery Versus Wide Local Excision: A Systematic Review and Meta-Analysis.

BACKGROUND: Although advances have been made in the understanding of recurrence patterns in dermatofibrosarcoma protuberans, the current understanding of disease-specific mortality after surgical management is limited. OBJECTIVE: To understand disease-specific mortality rates associated with dermatofibrosarcoma protuberans treated with wide local excision (WLE) versus Mohs micrographic surgery (MMS). MATERIALS AND METHODS: A systematic literature search was conducted on March 6, 2023, to identify patients treated with MMS or WLE for dermatofibrosarcoma protuberans. RESULTS: A total of 136 studies met inclusion criteria. Overall, the disease-specific mortality rate was not significantly different after treatment with MMS (0.7%, confidence interval [CI] 0.1-1.2, p : 0.016) versus WLE (0.9%, CI 0.6-1.2, p < .001). For recurrent tumors, the MMS treatment group had a statistically significantly lower disease-specific mortality rate (1.0%, CI 0.0-2.0, p 0.046) compared with the WLE treatment group (3.5%, CI 2.0-5.1, p < .001). The mean follow-up for all studies was 57.6 months. CONCLUSION AND RELEVANCE: The authors' meta-analysis suggests there is no substantial difference in disease-specific mortality between MMS and WLE in patients with dermatofibrosarcoma protuberans, except in the case of recurrent tumors, where MMS seems to confer a survival advantage.

Identifying critical quality metrics in Mohs Surgery: A national expert consensus process.

BACKGROUND: Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. OBJECTIVE: The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. METHODS: Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. RESULTS: Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. LIMITATIONS: Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. CONCLUSION: With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.

Increasing Incidence and Decreasing Mortality of Melanoma in Elderly Adults: An Epidemiologic Study in Olmsted County, Minnesota.

BACKGROUND AND OBJECTIVE: Primary cutaneous melanoma incidence is increasing in elderly individuals. This population-based cohort examines incidence and mortality rates among adults aged 61 years and older with cutaneous melanoma. MATERIALS AND METHODS: Using the Rochester Epidemiology Project, patients aged 61 years of age or older with a first lifetime diagnosis of cutaneous melanoma between January 1, 1970 and December 31, 2020 were identified. RESULTS: The age- and sex-adjusted incidence rate increased from 16.4 (95% CI, 8.2-24.6) per 100,000 person-years in 1970 to 1979 to 201.5 (95% CI, 185.1-217.8) per 100,000 person-years in 2011 to 2020 (12.3-fold increase). There was a 16.0x increase in males and an 8.5× increase in females. Melanoma incidence has stabilized in males (1.2-fold increase, p = .11) and continues to significantly increase in females (2.7-fold increase, p < .001). Older age at diagnosis was significantly associated with an increased risk of death (HR 1.23 per 5-year increase in age at diagnosis, 95% CI, 1.02-1.47). CONCLUSION: Melanoma incidence continues to increase since 1970. The incidence has risen in elderly females, but has stabilized in males. Mortality has decreased throughout this period.

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

Background: During Mohs surgery for melanoma, evidence has demonstrated that many surgeons opt for smaller initial margins than traditionally recommended (0.5 cm for in situ and 1 cm for invasive). Literature regarding surgical outcomes based on initial margin is sparse. Objective: To determine differences in disease-specific survival of melanoma after Mohs micrographic surgery for varied initial surgical margins. Methods: 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. Results: 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 10 mm 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. Limitations: Early-stage melanomas have low overall mortality rates. In our associated article, initial margins of 5 to 10 mm were shown to have the lowest rates of local recurrence. Conclusions: In this systematic review and meta-analysis, melanoma-specific mortality was not significantly impacted by the initial surgical margin taken during Mohs micrographic surgery.

Mohs surgery for female genital Paget's disease: a prospective observational trial.

