Immune checkpoint inhibitors as the second-line treatment for advanced esophageal squamous cell carcinoma: a cost-effectiveness analysis based on network meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have demonstrated superior clinical efficacy in prolonging overall survival (OS) as the second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC), and were recommended by the guidelines. However, it remains uncertain which ICI is the most cost-effective. This study assessed the cost-effectiveness of ICIs as the second-line treatment for ESCC based on the perspective of the Chinese healthcare system. METHODS: A network meta-analysis (NMA) was performed to obtain the Hazard ratios (HRs) for indirect comparisons. A three-state Markov model with a 10-year time horizon was conducted to assess the cost-effectiveness. The state transition probabilities were calculated with Kaplan-Meier (KM) curves data from clinical trial and HRs from the NMA. Utilities and costs were derived from local charges or previously published studies. Univariate and probabilistic sensitivity analyses (PSA) were performed to examine model robustness. The results were assessed based on the total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Five clinical trials (ATTRACTION-3, ESCORT, KEYNOTE-181, ORIENT-2, RATIONALE-302) with a total of 1797 patients were included in the NMA. The NMA showed that both camrelizumab and tislelizumab received relatively high rankings for progression-free survival (PFS) and OS. Compared with sintilimab, treatment with tislelizumab and camrelizumab gained 0.018 and 0.034 additional QALYs, resulting in incremental ICERs of $75,472.65/QALY and $175,681.9/QALY, respectively. Nivolumab and pembrolizumab produced lower QALYs and greater costs, suggesting that both were dominated in comparison to sintilimab. HRs and health state utilities were the most influential parameters in most univariate sensitivity analyses of paired comparisons. PSA results suggested that sintilimab had an 84.4% chance of being the most cost-effective treatment regimen at the WTP threshold of $38,223.34/QALY. In the scenario analysis, sintilimab would no longer be cost-effective, if the price of camrelizumab was assumed to decrease by 64.6% or the price of tislelizumab was assumed to decrease by 16.9%. CONCLUSIONS AND RELEVANCE: Among the five potential competing ICIs, sintilimab was likely to be the most cost-effective regimen as the second-line treatment for locally advanced or metastatic ESCC in China.

Cost-effectiveness analysis of tislelizumab plus chemotherapy as the first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma in China.

OBJECTIVE: We aimed to investigate the cost-effectiveness of tislelizumab plus chemotherapy compared to chemotherapy alone as a first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (OSCC). METHODS: A partitioned survival model was developed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy versus chemotherapy alone in patients with advanced or metastatic OSCC over a 10-year lifetime horizon from the perspective of the Chinese healthcare system. Costs and utilities were derived from the drug procurement platform and published literature. The model outcomes comprised of costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were conducted to address uncertainty and ensure the robustness of the model. RESULTS: Tislelizumab plus chemotherapy yielded an additional 0.337 QALYs and incremental costs of $7,117.007 compared with placebo plus chemotherapy, generating an ICER of $21,116.75 per QALY, which was between 1 time ($12,674.89/QALY) and 3 times GDP ($38,024.67/QALY) per capita. In one-way sensitivity analysis, the ICER is most affected by the cost of oxaliplatin, paclitaxel and tislelizumab. In the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set as 1 or 3 times GDP per capita, the probability of tislelizumab plus chemotherapy being cost-effective was 1% and 100%, respectively. CONCLUSION: Tislelizumab plus chemotherapy was probably cost-effective compared with chemotherapy alone as the first-line treatment for advanced or metastatic OSCC in China.

Cost-effectiveness analysis of PD-1 inhibitors as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma in China: an economic evaluation based on network meta-analysis.

