Skip to main content

A cost-effectiveness modeling study of treatment interventions for stage I to III esophageal squamous cell carcinoma

Abstract

Background

Esophageal cancer causes considerable costs for health systems. Appropriate treatment options for patients with esophageal squamous cell carcinoma (ESCC) can reduce medical costs and provide more improved outcomes for health systems and patients. This study evaluates the cost-effectiveness of treatment interventions for patients with ESCC according to the Iranian health system.

Material and methods

A five-state Markov model with a 15-year time horizon was performed to evaluate the cost-effectiveness of treatment interventions based on stage for ESCC patients. Costs ($US 2021) and outcomes were calculated from the Iranian health system, with a discount rate of 3%. One-way sensitivity analyses were performed to assess the potential effects of uncertain variables on the model results.

Results

In stage I, the Endoscopic Mucosal Resection (EMR) treatment yielded the lowest total costs and highest total QALY for a total of $1473 per QALY, making it the dominant strategy compared with esophagectomy and EMR followed by ablation. In stages II and III, chemoradiotherapy (CRT) followed by surgery dominated esophagectomy. CRT followed by surgery was also cost-effective with an incremental cost-effectiveness ratio (ICER) of $2172.8 per QALY compared to CRT.

Conclusion

From the Iranian health system’s perspective, EMR was the dominant strategy versus esophagectomy and EMR followed by ablation for ESCC patients in stage I. The CRT followed by surgery was a cost-effective intervention compared to CRT and esophagectomy in stages II and III.

Introduction

According to the GLOBOCAN estimates, esophageal cancer (EC) is the seventh most common cancer type globally. Iran has been a high-incidence area of EC for many years and is located on the esophageal cancer belt. The EC incidence rate was 2.53 per 100,000 population and 5.3 per 100,000 population in 2001 and 2018, respectively [1, 2]. In developing countries, esophageal squamous cell carcinoma (ESCC) is the most common subtype of EC. For example, more than 64% of EC patients are diagnosed with ESCC in Iran [3, 4].

Generally, appropriate treatment interventions for patients with ESCC depend on variables such as cancer histology, age of patients, comorbidities, and stage detecting. In the initial stage, curers are usually adopted Endoscopic Mucosal Resection (EMR), esophagectomy, and EMR followed by ablation. In the middle stage (II and III), esophagectomy, CRT followed by surgery or CRT alone is applied [5].

Overall, physicians face challenges in using a suitable intervention for patients with EC. Esophagectomy is the most commonly used treatment for EC patients, although it is accompanied by considerable mortality and morbidity [6, 7]. Studies reported that after esophagectomy, the postoperative mortality rate was 1% to 11%, and postoperative complications were reported at 11% to 35% [8, 9]. In contrast, EMR and CRT followed by surgery are recommended to treat ESCC patients as an alternative to esophagectomy. Studies showed that after the treatment with EMR, approximately 3% to 6% of patients would incur a complication, with about a 17% to 28% complication rate seen in chemoradiotherapy followed by surgery [10, 11]. Also, studies reported death rates of 2 to 5% for CRT but did report any death rates for the use of EMR [12,13,14]. Additionally, the treatment cost is a substantial factor in the use of therapeutic interventions by patients. Thus comparing the effectiveness and the treatment cost on therapeutic procedurals may be helpful in selecting competing strategies, especially under conditions of uncertainty [15]. Cost-effectiveness analysis (CEA) is a practical tool to evaluate therapeutic interventions based on costs and outcomes. In this analysis, consequences are presented as a unit, such as cases of a disease prevented and years of life gained— with results inferenced in terms of the incremental cost-effectiveness ratio (ICER) [16].

Most studies on economic evaluation analysis associated with EC have been conducted to screen and treat Barret’s esophagus [17,18,19]. Besides, most CEA studies related to the treatment interventions on EC have been performed on the subtype of adenocarcinoma, most of which were conducted in developed countries [20,21,22,23]. We believe that the curing of ESCC patients based on the disease stage can reduce the cost of treatment and provide improved results for health systems and patients. Therefore, we designed a study to evaluate the cost-effectiveness of treatment interventions for patients with ESCC, based on the disease stage in Iran.

Methods

To help decision-makers, in identifying appropriate treatment options for their patients, we performed a CEA to evaluate the costs and effectiveness of therapeutic procedures, based on disease stage for patients with ESCC.

