Cost-effectiveness of Contrast-Enhanced Ultrasound for Diagnosis and Active Surveillance of Complex Cystic Renal Lesions.

Purpose: To determine the cost-effectiveness of Contrast-Enhanced Ultrasound (ceUS) for the active surveillance of complex renal masses compared to the more established imaging modalities of CT and MRI. Methods: A decision-analytic Markov state microsimulation model was constructed in TreeAge Pro. We simulated independent cohorts of 100,000 60-year-old individuals with either a Bosniak IIF or Bosniak III complex renal mass who were followed for 10 years or until death. The model compared three imaging strategies: (1) ceUS, (2) contrast-enhanced magnetic-resonance imaging (ceMRI), and (3) contrast-enhanced computed tomography (ceCT) for active surveillance of a complex renal mass. Results: For 60-year-old patients with either Bosniak IIF or III renal masses, ceUS was the most cost-effective strategy even after varying rates of active surveillance from 10-100%. Conclusion: ceUS is a viable and cost-effective option in the active surveillance of Bosniak class IIF and III renal cysts. Even after varying the rates of active surveillance usage, ceUS was robust and remained the most dominant strategy. For patients who have impaired kidney functions, ceUS is can be a safer alternative than non-contrast enhanced CT or MRI in the management of patients with Bosniak III renal cysts.

If the price is right: Cost-effectiveness of radiofrequency ablation versus thyroidectomy in the treatment of benign thyroid nodules.

BACKGROUND: Radiofrequency ablation is an emerging technology in the United States to treat benign thyroid nodules. The cost-effectiveness of radiofrequency ablation in comparison with traditional thyroidectomy is unknown. METHODS: A patient-level state transition microsimulation decision model was constructed comparing radiofrequency ablation with lobectomy in the management of benign thyroid nodules. Our base case was a 45-year-old woman with a solitary 30-cm3 nodule. Estimates of health utilities, complications, and mortality were obtained from the literature, and costs were estimated using Medicare reimbursement data. The primary outcomes of interest included total cost, quality-adjusted life years, and incremental cost-effectiveness ratios. All model estimates were subjected to 1-way sensitivity analyses to identify factors that strongly influence cost-effectiveness. A probabilistic sensitivity analysis was run across 1 million simulations to gauge outcome confidence with a willingness-to-pay threshold set at $100,000/quality-adjusted life year. RESULTS: Radiofrequency ablation was assumed to cost $5,000, with an initial success rate of 78%. Patients with volume reduction ratio <50% underwent a second treatment of radiofrequency ablation. Radiofrequency ablation represented the dominant strategy, yielding 21.31 quality-adjusted life years for a total cost of $16,563 in comparison to lobectomy, which yielded 21.13 quality-adjusted life years for a total cost of $19,262. In a 1-way sensitivity analysis varying the cost of radiofrequency ablation across of range of values, the radiofrequency ablation strategy remained cost-effective until the cost of radiofrequency ablation exceeded $12,330 at willingness-to-pay $50,000 or $17,950 at willingness-to-pay $100,000. CONCLUSION: Radiofrequency ablation is a cost-effective strategy in the treatment of benign thyroid nodules but is most sensitive to the cost of radiofrequency ablation.

Cost-effectiveness of screening with polymerase chain reaction for Helicobacter pylori to prevent gastric cancer and peptic ulcers.

Background: Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer. Screening and treatment of H. pylori may reduce the risk of gastric cancer and peptic ulcer disease (PUD). Polymerase chain reaction (PCR) of gastric biopsies provides superior sensitivity and specificity for the detection of H. pylori. This study explores whether population-based H. pylori screening with PCR is cost-effective in the US. Methods: A Markov cohort state-transition model was developed to compare three strategies: no screening with opportunistic eradication, 13C-UBT population screening and treating of H. pylori, and PCR population screening and treating of H. pylori. Estimates of risks and costs were obtained from published literature. Since the efficacy of H. pylori therapy in gastric cancer prevention is not certain, we broadly varied the benefit 30-100% in sensitivity analysis. Results: PCR screening was cost-effective and had an incremental-cost effectiveness ratio per quality adjusted life-year (QALY) of $38,591.89 when compared to 13C-UBT strategy with an ICER of $2,373.43 per QALY. When compared to no screening, PCR population screening reduced cumulative gastric cancer incidence from 0.84% to 0.74% and reduced PUD risk from 14.8% to 6.0%. The cost-effectiveness of PCR screening was robust to most parameters in the model. Conclusions: Our modeling study finds PCR screening and treating of H. pylori to be cost-effective in the prevention of gastric cancer and PUD. However, the potential negative consequences of H. pylori eradication such as antibiotic resistance could change the balance of benefits of population screening.

