Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer.

BACKGROUND: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. METHODS: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. RESULTS: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year's testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. CONCLUSIONS: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.

The impact of opportunistic salpingectomy on ovarian cancer mortality and healthcare costs: a call for universal insurance coverage.

BACKGROUND: Opportunistic salpingectomy at the time of hysterectomy or as an alternative to bilateral tubal ligation may reduce the incidence of ovarian cancer, because it has been demonstrated that most serous ovarian cancers begin in the fallopian tubes. However, salpingectomy at the time of sterilization is not always financially covered by third-party payers, and this represents a barrier to adoption. Routine salpingectomy has become more common but is not always practiced at the time of hysterectomy. OBJECTIVE: This study aimed to determine the impact of opportunistic salpingectomy as an alternative tubal ligation and routine salpingectomy at the time of hysterectomy on ovarian cancer mortality and overall cost. STUDY DESIGN: An 8-state Markov state transition model was constructed, including hysterectomy, tubal ligation, and ovarian cancer. Transition probabilities were informed by previously reported population data and include age-adjusted rates of elective sterilization and hysterectomy. This model was used to predict ovarian cancer incidence and the cost effectiveness of opportunistic salpingectomy. Testing of this model suggested that it accurately predicted overall life expectancy and closely predicted the rate of hysterectomy in the population. The model may underestimate the rate of tubal sterilization, making it conservative with respect to the benefits of salpingectomy. RESULTS: The recursive Markov model was run from ages 20 to 85 years in 1-year intervals with a half step correction and included age-adjusted rates of tubal ligation, hysterectomy (with and without oophorectomy), and ovarian cancer. The model predicts that opportunistic salpingectomy at the time of tubal ligation will reduce ovarian cancer mortality by 8.13%. Opportunistic salpingectomy at the time of hysterectomy will reduce ovarian cancer mortality by 6.34% for a combined decrease of 14.5%. Both strategies are cost effective when considering only the cost of the opportunistic salpingectomy. The excess cost of opportunistic salpingectomy at the time of tubal ligation was $433.91 with an incremental cost-effective ratio of $6401 per life-year and $5469 per quality-adjusted life year gained when adjusting for ovarian cancer with a utility of 0.64. The incremental cost-effective ratio for opportunistic salpingectomy during hysterectomy at a cost of $124.70 was $2006 per life-year and $1667 per quality-adjusted life year. When considering the impact of ovarian cancer prevention with respect to the cost of ovarian cancer treatment, opportunistic salpingectomy may produce a substantial healthcare savings. Utilizing a 3% discount rate, it is estimated that the total savings for universal salpingectomy could be as high as $445 million annually in the United States. A sensitivity analysis around the benefit of opportunistic salpingectomy suggests that this procedure will be cost effective even if salpingectomy provides only a modest reduction in the risk of ovarian cancer. CONCLUSION: It is estimated that universal opportunistic salpingectomy may prevent 1854 deaths per year from ovarian cancer and may reduce healthcare costs. Given these data, universal opportunistic salpingectomy should be considered at the time of tubal ligation and hysterectomy and covered by third-party payers.

Prognostic impact of socioeconomic status on long-term survival of non-localized epithelial ovarian cancer ꟷ The Extreme study.

OBJECTIVE: To examine the influence of socioeconomic status (SES) on long-term survival of non-localized ovarian cancer. METHODS: All women in Denmark with a first diagnosis of non-localized epithelial ovarian cancer 1982-2007 were identified in the Cancer Registry and/or the Pathology Registry and followed up until December 2017. The survival probability was estimated after respectively 5 and 10 years, using so-called pseudo observations, and analyzed according to education, income, and marital status defined from nationwide registries. RESULTS: The study cohort included 6486 women, and the estimated 5- and 10-year survival probabilities were 21.4% and 12.7%, respectively. Compared to women with short education, the 5-year survival probability was 7% higher for women with medium (relative survival probability = 1.07, 95% CI: 0.97, 1.19) and long education (relative survival probability = 1.07, 95% CI: 0.93, 1.24). Compared with married women, the 5-year survival probability for divorced women/widower was slightly lower (0.85, 95% CI: 0.69, 1.04) and for unmarried women slightly higher (1.08, 95% CI: 0.94, 1.23). Finally, the probability of being alive 5 years after diagnosis was 1.09 times higher (95% CI: 0.95, 1.24) for medium-income women and 1.23 times higher (95% CI: 1.08, 1.41) for high-income women compared with low-income women. Similar patterns were observed for 10-year survival. CONCLUSIONS: Non-localized ovarian cancer patients have a poor prognosis. Our data suggest that among Danish women with advanced ovarian cancer, higher personal income is associated with slightly higher probability of long-term survival, whereas education and marital status did not affect the probability of long-term survival.

