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Does oesophageal stenosis have any impact on survival of oesophageal cancer patients?

Does oesophageal stenosis have any impact on survival of oesophageal cancer patients? Abstract A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was ‘Does oesophageal stenosis have any impact on survival of oesophageal cancer patients?’. A total of 542 papers were found using the reported search, of which 8 cohort studies represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Most of these studies defined stenosis as failure to cross the tumour at endoscopic ultrasonography. Seven studies demonstrated that oesophageal cancer patients with stenosis had significantly poorer survival than those without, while 2 studies found that oesophageal stenosis was also a predictor of poor recurrence-free survival. We conclude that oesophageal stenosis is a predictor of poor prognosis in patients with oesophageal cancer. Oesophageal cancer , Stenosis , Survival INTRODUCTION A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1]. THREE-PART QUESTION In [patients with oesophageal cancer] does [oesophageal stenosis] have any impact on [survival]? CLINICAL SCENARIO A patient newly diagnosed with oesophageal cancer was intended to undergo oesophageactomy with lymphadenectomy in our department. This patient was found to have non-traversable oesophageal stenosis during preoperative endoscopic examination. The patient asked whether his stenosis could influence his long-term survival. One of my colleagues answered that there was an evidence that oesophageal stenosis was correlated with poor survival of oesophageal cancer patients. You resolve to check the literature yourself. SEARCH STRATEGY We searched Medline by using the PubMed interface from 1950 to November 2017 with the search terms: (((((((oesophageal[Title/Abstract]) OR esophageal[Title/Abstract]) OR oesophagus[Title/Abstract]) OR esophagus[Title/Abstract])) AND (((cancer[Title/Abstract]) OR carcinoma[Title/Abstract]) OR tumor[Title/Abstract])) AND (((survival[Title/Abstract]) OR prognosis[Title/Abstract]) OR prognostic[Title/Abstract])) AND ((stricture[All Fields]) OR stenosis[All Fields]). SEARCH OUTCOME A total of 542 papers were found using the reported search from the Medline. From these, 8 papers were identified that provided the best evidence to answer the question. These are presented in Table 1. Table 1: Best evidence papers Author, date, journal and country Study type (level of evidence)  Patient group  Outcomes  Key results  Comments  Hiele et al. (1997), Gastrointest Endosc, Belgium [2] Cohort study (level 3)  86 patients with oesophageal cancer mainly undergoing surgery (stenosis group: 27 patients; non-stenosis group: 59 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 20 months (P = 0.02)    Mariette et al. (2003), Br J Surg, France [3] Cohort study (level 3)  150 patients with oesophageal cancer undergoing curative resection (stenosis group: 23 patients; non-stenosis group: 127 patients) Stenosis definition: failure to be traversed at endoscopic ultrasonography  Median survival time  Stenosis group: 23 months vs non-stenosis group: 54 months (P = 0.004)    Morgan et al. (2008), Dis Esophagus, UK [4] Cohort study (level 3)  411 patients with oesophageal cancer undergoing surgery, chemoradiotherapy or palliative therapy (stenosis group: 12 patients; non-stenosis group: 399 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 24 months (P = 0.105)  The sample size of patients in the stenosis group was small  du Rieu et al, 2013, J Cardiothorac Surg, France [5] Cohort study (level 3)  120 patients with oesophageal cancer undergoing oesophagectomy (stenosis group: 69 patients; non-stenosis group: 51 patients) Stenosis definition: difficulty or inability for the fibrescope to pass through the lesion and/or at least a hemicircumferential narrowing light on barium swallow  5-year relapse-free survival rate  Stenosis group: 31.8% vs non-stenosis group: 77.9% (P < 0.0001)     Relapse-free survival  HR 3.36, 95% CI 1.68–6.72; P = 0.001  Clavier et al. (2014), Dis Esophagus, France [6] Cohort study (level 3)  143 patients with oesophageal cancer undergoing definitive chemoradiotherapy (stenosis group: 40 patients; non-stenosis group: 103 patients) Stenosis definition: non-traversable oesophageal stricture by a conventional endoscope  Median survival time  Stenosis group: 16.6 months vs non-stenosis group: 24.3 months (P = 0.12)     Locoregional recurrence-free survival  HR 1.35, 95% CI 1.05–1.75; P = 0.021  Cho et al. (2017), Korean J Intern Med, Korea [7] Cohort study (level 3)  89 patients with locoregional oesophageal cancer undergoing multimodality therapy (stenosis group: 26 patients; non-stenosis group: 63 patients) Stenosis definition: endoscopic ultrasonography non-traversable  5-year survival rates  