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.

The management of patients with cancer of unknown primary in middle-income countries: an ESO-AROME survey.

Aim: To report on the management strategies in patients with cancer of unknown primary (CUP) in middle-income countries. Methods: We conceived a survey of 20 items concerning the management of patients with CUP in daily clinical practice. Only participants from lower- and higher-middle-income countries, as per the World Bank Classification, were eligible for this study. Results: The indications for the first-line treatment did not differ between the two economic regions, whereas those for second-line treatment were more prevalent in higher-middle-income countries. The use of targeted therapy based on immunohistochemistry alone was higher in lower-middle-income countries, although the access to CUP classifiers was similar between the two regions. Conclusions: Proper recommendations must ensure that the economic burden is minimized and that other benefits outweigh the limited survival benefit achieved in patients with CUP.

In patients with unprovoked VTE, does the addition of FDG PET/CT to a limited occult cancer screening strategy offer good value for money? A cost-effectiveness analysis from the publicly funded health care systems.

INTRODUCTION: Unprovoked venous thromboembolism (VTE) may be the first manifestation of an undiagnosed cancer. We assessed the cost-effectiveness of 18F-Fluorodesoxyglucose Positron Emission/Computed Tomography (FDG PET/CT) plus limited screening and limited screening strategies in patients with unprovoked VTE from the perspectives of the Ontario (Canada) and French health care systems. METHODS: We conducted a cost-effectiveness analysis based on a published randomized controlled trial of 394 patients aged 18 years or older who were diagnosed with unprovoked VTE. We obtained data with respect to efficacy and health care utilization from the published trial. The primary measure of effectiveness was the number of avoided cases of delayed cancer diagnosis and the secondary measure of effectiveness was the quality adjusted life year (QALY) at the end of the study in each group. We used generalized linear models to estimate incremental cost-effectiveness ratios (ICER) while controlling for patient demographic and clinical characteristics. Results were presented as the incremental cost to avoid one case of delayed cancer diagnosis and the incremental cost per QALY gained. The 95% confidence intervals (CIs) were estimated using bootstrap re-sampling procedures with 5000 iterations. RESULTS: Compared to a limited screening strategy, the ICER of limited strategy plus FDG PET/CT scan was C$ 26,840.19 (95% CI: C$ 24,046.51; C$ 34,581.53) per one avoided case of delayed cancer diagnosis from the Ontario health system perspective and €16,370.45 (95% CI: € 9904.48; € 39,578.91) per one avoided case of delayed cancer diagnosis from the French health system perspective. The probabilities that addition of FDG PET/CT to limited screening is cost-effective rose with increasing willingness to pay values. Compared with the limited screening, the extensive screening was associated with C$ 3412.85 per QALY gained (95% CI: 1463.89; -13,935.88) from the Ontario health system perspective and €2162.83 per QALY gained (95% CI 958.78; -10,544.42) from the French health system perspective. CONCLUSION: Addition of a FDG PET/CT for occult cancer diagnosis was associated with better health outcomes (fewer cases of delayed cancer diagnosis and greater QALYs) and a higher cost from the perspective of publicly funded health care systems; the cost-effectiveness results are however highly uncertain.

Cancer of unknown primary site.

BACKGROUND: Cancer of unknown primary (CUP) is the diagnosis given to patients with metastatic cancer with no known site of origin. OBJECTIVE: This review summarises the current knowledge regarding the epidemiology, diagnosis, treatment and care of CUP. DISCUSSION: The incidence and mortality rates of CUP are declining in Australia. CUP was the twelfth most common cancer and fifth most common cause of cancer death in 2011. Smoking is the only identified risk factor. Incidence patterns implicate reduced access to healthcare and many registered cases have only a clinical diagnosis. Favourable prognosis subtypes with specific clinical and histopathological criteria must be recognised and treated on the basis of the presumed primary site. Emerging data reveal high rates of emergency department admission, hospitalisations and psychological distress, and low rates of specialist consultations for patients with CUP. General practitioners (GPs) have a key role in earlier identification, integrated care and preventing patients with CUP from falling through the cracks.