We used the ICER, the ratio of the incremental cost to the incremental benefit of two competing interventions, for our analysis. The thresholds that WHO defined for low-income and middle-income countries were used. This threshold is one to three-times the gross domestic product (GDP) per capita [24]. The one to three-times GDP per capita for Iran is US$ 5627 to $16,881 [25]. We conducted deterministic sensitivity analyses to evaluate the potential effects of uncertain variables on the model results. For this reason, one-way sensitivity analyses were applied. We obtained the value for possible variables, using the maximum and minimum values for all variables extracted from the literature and medical records.

Patients and interventions

We considered patients 60-years-old with stage I to III ESCC who received a treatment intervention as the target population because the studies displayed that most patients with esophageal cancer develop the disease in the aged 50 to 70 years [12, 26, 27]. Also, the medical records at the cancer institute of Iran demonstrated that the average age of ESCC patients was about 60-years. Patients were excluded if they were in the IV stage or high-grade dysplasia, as well as patients who had adenocarcinoma esophageal cancer. Also, we excluded patients that had other comorbid cancers simultaneously, such as gastric cancer, gastroesophageal junction cancer, oral cancer, Barrett’s esophagus, and other cancers. Patients were simulated based on the disease stage and followed until 75 years or death. We used the National Comprehensive Cancer Network (NCCN) guidelines and expert opinions to classify patients and identify interventions [28, 29]; therefore, the patients were identified stage I if they were graded as T1N0M0. Also, patients at stages II and III were graded as T2-4N0-2M0. Furthermore, we selected interventions of esophagectomy, EMR, and EMR followed by ablation for stage I patients. Esophagectomy, CRT, and CRT followed by surgery were chosen for stages II and III [29]. In the esophagectomy group, surgery was performed open. The esophageal resection among esophageal cancer patients could be performed in an open or minimally invasive manner. The minimally invasive technique causes fewer side effects in some variables (intraoperative blood loss, in-hospital mortality, and cardiovascular complication) [30]. However, open esophagectomy is most common [31, 32]. In the CRT group, the drug regimens were Cisplatin and Fluorouracil or Cisplatin with Docetaxel, with a total radiation dose of 5000 Gy was given in 25 fractions. The period of treatment was 4 to 6 months [28].

Model design and assumptions

Using tree age software (Tree age, Williamstown, MA, 2018), we employed a Markov model to perform a CEA of treatment interventions for patients with stage I to III of ESCC, based on disease stage. We adopted the Markov model for this cost-effectiveness study because the patients with esophageal cancer could be exposed to different health states after receiving therapeutic interventions during the natural history of the disease. In designing the Markov model, we conducted a systematic review associated with the economic evaluation of EC treatments. This systematic review is explained elsewhere [23]. Based on the results of the systematic review, we created a 5-state Markov model. Health states in the Markov model included: no-recurrence, local recurrence, metastasis, complication, and dead. The Markov model evaluated the outcomes over a 15-year time horizon (after which > 95% of patients had died in all interventions), using a 6-month cycle length. Figure 1 shows the Markov model and the transitions between the health state for each treatment. We assumed the initial probability at zero (for treatment) for the metastasis and local recurrence state in the Markov modeling. Patients then entered these states via the transition probabilities in the following cycles. The initial and transition probabilities for every treatment modality were extracted from previously published literature and then adopted for the 6-month cycles. Table 1 displays the transition probability for treatment interventions.

Fig. 1
figure 1

Markov model

Table 1 Model input estimates

Costs and effectiveness outcomes

We used the Iranian health care system as the perspective to estimate the costs. To calculate intervention costs, we used the medical records of ESCC patients at Iran's cancer institute in 2018. For this purpose, we identified direct costs, including direct medical costs and direct non-medical costs. The direct medical costs were considered for diagnosis cost, treatment, follow-up, and terminal care. The unit cost is defined for diagnostic tests, follow-up care, and treatment modalities from the Iranian health system perspective. The diagnosis costs are considered for services such as endoscopy, biopsies, endoscopic ultrasound, complete blood count (CBC), blood urea nitrogen (BUN), creatinine, serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphates, fasting blood sugar (FBS), and computed tomography (CT) scan. The follow-up cost includes visits, counseling, and CT scan. Direct non-medical cost refers to a proportion of out-of-pocket payment that must be paid by the patient [59]. Since the data and studies about the direct non-medical costs associated with esophageal cancer patients were lacking, we estimated only the traveling costs. In this regard, the number of clinical visits was extracted from medical records, assuming it was equal to the number of outpatient visit days. Then the cost of a trip was calculated based on expert' opinion. All costs were adjusted to $US 2021. The costs and outcomes were discounted at 3% [60, 61].