BACKGROUND: Several economic studies have assessed the cost-effectiveness of programmed cell death protein-1 (PD-1) inhibitors compared to second-line chemotherapy in treating esophageal squamous cell carcinoma (ESCC). However, there is a lack of economic comparisons among the different PD-1 inhibitors. AIM: This study aimed to assess the cost-effectiveness of PD-1 inhibitors (nivolumab, pembrolizumab, camrelizumab, and tislelizumab) in second-line treatment for advanced or metastatic ESCC within the Chinese healthcare system. METHOD: The clinical trials were systematically retrieved from PubMed, Embase, Web of Science, and the Cochrane Library. We established a fractional polynomials model to conduct a network meta-analysis, enabling the calculation of hazard ratios and expected survival rates. Economic outcomes were estimated using a partitioned survival model. The costs and utilities were gathered from published sources. The threshold for willingness-to-pay (WTP) for a quality-adjusted life year (QALY) was set at three times China's per capita gross domestic product in 2022. Sensitivity analyses (SA) were performed to address uncertainties in the model. RESULTS: Four phase III randomized controlled trials were included, evaluating the cost-effectiveness of four PD-1 inhibitors, camrelizumab, nivolumab, tislelizumab, and pembrolizumab, compared to chemotherapy for the second-line treatment of advanced or metastatic ESCC. For camrelizumab, nivolumab, tislelizumab, and pembrolizumab, the corresponding incremental cost-effectiveness ratios were $27,375.43/QALY, $205,312.19/QALY, $9,266.73/QALY, and $220,368.10/QALY, respectively. The SA results indicated the robustness of the base analysis findings. CONCLUSION: From the Chinese healthcare system, under the WTP of $38,253.48/QALY, tislelizumab is a cost-effective treatment option for the second-line treatment of advanced or metastatic ESCC.

Impact of assumptions on future costs, disutility and mortality in cost-effectiveness analysis; a model exploration.

INTRODUCTION: In cost-effectiveness analyses, the future costs, disutility and mortality from alternative causes of morbidity are often not completely taken into account. We explored the impact of different assumed values for each of these factors on the cost-effectiveness of screening for colorectal cancer (CRC) and esophageal adenocarcinoma (EAC). METHODS: Twenty different CRC screening strategies and two EAC screening strategies were evaluated using microsimulation. Average health-related expenses, disutility and mortality by age for the U.S. general population were estimated using surveys and lifetables. First, we evaluated strategies under default assumptions, with average mortality, and no accounting for health-related costs and disutility. Then, we varied costs, disutility and mortality between 100% and 150% of the estimated population averages, with 125% as the best estimate. Primary outcome was the incremental cost per quality-adjusted life-year (QALY) gained among efficient strategies. RESULTS: The set of efficient strategies was robust to assumptions on future costs, disutility and mortality from other causes of morbidity. However, the incremental cost per QALY gained increased with higher assumed values. For example, for CRC, the ratio for the recommended strategy increased from $15,600 with default assumptions, to $32,600 with average assumption levels, $61,100 with 25% increased levels, and $111,100 with 50% increased levels. Similarly, for EAC, the incremental costs per QALY gained for the recommended EAC screening strategy increased from $106,300 with default assumptions to $198,300 with 50% increased assumptions. In sensitivity analyses without discounting or including only above-average expenses, the impact of assumptions was relatively smaller, but best estimates of the cost per QALY gained remained substantially higher than default estimates. CONCLUSIONS: Assumptions on future costs, utility and mortality from other causes of morbidity substantially impact cost-effectiveness outcomes of cancer screening. More empiric evidence and consensus are needed to guide assumptions in future analyses.

Endoscopic Submucosal Dissection in Europe: Results of 1000 Neoplastic Lesions From the German Endoscopic Submucosal Dissection Registry.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) enables the curative resection of early malignant lesions and is associated with reduced recurrence risk. Due to the lack of comprehensive ESD data in the West, the German ESD registry was set up to evaluate relevant outcomes of ESD. METHODS: The German ESD registry is a prospective uncontrolled multicenter study. During a 35-month period, 20 centers included 1000 ESDs of neoplastic lesions. The results were evaluated in terms of en bloc, R0, curative resection rates, and recurrence rate after a 3-month and 12-month follow-up. Additionally, participating centers were grouped into low-volume (≤20 ESDs/y), middle-volume (20-50/y), and high-volume centers (>50/y). A multivariate analysis investigating risk factors for noncurative resection was performed. RESULTS: Overall, en bloc, R0, and curative resection rates of 92.4% (95% confidence interval [CI], 0.90-0.94), 78.8% (95% CI, 0.76-0.81), and 72.3% (95% CI, 0.69-0.75) were achieved, respectively. The overall complication rate was 8.3% (95% CI, 0.067-0.102), whereas the recurrence rate after 12 months was 2.1%. High-volume centers had significantly higher en bloc, R0, curative resection rates, and recurrence rates and lower complication rates than middle- or low-volume centers. The lesion size, hybrid ESD, age, stage T1b carcinoma, and treatment outside high-volume centers were identified as risk factors for noncurative ESD. CONCLUSION: In Germany, ESD achieves excellent en bloc resection rates but only modest curative resection rates. ESD requires a high level of expertise, and results vary significantly depending on the center's yearly case volume.