Cost-effectiveness of Maintenance Therapy Based on Molecular Classification Following Treatment of Primary Epithelial Ovarian Cancer in the United States.

Importance: There are large randomized clinical trials-SOLO-1 (Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy [December 2018]), PRIMA (A Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy [September 2019]), and PAOLA-1 (Platine, Avastin and Olaparib in 1st Line [December 2019])-reporting positive efficacy results for maintenance regimens for women with primary, advanced epithelial ovarian cancer. The findings resulted in approval by the US Food and Drug Administration of the treatments studied as of May 2020. However, there are pressing economic considerations given the many eligible patients and substantial associated costs. Objective: To evaluate the cost-effectiveness of maintenance strategies for patients with (1) a BRCA variant, (2) homologous recombination deficiency without a BRCA variant, or (3) homologous recombination proficiency. Design, Setting, and Participants: In this economic evaluation of the US health care sector using simulated patients with primary epithelial ovarian cancer, 3 decision trees were developed, one for each molecular signature. The maintenance strategies evaluated were olaparib (SOLO-1), olaparib-bevacizumab (PAOLA-1), bevacizumab (PAOLA-1), and niraparib (PRIMA). Base case 1 assessed olaparib, olaparib-bevacizumab, bevacizumab, and niraparib vs observation of a patient with a BRCA variant. Base case 2 assessed olaparib-bevacizumab, bevacizumab, and niraparib vs observation in a patient with homologous recombination deficiency without a BRCA variant. Base case 3 assessed olaparib-bevacizumab, bevacizumab, and niraparib vs observation in a patient with homologous recombination proficiency. The time horizon was 24 months. Costs were estimated from Medicare claims, wholesale acquisition prices, and published sources. Probabilistic sensitivity analyses with microsimulation were then conducted to account for uncertainty and assess model stability. One-way sensitivity analyses were also performed. The study was performed from January through June 2020. Main Outcomes and Measures: Incremental cost-effectiveness ratios (ICERs) in US dollars per progression-free life-year saved (PF-LYS). Results: Assuming a willingness-to-pay threshold of $100 000/PF-LYS, none of the drugs could be considered cost-effective compared with observation. In the case of a patient with a BRCA variant, olaparib was the most cost-effective (ICER, $186 777/PF-LYS). The third-party payer price per month of olaparib would need to be reduced from approximately $17 000 to $9000 to be considered cost-effective. Olaparib-bevacizumab was the most cost-effective in the case of a patient with homologous recombination deficiency without a BRCA variant (ICER, $629 347/PF-LYS), and bevacizumab was the most cost-effective in the case of patient with homologous recombination proficiency (ICER, $557 865/PF-LYS). Even at a price of $0 per month, niraparib could not be considered cost-effective as a maintenance strategy for patients with homologous recombination proficiency. Conclusions and Relevance: The findings of this study suggest that, at current costs, maintenance therapy for primary ovarian cancer is not cost-effective, regardless of molecular signature. For certain therapies, lowering the drug price alone may not make them cost-effective.

Cost-effectiveness analysis comparing "PARP inhibitors-for-all" to the biomarker-directed use of PARP inhibitor maintenance therapy for newly diagnosed advanced stage ovarian cancer.