Bone metastases of unknown origin: epidemiology and principles of management.

UNLABELLED: Metastases are the most common malignancies involving bone; breast, prostate, lung and thyroid are the main sites of primary cancer. However, up to 30 % of patients present with bone metastases of unknown origin, where the site of the primary neoplasm cannot be identified at the time of diagnosis despite a thorough history, physical examination, appropriate laboratory testing and modern imaging technology (CT, MRI, PET). Sometimes only extensive histopathological investigations on bone specimens from biopsy can suggest the primary malignancy. At other times, a bone lesion can have such a highly undifferentiated histological appearance that a precise pathological classification on routine hematoxylin-eosin-stained section is not possible. The authors reviewed the relevant literature in an attempt to investigate the epidemiology of the histological primaries finally identified in patients with bone metastases from occult cancer, and a strategy of management and treatment of bone metastases from occult carcinomas is suggested. Lung, liver, pancreas and gastrointestinal tract are common sites for primary occult tumors. Adenocarcinoma is the main histological type, accounting for 70 % of all cases, while undifferentiated cancer accounts for 20 %. Over the past 30 years, lung cancer is the main causative occult primary for bone metastases and has a poor prognosis with an average survival of 4-8 months. Most relevant literature focuses on the need for standardized diagnostic workup, as surgery for bone lesions should be aggressive only when they are solitary and/or the occult primaries have a good prognosis; in these cases, identification of the primary tumor may be important and warrants special diagnostic efforts. However, in most cases, the primary site remains unknown, even after autopsy. Thus, orthopedic surgery has a mainly palliative role in preventing or stabilizing pathological fractures, relieving pain and facilitating the care of the patient in an attempt to provide the most appropriate therapy for the primary tumor as soon as possible. LEVEL OF EVIDENCE: 5.

PET and PET/CT for unknown primary tumors.

Carcinoma of unknown primary (CUP) is defined as histologically proven metastatic disease that, after a complete diagnostic work-up, yields no primary detectable tumor. CUP is one of the ten most frequent cancers, with overall poor outcome. Detection of the unknown primary tumor is of crucial importance in this scenario, since it might help to select and offer definitive treatment, which, in turn, may improve patient prognosis. Additional diagnostic work-up, usually consisting of a combination of several radiological and endoscopic investigations and serum tumor marker studies, can be time consuming, expensive, and pose a significant burden to the patient. The final diagnostic yield of these tests is often limited. Combined positron emission tomography/computed tomography (PET/CT), using the radiotracer (18)F-fluoro-2-deoxyglucose (FDG), may be of great value in the management of patients with CUP for the detection of primary tumors. This chapter gives a brief introduction to the syndrome of CUP, followed by an outline of the rationale, use, and utility of FDG-PET/CT in CUP, and concludes with a discussion on the challenges and future directions in the diagnostic management of patients with CUP.

The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society.

BACKGROUND: This study reviews the case-mix characteristics, management, and outcomes of melanoma cases occuring in the U.S. within the last decade. METHODS: Analyses of the National Cancer Data Base (NCDB) were performed on cases diagnosed between 1985 through 1994. A total of 84,836 cases comprised of cutaneous and noncutaneous melanomas were evaluated. RESULTS: The percentages of melanomas that were cutaneous, ocular, mucosal, and unknown primaries were 91.2%, 5.2%, 1.3%, and 2.2%, respectively. For cutaneous melanomas, the proportion of patients presenting with American Joint Committee on Cancer Stages 0, I, II, III, and IV were 14.9%, 47.7%, 23.1%, 8.9%, and 5.3%, respectively. Factors associated with decreased survival included more advanced stage at diagnosis, nodular or acral lentiginous histology, increased age, male gender, nonwhite race, and lower income. Multivariate analysis identified stage, histology, gender, age, and income as independent prognostic factors. For ocular melanomas, 85.0% were uveal, 4.8% were conjunctival, and 10.2% occurred at other sites. During the study period, there was a large increase in the proportion of ocular melanoma patients treated with radiation therapy alone. For mucosal melanomas, the distribution of head and neck, female genital tract, anal/rectal, and urinary tract sites was 55.4%, 18.0%, 23.8%, and 2.8%, respectively. Patients with lymph node involvement had a poor prognosis. For unknown primary melanomas, the distribution of metastases as localized to a region or multiple sites at presentation was 43.0% and 57.0%, respectively. Surgical treatment of patients with unknown primary site of the melanoma resulted in better survival compared with no treatment. CONCLUSIONS: Treatment of early stage cutaneous melanoma resulted in excellent patient outcomes. In addition to conventional prognostic factors, socioeconomic factors were found to be associated with survival.