Threshold Analysis of the Cost-effectiveness of Endoscopic Ultrasound in Patients at High Risk for Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Data from the International Cancer of the Pancreas Screening Consortium studies have demonstrated that screening for pancreatic ductal adenocarcinoma can be effective and that surveillance improves survival in high-risk individuals. Endoscopic ultrasound (EUS) and cross-sectional imaging are both used, although there is some suggestion that EUS is superior. Demonstration of the cost-effectiveness of screening is important to implement screening in high-risk groups. METHODS: Results from centers with EUS-predominant screening were pooled to evaluate efficacy of index EUS in screening. A decision analysis model simulated the outcome of high-risk patients who undergo screening and evaluated the parameters that would make screening cost-effective at a US $100,000 per quality-adjusted life-year willingness to pay. RESULTS: One-time index EUS has a sensitivity of 71.25% and specificity of 99.82% to detection to detect high-risk lesions. Screening with index EUS was cost-effective, particularly at lifetime pancreatic cancer probabilities of greater than 10.8%, or at lower probabilities if life expectancy after resection of a lesion that was at least 16 years, and if missed, lesion rates on index EUS are 5% or less. CONCLUSIONS: Pancreatic cancer screening can be cost-effective through index EUS, particularly for those individuals at high-lifetime risk of cancer.

Initiation of Somatostatin analogues for neuroendocrine tumor patients: a cost-effectiveness analysis.

BACKGROUND & AIMS: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous neoplasms. Although some have a relatively benign and indolent natural history, others can be aggressive and ultimately fatal. Somatostatin analogues (SSAs) improve both quality of life and survival for these patients once they develop metastatic disease. However, these drugs are costly and their cost-effectiveness is not known. METHODS: A decision-analytic model was developed and analyzed to compare two treatment strategies for patients with Stage IV GEP-NETs. The first strategy had all patients start SSA immediately while the second strategy waited, reserving SSA initiation until the patient showed signs of progression. Sensitivity analysis was performed to explore model parameter uncertainty. RESULTS: Our model of patients age 60 with metastatic GEP-NETs suggests empiric initiation of SSA led to an increase 0.62 unadjusted life-years and incremental increase in quality-adjusted life years (QALYs) of 0.44. The incremental costs were $388,966 per QALY and not cost-effective at a willingness-to-pay threshold of $100,000. Death was attributed to GEP-NETs for 94.1% of patients in the SSA arm vs. 94.9% of patients in the DELAY SSA arm. Sensitivity analysis found that the model was most sensitive to costs of SSAs. Using probabilistic sensitivity analysis, the SSA strategy was only cost-effective 1.4% of the time at a WTP threshold of $100,000 per QALY. CONCLUSIONS: Our modeling study finds it is not cost-effective to initiate SSAs at time of presentation for patients with metastatic GEP-NETs. Further clinical studies are needed to identify the optimal timing to initiate these drugs.

Gene-Specific Variation in Colorectal Cancer Surveillance Strategies for Lynch Syndrome.

BACKGROUND AND AIMS: Lynch syndrome is associated with pathogenic variants in 4 mismatch repair (MMR) genes that increase lifetime risk of colorectal cancer. Guidelines recommend intensive colorectal cancer surveillance with colonoscopy every 1-2 years starting at age 25 years for all carriers of Lynch syndrome-associated variants, regardless of gene product. We constructed a simulation model to analyze the effects of different ages of colonoscopy initiation and surveillance intervals for each MMR gene (MLH1, MSH2, MSH6, and PMS2) on colorectal cancer incidence and mortality, quality-adjusted life-years, and cost. METHODS: Using published literature, we developed a Markov simulation model of Lynch syndrome progression for patients with each MMR variant. The model simulated clinical trials of Lynch syndrome carriers, varying age of colonoscopy initiation (5-year increments from 25-40 years), and surveillance intervals (1-5 years). We assessed the optimal strategy for each gene, defined as the strategy with the highest quality-adjusted life-years and incremental cost-effectiveness ratio below a $100,000 willingness-to-pay threshold. RESULTS: Optimal surveillance for patients with pathogenic variants in the MLH1 and MSH2 genes was colonoscopy starting at age 25 years, with 1- to 2-year surveillance intervals. Initiating colonoscopy at age 35 and 40 years, with 3-year intervals, was cost-effective for patients with pathogenic variants in MSH6 or PMS2, respectively. CONCLUSIONS: We developed a simulation model to select optimal surveillance starting ages and intervals for patients with Lynch syndrome based on MMR variant. The model supports recommendations for intensive surveillance of patients with Lynch syndrome-associated variants in MLH1 or MSH2. However, for patients with Lynch syndrome-associated variants of MSH6 or PMS2, later initiation of surveillance at 35 and 40 years, respectively, and at 3-year intervals, can be considered.

