Health Economic Consequences Associated With COVID-19-Related Delay in Melanoma Diagnosis in Europe.

Importance: The COVID-19 pandemic resulted in delayed access to medical care. Restrictions to health care specialists, staff shortages, and fear of SARS-CoV-2 infection led to interruptions in routine care, such as early melanoma detection; however, premature mortality and economic burden associated with this postponement have not been studied yet. Objective: To determine the premature mortality and economic costs associated with suspended melanoma screenings during COVID-19 pandemic lockdowns by estimating the total burden of delayed melanoma diagnoses for Europe. Design, Setting, and Participants: This multicenter economic evaluation used population-based data from patients aged at least 18 years with invasive primary cutaneous melanomas stages I to IV according to the American Joint Committee on Cancer (AJCC) seventh and eighth editions, including melanomas of unknown primary (T0). Data were collected from January 2017 to December 2021 in Switzerland and from January 2019 to December 2021 in Hungary. Data were used to develop an estimation of melanoma upstaging rates in AJCC stages, which was verified with peripandemic data. Years of life lost (YLL) were calculated and were, together with cost data, used for financial estimations. The total financial burden was assessed through direct and indirect treatment costs. Models were building using data from 50 072 patients aged 18 years and older with invasive primary cutaneous melanomas stages I to IV according to the AJCC seventh and eighth edition, including melanomas of unknown primary (T0) from 2 European tertiary centers. Data from European cancer registries included patient-based direct and indirect cost data, country-level economic indicators, melanoma incidence, and population rates per country. Data were analyzed from July 2021 to September 2022. Exposure: COVID-19 lockdown-related delay of melanoma detection and consecutive public health and economic burden. As lockdown restrictions varied by country, lockdown scenario was defined as elimination of routine medical examinations and severely restricted access to follow-up examinations for at least 4 weeks. Main Outcomes and Measures: Primary outcomes were the total burden of a delay in melanoma diagnosis during COVID-19 lockdown periods, measured using the direct (in US$) and indirect (calculated as YLL plus years lost due to disability [YLD] and disability-adjusted life-years [DALYs]) costs for Europe. Secondary outcomes included estimation of upstaging rate, estimated YLD, YLL, and DALY for each European country, absolute direct and indirect treatment costs per European country, proportion of the relative direct and indirect treatment costs for the countries, and European health expenditure. Results: There were an estimated 111 464 (range, 52 454-295 051) YLL due to pandemic-associated delay in melanoma diagnosis in Europe, and estimated total additional costs were $7.65 (range, $3.60 to $20.25) billion. Indirect treatment costs were the main cost driver, accounting for 94.5% of total costs. Estimates for YLD in Europe resulted in 15 360 years for the 17% upstaging model, ranging from 7228 years (8% upstaging model) to 40 660 years (45% upstaging model). Together, YLL and YLD constitute the overall disease burden, ranging from 59 682 DALYs (8% upstaging model) to 335 711 DALYs (45% upstaging model), with 126 824 DALYs for the real-world 17% scenario. Conclusions and Relevance: This economic analysis emphasizes the importance of continuing secondary skin cancer prevention measures during pandemics. Beyond the personal outcomes of a delayed melanoma diagnosis, the additional economic and public health consequences are underscored, emphasizing the need to include indirect economic costs in future decision-making processes. These estimates on DALYs and the associated financial losses complement previous studies highlighting the cost-effectiveness of screening for melanoma.

Quantitative associations between health insurance and stage of melanoma at diagnosis among nonelderly adults in the United States.

BACKGROUND: Health insurance plays a critical role in the accessibility to and quality of health care for patients with melanoma in the United States. Current knowledge regarding the association between insurance status and stage of melanoma is limited because few studies to date have simultaneously controlled for factors known to influence the risk of diagnosis of late-stage melanoma. The current study was conducted to examine the association between health insurance status and stage of melanoma at the time of diagnosis in nonelderly adults, accounting for known risk factors for late-stage diagnosis. METHODS: In this cross-sectional study, the authors analyzed the National Cancer Data Base for cases of invasive melanoma diagnosed between 2004 and 2015 among individuals aged 26 to 64 years. Using the American Joint Committee on Cancer melanoma staging system, early-stage melanoma was defined as stage I or stage II whereas late-stage melanoma was defined as stage III or stage IV. Late-stage diagnosis was the primary outcome compared across 4 insurance types (private, Medicaid, none, and unknown). Adjusted covariates were age, sex, race/ethnicity, educational level, income, year of diagnosis, number of comorbidities, and facility location. Logistic regression was used for univariable and multivariable analyses. RESULTS: Among 177,247 cases, individuals with Medicaid or no health insurance were found to have 3.12 (95% CI, 2.97-3.28) and 2.21 (95% CI, 2.10-2.33) times greater odds, respectively, of being diagnosed with late-stage melanoma compared with individuals with private insurance after adjusting for risk factors in late-stage diagnosis. CONCLUSIONS: Future investigation into insurance disparities in the diagnosis of late-stage melanoma may help to prioritize melanoma screening in populations with nonprivate insurance.