The primary outcome was life-years gained (LYG) and quality-adjusted life-years (QALYs). We calculated the QALY for the treatment interventions using the utility weights in the various health states. Utility weights were derived from the published literature [57, 58]. As in previous studies, we assumed a perfect quality of life (QOL = 1) for people with non-esophageal cancer [62, 63]. Other outcomes, such as complications (adverse events that occur as a direct result of the treatment used), postoperative mortality, and transition probability associated with the baseline health state, were derived from the literature (See Table 1 below for references).

Results

Base case results

In the base case analysis, the use of EMR yielded the lowest total costs ($4485), and highest total life-years gained (4.363) and QALY (3.045), making it the dominant strategy in stage I. Table 2 shows the CEA results for the base case model in patients with ESCC.

Table 2 Cost-effectiveness analysis of base-case for patients with ESCC

For stage II and III on ESCC, the CRT followed by surgery strategy resulted in 3.048 QALYs, while the CRT intervention yielded 2.143 QALYs and esophagectomy 2.664 QALYs. The total costs for the patient with ESCC were $4738 for CRT treatment, $6707 on CRT followed by surgery, and $7622 at esophagectomy. CRT followed by surgery dominated esophagectomy and; compared to CRT was cost-effective with an ICER of $2172 per QALY.

Sensitivity analysis

The one-way sensitivity analysis can be found in Table 3. There was no change in the base case analysis for the results on stage I, and EMR was a dominant strategy. If the probability of death for the esophagectomy intervention was reduced by 0.041, the ICER of esophagectomy versus EMR would be $34,768 per QALY. The ICER would be $24,377 per QALY if the transition probability of no-recurrence to the metastasis state was reduced from 0.0139 to 0.0109 for esophagectomy. In stages II and III of ESCC, the results were sensitive to transition no-recurrence to the dead state in esophagectomy. By reducing this probability from 0.085 to 0.0452, esophagectomy was cost-effective compared to CRT followed by surgery with an ICER of $3513 per QALY. The graph of one-way sensitivity analysis can be found in the Additional file 1.

Table 3 Results of one-way sensitivity analyses of selected parameters

The sensitivity analysis of costs can be found in Fig. 2. Each area represents the cost-effectiveness of a particular intervention under specific costs. The esophagectomy intervention would not be a cost-effective strategy unless the cost of esophagectomy sharply decreased to less than $866 in stage I and less than $1232 in stages II and III.

Fig. 2
figure 2

Results of sensitivity analysis for costs. EMR, endoscopic mucosal resection, EMR & ABL, endoscopic mucosal resection followed by ablation, ESO, esophagectomy, CRT, chemoradiotherapy, CRT_ESO, chemoradiotherapy followed by surgery

Discussion

This study aimed to evaluate the cost-effectiveness of treatment interventions for patients with ESCC according to the disease stage, using the Iranian health system (The clinical guidelines for treating patients with esophageal cancer in the Iranian health system have been developed based on NCCN guidelines). The EMR was a dominant intervention (lower cost and increased LYG and QALY) over esophagectomy and EMR followed by ablation in stage I. For patients with stages II and III ESCC, the CRT followed by surgery compared with CRT alone was cost-effective with an ICER of $2172 per QALY. CRT followed by surgery was also a dominant strategy over esophagectomy.

Our economic evaluation showed that the optimal treatment would be EMR in stage I of ESCC. A cost-saving of $1097 and $268 per patient was obtained for EMR treatment compared with esophagectomy and EMR followed by ablation, respectively. Furthermore, for patients with advanced ESCC (stage II and III), CRT followed by surgery saved $915 and 0.384 QALY compared to esophagectomy, and CRT followed by surgery was a cost-effective treatment with an ICER of $2172 per QALY versus CRT.

The number of studies associated with the economic evaluation of EC treatment is limited. However, studies have been conducted in recent years, evaluating the economics of EC intervention. Chu et al. developed a Markov model to evaluate treatment procedurals in the T1a and T1b of esophageal adenocarcinoma. They compared esophagectomy versus endoscopic treatment in terms of CEA. The results showed that esophagectomy in patients with T1a of EC resulted in more life-years gained than endoscopic therapy but lower QALYs compared to endoscopy. Also, they indicated that in patients with T1b, esophagectomy was not cost-effective compared to endoscopic treatment [22]. Khioe et al. reported that adjuvant statin therapy followed by surgery was dominant over no-statin therapy. This study reported a cost-saving of £6781 per patient [64]. Another study by Lin et al. evaluated the cost-effectiveness of neoadjuvant concurrent chemoradiotherapy (NCCRT) versus esophagectomy in locally advanced ESCC, using a payer’s perspective. They showed that NCCRT had higher costs and survival rates compared to esophagectomy. The ICER was estimated at US$ 39,060 per LYG [65].