OBJECTIVES: Clinical trials evaluating universal PARP inhibitor (PARPi) frontline maintenance therapy for advanced stage ovarian cancer have reported progression-free survival (PFS) benefit. It is unclear whether PARPi maintenance therapy will universally enhance value (clinical benefits relative to cost of delivery). We compared a "PARPi-for-all" to a biomarker-directed frontline maintenance therapy approach as a value-based care strategy. METHODS: The cost of two frontline PARPi maintenance strategies, PARPi-for-all and biomarker-directed maintenance, was compared using modified Markov decision models simulating the study designs of the PRIMA, VELIA, and, PAOLA-1 trials. Outcomes of interest included overall costs and incremental cost-effectiveness ratios (ICERs) reported in US dollars per quality adjusted progression-free life-year (QA-PFY) gained. RESULTS: PARPi-for-all was more costly and provided greater PFS benefit than a biomarker-directed strategy for each trial. The mean cost per patient for the PARPi-for-all strategy was $166,269, $286,715, and $366,506 for the PRIMA, VELIA, and PAOLA-1 models, respectively. For the biomarker-directed strategy, the mean cost per patient was $98,188, $167,334, and $260,671 for the PRIMA, VELIA, and PAOLA-1 models. ICERs of PARPi-for-all compared to biomarker-directed maintenance were: $593,250/QA-PFY (PRIMA), $1,512,495/QA-PFY (VELIA), and $3,347,915/QA-PFY (PAOLA-1). At current drug pricing, there is no PFS improvement in a biomarker negative cohort that would make PARPi-for-all cost-effective compared to biomarker-directed maintenance. CONCLUSIONS: This study highlights the high costs of universal PARPi maintenance treatment, compared with a biomarker-directed PARPi strategy. Maintenance therapy in the front-line setting should be reserved for those with germline or somatic HRD mutations until the cost of therapy is significantly reduced.

Current status of hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer in the United States.

OBJECTIVES: 1.) To compare frequency of HIPEC use in ovarian cancer treatment before and after publication of the phase III study by van Driel et al. in January 2018. 2.) To compare associated rates of hospital-based outcomes, including length of stay, intensive care unit (ICU) admission, complications, and costs in ovarian cancer surgery with or without HIPEC. METHODS: We queried Vizient's administrative claims database of 550 US hospitals for ovarian cancer surgeries from January 2016-January 2020 using ICD-10 diagnosis and procedure codes. Sodium thiosulfate administration was used to identify HIPEC cases according to the published protocol. Student t-tests and relative risk (RR) were used to compare continuous variables and contingency tables, respectively. RESULTS: 152 ovarian cancer patients had HIPEC at 39 hospitals, and 20,014 ovarian cancer patients had surgery without HIPEC at 256 hospitals. Following the trial publication, 97% of HIPEC cases occurred. During the index admission, HIPEC patients had longer median length of stay (8.4 vs. 5.7 days, p < 0.001) and higher percentage of ICU admissions (63.1% vs. 11.0%, p < 0.001) and complication rates (RR = 1.87, p = 0.002). Index admission direct costs ($21,825 vs. $12,038, p < 0.001) and direct cost index (observed/expected costs) (1.87 vs. 1.11, p < 0.001) were also greater in the HIPEC patients. No inpatient deaths or 30-day readmissions were identified after HIPEC. CONCLUSIONS: Use of HIPEC for ovarian cancer increased in the US after publication of a phase III clinical trial in a high-impact journal, though the absolute number of cases remains modest. Incorporation of HIPEC was associated with increased cost, hospital length of stay, ICU admission, and hospital-acquired complication rates. Further studies are needed in order to evaluate long-term outcomes, including morbidity and survival.

Niraparib maintenance in frontline management of ovarian cancer: a cost effectiveness analysis.