Complex General Surgical Oncology Fellowship Applicants: Trends over Time and the Impact of Board Certification Eligibility.

BACKGROUND: Complex general surgical oncology (CGSO) fellowships recently obtained Accreditation Council for Graduate Medical Education (ACGME) accreditation and board certification eligibility. We aimed to characterize the applicant pool and identify factors predictive of matching into our program. METHODS: We conducted a retrospective review of CGSO fellowship applications to a major cancer center from 2008 to 2018. Data were analyzed for trends over time, including a comparison of pre- versus post-American Board of Surgery (ABS) certification eligibility. RESULTS: A total of 846 applications were reviewed. Most applicants (86.2%) trained in a US residency program; 58.4% performed ≥ 1 research year during residency; 29.6% had a dual degree. Fewer applicants (34.5%) were female, a trend which did not change over time. Post-ABS, applicants were more likely to complete ≥ 1 year between residency and fellowship (20.9% versus 13.2%, p = 0.003), to be in practice at the time of application (12.2% versus 6.6%, p = 0.005), and to reapply (5.5% versus 1.0%, p < 0.001). Post-ABS applicants listed more peer-reviewed publications (8 [interquartile range (IQR) 4, 15] versus 5 [IQR 2, 10]; p < 0.001). On multivariable analysis, factors associated with matching into our program included: US allopathic medical school graduation [odds ratio (OR) 4.6, 95% confidence interval (CI) 1.8-11.7], Alpha Omega Alpha (AOA) Honor Medical Society distinction (OR 2.7, 95% CI 1.6-4.7), dual degree (OR 2.0, 95% CI 1.1-3.4), and performance of a clinical/research rotation at our institution (OR 4.9, 95% CI 2.2-10.7). CONCLUSIONS: After establishment of CGSO board certification eligibility, applicants were more likely to apply while in practice and to reapply. A number of factors, including having a dual degree and rotating at our institution, were associated with matriculation.

Critical Assessment of Clinical Prognostic Tools in Melanoma.

The 7th edition American Joint Committee on Cancer (AJCC) melanoma staging system classifies patients according to prognosis. Significant within-stage heterogeneity remains and the inclusion of additional clinicopathologic and other host- and tumor-based prognostic factors have been proposed. Clinical prognostic tools have been developed for use in clinical practice to refine survival estimates. Little is known about the comparative features of tools in melanoma. We performed a systematic search of the scientific published literature for clinical prognostic tools in melanoma and web-based resources. A priori criteria were used to evaluate their quality and clinical relevance, and included intended clinical use, model development approaches, validation strategies, and performance metrics. We identified 17 clinical prognostic tools for primary cutaneous melanoma. Patients with stages I-III and T1 or thin melanoma were the most frequently considered populations. Seventy-five percent of tools were developed using data collected from patients diagnosed in 2006 or earlier, and the well-established factors of tumor thickness, ulceration, and age were included in 70 % of tools. Internal validity using cross-validation or bootstrapping techniques was performed for two tools only. Fewer than half were evaluated for external validity; however, when done, the appropriate statistical methodology was applied and results indicated good generalizability. Several clinical prognostic tools have the potential to refine survival estimates for individual melanoma patients; however, there is a great opportunity to improve these tools and to foster the development of new, validated tools by the inclusion of contemporary clinicopathological covariates and by using improved statistical and methodological approaches.

Prospective assessment of lymphedema incidence and lymphedema-associated symptoms following lymph node surgery for melanoma.