The current study results were robust to variability and uncertainty using the Markov model’s estimates, as shown in Table 3. The sensitivity analysis indicated that changing individual parameters to the maximum and minimum levels did not change the base case results. For patients with intermediate ESCC, the probability of death and transition of no-recurrence state to metastasis in the esophagectomy strategy had a minor impact on the ICER. Esophagectomy could be cost-effective versus EMR, with an ICER of $34,768 per QALY, if the probability of mortality was reduced to less than 4% for the esophagectomy intervention. This ICER of $34,768 is more than three-times the Iranian GDP per capita. Most studies have reported a probability of more than 4% for postoperative mortality in esophagectomy [8, 66]. For patients with advanced ESCC, the base case results were only sensitive to the transition from no-recurrence to a dead state in esophagectomy. If this probability is reduced to less than 4%, compared to CRT followed by surgery, the esophagectomy intervention would be cost-effective with an ICER of $3513 per QALY. Furthermore, the cost sensitivity analysis showed that varying interventions cost did not change the base case results. If the cost of esophagectomy is reduced to more than 60%, the esophagectomy intervention would be cost-effective. At present, the Iran’s health system cannot reduce the cost of interventions to this level.

The current study has some limitations due to data availability and assumptions. First, we calculated the costs of treatment interventions based on the Iranian health system's perspective. Since health care systems in countries are different in terms of health services costs, generalizing the study findings is cautioned. Second, we extracted the Markov model data from different studies due to the lack of randomized controlled trials. These studies evaluated different patient populations with confounding variables that may have affected the results found herein. Third, the studies on the economic evaluation of cancer treatment interventions depended on the time of diagnosis. We assumed that patients would be diagnosed early. However, many patients were in the advanced stage when referred for treatment, especially in EC, due high mortality rates identified.

Despite the stated limitations, the study has several strengths. Most importantly, this study evaluated the cost-effectiveness of treatment strategies for ESCC patients based on stage. It can be a guide for therapists to determine the most cost-effective treatment for patients with ESCC. These results can reduce the treatment expenditure for patients and their families. This result is also relevant for countries with high EC rates, especially for low and middle-income countries.

Conclusion

Based on available evidence, EMR appears to be the dominant strategy versus esophagectomy and EMR followed by ablation in the early stage. CRT followed by surgery is a cost-effective intervention compared to CRT alone and esophagectomy for patients with advanced ESCC. These results are sensitive to postoperative mortality, and the transition from no-recurrence to dead state on interventions. Since evidence-based policymaking for selecting the therapeutic producers depends on the analysis of clinical data and economic data to control the costs of cancers and resource allocation in the health sector, this study could provide insights to health care systems similar to Iran's.

Availability of data and materials

The essential data is available in the article and we can provide upon request.

Abbreviations

EC:

Esophageal cancer

ESCC:

Esophageal squamous cell carcinoma

CRT:

Chemoradiotherapy

ICER:

Incremental cost-effectiveness ratio

CEA:

Cost-effectiveness analysis

ACER:

Average cost-effectiveness ratio

WHO:

World Health Organization

GDP:

Gross domestic product

QALYs:

Quality-adjusted life-years

NCCRT:

Neoadjuvant concurrent chemoradiotherapy

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. 2018;68(6):394–424.

    PubMed  Google Scholar 

  2. Darabi M, Lari MA, Motevalian SA, Motlagh A, Arsang-Jang S, Jaberi MK. Trends in gastrointestinal cancer incidence in Iran, 2001–2010: a joinpoint analysis. Epidemiol Health. 2016. https://doi.org/10.4178/epih.e2016056.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Zhang H-Z, Jin G-F, Shen H-B. Epidemiologic differences in esophageal cancer between Asian and Western populations. Chin J Cancer. 2012;31(6):281.

    PubMed  PubMed Central  Google Scholar 

  4. Rafiemanesh H, Maleki F, Mohammadian-Hafshejani A, Salemi M, Salehiniya H. The trend in histological changes and the incidence of esophagus cancer in Iran (2003–2008). Int J Prev Med. 2016. https://doi.org/10.4103/2008-7802.175990.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kim HL, Puymon MR, Qin M, Guru K, Mohler JL. NCCN Clinical practice guidelines in oncology™. J NatlCompr Cancer Netw. 2013.

  6. Chen ZY, Yang YC, Liu LM, Liu XG, Li Y, Li LP, et al. Comparison of the clinical value of multi-band mucosectomy versus endoscopic mucosal resection for the treatment of patients with early-stage esophageal cancer. Oncol Lett. 2015;9(6):2716–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Watanabe M, Otake R, Kozuki R, Toihata T, Takahashi K, Okamura A, et al. Recent progress in multidisciplinary treatment for patients with esophageal cancer. Surg Today. 2019;50(1):12–20.