BACKGROUND: Extramammary Paget's disease recurs often after traditional surgical excision. Margin-controlled surgery improves the recurrence rate for male genital disease but is less studied for female anatomy. OBJECTIVE: This study aimed to compare surgical and oncologic outcomes of margin-controlled surgery vs traditional surgical excision for female genital Paget's disease. STUDY DESIGN: We conducted a prospective observational trial of patients with vulvar or perianal Paget's disease treated with surgical excision guided by Mohs micrographic surgery between 2018 and 2022. The multidisciplinary protocol consisted of office-based scouting biopsies and modified Mohs surgery followed by surgical excision with wound closure under general anesthesia. Modified Mohs surgery cleared peripheral disease margins using a moat technique with cytokeratin 7 staining. Medial disease margins (the clitoris, urethra, vagina, and anus) were assessed using a hybrid of Mohs surgery and intraoperative frozen sections. Surgical and oncologic outcomes were compared with the outcomes of a retrospective cohort of patients who underwent traditional surgical excision. The primary outcome was 3-year recurrence-free survival. RESULTS: Three-year recurrence-free survival was 93.3% for Mohs-guided excision (n=24; 95% confidence interval, 81.5%-100.0%) compared to 65.9% for traditional excision (n=63; 95% confidence interval, 54.2%-80.0%) (P=.04). The maximum diameter of the excisional specimen was similar between groups (median, 11.3 vs 9.5 cm; P=.17), but complex reconstructive procedures were more common with the Mohs-guided approach (66.7% vs 30.2%; P<.01). Peripheral margin clearance was universally achieved with modified Mohs surgery, but positive medial margins were noted in 9 patients. Reasons included intentional organ sparing and poor performance of intraoperative hematoxylin and eosin frozen sections without cytokeratin 7. Grade 3 or higher postoperative complications were rare (0.0% for Mohs-guided excision vs 2.4% for traditional excision; P=.99). CONCLUSION: Margin control with modified Mohs surgery significantly improved short-term recurrence-free survival after surgical excision for female genital Paget's disease. Use on medial anatomic structures (the clitoris, urethra, vagina, and anus) is challenging, and further optimization is needed for margin control in these areas. Mohs-guided surgical excision requires specialized, collaborative care and may be best accomplished at designated referral centers.

Psoriasis Patients Treated With Methotrexate Have an Increased Risk of Nonmelanoma Skin Cancer: A Systematic Review and Meta-Analysis.

Both psoriasis and methotrexate are associated with an increased risk of nonmelanoma skin cancer. The effect of methotrexate on the development of nonmelanoma skin cancer in patients with psoriasis is currently unknown. To evaluate this relationship, a systematic review of the literature was conducted using databases including Ovid Medline (from 1946), Scopus (from 1970), and Embase (from 1974) through June 2019. Observational comparative and case-control studies comparing psoriasis patients treated with methotrexate to those not treated with methotrexate with data on the subsequent development of nonmelanoma skin cancer in both cohorts were included based on prespecified criteria. Two reviewers analyzed all studies for relevant data, which were analyzed using OpenMeta-Analyst statistical software. Quality was assessed with the Newcastle-Ottawa method. Nine cohort and case-control comparative studies of 1,486 screened abstracts met the inclusion criteria. Of 11,875 reported patients with psoriasis, 2,192 were taking methotrexate. A meta-analysis demonstrated an odds ratio of 2.8 (95% confidence interval = 1.47-5.39; p = 0.002) for nonmelanoma skin cancer development in patients with psoriasis taking methotrexate compared with those not taking methotrexate. Based on these findings, psoriasis patients treated with methotrexate are at a significantly increased (2.8 times higher) risk of developing nonmelanoma skin cancer. Risk counseling can improve healthcare outcomes in patients with psoriasis.

Increasing Incidence and Decreasing Mortality of Cutaneous Melanoma in Middle-Aged Adults: An Epidemiologic Study in Olmsted County, Minnesota.