Stenosis group: 30.8% vs non-stenosis group: 49.3% (P = 0.023)     Overall survival  HR 2.47, 95% CI 1.37–4.46; P = 0.003  Yang et al. (2017), Oncotarget, China [8] Cohort study (level 3)  508 patients with oesophageal squamous cell carcinoma undergoing oesophagectomy (stenosis group: 139 patients; non-stenosis group: 369 patients) Stenosis definition: significant stenosis allowing endoscopic passage with remarkable resistance or severe stenosis, preventing passage of the endoscope through the tumour site  5-year survival rates  Stenosis group: 27.7% vs non-stenosis group: 40.5% (P < 0.001)   The sample size of patients in the stenosis group was relatively large (compared with Morgan, above)  Overall survival  HR 1.31, 95% CI 1.02–1.69; P = 0.036  Okuno et al. (2017), Int J Clin Oncol, Japan [9] Cohort study (level 3)  131 patients with oesophageal cancer undergoing chemoradiotherapy (stenosis group: 61 patients; non-stenosis group: 70 patients) Stenosis definition: patients who experienced dysphagia or patients whose primary lesions were too narrow for an endoscopy to be performed  Median survival time  Stenosis group: 9.9 months vs non-stenosis group: 16.0 months (P = 0.001)   Definition of stenosis included dysphagia, which is different from other papers, and, therefore, may be less robust  Overall survival  HR 2.01, 95% CI 1.29–3.14; P = 0.002  Author, date, journal and country Study type (level of evidence)  Patient group  Outcomes  Key results  Comments  Hiele et al. (1997), Gastrointest Endosc, Belgium [2] Cohort study (level 3)  86 patients with oesophageal cancer mainly undergoing surgery (stenosis group: 27 patients; non-stenosis group: 59 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 20 months (P = 0.02)    Mariette et al. (2003), Br J Surg, France [3] Cohort study (level 3)  150 patients with oesophageal cancer undergoing curative resection (stenosis group: 23 patients; non-stenosis group: 127 patients) Stenosis definition: failure to be traversed at endoscopic ultrasonography  Median survival time  Stenosis group: 23 months vs non-stenosis group: 54 months (P = 0.004)    Morgan et al. (2008), Dis Esophagus, UK [4] Cohort study (level 3)  411 patients with oesophageal cancer undergoing surgery, chemoradiotherapy or palliative therapy (stenosis group: 12 patients; non-stenosis group: 399 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 24 months (P = 0.105)  The sample size of patients in the stenosis group was small  du Rieu et al, 2013, J Cardiothorac Surg, France [5] Cohort study (level 3)  120 patients with oesophageal cancer undergoing oesophagectomy (stenosis group: 69 patients; non-stenosis group: 51 patients) Stenosis definition: difficulty or inability for the fibrescope to pass through the lesion and/or at least a hemicircumferential narrowing light on barium swallow  5-year relapse-free survival rate  Stenosis group: 31.8% vs non-stenosis group: 77.9% (P < 0.0001)     Relapse-free survival  HR 3.36, 95% CI 1.68–6.72; P = 0.001  Clavier et al. (2014), Dis Esophagus, France [6] Cohort study (level 3)  143 patients with oesophageal cancer undergoing definitive chemoradiotherapy (stenosis group: 40 patients; non-stenosis group: 103 patients) Stenosis definition: non-traversable oesophageal stricture by a conventional endoscope  Median survival time  Stenosis group: 16.6 months vs non-stenosis group: 24.3 months (P = 0.12)     Locoregional recurrence-free survival  HR 1.35, 95% CI 1.05–1.75; P = 0.021  Cho et al. (2017), Korean J Intern Med, Korea [7] Cohort study (level 3)  89 patients with locoregional oesophageal cancer undergoing multimodality therapy (stenosis group: 26 patients; non-stenosis group: 63 patients) Stenosis definition: endoscopic ultrasonography non-traversable  5-year survival rates  Stenosis group: 30.8% vs non-stenosis group: 49.3% (P = 0.023)     Overall survival  HR 2.47, 95% CI 1.37–4.46; P = 0.003  Yang et al. (2017), Oncotarget, China [8] Cohort study (level 3)  508 patients with oesophageal squamous cell carcinoma undergoing oesophagectomy (stenosis group: 139 patients; non-stenosis group: 369 patients) Stenosis definition: significant stenosis allowing endoscopic passage with remarkable resistance or severe stenosis, preventing passage of the endoscope through the tumour site  5-year survival rates  Stenosis group: 27.7% vs non-stenosis group: 40.5% (P < 0.001)   The sample size of patients in the stenosis group was relatively large (compared with Morgan, above)  Overall survival  HR 1.31, 95% CI 1.02–1.69; P = 0.036  Okuno et al. (2017), Int J Clin Oncol, Japan [9] Cohort study (level 3)  131 patients with oesophageal cancer undergoing chemoradiotherapy (stenosis group: 61 patients; non-stenosis group: 70 patients) Stenosis definition: patients who experienced dysphagia or patients whose primary lesions were too narrow for an endoscopy to be