    PubMed  PubMed Central  Google Scholar 

  8. Blencowe NS, Strong S, McNair AG, Brookes ST, Crosby T, Griffin SM, et al. Reporting of short-term clinical outcomes after esophagectomy: a systematic review. Ann Surg. 2012;255(4):658–66.

    PubMed  Google Scholar 

  9. Arya S, Markar S, Karthikesalingam A, Hanna G. The impact of pyloric drainage on clinical outcome following esophagectomy: a systematic review. Dis Esophagus. 2015;28(4):326–35.

    CAS  PubMed  Google Scholar 

  10. Guo H-M, Zhang X-Q, Chen M, Huang S-L, Zou X-P. Endoscopic submucosal dissection vs endoscopic mucosal resection for superficial esophageal cancer. World J Gastroenterol. 2014;20(18):5540.

    PubMed  PubMed Central  Google Scholar 

  11. Hauser C, Patett C, Von Schoenfels W, Heits N, Schafmayer C, Malchow B, et al. Does neoadjuvant treatment before oncologic esophagectomy affect the postoperative quality of life? A prospective, longitudinal outcome study. Dis Esophagus. 2015;28(7):652–9.

    CAS  PubMed  Google Scholar 

  12. Jin X-F, Gai W, Chai T-H, Li L, Guo J-Q. Comparison of endoscopic resection and minimally invasive esophagectomy in patients with early esophageal cancer. J Clin Gastroenterol. 2017;51(3):223–7.

    PubMed  Google Scholar 

  13. Tie H, He F, Shen J, Zhang B, Ye M, Chen B, et al. Prolonged interval between neoadjuvant chemoradiotherapy and esophagectomy does not benefit the outcome in esophageal cancer: a systematic review and meta-analysis. Dis Esophagus. 2018;31(1):dox116.

    Google Scholar 

  14. Goense L, van der Sluis PC, van Rossum PS, van der Horst S, Meijer GJ, Haj Mohammad N, et al. Perioperative chemotherapy versus neoadjuvant chemoradiotherapy for esophageal or GEJ adenocarcinoma: a propensity score-matched analysis comparing toxicity, pathologic outcome, and survival. J Surg Oncol. 2017;115(7):812–20.

    CAS  PubMed  Google Scholar 

  15. Sanders GD, Neumann PJ, Basu A, Brock DW, Feeny D, Krahn M, et al. Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine. JAMA. 2016;316(10):1093–103.

    PubMed  Google Scholar 

  16. Gray AM, Clarke PM, Wolstenholme JL, Wordsworth S. Applied methods of cost-effectiveness analysis in healthcare. Oxford: Oxford University Press; 2011.

    Google Scholar 

  17. Inadomi JM, Somsouk M, Madanick RD, Thomas JP, Shaheen NJ. A cost-utility analysis of ablative therapy for Barrett’s esophagus. Gastroenterology. 2009;136(7):2101-14 e6.

    PubMed  Google Scholar 

  18. Das A, Wells C, Kim H, Fleischer D, Crowell M, Sharma V. An economic analysis of endoscopic ablative therapy for management of nondysplastic Barrett’s esophagus. Endoscopy. 2009;41(05):400–8.

    CAS  PubMed  Google Scholar 

  19. Patel A, Gyawali CP. Screening for Barrett’s esophagus: balancing clinical value and cost-effectiveness. J Neurogastroenterol Motil. 2019;25(2):181.

    PubMed  PubMed Central  Google Scholar 

  20. Gordon LG, Hirst NG, Mayne GC, Watson DI, Bright T, Cai W, et al. Modeling the cost-effectiveness of strategies for treating esophageal adenocarcinoma and high-grade dysplasia. J Gastrointest Surg. 2012;16(8):1451–61.

    PubMed  Google Scholar 

  21. Meads DM, Marshall A, Hulme CT, Dunn JA, Ford HE. The cost effectiveness of docetaxel and active symptom control versus active symptom control alone for refractory oesophagogastric adenocarcinoma: economic analysis of the COUGAR-02 trial. Pharmacoeconomics. 2016;34(1):33–42.

    PubMed  Google Scholar 

  22. Chu JN, Choi J, Tramontano A, Morse C, Forcione D, Nishioka NS, et al. Surgical vs endoscopic management of T1 esophageal adenocarcinoma: a modeling decision analysis. Clin Gastroenterol Hepatol. 2018;16(3):392-400 e6.