International cost-effectiveness analysis evaluating endoscopic screening for gastric cancer for populations with low and high risk.

BACKGROUND: Gastric cancer remains one of the 3 most common causes of cancer death worldwide. Understanding the health and economic factors that affect screening cost-effectiveness in different countries will help address when and where it makes most sense to screen for gastric cancer. METHODS: We performed a cost-effectiveness analysis using a Markov model to compare screening and surveillance strategies for gastric cancer in Brazil, France, Japan, Nigeria, and the United States. Primary outcome was the incremental cost-effectiveness ratio. We then performed a sensitivity analysis to determine how each variable affected the overall model. RESULTS: In all countries, the most cost-effective strategies, measured by incremental cost-effectiveness ratio relative to no screening, were screening every 10 years, surveillance of high- and low-risk patients every 5 and 10 years, respectively, and screening every 5 years. Only Japan had at least one cost-effective screening strategy. The most important variables across different screening strategies and countries were starting age of screening, cost of endoscopy, and baseline probability of local gastric cancer at time of diagnosis. CONCLUSIONS: Our model suggests that screening for gastric cancer is cost-effective in countries with higher incidence and lower costs of screening, but screening may still be a viable option in high-risk populations within low incidence countries.

Timing of parathyroidectomy for tertiary hyperparathyroidism with end-stage renal disease: A cost-effectiveness analysis.

BACKGROUND: Tertiary hyperparathyroidism associated with end-stage renal disease is characterized by progression from secondary hyperparathyroidism to an autonomous overproduction of parathyroid hormone that leads to adverse health outcomes. Rates of parathyroidectomy (PTX) have decreased with the use of calcimimetics. Optimal timing of PTX in relation to kidney transplant remains controversial. We aimed to identify the most cost-effective strategy for patients with tertiary hyperparathyroidism undergoing kidney transplant. METHODS: We constructed a patient level state transition microsimulation to compare 3 management schemes: cinacalcet with kidney transplant, cinacalcet with PTX before kidney transplant, or cinacalcet with PTX after kidney transplant. Our base case was a 55-year-old on dialysis with tertiary hyperparathyroidism awaiting kidney transplant. Outcomes, including quality-adjusted life years, surgical complications, and mortality, were extracted from the literature, and costs were estimated using Medicare reimbursement data. RESULTS: Our base case analysis demonstrated that cinacalcet with PTX before kidney transplant was dominant, with a lesser cost of $399,287 and greater quality-adjusted life years of 10.3 vs $497,813 for cinacalcet with PTX after kidney transplant (quality-adjusted life years 9.4) and $643,929 for cinacalcet with kidney transplant (quality-adjusted life years 7.4). CONCLUSION: Cinacalcet alone with kidney transplant is the least cost-effective strategy. Patients with end-stage renal disease-related tertiary hyperparathyroidism should be referred for PTX, and it is most cost-effective if performed prior to kidney transplant.

Low sodium diet for gastric cancer prevention in the United States: Results of a Markov model.

BACKGROUND AND AIMS: High sodium consumption has been associated with an increased risk of gastric cancer. The mean daily sodium intake in the United States substantially exceeds the national recommended amount. The low sodium-DASH diet has been shown to decrease the risk of cardiovascular disease in the United States, but its impact on gastric cancer has not been well studied. We therefore aimed to model the impact and cost-effectiveness of the low sodium-DASH diet for gastric cancer prevention in the U.S. METHODS: A Markov cohort state-transition model was developed to simulate the impact of the low sodium-DASH diet on gastric cancer outcomes for the average 40-year-old in the United States compared to no intervention. Primary outcomes of interest were gastric cancer incidence and incremental cost-effectiveness ratios (ICER). RESULTS: Our model found that compared to the no intervention cohort, the risk of gastric cancer decreased by 24.8% for males and 21.2% for females on the low sodium-DASH diet. 27 cases and 14 cases per 10,000 individuals were prevented for males and females, respectively, in the intervention group. The ICER for the low sodium-DASH diet strategy was $287,726 for males and $423,878 for females compared to the no intervention strategy. CONCLUSIONS: Using a Markov model of gastric cancer risk, we found that adherence to a low sodium-DASH diet could decrease the risk of gastric cancer. This intervention was not cost-effective due to the high cost of a low sodium-DASH accordant diet, but significantly improved for high-risk populations and when the cost of the diet became slightly more affordable.