OBJECTIVES: Niraparib maintenance after frontline chemotherapy for advanced ovarian cancer extends progression free survival. The objective of this study was to determine the cost effectiveness of niraparib maintenance therapy in patients with newly diagnosed ovarian cancer. METHODS: Decision analysis models compared the cost of observation versus niraparib maintenance following chemotherapy for five groups: all newly diagnosed ovarian cancer patients (overall), those with homologous recombination deficiency, those harboring BRCA mutations (BRCA), homologous recombination deficiency patients without BRCA mutations (homologous recombination deficiency non-BRCA), and non-homologous recombination deficiency patients. Drug costs were estimated using average wholesale prices. Progression free survival was estimated from published data and used to estimate projected overall survival. Incremental cost effectiveness ratios per quality adjusted life year were calculated. Sensitivity analyses varying the cost of niraparib were performed. The willingness-to-pay threshold was set at US$100 000 per quality adjusted life year saved. RESULTS: For the overall group, the cost of observation was US$5.8 billion versus $20.5 billion for niraparib maintenance, with an incremental cost effectiveness ratio of $72 829. For the homologous recombination deficiency group, the observation cost was $3.0 billion versus $14.8 billion for niraparib maintenance (incremental cost effectiveness ratio $56 329). Incremental cost effectiveness ratios for the BRCA, homologous recombination deficiency non-BRCA, and non-homologous recombination deficiency groups were $58 348, $50 914, and $88 741, respectively. For the overall and homologous recombination deficiency groups, niraparib remained cost effective if projected overall survival was 2.2 and 1.5 times progression free survival, respectively. CONCLUSIONS: For patients with newly diagnosed ovarian cancer, maintenance therapy with niraparib was cost effective. Cost effectiveness was improved when analyzing those patients with homologous recombination deficiency and BRCA mutations. Efforts should continue to optimize poly-ADP-ribose polymerase utilization strategies.

Cost-effectiveness of niraparib, rucaparib, and olaparib for treatment of platinum-resistant, recurrent ovarian carcinoma.

BACKGROUND: Olaparib was approved on December 19, 2014 by the US FDA as 4th-line therapy (and beyond) for patients with germline BRCA1/2 mutations; rucaparib was approved on December 19, 2016 as 3rd-line therapy (and beyond) for germline or somatic BRCA1/2-mutated recurrent disease. On October 23, 2019, niraparib was approved for treatment of women with damaging mutations in BRCA1/2 or other homologous recombination repair genes who had been treated with three or more prior regimens. We compared the cost-effectiveness of PARPi(s) with intravenous regimens for platinum-resistant disease. METHODS: Median progression-free survival (PFS) and toxicity data from regulatory trials were incorporated in a model which transitioned patients through response, hematologic complications, non-hematologic complications, progression, and death. Using TreeAge Pro 2017, each PARPi(s) was compared separately to non­platinum-based and bevacizumab-containing regimens. Costs of IV drugs, managing toxicities, infusions, and supportive care were estimated using 2017 Medicare data. Incremental cost-effectiveness ratios (ICERs) were calculated and PFS was reported in quality adjusted life months for platinum-resistant populations. RESULTS: Non­platinum-based intravenous chemotherapy was most cost effective ($6,412/PFS-month) compared with bevacizumab-containing regimens ($12,187/PFS-month), niraparib ($18,970/PFS-month), olaparib ($16,327/PFS-month), and rucaparib ($16,637/PFS-month). ICERs for PARPi(s) were 3-3.5× times greater than intravenous non­platinum-based regimens. CONCLUSION: High costs of orally administered PARPi(s) were not mitigated or balanced by costs of infusion and managing toxicities of intravenous regimens typically associated with lower response and shorter median PFS. Balancing modest clinical benefit with costs of novel therapies remains problematic and could widen disparities among those with limited access to care.

Budget impact of niraparib as maintenance treatment in recurrent ovarian cancer following platinum-based chemotherapy.

Aim: To estimate financial implications of adopting niraparib as maintenance treatment in recurrent ovarian cancer. Materials & methods: A model was developed to estimate the budget impact of treating patients with niraparib compared with alternative maintenance treatment options (olaparib, rucaparib, bevacizumab or 'watch and wait') over 3 years. Results: For a hypothetical plan with 1 million lives representative of US/Medicare-only populations, projected cost savings with niraparib were US$78,721/$293,723, $276,671/$1,009,729 and $353,585/$1,289,712 at years 1, 2 and 3, respectively. Sensitivity analyses showed prices of niraparib, rucaparib and olaparib to have the most significant impact on the budget. Conclusion: Factoring in all treatment-related costs, the use of niraparib could result in significant cost savings compared with other maintenance treatment options.

Targeted surgical prevention of epithelial ovarian cancer is cost effective and saves money in BRCA mutation carrying family members of women with epithelial ovarian cancer. A Canadian model.