The Optimal Age to Stop Endoscopic Surveillance of Patients With Barrett's Esophagus Based on Sex and Comorbidity: A Comparative Cost-Effectiveness Analysis.

BACKGROUND AND AIMS: Current guidelines recommend surveillance for patients with nondysplastic Barrett's esophagus (NDBE) but do not include a recommended age for discontinuing surveillance. This study aimed to determine the optimal age for last surveillance of NDBE patients stratified by sex and level of comorbidity. METHODS: We used 3 independently developed models to simulate patients diagnosed with NDBE, varying in age, sex, and comorbidity level (no, mild, moderate, and severe). All patients had received regular surveillance until their current age. We calculated incremental costs and quality-adjusted life-years (QALYs) gained from 1 additional endoscopic surveillance at the current age versus not performing surveillance at that age. We determined the optimal age to end surveillance as the age at which incremental cost-effectiveness ratio of 1 more surveillance was just less than the willingness-to-pay threshold of $100,000/QALY. RESULTS: The benefit of having 1 more surveillance endoscopy strongly depended on age, sex, and comorbidity. For men with NDBE and severe comorbidity, 1 additional surveillance at age 80 years provided 4 more QALYs per 1000 patients with BE at an additional cost of $1.2 million, whereas for women with severe comorbidity the benefit at that age was 7 QALYs at a cost of $1.3 million. For men with no, mild, moderate, and severe comorbidity, the optimal ages of last surveillance were 81, 80, 77, and 73 years, respectively. For women, these ages were younger: 75, 73, 73, and 69 years, respectively. CONCLUSIONS: Our comparative modeling analysis illustrates the importance of considering comorbidity status and sex when deciding on the age to discontinue surveillance in patients with NDBE.

Cost-Effectiveness of Screening, Surveillance, and Endoscopic Eradication Therapies for Managing the Burden of Esophageal Adenocarcinoma.

The authors conducted a review of the literature of cost-effectiveness analyses regarding management of Barrett's esophagus, including screening, surveillance, and treatment strategies. Because of the presence of multiple systematic reviews on this topic, they chose to focus on more recent economic analyses, with an emphasis on comparative modeling because these analyses have been demonstrated to achieve greater validity and impact when there are multiple competing strategies that are clinically reasonable to pursue. The authors identified areas of consensus across studies regarding management strategies and also areas that require additional empirical data.

Opportunistic upper endoscopy during colonoscopy as a screening strategy for countries with intermediate gastric cancer risk.

BACKGROUND AND AIM: Screening upper endoscopy can detect esophagogastric (OG) cancers early with improved outcomes. Recent cost-utility studies suggest that opportunistic upper endoscopy at the same setting of colonoscopy might be a useful strategy for screening of OG cancers, and it may be more acceptable to the patients due to cost-saving and convenience. We aim to study the diagnostic performance of this screening strategy in a country with intermediate gastric cancer risk. METHODS: A retrospective cohort study using a prospective endoscopy database from 2015 to 2017 was performed. Patients included were individuals age > 40 who underwent opportunistic upper endoscopy at the same setting of colonoscopy without any OG symptoms. Neoplastic OG lesions are defined as cancer and high-grade dysplasia. Pre-neoplastic lesions include Barrett's esophagus (BE), intestinal metaplasia (IM), and atrophic gastritis (AG). RESULTS: The study population involved 1414 patients. Neoplastic OG lesions were detected in five patients (0.35%). Pre-neoplastic lesions were identified in 174 (12.3%) patients. IM was found in 146 (10.3%) patients with 21 (1.4%) having extensive IM. The number needed to scope to detect a neoplastic OG lesion is 282.8 with an estimated cost of USD$141 400 per lesion detected. On multivariate regression, age ≥ 60 (RR: 1.84, 95% CI: 1.29-2.63) and first-degree relatives with gastric cancer (RR: 1.64, 95% CI: 1.06-2.55) were independent risk factors for neoplastic or pre-neoplastic OG lesion. CONCLUSION: For countries with intermediate gastric cancer risk, opportunistic upper endoscopy may be an alternative screening strategy in a selected patient population. Prospective trials are warranted to validate its performance.