performed  Median survival time  Stenosis group: 9.9 months vs non-stenosis group: 16.0 months (P = 0.001)   Definition of stenosis included dysphagia, which is different from other papers, and, therefore, may be less robust  Overall survival  HR 2.01, 95% CI 1.29–3.14; P = 0.002  CI: confidence interval; HR: hazard ratio. Table 1: Best evidence papers Author, date, journal and country Study type (level of evidence)  Patient group  Outcomes  Key results  Comments  Hiele et al. (1997), Gastrointest Endosc, Belgium [2] Cohort study (level 3)  86 patients with oesophageal cancer mainly undergoing surgery (stenosis group: 27 patients; non-stenosis group: 59 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 20 months (P = 0.02)    Mariette et al. (2003), Br J Surg, France [3] Cohort study (level 3)  150 patients with oesophageal cancer undergoing curative resection (stenosis group: 23 patients; non-stenosis group: 127 patients) Stenosis definition: failure to be traversed at endoscopic ultrasonography  Median survival time  Stenosis group: 23 months vs non-stenosis group: 54 months (P = 0.004)    Morgan et al. (2008), Dis Esophagus, UK [4] Cohort study (level 3)  411 patients with oesophageal cancer undergoing surgery, chemoradiotherapy or palliative therapy (stenosis group: 12 patients; non-stenosis group: 399 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 24 months (P = 0.105)  The sample size of patients in the stenosis group was small  du Rieu et al, 2013, J Cardiothorac Surg, France [5] Cohort study (level 3)  120 patients with oesophageal cancer undergoing oesophagectomy (stenosis group: 69 patients; non-stenosis group: 51 patients) Stenosis definition: difficulty or inability for the fibrescope to pass through the lesion and/or at least a hemicircumferential narrowing light on barium swallow  5-year relapse-free survival rate  Stenosis group: 31.8% vs non-stenosis group: 77.9% (P < 0.0001)     Relapse-free survival  HR 3.36, 95% CI 1.68–6.72; P = 0.001  Clavier et al. (2014), Dis Esophagus, France [6] Cohort study (level 3)  143 patients with oesophageal cancer undergoing definitive chemoradiotherapy (stenosis group: 40 patients; non-stenosis group: 103 patients) Stenosis definition: non-traversable oesophageal stricture by a conventional endoscope  Median survival time  Stenosis group: 16.6 months vs non-stenosis group: 24.3 months (P = 0.12)     Locoregional recurrence-free survival  HR 1.35, 95% CI 1.05–1.75; P = 0.021  Cho et al. (2017), Korean J Intern Med, Korea [7] Cohort study (level 3)  89 patients with locoregional oesophageal cancer undergoing multimodality therapy (stenosis group: 26 patients; non-stenosis group: 63 patients) Stenosis definition: endoscopic ultrasonography non-traversable  5-year survival rates  Stenosis group: 30.8% vs non-stenosis group: 49.3% (P = 0.023)     Overall survival  HR 2.47, 95% CI 1.37–4.46; P = 0.003  Yang et al. (2017), Oncotarget, China [8] Cohort study (level 3)  508 patients with oesophageal squamous cell carcinoma undergoing oesophagectomy (stenosis group: 139 patients; non-stenosis group: 369 patients) Stenosis definition: significant stenosis allowing endoscopic passage with remarkable resistance or severe stenosis, preventing passage of the endoscope through the tumour site  5-year survival rates  Stenosis group: 27.7% vs non-stenosis group: 40.5% (P < 0.001)   The sample size of patients in the stenosis group was relatively large (compared with Morgan, above)  Overall survival  HR 1.31, 95% CI 1.02–1.69; P = 0.036  Okuno et al. (2017), Int J Clin Oncol, Japan [9] Cohort study (level 3)  131 patients with oesophageal cancer undergoing chemoradiotherapy (stenosis group: 61 patients; non-stenosis group: 70 patients) Stenosis definition: patients who experienced dysphagia or patients whose primary lesions were too narrow for an endoscopy to be performed  Median survival time  Stenosis group: 9.9 months vs non-stenosis group: 16.0 months (P = 0.001)   Definition of stenosis included dysphagia, which is different from other papers, and, therefore, may be less robust  Overall survival  HR 2.01, 95% CI 1.29–3.14; P = 0.002  Author, date, journal and country Study type (level of evidence)  Patient group  Outcomes  Key results  Comments  Hiele et al. (1997), Gastrointest Endosc, Belgium [2] Cohort study (level 3)  86 patients with oesophageal cancer mainly undergoing surgery (stenosis group: 27 patients; non-stenosis group: 59 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 20 months (P = 0.02)    Mariette et al. (2003), Br J Surg, France [3] Cohort study (level 3)  150 patients with oesophageal cancer undergoing curative resection (stenosis group: 23 patients; non-stenosis group: 127 patients) Stenosis definition: failure to be traversed at endoscopic ultrasonography  Median survival time  Stenosis group: 23 months vs non-stenosis group: 54 