We aimed to prospectively assess limb volume change (LVC) and associated symptoms in patients with melanoma undergoing sentinel lymph node biopsy and/or therapeutic lymph node dissection. Limb volume was measured preoperatively and postoperatively at 6 and 12 months using a perometer (1000 mol/l). LVC was calculated and used to define three groups: less than 5%, 5-10%, and greater than 10%. A 19-item lymphedema symptom questionnaire was administered at baseline, 6, and 12 months. One hundred and eighty-two patients were enrolled. Twelve months after axillary surgery, 9% had LVC 5-10% and 13% had LVC greater than 10%. Twelve months after inguinofemoral surgery, 10% had LVC 5-10% and 13% had LVC greater than 10%. There was a significant seven- to nine-fold increase in symptoms for patients with LVC greater than 10% compared with those with LVC less than 5% (P<0.05). On multivariate analysis, therapeutic lymph node dissection versus sentinel lymph node biopsy (odds ratio=3.18; P<0.01) and borderline significance for lower-extremity versus upper-extremity procedures (odds ratio=1.72; P=0.07) were associated with LVC greater than 5%. LVC greater than 5% is common at 12 months following nodal surgery for melanoma and is associated with symptoms. Informed consent for melanoma patients undergoing lymph node surgery should include a discussion of the risks of postoperative lymphedema.

Sentinel lymph node biopsy for melanoma: critical assessment at its twentieth anniversary.

The technique of lymphatic mapping and sentinel lymph node (SLN) biopsy was introduced 20 years ago as an important advance in the management of patients with stage I and II melanoma. After 2 decades of experience, SLN biopsy and the practice of selective lymphadenectomy represents a minimally invasive standard of care that facilitates the accurate staging of the clinically negative regional lymph node basin, provides durable regional disease control, and improves survival in node-positive patients.

Prospective assessment of postoperative complications and associated costs following inguinal lymph node dissection (ILND) in melanoma patients.

BACKGROUND: We prospectively assessed the incidence, risk factors, and costs associated with wound complications and lymphedema in melanoma patients undergoing inguinal lymph node dissection (ILND). MATERIALS AND METHODS: A total of 53 melanoma patients were accrued to 2 trials (June 2005 to July 2008) that included prospective evaluations of postoperative complications; 30-day wound complications included infection, seroma, and/or dehiscence. There were 20 patients who underwent limb volume measurement and completed a 19-item lymphedema symptom assessment questionnaire preoperatively and 3 months postoperatively. A multivariate analysis was performed to evaluate potential risk factors for complications. A microcosting analysis was also performed to evaluate the direct costs associated with wound complications. RESULTS: The 30-day wound complications were noted in 77.4% of patients. A BMI ≥ 30 (n = 28) increased the risk for wound complications (odds ratio [OR] = 11.4, 95% confidence interval [95%CI] 1.6-78.5, P = .01), while advanced nodal disease approached significance (OR = 9.0, 95%CI: 0.79-103.1, P = .08). Other risk factors, including diabetes, smoking, and the addition of a deep pelvic (iliac/obturator) dissection to ILND, were not significant. Of 20 patients, 9 (45%) developed limb volume change (LVC) ≥5% at 3 months, with associated mean symptom scores of 6.1 versus 4.6 for those without LVC. Costs for patients with wound complications were significantly higher than for those without wound complications. CONCLUSIONS: Postoperative wound complications and early onset lymphedema occur frequently following ILND for melanoma. Obesity is an adverse risk factor for 30-day wound complications that can significantly increase postoperative costs, as is likely the case for advanced disease. Risk reduction practices and novel treatment approaches are needed to reduce postoperative morbidity.

Fibrin sealant does not decrease seroma output or time to drain removal following inguino-femoral lymph node dissection in melanoma patients: a randomized controlled trial (NCT00506311).

BACKGROUND: This study assessed the impact of closed suction drains and evaluated whether the intraoperative use of a fibrin sealant decreased time to drain removal and wound complications in melanoma patients undergoing inguino-femoral lymph node dissection. METHODS: A pilot study (n = 18) assessed the impact of a closed suction drain following inguino-femoral lymph node dissection. A single-institution, prospective trial was then performed in which patients were randomized to a group that received intraoperative application of a fibrin sealant following inguino-femoral lymph node dissection or to a control group that did not receive sealant. RESULTS: The majority of the patients enrolled felt the drains caused moderate or severe discomfort and difficulties with activities of daily living. Thirty patients were then randomized; the median time to drain removal in the control group (n = 14) was 30 days (range, 13-74) compared to 29 days (range, 11-45) in the fibrin sealant group (n = 16; P = 0.6). Major and minor complications were similar in the two groups. CONCLUSION: Postoperative closed suction drains were associated with major patient inconvenience. Applying a fibrin sealant at the time of inguino-femoral lymph node dissection in melanoma patients did not reduce the time to drain removal or postoperative morbidity. Alternative strategies are needed.