Healthcare utilization and total costs of care among patients with advanced metastatic gastric and esophageal cancer.

Aim: Study first-line (1L) treatment patterns and economic outcomes among patients with advanced metastatic gastric cancer (GC) and esophageal cancer (EC). Materials & methods: Newly diagnosed patients with systemic GC and EC treatments were identified between 1 January 2011 and 31 July 2017; costs were presented as per patient per month (PPPM) basis. Results: Study included 392 GC and 436 EC patients. Most frequently used 1L regimens were: 5-fluorouracil (5-FU) + oxaliplatin (22.5%) and epirubicin + cisplatin + 5-FU (ECF)/ECF modifications (21.9%) in patients with GC; and carboplatin + paclitaxel (29.6%) and 5-FU + oxaliplatin (11.5%) in EC patients. Mean all-cause costs were US$16,242 PPPM for GC, and $18,384 PPPM for EC during 1L treatment. Conclusion: GC and EC were resource intensive and costly. High costs and short treatment durations underscored a gap in care in 1L treatment.

Wide Area Transepithelial Sampling with Computer-Assisted Analysis (WATS3D) Is Cost-Effective in Barrett's Esophagus Screening.

BACKGROUND: Wide area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D) is an adjunct to the standard random 4-quadrant forceps biopsies (FB, "Seattle protocol") that significantly increases the detection of Barrett's esophagus (BE) and associated neoplasia in patients undergoing screening or surveillance. AIMS: To examine the cost-effectiveness of adding WATS3D to the Seattle protocol in screening patients for BE. METHODS: A decision analytic model was used to compare the effectiveness and cost-effectiveness of two alternative BE screening strategies in chronic gastroesophageal reflux disease patients: FB with and without WATS3D. The reference case was a 60-year-old white male with gastroesophageal reflux disease (GERD). Effectiveness was measured by the number needed to screen to avert one cancer and one cancer-related death, and quality-adjusted life years (QALYs). Cost was measured in 2019 US$, and the incremental cost-effectiveness ratio (ICER) was measured in $/QALY using thresholds for cost-effectiveness of $100,000/QALY and $150,000/QALY. Cost was measured in 2019 US$. Cost and QALYs were discounted at 3% per year. RESULTS: Between 320 and 337 people would need to be screened with WATS3D in addition to FB to avert one additional cancer, and 328-367 people to avert one cancer-related death. Screening with WATS3D costs an additional $1219 and produced an additional 0.017 QALYs, for an ICER of $71,395/QALY. All one-way sensitivity analyses resulted in ICERs under $84,000/QALY. CONCLUSIONS: Screening for BE in 60-year-old white male GERD patients is more cost-effective when WATS3D is used adjunctively to the Seattle protocol than with the Seattle protocol alone.

Esophageal cancer surgery in Greece during the era of the financial crisis.