months (P = 0.004)    Morgan et al. (2008), Dis Esophagus, UK [4] Cohort study (level 3)  411 patients with oesophageal cancer undergoing surgery, chemoradiotherapy or palliative therapy (stenosis group: 12 patients; non-stenosis group: 399 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 24 months (P = 0.105)  The sample size of patients in the stenosis group was small  du Rieu et al, 2013, J Cardiothorac Surg, France [5] Cohort study (level 3)  120 patients with oesophageal cancer undergoing oesophagectomy (stenosis group: 69 patients; non-stenosis group: 51 patients) Stenosis definition: difficulty or inability for the fibrescope to pass through the lesion and/or at least a hemicircumferential narrowing light on barium swallow  5-year relapse-free survival rate  Stenosis group: 31.8% vs non-stenosis group: 77.9% (P < 0.0001)     Relapse-free survival  HR 3.36, 95% CI 1.68–6.72; P = 0.001  Clavier et al. (2014), Dis Esophagus, France [6] Cohort study (level 3)  143 patients with oesophageal cancer undergoing definitive chemoradiotherapy (stenosis group: 40 patients; non-stenosis group: 103 patients) Stenosis definition: non-traversable oesophageal stricture by a conventional endoscope  Median survival time  Stenosis group: 16.6 months vs non-stenosis group: 24.3 months (P = 0.12)     Locoregional recurrence-free survival  HR 1.35, 95% CI 1.05–1.75; P = 0.021  Cho et al. (2017), Korean J Intern Med, Korea [7] Cohort study (level 3)  89 patients with locoregional oesophageal cancer undergoing multimodality therapy (stenosis group: 26 patients; non-stenosis group: 63 patients) Stenosis definition: endoscopic ultrasonography non-traversable  5-year survival rates  Stenosis group: 30.8% vs non-stenosis group: 49.3% (P = 0.023)     Overall survival  HR 2.47, 95% CI 1.37–4.46; P = 0.003  Yang et al. (2017), Oncotarget, China [8] Cohort study (level 3)  508 patients with oesophageal squamous cell carcinoma undergoing oesophagectomy (stenosis group: 139 patients; non-stenosis group: 369 patients) Stenosis definition: significant stenosis allowing endoscopic passage with remarkable resistance or severe stenosis, preventing passage of the endoscope through the tumour site  5-year survival rates  Stenosis group: 27.7% vs non-stenosis group: 40.5% (P < 0.001)   The sample size of patients in the stenosis group was relatively large (compared with Morgan, above)  Overall survival  HR 1.31, 95% CI 1.02–1.69; P = 0.036  Okuno et al. (2017), Int J Clin Oncol, Japan [9] Cohort study (level 3)  131 patients with oesophageal cancer undergoing chemoradiotherapy (stenosis group: 61 patients; non-stenosis group: 70 patients) Stenosis definition: patients who experienced dysphagia or patients whose primary lesions were too narrow for an endoscopy to be performed  Median survival time  Stenosis group: 9.9 months vs non-stenosis group: 16.0 months (P = 0.001)   Definition of stenosis included dysphagia, which is different from other papers, and, therefore, may be less robust  Overall survival  HR 2.01, 95% CI 1.29–3.14; P = 0.002  CI: confidence interval; HR: hazard ratio. RESULTS In 1997, Hiele et al. [2] explored the relationship between endoscopic ultrasound (EUS) findings and outcomes of patients with tumours of the oesophagus or oesophagogastric junction for the first time. They found that patients with oesophageal stenosis that could not be passed by EUS yielded significantly shorter median survival time than those whose stenosis could be passed (10 and 20 months, respectively; P = 0.02), indicating that oesophageal stenosis had a negative impact on the prognosis of oesophageal cancer patients. Mariette et al. [3] also explored the value of EUS as a predictor of long-term survival in oesophageal cancer patients treated with surgery, and they found that the median survival time of patients with oesophageal stenosis was significantly shorter than that of patients without stenosis (23 and 54 months, respectively; P = 0.004). Their study indicated that oesophageal stenosis was significantly correlated with poor survival of oesophageal cancer patients. However, Morgan et al. [4] conducted a study especially focusing on the prognostic value of failure to cross oesophageal cancer by EUS. Although there was shorter median survival in patients with oesophageal stenosis when compared to those without (10 and 24 months, respectively), this was not significant (P = 0.105). However, there were only 12 patients with oesophageal stenosis in their study population with 411 patients. In 2013, du Rieu et al. [5] explored the recurrence risk of oesophageal cancer patients after oesophagectomy. They found that patients with oesophageal stenosis had significantly lower 5-year recurrence-free survival than patients without (31.8% and 77.9%, respectively; P < 0.0001). Moreover, in the multivariate analysis of recurrence risk, they found