Cost-Effectiveness Analysis of Biomarker-Guided Treatment for Metastatic Gastric Cancer in the Second-Line Setting.

BACKGROUND: The 5-year survival rate of patients with metastatic gastric cancer (GC) is only 5%. However, trials have demonstrated promising antitumor activity for targeted therapies/immunotherapies among chemorefractory metastatic GC patients. Pembrolizumab has shown particular efficacy among patients with programmed death ligand-1 (PD-L1) expression and high microsatellite instability (MSI-H). The aim of this study was to assess the effectiveness and cost-effectiveness of biomarker-guided second-line GC treatment. METHODS: We constructed a Markov decision-analytic model using clinical trial data. Our model compared pembrolizumab monotherapy and ramucirumab/paclitaxel combination therapy for all patients and pembrolizumab for patients based on MSI status or PD-L1 expression. Paclitaxel monotherapy and best supportive care for all patients were additional comparators. Costs of drugs, treatment administration, follow-up, and management of adverse events were estimated from a US payer perspective. The primary outcomes were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100,000/QALY over 60 months. Secondary outcomes were unadjusted life years (survival) and costs. Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty. RESULTS: The most effective strategy was pembrolizumab for MSI-H patients and ramucirumab/paclitaxel for all other patients, adding 3.8 months or 2.0 quality-adjusted months compared to paclitaxel. However, this strategy resulted in a prohibitively high ICER of $1,074,620/QALY. The only cost-effective strategy was paclitaxel monotherapy for all patients, with an ICER of $53,705/QALY. CONCLUSION: Biomarker-based treatments with targeted therapies/immunotherapies for second-line metastatic GC patients substantially improve unadjusted and quality-adjusted survival but are not cost-effective at current drug prices.

Cost-effectiveness Evaluation of Targeted Surgical and Endoscopic Therapies for Early Colorectal Adenocarcinoma Based on Biomarker Profiles.

Importance: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States. The prognosis for patients with CRC varies widely, but new prognostic biomarkers provide the opportunity to implement a more individualized approach to treatment selection. Objective: To assess the cost-effectiveness of 3 therapeutic strategies, namely, endoscopic therapy (ET), laparoscopic colectomy (LC), and open colectomy (OC), for patients with T1 CRC with biomarker profiles that prognosticate varying levels of tumor progression in the US payer perspective. Design, Setting, and Participants: In this economic evaluation study, a Markov model was developed for the cost-effectiveness analysis. Risks of all-cause mortality and recurrent cancer after ET, LC, or OC were estimated with a 35-year time horizon. Quality of life was based on EuroQoL 5 Dimensions scores reported in the published literature. Hospital and treatment costs reflected Medicare reimbursement rates. Deterministic and probabilistic sensitivity analyses were performed. Data from patients with T1 CRC and 6 biomarker profiles that included adenomatous polyposis coli (APC), TP53 and/or KRAS, or BRAFV600E were used as inputs for the model. Data analyses were conducted from February 27, 2019, to May 13, 2019. Exposures: Endoscopic therapy, LC, and OC. Main Outcomes and Measures: The primary outcomes were unadjusted life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) between competing treatment strategies. Results: Endoscopic therapy had the highest QALYs and the lowest cost and was the dominant treatment strategy for T1 CRC with the following biomarker profiles: BRAFV600E, APC(1)/KRAS/TP53, APC(2) or APC(2)/KRAS or APC(2)/TP53, or APC(1) or APC(1)/KRAS or APC(1)/TP53. The QALYs gained ranged from 16.97 to 17.22, with costs between $68 902.75 and $77 784.53 in these subgroups. For the 2 more aggressive biomarker profiles with worse prognoses (APC(2)/KRAS/TP53 and APCwt [wild type]), LC was the most effective strategy (with 16.45 and 16.61 QALYs gained, respectively) but was not cost-effective. Laparoscopic colectomy cost $65 234.87 for APC(2)/KRAS/TP53 and $71 250.56 for APCwt, resulting in ICERs of $113 290 per QALY and $178 765 per QALY, respectively. Conclusions and Relevance: This modeling analysis found that ET was the most effective strategy for patients with T1 CRC with less aggressive biomarker profiles. For patients with more aggressive profiles, LC was more effective but was costly, rendering ET the cost-effective option. This study highlights the potential utility of prognostic biomarkers in T1 CRC treatment selection.