The aim of this study is to describe outcomes of esophageal cancer surgery in a quaternary upper gastrointestinal (GI) center in Athens during the era of the Greek financial crisis. We performed a retrospective analysis of patients that underwent esophagectomy for esophageal or gastroesophageal junction (GEJ) cancer at an upper GI unit of the University of Athens, during the period January 2004-June 2019. Time-to-event analyses were performed to explore trends in survival and recurrence. A total of 146 patients were identified. Nearly half of the patients (49.3%) underwent surgery during the last 4 years of the financial crisis (2015-2018). Mean age at the time of surgery was 62.3 ± 10.3 years, and patients did not present at older ages during the recession (P = 0.50). Most patients were stage III at the time of surgery both prior to the recession (35%) and during the financial crisis (39.8%, P = 0.17). Ivor-Lewis was the most commonly performed procedure (67.1%) across all eras (P = 0.06). Gastric conduit was the most common form of GI reconstruction (95.9%) following all types of surgery (P < 0.001). Pre-recession anastomoses were usually performed using a circular stapler (65%). Both during (88.1%) and following the recession (100%), the vast majority of anastomoses were hand-sewn. R0 resection was achieved in 142 (97.9%) patients. Anastomosis technique did not affect postoperative leak (P = 0.3) or morbidity rates (P = 0.1). Morbidity rates were not significantly different prior to (25%), during (46.9%), and after (62.5%) the financial crisis, P = 0.16. Utilization of neoadjuvant chemotherapy (26.9%, P = 0.90) or radiation (8.4%, P = 0.44) as well as adjuvant chemotherapy (54.8%, P = 0.85) and irradiation (13.7%, P = 0.49) was the same across all eras. Disease-free survival (DFS) and all-cause mortality rates were 41.2 and 47.3%, respectively. Median DFS and observed survival (OS) were 11.3 and 22.7 months, respectively. The financial crisis did not influence relapse (P = 0.17) and survival rates (P = 0.91). The establishment of capital controls also had no impact on recurrence (P = 0.18) and survival (P = 0.94). Austerity measures during the Greek financial crisis did not influence long-term esophageal cancer outcomes. Therefore, achieving international standards in esophagectomy may be possible in resource-limited countries when centralizing care.

The CARDIA-trial protocol: a multinational, prospective, randomized, clinical trial comparing transthoracic esophagectomy with transhiatal extended gastrectomy in adenocarcinoma of the gastroesophageal junction (GEJ) type II.

BACKGROUND: Adenocarcinoma of the gastroesophageal junction (GEJ) Siewert type II can be resected by transthoracic esophagectomy or transhiatal extended gastrectomy. Both allow for a complete tumor resection, yet there is an ongoing controversy about which surgical approach is superior with regards to quality of life, oncological outcomes and survival. While some studies suggest a better oncological outcome after transthoracic esophagectomy, others favor transhiatal extended gastrectomy for a better postoperative quality of life. To date, only retrospective studies are available, showing ambiguous results. METHODS: This study is a multinational, multicenter, randomized, clinical superiority trial. Patients (n = 262) with a GEJ type II tumor resectable by both transthoracic esophagectomy and transhiatal extended gastrectomy will be enrolled in the trial. Type II tumors are defined as tumors with their midpoint between ≤1 cm proximal and ≤ 2 cm distal of the top of gastric folds on preoperative endoscopy. Patients will be included in one of the participating European sites and are randomized to either transthoracic esophagectomy or transhiatal extended gastrectomy. The trial is powered to show superiority for esophagectomy with regards to the primary efficacy endpoint overall survival. Key secondary endpoints are complete resection (R0), number and localization of tumor infiltrated lymph nodes at dissection, post-operative complications, disease-free survival, quality of life and cost-effectiveness. Postoperative survival and quality of life will be followed-up for 24 months after discharge. Further survival follow-up will be conducted as quarterly phone calls up to 60 months. DISCUSSION: To date, as level 1 evidence is lacking, there is no consensus on which surgery is superior and both surgeries are used to treat GEJ type II carcinoma worldwide. The CARDIA trial is the first randomized trial to compare transthoracic esophagectomy versus transhiatal extended gastrectomy in patients with GEJ type II tumors. Several quality control measures were implemented in the protocol to ensure data reliability and increase the trial's significance. It is hypothesized that esophagectomy allows for a higher rate of radical resections and a more complete mediastinal lymph node dissection, resulting in a longer overall survival, while still providing an acceptable quality of life and cost-effectiveness. TRIAL REGISTRATION: The trial was registered on August 2nd 2019 at the German Clinical Trials Register under the trial-ID DRKS00016923 .

Cost-Effectiveness of ramucirumab plus paclitaxel as a second-line therapy for advanced gastric or gastro-oesophageal cancer in China.