    PubMed  Google Scholar 

  23. Faramarzi A, Daroudi R, Nahvijou A, Sari AA, Arab M, Kalaghchi B. Economic evaluation of treatments for patients with esophageal cancer: a systematic review. Int J Cancer Manag. 2019;12(3):631.

    Google Scholar 

  24. Bertram MY, Lauer JA, De Joncheere K, Edejer T, Hutubessy R, Kieny M-P, et al. Cost–effectiveness thresholds: pros and cons. Bull World Health Organ. 2016;94(12):925.

    PubMed  PubMed Central  Google Scholar 

  25. The World Bank Data, World Development Indicators. https://data.worldbank.org/indicator/SL.GDP.PCAP.EM.KD. Accessed 27 Nov 2020.

  26. Chen J, Lin Y, Cai W, Su T, Wang B, Li J, et al. A new clinical staging system for esophageal cancer to predict survival after definitive chemoradiation or radiotherapy. Dis Esophagus. 2018;31(11):043.

    Google Scholar 

  27. Childs DS, Yoon HH, Eiring RA, Jin Z, Jochum JA, Pitot HC, et al. Falls: descriptive rates and circumstances in age-unspecified patients with locally advanced esophageal cancer. Support Care Cancer. 2021;29:733–9.

    PubMed  Google Scholar 

  28. The National Comprehensive Cancer Network® (NCCN®). https://www.nccn.org/patientresources/patient-resources/. Accessed 10 Dec 2021.

  29. Ajani JA, D’Amico TA, Bentrem DJ, Chao J, Corvera C, Das P, et al. Esophageal and esophagogastric junction cancers, version 2. 2019, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2019;17(7):855–83.

    CAS  Google Scholar 

  30. Yibulayin W, Abulizi S, Lv H, Sun W. Minimally invasive oesophagectomy versus open esophagectomy for resectable esophageal cancer: a meta-analysis. World J Surg Oncol. 2016;14(1):1–17.

    Google Scholar 

  31. van der Sluis PC, van der Horst S, May AM, Schippers C, Brosens LA, Joore HC, et al. Robot-assisted minimally invasive thoracolaparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer: a randomized controlled trial. Ann Surg. 2019;269(4):621–30.

    PubMed  Google Scholar 

  32. Gottlieb-Vedi E, Kauppila JH, Mattsson F, Lindblad M, Nilsson M, Lagergren P, et al. Long-term survival in esophageal cancer after minimally invasive esophagectomy compared to open esophagectomy. Annals Surg. 2021. https://doi.org/10.1097/sla.0000000000004645.

    Article  Google Scholar 

  33. Liu J, Liu X, Zhang J, Liu Q, Hu W. Impact of splenic node dissection on short-term outcome and survival following esophagectomy. Eur J Surg Oncol. 2017;43(2):440–4.

    CAS  PubMed  Google Scholar 

  34. Hu Y, Puri V, Shami VM, Stukenborg GJ, Kozower BD. Comparative effectiveness of esophagectomy versus endoscopic treatment for esophageal high-grade dysplasia. Ann Surg. 2016;263(4):719–26.

    PubMed  Google Scholar 

  35. Miyata H, Yamasaki M, Makino T, Miyazaki Y, Takahashi T, Kurokawa Y, et al. Clinical outcome of esophagectomy in elderly patients with and without neoadjuvant therapy for thoracic esophageal cancer. Ann Surg Oncol. 2015;22(3):794–801.

    Google Scholar 

  36. Matsuda S, Takeuchi H, Kawakubo H, Shimada A, Fukuda K, Nakamura R, et al. Clinical outcome of transthoracic esophagectomy with thoracic duct resection: number of dissected lymph node and distribution of lymph node metastasis around the thoracic duct. Medicine. 2016. https://doi.org/10.1097/MD.0000000000003839.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Nelson DB, Dhupar R, Katkhuda R, Correa A, Goltsov A, Maru D, et al. Outcomes after endoscopic mucosal resection or esophagectomy for submucosal esophageal adenocarcinoma. J Thorac Cardiovasc Surg. 2018;156(1):406-13 e3.

    PubMed  Google Scholar 

  38. McCann P, Stafinski T, Wong C, Menon D. The safety and effectiveness of endoscopic and non-endoscopic approaches to the management of early esophageal cancer: a systematic review. Cancer Treat Rev. 2011;37(1):11–62.

    PubMed  Google Scholar 

  39. Peters JH, Watson TA. Endoscopic mucosal resection of Barrett’s esophagus and early esophageal cancer. J Gastrointest Surg. 2011;15(8):1299.