that oesophageal stenosis was a significant prognostic factor associated with an increased risk of local relapse [hazard ratio (HR) 3.36, 95% confidence interval (CI) 1.68–6.72; P = 0.001]. Clavier et al. [6] explored the prognostic factors of oesophageal cancer patients treated with definitive chemoradiotherapy and found that there was no significant difference of overall survival time between patients with oesophageal stenosis and those without (16.6 and 24.3 months, respectively; P = 0.12). However, they found that oesophageal stenosis was significantly correlated with poor recurrence-free survival of oesophageal cancer patients (HR 1.35, 95% CI 1.05–1.75; P = 0.021). Recently, Cho et al. [7] explored the role of EUS non-traversability in patients with oesophageal cancer treated with multimodality therapy. They found that patients with oesophageal stenosis yielded significantly lower 5-year survival rate than patients without (30.8% and 49.3%, respectively; P = 0.023) and oesophageal stenosis was a significant prognostic factor of poor overall survival of oesophageal cancer patients treated with multimodality therapy (HR 2.47, 95% CI 1.37–4.46; P = 0.003). Yang et al. [8] conducted a similar study in patients treated with oesophagectomy and also found that patients with oesophageal stenosis yielded significantly lower 5-year survival rate than patients without (27.7% and 40.5%, respectively; P < 0.001), and oesophageal stenosis was a significant prognostic factor of poor overall survival of oesophageal cancer patients (HR 1.31, 95% CI 1.02–1.69; P = 0.036). Okuno et al. [9] also confirmed that oesophageal stenosis was significantly correlated with poor survival of oesophageal cancer patients treated with chemoradiotherapy (HR 2.01, 95% CI 1.29–3.14; P = 0.002). However, their definition of stenosis differed from previous studies by defining both patients who experienced dysphagia and patients whose primary lesions were too narrow for an endoscopy to be performed as stenosis. CLINICAL BOTTOM LINE Oesophageal stenosis is a predictor of poor median, overall and recurrence-free survival in patients with oesophageal cancer. This remains the case whether treated with surgical resection, chemoradiotherapy or palliative treatment. ACKNOWLEDGEMENTS We thank the great efforts of Ralph William White from the James Cook University Hospital, Middlesbrough, UK. Conflict of interest: none declared. REFERENCES 1 Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact CardioVasc Thorac Surg  2003; 2: 405– 9. Google Scholar CrossRef Search ADS PubMed  2 Hiele M, De Leyn P, Schurmans P, Lerut A, Huys S, Geboes K et al.   Relation between endoscopic ultrasound findings and outcome of patients with tumors of the esophagus or esophagogastric junction. Gastrointest Endosc  1997; 45: 381– 6. Google Scholar CrossRef Search ADS PubMed  3 Mariette C, Balon JM, Maunoury V, Taillier G, Van Seuningen I, Triboulet JP. Value of endoscopic ultrasonography as a predictor of long-term survival in oesophageal carcinoma. Br J Surg  2003; 90: 1367– 72. Google Scholar CrossRef Search ADS PubMed  4 Morgan MA, Twine CP, Lewis WG, Lambe R, Oliphant HE, Robinson M et al.   Prognostic significance of failure to cross esophageal tumors by endoluminal ultrasound. Dis Esophagus  2008; 21: 508– 13. Google Scholar CrossRef Search ADS PubMed  5 Du Rieu MC, Filleron T, Beluchon B, Humeau M, Julio CH, Bloom E et al.   Recurrence risk after Ivor Lewis oesophagectomy for cancer. J Cardiothorac Surg  2013; 8: 215. Google Scholar CrossRef Search ADS PubMed  6 Clavier JB, Antoni D, Atlani D, Ben Abdelghani M, Schumacher C, Dufour P et al.   Baseline nutritional status is prognostic factor after definitive radiochemotherapy for esophageal cancer. Dis Esophagus  2014; 27: 560– 7. Google Scholar CrossRef Search ADS PubMed  7 Cho CJ, Song HJ, Lee GH, Choi KD, Kim YH, Ryu JS et al.   Clinical implications of endoscopic ultrasonography non-traversability in patients with locoregional esophageal cancer receiving multimodality therapy. Korean J Intern Med  2017; 32: 443– 51. Google Scholar CrossRef Search ADS PubMed  8 Yang YS, Hu WP, Ni PZ, Wang WP, Yuan Y, Chen LQ. Esophageal luminal stenosis is an independent prognostic factor in esophageal squamous cell carcinoma. Oncotarget  2017; 8: 43397– 405. Google Scholar PubMed  9 Okuno T, Wakabayashi M, Kato K, Shinoda M, Katayama H, Igaki H et al.   Esophageal stenosis and the Glasgow Prognostic Score as independent factors of poor prognosis for patients with locally advanced unresectable esophageal cancer treated with chemoradiotherapy (exploratory analysis of JCOG0303). Int J Clin Oncol  2017; 22: 1042– 9. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Interactive CardioVascular and Thoracic Surgery Oxford University Press

Does oesophageal stenosis have any impact on survival of oesophageal cancer patients?