AIM: That clinical trial (RAINBOW) showed that a 7.4 months overall survival benefit with the combination therapy with ramucirumab (RAM) and paclitaxel (PAC) as second-line therapy for patients with recurrent or metastatic gastric or gastro-oesophageal junction adenocarcinoma, compared with placebo (PLA) plus paclitaxel. We performed an analysis to assess the cost-effectiveness of RAM from a Chinese perspective and recognized the range of drug costs. METHODS: By building a Markov model to estimate quality-adjusted life-years (QALYs), life-years (LYs) and lifetime costs. Transition probabilities, costs and utilities were estimated for the published literature, Chinese health care system and local price setting. We performed threshold analyses and probabilistic sensitivity analyses to evaluate the uncertainty of the model. RESULTS: Compared with PLA strategy, RAM strategy provided an incremental survival benefit of 1.22 LYs and 0.64 QALYs. The probabilistic sensitivity analysis showed that when RAM costs less than $151 or $753 per 4 weeks, the incremental cost-effectiveness ratio (ICER) approximated the willingness-to-pay threshold (WTP), suggesting that there was 50% likelihood that the ICER for RAM + PAC would be less than $44528.4 per QALY or $48121 per QALY, respectively. CONCLUSIONS: For patients with advanced gastric or gastro-oesophageal junction adenocarcinoma who fail first-line chemotherapy, our results are conducive to the multilateral drug price guidance negotiations of RAM in China.

Lifetime risks, expected years of life lost, and cost-per-life year of esophageal cancer in Taiwan.

Besides lifetime risks, we estimated life expectancy (LE), expected years of life lost (EYLL), lifetime costs, and cost-per-LY (life-year) stratified by different stages of esophageal cancer (EC). From the Taiwan Cancer Registry, we collected 14,420 EC to estimate the incidence rates during 2008-2014. They were followed to 2015 to obtain the survival function, which was extrapolated to lifetime by a semiparametric method. We abstracted the monthly healthcare expenditures from the reimbursement database of National Health Insurance, which were multiplied with the corresponding survival probabilities to quantify lifetime cost and cost-per-LY after adjustments. About 93.7% of patients were male; 90.8% had squamous cell carcinoma. Most patients were diagnosed at advanced stages, with 44.6% and 28.3% at stages III and IV. The lifetime risk of EC in males increased in Taiwan with a cumulative incidence rate (CIR30-84) of 0.0146% (2008~2010) to 0.0165% (2013-2014). The EYLL for stages I-IV were 15.8, 17.5, 20.5, and 22.5, while the average of cost-per-LY for stages I-IV were US$ 6,987, $8,776, $12,153, and $22,426. EC in Taiwan appears to have shifted into younger ages groups and incidence is still increasing. Strategies for prevention, early diagnosis and treatment are warranted to improve the cost-effectiveness and control of this cancer.

Age at Initiation and Frequency of Screening to Prevent Esophageal Squamous Cell Carcinoma in High-risk Regions: an Economic Evaluation.

The aim of this study was to identify the economic screening strategies for esophageal squamous cell carcinoma (ESCC) in high-risk regions. We used a validated ESCC health policy model for comparing different screening strategies for ESCC. Strategies varied in terms of age at initiation and frequency of screening. Model inputs were derived from parameter calibration and published literature. We estimated the effects of each strategy on the incidence of ESCC, costs, quality-adjusted life-year (QALY), and incremental cost-effectiveness ratios (ICERs). Compared with no screening, all competing screening strategies decreased the incidence of ESCC from 0.35% to 72.8%, and augmented the number of QALYs (0.002-0.086 QALYs per person) over a lifetime horizon. The screening strategies initiating at 40 years of age and repeated every 1-3 years, which gained over 70% of probabilities that was preferred in probabilistic sensitivity analysis at a $1,151/QALY willingness-to-pay threshold. Results were sensitive to the parameters related to the risks of developing basal cell hyperplasia/mild dysplasia. Endoscopy screening initiating at 40 years of age and repeated every 1-3 years could substantially reduce the disease burden and is cost-effective for the general population in high-risk regions.

Disparities in esophageal cancer: less treatment, less surgical resection, and poorer survival in disadvantaged patients.