Prospective assessment of the reliability, validity, and sensitivity to change of the Functional Assessment of Cancer Therapy-Melanoma questionnaire.

BACKGROUND: The authors previously developed a melanoma-specific module for the Functional Assessment of Cancer Therapy (FACT-Melanoma), a tool for the assessment of quality of life (QOL) in patients with melanoma. The reliability and validity of the FACT-Melanoma was examined in this study. METHODS: Patients with melanoma (N = 273; stages I-IV) completed a battery of questionnaires at the time of enrollment. The validity of the instrument was examined by comparing FACT-Melanoma scores with performance status, disease stage, treatment status, and other scales, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Melanoma Module, the Profile of Mood States, and the Marlowe-Crowne Social Desirability Scale. Patients were assessed after 1 week to assess test-retest reliability and at 3 months to determine the sensitivity of the instrument to change in performance status. RESULTS: The internal consistency and test-retest reliability (r) of the melanoma subscale (Cronbach alpha = .85; r = .81) and the total FACT-Melanoma (alpha = .95; r = .90) were excellent. Overall, the scales were correlated with other measures, as anticipated. Total FACT-Melanoma scores, along with scores for physical well-being, emotional well-being, functional well-being, and melanoma-specific scales, were lower for patients with advanced (stage III/IV) melanoma, poor performance status, and patients who were receiving active treatment. The FACT-Melanoma total score and the score for physical well-being were sensitive to changes in performance status (P = .0012 and P = .004, respectively). CONCLUSIONS: The results of the current study indicated that the FACT-Melanoma questionnaire is a reliable and valid instrument for patients with melanoma that can be used for the assessment of QOL in clinical trials.

Cost effectiveness of adjuvant interferon in node-positive melanoma.

PURPOSE: To assess the benefits of adjuvant high-dose interferon alfa (HDI) treatment for patients with high-risk melanoma. METHODS: We designed a decision-analytic probabilistic Markov model to simulate the natural history of patients with stage IIIA, IIIB, and IIIC melanoma and evaluate the outcomes with and without HDI treatment. Outcomes were in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Probability estimates and costs were derived from primary patient level data, while the efficacy of HDI and associated utilities were determined from published reports. The base-case analysis was a cohort of 50-year-old patients. RESULTS: HDI increased the median life expectancy in patients with stage III melanoma from 3.75 years in the observation cohort to 4.42 years in the HDI cohort. The difference in QALYs ranged from 0.31 years for stage IIIA patients to 0.60 years for stage IIIC patients treated with HDI. HDI was cost effective in patients with stage IIIB and IIIC melanoma, with ICERs of $95,304 and $76,068 per QALY gained, respectively. Using a threshold of $100,000 per QALY gained, HDI was cost effective for all stage III patients younger than 52 years. HDI was not cost effective for patients with stage IIIA disease and for subsets of patients older than 63 years with stage IIIB disease. CONCLUSION: Our model demonstrates that the probability of HDI being cost effective varies substantially by melanoma substage. HDI showed the greatest benefit in terms of QALYs and was most cost effective in patients younger than 60 years with stage IIIC disease.

Assessment of the role of sentinel lymph node biopsy for primary cutaneous desmoplastic melanoma.