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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1569-9293
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1569-9285
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Abstract

Abstract A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was ‘Does oesophageal stenosis have any impact on survival of oesophageal cancer patients?’. A total of 542 papers were found using the reported search, of which 8 cohort studies represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Most of these studies defined stenosis as failure to cross the tumour at endoscopic ultrasonography. Seven studies demonstrated that oesophageal cancer patients with stenosis had significantly poorer survival than those without, while 2 studies found that oesophageal stenosis was also a predictor of poor recurrence-free survival. We conclude that oesophageal stenosis is a predictor of poor prognosis in patients with oesophageal cancer. Oesophageal cancer , Stenosis , Survival INTRODUCTION A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1]. THREE-PART QUESTION In [patients with oesophageal cancer] does [oesophageal stenosis] have any impact on [survival]? CLINICAL SCENARIO A patient newly diagnosed with oesophageal cancer was intended to undergo oesophageactomy with lymphadenectomy in our department. This patient was found to have non-traversable oesophageal stenosis during preoperative endoscopic examination. The patient asked whether his stenosis could influence his long-term survival. One of my colleagues answered that there was an evidence that oesophageal stenosis was correlated with poor survival of oesophageal cancer patients. You resolve to check the literature yourself. SEARCH STRATEGY We searched Medline by using the PubMed interface from 1950 to November 2017 with the search terms: (((((((oesophageal[Title/Abstract]) OR esophageal[Title/Abstract]) OR oesophagus[Title/Abstract]) OR esophagus[Title/Abstract])) AND (((cancer[Title/Abstract]) OR carcinoma[Title/Abstract]) OR tumor[Title/Abstract])) AND (((survival[Title/Abstract]) OR prognosis[Title/Abstract]) OR prognostic[Title/Abstract])) AND ((stricture[All Fields]) OR stenosis[All Fields]). SEARCH OUTCOME A total of 542 papers were found using the reported search from the Medline. From these, 8 papers were identified that provided the best evidence to answer the question. These are presented in Table 1. Table 1: Best evidence papers Author, date, journal and country Study type (level of evidence)  Patient group  Outcomes  Key results  Comments  Hiele et al. (1997), Gastrointest Endosc, Belgium [2] Cohort study (level 3)  86 patients with oesophageal cancer mainly undergoing surgery (stenosis group: 27 patients; non-stenosis group: 59 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 20 months (P = 0.02)    Mariette et al. (2003), Br J Surg, France [3] Cohort study (level 3)  150 patients with oesophageal cancer undergoing curative resection (stenosis group: 23 patients; non-stenosis group: 127 patients) Stenosis definition: failure to be traversed at endoscopic ultrasonography  Median survival time  Stenosis group: 23 months vs non-stenosis group: 54 months (P = 0.004)    Morgan et al. (2008), Dis Esophagus, UK [4] Cohort study (level 3)  411 patients with oesophageal cancer undergoing surgery, chemoradiotherapy or palliative therapy (stenosis group: 12 patients; non-stenosis group: 399 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 24 months (P = 0.105)  The sample size of patients in the stenosis group was small  du Rieu et al, 2013, J Cardiothorac Surg, France [5] Cohort study (level 3)  120 patients with oesophageal cancer undergoing oesophagectomy (stenosis group: 69 patients; non-stenosis group: 51 patients) Stenosis definition: difficulty or inability for the fibrescope to pass through the lesion and/or at least a hemicircumferential narrowing light on barium swallow  5-year relapse-free survival rate  Stenosis group: 31.8% vs non-stenosis group: 77.9% (P < 0.0001)     Relapse-free survival  HR 3.36, 95% CI 1.68–6.72; P = 0.001  Clavier et al. (2014), Dis Esophagus, France [6] Cohort study (level 3)  143 patients with oesophageal cancer undergoing definitive chemoradiotherapy (stenosis group: 40 patients; non-stenosis group: 103 patients) Stenosis definition: non-traversable oesophageal stricture by a conventional endoscope  Median survival time  Stenosis group: 16.6 months vs non-stenosis group: 24.3 months (P = 0.12)     Locoregional recurrence-free survival  HR 1.35, 95% CI 1.05–1.75; P = 0.021  Cho et al. (2017), Korean J Intern Med, Korea [7] Cohort study (level 3)  89 patients with locoregional oesophageal cancer undergoing multimodality therapy (stenosis group: 26 patients; non-stenosis group: 63 patients) Stenosis definition: endoscopic ultrasonography non-traversable  5-year survival rates  Stenosis group: 30.8% vs non-stenosis group: 49.3% (P = 0.023)     Overall survival  HR 2.47, 95% CI 1.37–4.46; P = 0.003  Yang et al. (2017), Oncotarget, China [8] Cohort study (level 3)  508 patients with oesophageal squamous cell carcinoma undergoing oesophagectomy (stenosis group: 139 patients; non-stenosis group: 369 patients) Stenosis definition: significant stenosis allowing endoscopic passage with remarkable resistance or severe stenosis, preventing passage of the endoscope through the tumour site  5-year survival rates  Stenosis group: 27.7% vs non-stenosis group: 40.5% (P < 0.001)   The sample size of patients in the stenosis group was relatively large (compared with Morgan, above)  Overall survival  HR 1.31, 95% CI 1.02–1.69; P = 0.036  Okuno et al. (2017), Int J Clin Oncol, Japan [9] Cohort study (level 3)  131 patients with oesophageal cancer undergoing chemoradiotherapy (stenosis group: 61 patients; non-stenosis group: 70 patients) Stenosis definition: patients who experienced dysphagia or patients whose primary lesions were too narrow for an endoscopy to be performed  Median survival time  Stenosis group: 9.9 months vs non-stenosis group: 16.0 months (P = 0.001)   Definition of stenosis included dysphagia, which is different from other papers, and, therefore, may be less robust  Overall survival  HR 2.01, 95% CI 1.29–3.14; P = 0.002  Author, date, journal and country Study type (level of evidence)  Patient group  Outcomes  Key results  Comments  Hiele et al. (1997), Gastrointest Endosc, Belgium [2] Cohort study (level 3)  86 patients with oesophageal cancer mainly undergoing surgery (stenosis group: 27 patients; non-stenosis group: 59 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 20 months (P = 0.02)    Mariette et al. (2003), Br J Surg, France [3] Cohort study (level 3)  150 patients with oesophageal cancer undergoing curative resection (stenosis group: 23 patients; non-stenosis group: 127 patients) Stenosis definition: failure to be traversed at endoscopic ultrasonography  Median survival time  Stenosis group: 23 months vs non-stenosis group: 54 months (P = 0.004)    Morgan et al. (2008), Dis Esophagus, UK [4] Cohort study (level 3)  411 patients with oesophageal cancer undergoing surgery, chemoradiotherapy or palliative therapy (stenosis group: 12 patients; non-stenosis group: 399 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 24 months (P = 0.105)  The sample size of patients in the stenosis group was small  du Rieu et al, 2013, J Cardiothorac Surg, France [5] Cohort study (level 3)  120 patients with oesophageal cancer undergoing oesophagectomy (stenosis group: 69 patients; non-stenosis group: 51 patients) Stenosis definition: difficulty or inability for the fibrescope to pass through the lesion and/or at least a hemicircumferential narrowing light on barium swallow  5-year relapse-free survival rate  Stenosis group: 31.8% vs non-stenosis group: 77.9% (P < 0.0001)     Relapse-free survival  HR 3.36, 95% CI 1.68–6.72; P = 0.001  Clavier et al. (2014), Dis Esophagus, France [6] Cohort study (level 3)  143 patients with oesophageal cancer undergoing definitive chemoradiotherapy (stenosis group: 40 patients; non-stenosis group: 103 patients) Stenosis definition: non-traversable oesophageal stricture by a conventional endoscope  Median survival time  Stenosis group: 16.6 months vs non-stenosis group: 24.3 months (P = 0.12)     Locoregional recurrence-free survival  HR 1.35, 95% CI 1.05–1.75; P = 0.021  Cho et al. (2017), Korean J Intern Med, Korea [7] Cohort study (level 3)  89 patients with locoregional oesophageal cancer undergoing multimodality therapy (stenosis group: 26 patients; non-stenosis group: 63 patients) Stenosis definition: endoscopic ultrasonography non-traversable  5-year survival rates  Stenosis group: 30.8% vs non-stenosis group: 49.3% (P = 0.023)     Overall survival  HR 2.47, 95% CI 1.37–4.46; P = 0.003  Yang et al. (2017), Oncotarget, China [8] Cohort study (level 3)  508 patients with oesophageal squamous cell carcinoma undergoing oesophagectomy (stenosis group: 139 patients; non-stenosis group: 369 patients) Stenosis definition: significant stenosis allowing endoscopic passage with remarkable resistance or severe stenosis, preventing passage of the endoscope through the tumour site  5-year survival rates  Stenosis group: 27.7% vs non-stenosis group: 40.5% (P < 0.001)   The sample size of patients in the stenosis group was relatively large (compared with Morgan, above)  Overall survival  HR 1.31, 95% CI 1.02–1.69; P = 0.036  Okuno et al. (2017), Int J Clin Oncol, Japan [9] Cohort study (level 3)  131 patients with oesophageal cancer undergoing chemoradiotherapy (stenosis group: 61 patients; non-stenosis group: 70 patients) Stenosis definition: patients who experienced dysphagia or patients whose primary lesions were too narrow for an endoscopy to be performed  Median survival time  Stenosis group: 9.9 months vs non-stenosis group: 16.0 months (P = 0.001)   Definition of stenosis included dysphagia, which is different from other papers, and, therefore, may be less robust  Overall survival  HR 2.01, 95% CI 1.29–3.14; P = 0.002  CI: confidence interval; HR: hazard ratio. Table 1: Best evidence papers Author, date, journal and country Study type (level of evidence)  Patient group  Outcomes  Key results  Comments  Hiele et al. (1997), Gastrointest Endosc, Belgium [2] Cohort study (level 3)  86 patients with oesophageal cancer mainly undergoing surgery (stenosis group: 27 patients; non-stenosis group: 59 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 20 months (P = 0.02)    Mariette et al. (2003), Br J Surg, France [3] Cohort study (level 3)  150 patients with oesophageal cancer undergoing curative resection (stenosis group: 23 patients; non-stenosis group: 127 patients) Stenosis definition: failure to be traversed at endoscopic ultrasonography  Median survival time  Stenosis group: 23 months vs non-stenosis group: 54 months (P = 0.004)    Morgan et al. (2008), Dis Esophagus, UK [4] Cohort study (level 3)  411 patients with oesophageal cancer undergoing surgery, chemoradiotherapy or palliative therapy (stenosis group: 12 patients; non-stenosis group: 399 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 24 months (P = 0.105)  The sample size of patients in the stenosis group was small  du Rieu et al, 2013, J Cardiothorac Surg, France [5] Cohort study (level 3)  120 patients with oesophageal cancer undergoing oesophagectomy (stenosis group: 69 patients; non-stenosis group: 