The incidence of esophageal cancer has increased steadily in the last decades in the United States. The aim of this paper was to characterize disparities in esophageal cancer treatment in different racial and socioeconomic population groups and compare long-term survival among different treatment modalities. A retrospective analysis of the National Cancer Database was performed including adult patients (≥18 years old) with a diagnosis of resectable (stages I-III) esophageal cancer between 2004 and 2015. Multivariable logistic regression models were used to determine the odds of being offered no treatment at all and surgical treatment across race, primary insurance, travel distance, income, and education levels. Multivariable Cox proportional hazards models were used to compare 5-year survival rates across different treatment modalities. A total of 60,621 esophageal cancer patients were included. Black patients, uninsured patients, and patients living in areas with lower levels of education were more likely to be offered no treatment. Similarly, black race, female patients, nonprivately insured patients, and those living in areas with lower median residential income and lower education levels were associated with lower rates of surgery. Patients receiving surgical treatment, compared to both no treatment and definitive chemoradiation, had significant better long-term survival in stage I, II, and III esophageal cancer. In conclusion, underserved patients with esophageal cancer appear to have limited access to surgical care, and are, in fact, more likely to not be offered any treatment at all. Considering the survival benefits associated with surgical resection, greater public health efforts to reduce disparities in esophageal cancer are needed.

Economic impacts of care by high-volume providers for non-curative esophagogastric cancer: a population-based analysis.

BACKGROUND: Esophagogastric cancer (EGC) is one of the deadliest and costliest malignancies to treat. Care by high-volume providers can provide better outcomes for patients with EGC. Cost implications of volume-based cancer care are unclear. We examined the cost-effectiveness of care by high-volume medical oncology providers for non-curative management of EGC. METHODS: We conducted a population-based cohort study of non-curative EGC over 2005-2017 by linking administrative datasets. High-volume was defined as ≥ 11 patients/provider/year. Healthcare costs ($USD/patient/month-survived) were computed from diagnosis to death or end of follow-up from the perspective of the healthcare system. Multivariable quantile regression examined the association between care by high-volume providers and costs. Sensitivity analyses were conducted by varying costing horizons and high-volume definitions. RESULTS: Among 7011 non-curative EGC patients, median overall survival was superior with care by high-volume providers with 7.0 (IQR 3.3-13.3) compared to 5.9 (IQR 2.6-12.1) months (p < 0.001) for low-volume providers. Median costs/patient/month-lived were lower for high-volume providers ($5518 vs. $5911; p < 0.001), owing to lower inpatient acute care costs, despite higher medication-associated and radiotherapy costs. Care by high-volume providers was independently associated with a reduction of $599 per patient/month-lived (95% confidence interval - 966 to - 331) compared to low-volume providers. The incremental cost-effectiveness ratio was - 393. Care by high-volume providers remained the dominant strategy when varying the costing horizon and the high-volume definition. CONCLUSION: Care by high-volume providers for non-curative EGC is associated with superior survival and lower healthcare costs, indicating a dominant strategy that may provide an opportunity to improve cost-effectiveness of care delivery.

Cost-effectiveness of chemoradiation followed by esophagectomy versus chemoradiation alone in squamous cell carcinoma of the esophagus.

BACKGROUND: Standard treatment for locally advanced esophageal cancer usually includes a combination of chemotherapy, radiation, and surgery. In squamous cell carcinoma (SCC), recent studies have indicated that esophagectomy after chemoradiation does not significantly improve survival but may reduce recurrence at the cost of treatment-related mortality. This study aims to evaluate the cost-effectiveness of chemoradiation with and without esophagectomy. METHODS: We developed a decision tree and Markov model to compare chemoradiation therapy alone (CRT) versus chemoradiation plus surgery (CRT+S) in a cohort of 57-year-old male patients with esophageal SCC, over 25 years. We used information on survival, cancer recurrence, and side effects from a Cochrane meta-analysis of two randomized trials. Societal utility values and costs of cancer care (2017, USD) were from medical literature. To test robustness, we conducted deterministic (DSA) and probabilistic sensitivity analyses (PSA). RESULTS: In our base scenario, CRT resulted in less cost for more quality-adjusted life years (QALYs) compared to CRT+S ($154 082 for 1.32 QALYs/patient versus $165 035 for 1.30 QALYs/patient, respectively). In DSA, changes resulted in scenarios where CRT+S is cost-effective at thresholds between $100 000-$150 000/QALY. In PSA, CRT+S was dominant 17.9% and cost-effective at willingness-to-pay of $150 000/QALY 38.9% of the time, and CRT was dominant 30.6% and cost-effective 61.1% of the time. This indicates that while CRT would be preferred most of the time, variation in parameters may change cost-effectiveness outcomes. CONCLUSIONS: Our results suggest that more data is needed regarding the clinical benefits of CRT+S for treatment of localized esophageal SCC, although CRT should be cautiously preferred.