OBJECTIVE: Survival but not cure rates have improved for epithelial ovarian cancer (EOC), demonstrating the need for effective prevention. Targeted prevention in BRCA carriers by risk reducing surgery (RRS) prevents 80% of cases but incurs additional up-front costs, compensated for by the potential for long term savings from treatment avoidance. Does prevention represent value for money? In the absence of long-term data from prospective trials, determining the cost effectiveness of a prevention strategy requires economic modelling. METHODS: A patient level simulation was developed comparing outcomes between two groups, using Canadian data. Group 1: no mutation testing with treatment if EOC developed. Group 2: cascade testing (index patient BRCA tested and the first and second-degree relatives tested if index patient or first-degree relative respectively were positive) with RRS in carriers. End points were Incremental Cost-Effectiveness Ratio (ICER) and budget impact. RESULTS: 2786 women with EOC (1 year incidence) had 766 first and 207 second-degree female relatives. BRCA mutations were present in 390 index cases, 366 first and 49 second-degree relatives. With 100% RRS uptake, 59 EOC were prevented and testing dominated no testing (more effective and less costly; ICER -$8919). The total cost saving over 50 years was $2,904,486 (cost saving of $9,660,381 in treatment costs versus increased cost from cascade testing/RRS of $6,755,895). At a threshold of $100,000 per QALY, prevention was cost effective in all modelled scenarios. CONCLUSIONS: Targeted prevention in BRCA mutation carriers not only prevents EOC but is cost-effective compared to treating EOC if it develops.

Cost-effectiveness of hyperthermic intraperitoneal chemotherapy (HIPEC) at interval debulking of epithelial ovarian cancer following neoadjuvant chemotherapy.

OBJECTIVES: A recent randomized controlled trial demonstrated an overall survival benefit to the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to neoadjuvant chemotherapy (NACT) for stage III epithelial ovarian cancer (EOC). The objective of the current study was to quantify the cost-effectiveness of HIPEC in this setting. METHODS: A decision analytic cost-effectiveness model was designed from a payer perspective to compare 2 surgical management strategies for EOC: (1) interval cytoreductive surgery (ICS); (2) ICS + HIPEC. Overall survival and ostomy rates with HIPEC were modeled from published studies. We assumed that 25% of each arm would later undergo secondary cytoreductive surgery, with the ICS arm eligible for HIPEC at that time. Costs were obtained from Medicare data, published studies, and the financial department of an academic hospital. Quality of life was not different between the arms; we assigned utilities based on a prior time-trade off study of ovarian cancer treatment. A Monte Carlo probabilistic sensitivity analysis was performed in the base case; primary outcome was the incremental cost-effectiveness ratio (ICER), expressed in 2017 US Dollars/quality-adjusted life years (QALYs). RESULTS: ICS was the least costly strategy at $78,849, compared to ICS + HIPEC at $79,954. ICS + HIPEC was more effective than ICS (2.9 QALYs versus 2.45 QALYs for ICS). ICS + HIPEC was highly cost-effective, with an ICER of $2436/QALY compared to ICS. In one-way sensitivity analyses, probability of ostomy reversal and use of HIPEC at secondary cytoreduction did not substantially impact the cost-effectiveness of ICS + HIPEC. CONCLUSION: ICS + HIPEC constitutes cost-effective management of stage III EOC when NACT is performed.

Cost-utility analysis of germline BRCA1/2 testing in women with high-grade epithelial ovarian cancer in Spain.

PURPOSE: Germline mutations in BRCA1 and/or BRCA2 genes (gBRCA1/2m) are associated with an increased risk of breast cancer (BC) and ovarian cancer (OC). The aim of this study was to estimate the efficiency of providing germline BRCA1/2 testing to high-grade epithelial ovarian cancer (HGEOC) patients without family history of OC or BC and the subsequent testing and management of their relatives with gBRCA1/2m in Spain. METHODS/PATIENTS: Incident HGEOC patients without family history of OC or BC who were gBRCA1/2m carriers and their relatives were simulated in a 50-year time horizon. The study compared two scenarios: BRCA1/2 testing vs no testing, using the perspective of the Spanish National Health Service. Cancer risk among gBRCA1/2m carriers was estimated based on their age and whether they had undergone risk-reducing surgeries. Direct healthcare costs and utilities of patients who developed EOC and BC were also included. A probabilistic sensitivity analysis (PSA) with 5 thousand simulations was developed considering ± 25% of the base-case value. RESULTS: The BRCA1/2-testing scenario amounted to €13,437,897.43 while the no-testing scenario amounted to €12,053,291.17. It was estimated that the screening test improved the quality of life among the patients' relatives by 43.8 quality-adjusted life years (QALYs). The incremental cost-utility ratio (ICUR) was €31,621.33/QALY in the base case. The PSA showed that 89.12% of the simulations were below the €50,000/QALY threshold. CONCLUSION: Providing this screening test to HGEOC patients and their relatives is cost-effective and it allows one to identify a target population with high risk of cancer to provide effective prevention strategies.