    PubMed  Google Scholar 

  40. Pouw RE, Gondrie JJ, Sondermeijer CM, Fiebo J, Van Gulik TM, Krishnadath KK, et al. Eradication of Barrett esophagus with early neoplasia by radiofrequency ablation, with or without endoscopic resection. J Gastrointest Surg. 2008;12(10):1627–37.

    PubMed  Google Scholar 

  41. Qumseya BJ, Wani S, Desai M, Qumseya A, Bain P, Sharma P, et al. Adverse events after radiofrequency ablation in patients with Barrett’s esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2016;14(8):1086-95 e6.

    PubMed  Google Scholar 

  42. Schlottmann F, Patti MG, Shaheen NJ. Endoscopic treatment of high-grade dysplasia and early esophageal cancer. World J Surg. 2017;41(7):1705–11.

    PubMed  Google Scholar 

  43. Desai M, Saligram S, Gupta N, Vennalaganti P, Bansal A, Choudhary A, et al. Efficacy and safety outcomes of multimodal endoscopic eradication therapy in Barrett’s esophagus-related neoplasia: a systematic review and pooled analysis. Gastrointest Endosc. 2017;85(3):482–95.

    PubMed  Google Scholar 

  44. Cotton CC, Wolf WA, Pasricha S, Li N, Madanick RD, Spacek MB, et al. Recurrent intestinal metaplasia after radiofrequency ablation for Barrett’s esophagus: endoscopic findings and anatomic location. Gastrointest Endosc. 2015;81(6):1362–9.

    PubMed  PubMed Central  Google Scholar 

  45. Haidry RJ, Dunn JM, Butt MA, Burnell MG, Gupta A, Green S, et al. Radiofrequency ablation and endoscopic mucosal resection for dysplastic Barrett’s esophagus and early esophageal adenocarcinoma: outcomes of the UK National Halo RFA Registry. Gastroenterology. 2013;145(1):87–95.

    PubMed  Google Scholar 

  46. Gupta M, Iyer PG, Lutzke L, Gorospe EC, Abrams JA, Falk GW, et al. Recurrence of esophageal intestinal metaplasia after endoscopic mucosal resection and radiofrequency ablation of Barrett’s esophagus: results from a US Multicenter Consortium. Gastroenterology. 2013;145(1):79-86 e1.

    PubMed  Google Scholar 

  47. Hu W, Liang Y, Zhang S, Hu Y, Liu J. Impact of subcarinal dissection on short-term outcome and survival following esophagectomy. Am J Surg. 2013;206(3):314–9.

    PubMed  Google Scholar 

  48. Hong L, Zhang Y, Zhang H, Yang J, Zhao Q. The short-term outcome of three-field minimally invasive esophagectomy for Siewert type I esophagogastric junctional adenocarcinoma. Ann Thorac Surg. 2013;96(5):1826–31.

    PubMed  Google Scholar 

  49. Reeh M, Metze J, Uzunoglu FG, Nentwich M, Ghadban T, Wellner U, et al. The PER (preoperative esophagectomy risk) score: a simple risk score to predict short-term and long-term outcome in patients with surgically treated esophageal cancer. Medicine. 2016. https://doi.org/10.1097/MD.0000000000002724.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Wilke TJ, Bhirud AR, Lin C. A review of the impact of preoperative chemoradiotherapy on outcome and postoperative complications in esophageal cancer patients. Am J Clin Oncol. 2015;38(4):415–21.

    CAS  PubMed  Google Scholar 

  51. Bhatti ABH, Rizvi FH, Waheed A, Raza SH, Syed AA, Khattak S, et al. Does prior percutaneous endoscopic gastrostomy alter post-operative outcome after esophagectomy. World J Surg. 2015;39(2):441–5.

    PubMed  Google Scholar 

  52. Makino T, Doki Y. Treatment of T4 esophageal cancer. Definitive chemo-radiotherapy vs chemo-radiotherapy followed by surgery. Annals Thorac Cardiovas Surg. 2011;17(3):221–8.

    Google Scholar 

  53. Luu TD, Gaur P, Force SD, Staley CA, Mansour KA, Miller JI Jr, et al. Neoadjuvant chemoradiation versus chemotherapy for patients undergoing esophagectomy for esophageal cancer. Ann Thorac Surg. 2008;85(4):1217–24.

    PubMed  Google Scholar 

  54. Kim JW, Roh J-L, Gong G, Cho K-J, Choi S-H, Nam SY, et al. Treatment outcomes and risk factors for recurrence after definitive surgery of locally invasive well-differentiated papillary thyroid carcinoma. Thyroid. 2016;26(2):262–70.