Testing for occult cancer in patients with idiopathic deep vein thrombosis--a decision analysis.

OBJECTIVE: To determine the effectiveness and cost-effectiveness of testing for occult cancer in idiopathic deep vein thrombosis (IDVT). DESIGN: Threshold analysis was performed on the risk-adjusted cancer prevalence in a cost-effectiveness model of ideal testing for selecting cancers with potentially desirable utility (candidate cancers). Decision analysis was employed to compare different testing programs for candidate cancers with that of no testing. Life expectancy (LE) of early- and late-detected cancers and costs of testing were the dimensions of utility. Cost-effectiveness was expressed as marginal cost per year of life saved. The perspective of the third payer was adopted, and a discount rate of 3% was applied to both costs and benefits. DATA SOURCES: Risk of cancer in IDVT, testing policies, test characteristics, and LE were gathered from literature. Costs were provided from our hospital rate book and accounting service. RESULTS: Ideal testing would support a gain of LE of 40 days or more for prostate, colon and bladder cancer in males and for colon, breast and endometrium cancer in females aged from 60 to 69 years. Testing females with colonoscopy and mammography in any sequence provides 70 days of life gained. Testing males with colonoscopy provides 27 days of life gained. Lower and older ages reduce testing effectiveness. The qualitative results are stable over plausible ranges of test characteristics, while variations in the value of benefit for early cancer diagnosis may modify the strategy. Incremental cost-effectiveness ranges from $1,789 to $ 6,979 per year of life gained. CONCLUSIONS: According to the effectiveness criterion adopted, the only worthwhile investigation strategy includes colon and breast cancer in females. Testing for colon cancer in males is desirable at a lower criterion of effectiveness. All the strategies are cost effective.

[Longitudinal analysis of utilization of inpatient treatment based on insurance data of mandatory health insurance]. / Längsschnittanalyse der Inanspruchnahme stationärer Krankenhausbehandlungen auf der Basis von Versichertendaten der gesetzlichen Krankenversicherung.

AIM: To investigate which of the routinely collected claims data from the German "Legal sickness funds" on hospital utilisation may be used, in addition to that prescribed by the legislator. DESIGN: We used claims data to study a cohort of sickness fund beneficiaries who were insured during the complete year 1992 (n = 81,309). Six utilisation parameters, using the number of cases and in hospital days overall as well as diseases specific (i.e. readmission rates, in-hospital days per person with [at least] one hospital stay) were calculated. RESULTS: There are 88 persons with (at least) one hospital stay, 116 hospital cases and a total of 1306 in-hospital days per 1000 insured persons in the study cohort. The average hospital days per person (14.8 days) are ca. 30% higher than the average length of stay (11.2 days). Hospital utilisation increases with age. Hospital stays associated with ICD-239 (neoplasms of unknown origin) resulted in a higher than average number of hospital days in total although the mean length of stay is not above the average. This is due to a high readmission rate. Hospital stays associated with elective surgical procedures have a high prevalence rate but a low readmission ratio and short length of stay. CONCLUSION: The parameters related to insured persons, cases and specifically personal parameters of hospital utilisation allow a detailed analysis of hospital care; different utilisation and user patterns can be investigated and possible determinants of utilisation can be identified. After technical transformation, routine data of the sickness funds can be used to obtain information relevant for health care planners as well as for quality management.