Disparities in health-related quality of life in women undergoing treatment for advanced ovarian cancer: the role of individual-level and contextual social determinants.

PURPOSE: Social determinants may influence health-related quality of life (HRQOL) among women with ovarian cancer, potentially creating disparities in clinical outcomes. We investigated the relationship between HRQOL and social determinants of health, including travel distance to access cancer care and health insurance type, among women participating in a randomized trial of primary adjuvant treatment for advanced ovarian cancer. METHODS: The Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaire captured HRQOL (physical well-being, functional well-being, ovarian-specific, and trial outcome index [TOI]) prior to chemotherapy (baseline), during the trial, and 84 weeks after initiation of chemotherapy for women with advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. We constructed bivariate and multivariable linear mixed effects models examining the associations of social determinants of health (individual-level and contextual factors) with HRQOL scores at 84 weeks, clustering participants (n = 993) within treatment centers, and Census regions and controlling for baseline HRQOL. RESULTS: Most individual-level (race, age, cancer stage, adverse events) and contextual (travel distance to treatment center, community socioeconomic status) factors were not statistically significantly associated with HRQOL. Compared to participants with private health insurance, other participants had lower mean HRQOL (physical well-being: public insurance, - 1.00 (standard error[SE] = 0.49) points, uninsured, - 1.93 (SE = 0.63) points; functional well-being: public, - 1.29 (SE = 0.59), uninsured, - 1.98 (SE = 0.76); ovarian cancer-specific: public, - 1.60 (SE = 0.59), uninsured, - 1.66 (SE = 0.75); TOI: public, - 3.81 (SE = 1.46), uninsured, - 5.51 (SE = 1.86); all p < .05). CONCLUSIONS: Private health insurance was associated with improved HRQOL at the completion of treatment for advanced stage ovarian cancer. Implications of health insurance on HRQOL should be further investigated, particularly among women with ovarian cancer who receive standard of care treatment.

The economic burden of disease of epithelial ovarian cancer in Spain: the OvarCost study.

OBJECTIVE: To assess the economic burden of epithelial ovarian cancer (EOC) in incident patients and the burden by disease stage in Spain. METHODS: We developed a Markov model from a social perspective simulating the natural history of EOC and its four stages, with a 10-year time horizon, 3-week cycles, 3% discount rate, and 2016 euros. Healthcare resource utilization and costs were estimated by disease stage. Direct healthcare costs (DHC) included early screening, genetic counselling, medical visits, diagnostic tests, surgery, chemotherapy, hospitalizations, emergency services, and palliative care. Direct non-healthcare costs (DNHC) included formal and informal care. Indirect costs (IC) included labour productivity losses due to temporary and permanent leaves, and premature death. Epidemiology data and resource use were taken from the literature and validated for Spain by the OvarCost group using a Delphi method. RESULTS: The total burden of EOC over 10 years was 3102 mill euros: 15.1% in stage I, 3.9% in stage II, 41.0% in stage III, and 40.2% in stage IV. Annual average cost/patient was €24,111 and it was €8,641; €14,184; €33,858, and €42,547 in stages I-IV, respectively. Of total costs, 71.2% were due to DHC, 24.7% to DNHC, and 4.1% to IC. CONCLUSIONS: EOC imposes a significant economic burden on the national healthcare system and society in Spain. Investment in better early diagnosis techniques might increase survival and patients' quality of life. This would likely reduce costs derived from late stages, consequently leading to a substantial reduction of the economic burden associated with EOC.

Economic Analysis of Neoadjuvant Chemotherapy Versus Primary Debulking Surgery for Advanced Epithelial Ovarian Cancer Using an Aggressive Surgical Paradigm.