BACKGROUND: The role of sentinel lymph node biopsy (SLNB) in the treatment of desmoplastic melanoma (DM) remains undefined. The purpose of this study was to evaluate the use of SLNB for DM. METHODS: In all, 1850 patients with cutaneous melanoma underwent wide local excision and SLNB. Patients with DM were identified and stratified as 'pure' DM or 'mixed' DM (i.e., DM associated with at least one other common histologic subtype). RESULTS: Of the 1850 patients, 65 (3.5%) had DM. Of these, 46 (70.8%) had pure DM and 19 (29.2%) had mixed DM. Patients with pure DM had a median tumor thickness of 3.5 mm and 6.5% were ulcerated. Compared with patients with pure DM, patients with either mixed DM or non-DM (n = 1785) had thinner primary tumors (median, 1.7 mm and 1.5 mm, respectively, each P < 0.001 vs. pure DM) that were more likely to be ulcerated (27.7% and 21.3%, respectively, each P < 0.05 vs. pure DM). Although the incidence of a positive SLN was similar in patients with mixed DM (15.8%) and non-DM (17.5%), patients with pure DM were less likely to have a positive SLN (2.2%) (each P < 0.01 vs. non-DM and mixed DM). At a median follow-up of 2.9 years, no patient with pure DM had recurred. CONCLUSIONS: Despite having thicker primary tumors, patients with pure DM have a lower incidence of positive SLNs compared with patients with non-DM. Whereas the treatment approach for patients with mixed DM should be similar to that of other melanoma patients, patients with pure DM are unlikely to have metastatic disease in regional lymph nodes and SLNB may not be warranted.

Population-based assessment of surgical treatment trends for patients with melanoma in the era of sentinel lymph node biopsy.

PURPOSE: The surgical staging of melanoma dramatically changed with the introduction of sentinel lymph node (SLN) biopsy. In this study, Surveillance, Epidemiology, and End Results (SEER) data were examined to determine how surgical treatment is being carried out and whether SLN biopsy is being performed in melanoma patients in conformance with National Comprehensive Cancer Network (NCCN) guidelines. PATIENTS AND METHODS: The SEER database (1998 to 2001) was searched for all patients with invasive melanoma. NCCN guidelines were used to define optimal stage-specific surgical treatment. Treatment trends in patients with stages I to III disease were summarized, and multivariate analyses were performed to identify factors associated with nonadherence with treatment guidelines. RESULTS: A total of 21,867 melanoma patients were identified; 18,499 of these patients met the inclusion criteria. The number of patients diagnosed with stage III melanoma increased by 55.7% over the study period, and this corresponded to a 53% increase in the number of SLN biopsies performed annually. The odds ratios for nonadherence were 2.32, 2.27, and 1.54 for stages IB, II, and III disease, respectively, compared with stage IA melanoma. Multivariate analyses revealed that age more than 65 years, marital status, minority populations, and primary tumor location were associated with nonadherence with guidelines. Treatment patterns among tumor registries also varied significantly. CONCLUSION: Stage migration is evident in the SEER registries in consort with increasing use of SLN biopsy. Although treatment trends are improving, SLN biopsy continues to be underused, particularly in the elderly and minority populations, in patients with truncal and head/neck melanomas, and also in some geographic regions of the United States.

A critical assessment of adjuvant radiotherapy for inguinal lymph node metastases from melanoma.

BACKGROUND: Although patients with inguinal or pelvic lymph node (LN) metastases from melanoma may develop regional recurrence after dissection, the role of adjuvant radiotherapy remains controversial. METHODS: The medical records of 40 patients with inguinal and/or pelvic lymph node metastases from melanoma were reviewed retrospectively. Indications for adjuvant radiotherapy included the following nodal characteristics: extracapsular extension, LNs > or =3 cm in diameter, > or =4 involved LNs, and LN recurrence after prior nodal surgery. Thirty-seven of 40 patients underwent formal LN dissection. Three patients had only local excision of gross disease for recurrence after prior dissection. All patients received radiation to a median dose of 30 Gy at six Gy/fraction delivered twice weekly. RESULTS: With a median follow-up time of 22.5 months, the 3-year actuarial distant metastasis-free and overall survival rates were 35% and 38%, respectively. The 3-year regional control rate was 74%. Univariate analyses of patient, tumor, and treatment characteristics failed to reveal any association with distant metastasis-free survival, overall survival, or regional control. Regional failures occurred in nine patients; seven of these were isolated dermal failures within the field of irradiation. Only two patients (5%) had LN basin recurrences; one of these patients also developed dermal recurrence. Fifteen of 40 patients developed lymphedema; in seven of these, lymphedema was present before initiation of radiation therapy. CONCLUSIONS: Radiation may prevent recurrence of nodal disease in patients at high risk for regional failure, but in-field dermal recurrences may sometimes occur (8 of 40, 20%). Treatment-related lymphedema and death from metastatic melanoma were common.