    CAS  PubMed  Google Scholar 

  55. Jing Z, Chen T, Zhang X, Wu S. Long-term outcome of concurrent chemoradiotherapy with elective nodal irradiation for inoperable esophageal cancer. Cancer Sci. 2017;108(9):1828–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Schena M, La Rovere E, Solerio D, Bustreo S, Barone C, Daniele L, et al. Neoadjuvant chemo-radiotherapy for locally advanced esophageal cancer: a monocentric study. Tumori Journal. 2012;98(4):451–7.

    CAS  PubMed  Google Scholar 

  57. Wang Y, Shi J, Du L, Huang H, Wang L, Zhu J, et al. Health-related quality of life in patients with esophageal cancer or precancerous lesions assessed by EQ-5D: a multicenter cross-sectional study. Thoracic cancer. 2020;11(4):1076–89.

    PubMed  PubMed Central  Google Scholar 

  58. Doherty M, Leung Y, Su J, Naik H, Patel D, Eng L, et al. Health utility scores from EQ-5D and health-related quality of life in patients with esophageal cancer: a real-world cross-sectional study. Dis Esophagus. 2018;31(12):058.

    Google Scholar 

  59. Max W, Sung H-Y, Stark B. The economic burden of breast cancer in California. Breast Cancer Res Treat. 2009;116(1):201–7.

    PubMed  Google Scholar 

  60. Bonneux L, Birnie E. The discount rate in the economic evaluation of prevention: a thought experiment. J Epidemiol Community Health. 2001;55(2):123–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Zhan M, Zheng H, Yang Y, Xu T, Li Q. Cost-effectiveness analysis of neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced esophageal squamous cell carcinoma based on the NEOCRTEC5010 trial. Radiother Oncol. 2019;141:27–32.

    PubMed  Google Scholar 

  62. Pil L, Fobelets M, Putman K, Trybou J, Annemans L. Cost-effectiveness and budget impact analysis of a population-based screening program for colorectal cancer. Eur J Intern Med. 2016;32:72–8.

    CAS  PubMed  Google Scholar 

  63. Javadinasab H, Daroudi R, Salimzadeh H, Delavari A, Vezvaie P, Malekzadeh R. Cost-effectiveness of screening colonoscopy in Iranian high risk population. Arch Iran Med. 2017;20(9):564–71.

    PubMed  Google Scholar 

  64. Khioe RFS, Skedgel C, Hart A, Lewis MPN, Alexandre L. Adjuvant statin therapy for esophageal adenocarcinoma: a cost-utility analysis. Pharmacoeconomics. 2018;36(3):349–58.

    Google Scholar 

  65. Lin CY, Fang HY, Feng CL, Li CC, Chien CR. Cost-effectiveness of neoadjuvant concurrent chemoradiotherapy versus esophagectomy for locally advanced esophageal squamous cell carcinoma: a population-based matched case-control study. Thorac Cancer. 2016;7(3):288–95.

    PubMed  Google Scholar 

  66. Glatz T, Kulemann B, Marjanovic G, Bregenzer S, Makowiec F, Hoeppner J. Postoperative fluid overload is a risk factor for adverse surgical outcome in patients undergoing esophagectomy for esophageal cancer: a retrospective study in 335 patients. BMC Surg. 2017;17(1):6.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

All authors are appreciating from managers and staff of Imam Khomeini hospital at Tehran University medical of Sciences and Cancer Institute of Iran, for providing the data.

Funding

This work was supported by the Tehran University of Medical Sciences.

Author information

Authors and Affiliations

Authors

Contributions

AF and RD were the principal investigators of the research and designed the study. AF, AN and MA collected data, managed and analyzed the data. BK, AAS and JJN drafted the first version of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ahmad Faramarzi.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of the Cancer Institute of Iran at Tehran University of Medical Sciences. (IR.TUMS.SPH.REC.1396.3135).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1

: Appendix S1. Results of one-way sensitivity analyses in Stage I. EMR: Endoscopic Mucosal Resection, EMR &ABL: Endoscopic Mucosal Resection followed by ablation, ESO: Esophagectomy. Appendix S2. Results of one-way sensitivity analyses in Stage II and III. CRT: Chemoradiotherapy, CRT_ESO: Chemoradiotherapy followed by surgery, ESO: Esophagectomy.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Daroudi, R., Nahvijou, A., Arab, M. et al. A cost-effectiveness modeling study of treatment interventions for stage I to III esophageal squamous cell carcinoma. Cost Eff Resour Alloc 20, 16 (2022). https://doi.org/10.1186/s12962-022-00352-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12962-022-00352-5

Keywords

  • Esophageal cancer
  • Stage
  • Cost-effectiveness analysis