OBJECTIVES: Neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) for advanced epithelial ovarian cancer (AEOC) remains controversial in the United States. Generalizability of existing trial results has been criticized because of less aggressive debulking procedures than commonly used in the United States. As a result, economic evaluations using input data from these trials may not accurately reflect costs and outcomes associated with more aggressive primary surgery. Using data from an ongoing trial performing aggressive debulking, we investigated the cost-effectiveness and cost-utility of NACT versus PDS for AEOC. METHODS: A decision tree model was constructed to estimate differences in short-term outcomes and costs for a hypothetical cohort of 15,000 AEOC patients (US annual incidence of AEOC) treated with NACT versus PDS over a 1-year time horizon from a Medicare payer perspective. Outcomes included costs per cancer-related death averted, life-years and quality-adjusted life-years (QALYs) gained. Base-case probabilities, costs, and utilities were based on the Surgical Complications Related to Primary or Interval Debulking in Ovarian Neoplasms trial. Base-case analyses assumed equivalent survival; threshold analysis estimated the maximum survival difference that would result in NACT being cost-effective at $50,000/QALY and $100,000/QALY willingness-to-pay thresholds. Probabilistic sensitivity analysis was used to characterize model uncertainty. RESULTS: Compared with PDS, NACT was associated with $142 million in cost savings, 1098 fewer cancer-related deaths, and 1355 life-years and 1715 QALYs gained, making it the dominant treatment strategy for all outcomes. In sensitivity analysis, NACT remained dominant in 99.3% of simulations. Neoadjuvant chemotherapy remained cost-effective at $50,000/QALY and $100,000/QALY willingness-to-pay thresholds if survival differences were less than 2.7 and 1.4 months, respectively. CONCLUSIONS: In the short term, NACT is cost-saving with improved outcomes. However, if PDS provides a longer-term survival advantage, it may be cost-effective. Research is needed on the role of patient preferences in tradeoffs between survival and quality of life.

Estimating Cost-effectiveness of a Multimodal Ovarian Cancer Screening Program in the United States: Secondary Analysis of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

IMPORTANCE: The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is the largest randomized clinical trial to evaluate screening's impact on ovarian cancer mortality, assigning women to multimodal screening (MMS) with serum cancer antigen 125 (CA-125) interpreted using a risk algorithm. If the MMS screening method is eventually shown to reduce mortality and be cost-effective, then it may be accepted by the medical community as a feasible screening tool. OBJECTIVE: To estimate the cost-effectiveness of an MMS screening program in the United States. DESIGN, SETTING, AND PARTICIPANTS: A Markov simulation model was constructed using data from UKCTOCS to compare MMS with no screening in the United States. Screening would begin at the age of 50 years for women in the general population. Published estimates of the long-term effect of MMS screening on ovarian cancer mortality and the trial's published hazard ratios were used to simulate mortality estimates up to 40 years from start of screening. Base-case costs included CA-125, ultrasound, and false-positive work-up results, in addition to a risk algorithm cost estimate of $100. The utility and costs of ovarian cancer treatment were incorporated into the model. INTERVENTIONS: Screening strategies varied by costs of the algorithm and treatment for advanced ovarian cancer, rates of screening compliance, ovarian cancer incidence, and extrapolation of ovarian cancer mortality. MAIN OUTCOMES AND MEASURES: Costs, quality-adjusted life-years (QALYs), and mortality reduction of ovarian cancer screening. RESULTS: Multimodal screening is both more expensive and more effective in reducing ovarian cancer mortality over a lifetime than no screening. After accounting for uncertainty in the underlying parameters, screening women starting at age 50 years with MMS is cost-effective 70% of the time, when decision makers are willing to pay $150 000 per QALY. Screening reduced mortality by 15%, with an incremental cost-effectiveness ratio (ICER) ranging from $106 187 (95% CI, $97 496-$127 793) to $155 256 (95% CI, $150 369-$198 567). CONCLUSIONS AND RELEVANCE: Ovarian cancer screening is potentially cost-effective in the United States depending on final significance of mortality reduction and cost of the CA-125 risk algorithm. These results are limited by uncertainty around the effect of screening on ovarian cancer mortality beyond the 11 years of UKCTOCS.