OBJECTIVE: To identify changes in the incidence and mortality of cutaneous melanoma in the fastest-growing segment of the US population, middle-aged adults. PATIENTS AND METHODS: Using the Rochester Epidemiology Project, patients aged 40 to 60 years with a first lifetime diagnosis of cutaneous melanoma between January 1, 1970, and December 31, 2020, while a resident of Olmsted County, Minnesota, were identified. RESULTS: A total of 858 patients with a primary cutaneous first-time melanoma were identified. The overall age- and sex-adjusted incidence rate increased from 8.6 (95% CI, 3.9 to 13.3) per 100,000 person-years in 1970-1979 to 99.1 (95% CI, 89.5 to 108.7) per 100,000 person-years in 2011-2020 (11.6-fold increase). There was a 52.1-fold increase in women and a 6.3-fold increase in men between these 2 periods. In recent years (2005-2009 vs 2015-2020), the incidence has stabilized in men (1.01-fold increase; P=.96) and continues to significantly increase in women (1.5-fold increase; P=.002). Among 659 patients with invasive melanoma, 43 deaths were due to melanoma, and male sex was significantly associated with an increased risk of death (hazard ratio, 2.95; 95% CI, 1.45 to 6.00). A more recent diagnosis of melanoma was significantly associated with a decreased risk of death due to melanoma (hazard ratio, 0.66 per 5-year increase in calendar year of diagnosis; 95% CI, 0.59 to 0.75). CONCLUSION: Melanoma incidence has significantly increased since 1970. During the past 15 years, the incidence has continued to rise in middle-aged women (approximately 50% rise in incidence) but has stabilized in men. Mortality decreased in a linear fashion throughout this time.

Local Recurrence Rates of Malignant Melanoma After Mohs Micrographic Surgery Are Lowest With 5- to 10-mm Initial Margins: A Systematic Review and Meta-Analysis.

BACKGROUND: Current consensus guidelines have discouraged the use of sub-0.5-cm (in situ) and sub-1-cm (invasive) margins when performing Mohs micrographic surgery (Mohs) for melanoma, with minimal evidence to guide this recommendation. OBJECTIVE: To compare melanoma local recurrence rates after Mohs based on initial margin size. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted with search terms including Mohs micrographic surgery, surgical margin, recurrent disease, and melanoma. RESULTS: Forty-three studies were included. The 5- to 10-mm margin category had a statistically significant lower local recurrence compared with 1- to 5-mm and 5-mm categories. Recurrence for 1- to 5-mm, 5-mm, 5- to 10-mm, and 10-mm categories were 2.3% (CI 0.8-3.5, p < .001), 1.4% (CI 0.6-2.2, p < .001), 0.3% (CI 0.2-0.5, p < .001), and 6.1% (CI -6.7 - 18.8, p = .349), respectively. Number of stages for 1 to 5, 5, 5 to 10, and 10-mm categories were 1.8, 1.8, 1.6, and 1.6, respectively. There was no statistically significant difference between the groups (p = .694). CONCLUSION: Five- to 10-mm margins were associated with the lowest local recurrence rates. A 5- to 10-mm initial margin should be considered where other factors (tumor characteristics, anatomical or functional considerations) allow.

Local Recurrence Rates of Extramammary Paget Disease Are Lower After Mohs Micrographic Surgery Compared With Wide Local Excision: A Systematic Review and Meta-Analysis.

BACKGROUND: Extramammary Paget disease (EMPD) is a rare, slow growing neoplasm that presents most commonly in the anogenital region of older adults. OBJECTIVE: To analyze the difference in local recurrence rates of EMPD in patients treated with wide local excision (WLE) versus Mohs micrographic surgery (MMS). MATERIALS AND METHODS: A systematic review of the literature and meta-analysis were performed. Inclusion criteria were adults greater than 18 years of age with a diagnosis of EMPD who have undergone surgical intervention and had follow-up data. Studies were independently reviewed by 2 coinvestigators with discrepancies resolved by the principal investigator. RESULTS: Twenty-seven studies met the inclusion criteria. Patients had a 2.67 times higher chance of local recurrence after WLE than MMS (95% confidence interval [CI]:1.47, 4.85; p = .001). Meta-analysis of single-arm studies revealed a 7.3% local recurrence rate after MMS (95% CI: 0.039, 0.107; p < .001) versus a 26.3% recurrence rate after WLE (95% CI: 0.149, 0.376; p < .001). After excluding recurrent tumors, the odds ratio for recurrence in WLE versus MMS was 2.3 (95% CI: 0.285, 18.43, p = .435). CONCLUSION: There is a clinically and statistically increased risk of local recurrence of EMPD after WLE compared with MMS.