Laparoscopically assisted versus open oesophagectomy for patients with oesophageal cancer-the Randomised Oesophagectomy: Minimally Invasive or Open (ROMIO) study: protocol for a randomised controlled trial (RCT).

INTRODUCTION: Surgery (oesophagectomy), with neoadjuvant chemo(radio)therapy, is the main curative treatment for patients with oesophageal cancer. Several surgical approaches can be used to remove an oesophageal tumour. The Ivor Lewis (two-phase procedure) is usually used in the UK. This can be performed as an open oesophagectomy (OO), a laparoscopically assisted oesophagectomy (LAO) or a totally minimally invasive oesophagectomy (TMIO). All three are performed in the National Health Service, with LAO and OO the most common. However, there is limited evidence about which surgical approach is best for patients in terms of survival and postoperative health-related quality of life. METHODS AND ANALYSIS: We will undertake a UK multicentre randomised controlled trial to compare LAO with OO in adult patients with oesophageal cancer. The primary outcome is patient-reported physical function at 3 and 6 weeks postoperatively and 3 months after randomisation. Secondary outcomes include: postoperative complications, survival, disease recurrence, other measures of quality of life, spirometry, success of patient blinding and quality assurance measures. A cost-effectiveness analysis will be performed comparing LAO with OO. We will embed a randomised substudy to evaluate the safety and evolution of the TMIO procedure and a qualitative recruitment intervention to optimise patient recruitment. We will analyse the primary outcome using a multi-level regression model. Patients will be monitored for up to 3 years after their surgery. ETHICS AND DISSEMINATION: This study received ethical approval from the South-West Franchay Research Ethics Committee. We will submit the results for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN10386621.

[Cost-effectiveness and cost-benefit analysis of upper gastrointestinal cancer screening in Yangzhong City, Jiangsu Province, from 2009 to 2015].

Objective: To evaluate the effectiveness and benefit of the upper gastrointestinal cancer screening in Yangzhong city, Jiangsu province, from 2009 to 2015. Methods: From 2009 to 2015, 31 natural villages with high-incidence of upper gastrointestinal cancer were selected from Baqiao town, Youfang town and Xinglong sub-district in Yangzhong city. 13 776 residents aged 40 to 69 years old were recruited and screened for upper gastrointestinal cancer by using endoscopic examination and pathological diagnosis. Two economic evaluation methods, cost-effectiveness analysis and cost-benefit analysis, were performed to evaluate the current screening schemes. Results: The mean age of all respondents were (53.60±8.14) years old and the males accounted for 43.64% (6 012). A total of 502 cases of upper gastrointestinal tract lesions were detected, including 100 cases of cancer (62 cases of esophagus, gastric/cardiac early stage cancer, 38 cases of advanced stage cancer), 38 cases of severe esophageal hyperplasia/carcinoma in situ, and 15 cases of high-grade intraepithelial neoplasia in stomach/cardia, the detection rate was 0.73%, 0.28% and 0.11%, respectively; the early diagnosis rate was 75.16% (115/153). The cost of a precancerous lesion, a case diagnosed at the early stage and a positive case identified through the upper gastrointestinal cancer screening in Yangzhong City was 10 037.17, 30 460.64 and 22 895.25 RMB, respectively. The early detection cost index from 2009 to 2015 was 0.52, 0.56, 0.48, 0.48, 0.21, 0.30, and 0.26, respectively. The effectiveness-cost ratio from 2009 to 2015 was 3.41, 2.77, 2.66, 2.58, 4.99, 3.12, and 3.48, respectively. Conclusions: The project of early diagnosis and treatment of upper gastrointestinal tract cancer in Yangzhong city has achieved good results and benefits.