51 patients) Stenosis definition: difficulty or inability for the fibrescope to pass through the lesion and/or at least a hemicircumferential narrowing light on barium swallow  5-year relapse-free survival rate  Stenosis group: 31.8% vs non-stenosis group: 77.9% (P < 0.0001)     Relapse-free survival  HR 3.36, 95% CI 1.68–6.72; P = 0.001  Clavier et al. (2014), Dis Esophagus, France [6] Cohort study (level 3)  143 patients with oesophageal cancer undergoing definitive chemoradiotherapy (stenosis group: 40 patients; non-stenosis group: 103 patients) Stenosis definition: non-traversable oesophageal stricture by a conventional endoscope  Median survival time  Stenosis group: 16.6 months vs non-stenosis group: 24.3 months (P = 0.12)     Locoregional recurrence-free survival  HR 1.35, 95% CI 1.05–1.75; P = 0.021  Cho et al. (2017), Korean J Intern Med, Korea [7] Cohort study (level 3)  89 patients with locoregional oesophageal cancer undergoing multimodality therapy (stenosis group: 26 patients; non-stenosis group: 63 patients) Stenosis definition: endoscopic ultrasonography non-traversable  5-year survival rates  Stenosis group: 30.8% vs non-stenosis group: 49.3% (P = 0.023)     Overall survival  HR 2.47, 95% CI 1.37–4.46; P = 0.003  Yang et al. (2017), Oncotarget, China [8] Cohort study (level 3)  508 patients with oesophageal squamous cell carcinoma undergoing oesophagectomy (stenosis group: 139 patients; non-stenosis group: 369 patients) Stenosis definition: significant stenosis allowing endoscopic passage with remarkable resistance or severe stenosis, preventing passage of the endoscope through the tumour site  5-year survival rates  Stenosis group: 27.7% vs non-stenosis group: 40.5% (P < 0.001)   The sample size of patients in the stenosis group was relatively large (compared with Morgan, above)  Overall survival  HR 1.31, 95% CI 1.02–1.69; P = 0.036  Okuno et al. (2017), Int J Clin Oncol, Japan [9] Cohort study (level 3)  131 patients with oesophageal cancer undergoing chemoradiotherapy (stenosis group: 61 patients; non-stenosis group: 70 patients) Stenosis definition: patients who experienced dysphagia or patients whose primary lesions were too narrow for an endoscopy to be performed  Median survival time  Stenosis group: 9.9 months vs non-stenosis group: 16.0 months (P = 0.001)   Definition of stenosis included dysphagia, which is different from other papers, and, therefore, may be less robust  Overall survival  HR 2.01, 95% CI 1.29–3.14; P = 0.002  Author, date, journal and country Study type (level of evidence)  Patient group  Outcomes  Key results  Comments  Hiele et al. (1997), Gastrointest Endosc, Belgium [2] Cohort study (level 3)  86 patients with oesophageal cancer mainly undergoing surgery (stenosis group: 27 patients; non-stenosis group: 59 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 20 months (P = 0.02)    Mariette et al. (2003), Br J Surg, France [3] Cohort study (level 3)  150 patients with oesophageal cancer undergoing curative resection (stenosis group: 23 patients; non-stenosis group: 127 patients) Stenosis definition: failure to be traversed at endoscopic ultrasonography  Median survival time  Stenosis group: 23 months vs non-stenosis group: 54 months (P = 0.004)    Morgan et al. (2008), Dis Esophagus, UK [4] Cohort study (level 3)  411 patients with oesophageal cancer undergoing surgery, chemoradiotherapy or palliative therapy (stenosis group: 12 patients; non-stenosis group: 399 patients) Stenosis definition: failure to cross at endoscopic ultrasonography  Median survival time  Stenosis group: 10 months vs non-stenosis group: 24 months (P = 0.105)  The sample size of patients in the stenosis group was small  du Rieu et al, 2013, J Cardiothorac Surg, France [5] Cohort study (level 3)  120 patients with oesophageal cancer undergoing oesophagectomy (stenosis group: 69 patients; non-stenosis group: 51 patients) Stenosis definition: difficulty or inability for the fibrescope to pass through the lesion and/or at least a hemicircumferential narrowing light on barium swallow  5-year relapse-free survival rate  Stenosis group: 31.8% vs non-stenosis group: 77.9% (P < 0.0001)     Relapse-free survival  HR 3.36, 95% CI 1.68–6.72; P = 0.001  Clavier et al. (2014), Dis Esophagus, France [6] Cohort study (level 3)  143 patients with oesophageal cancer undergoing definitive chemoradiotherapy (stenosis group: 40 patients; non-stenosis group: 103 patients) Stenosis definition: non-traversable oesophageal stricture by a conventional endoscope  Median survival time  Stenosis group: 16.6 months vs non-stenosis group: 24.3 months (P = 0.12)     Locoregional recurrence-free survival  HR 1.35, 95% CI 1.05–1.75; P = 0.021  Cho et al. (2017), Korean J Intern Med, Korea [7] Cohort study (level 3)  89 patients with locoregional oesophageal cancer undergoing multimodality therapy (stenosis group: 26 patients; non-stenosis group: 63 patients) Stenosis definition: endoscopic ultrasonography non-traversable  5-year survival rates  Stenosis group: 30.8% vs non-stenosis group: 49.3% (P = 0.023)     Overall survival  HR 2.47, 95% CI 1.37–4.46; P = 0.003  Yang et al. (2017), Oncotarget, China [8] Cohort study (level 3)  508 patients with oesophageal squamous cell carcinoma undergoing oesophagectomy (stenosis group: 139 patients; non-stenosis group: 369 patients) Stenosis definition: significant stenosis allowing endoscopic passage with remarkable resistance or severe stenosis, preventing passage of the endoscope through the tumour site  5-year survival rates  Stenosis group: 27.7% vs non-stenosis group: 40.5% (P < 0.001)   The sample size of patients in the stenosis group was relatively large (compared with Morgan, above)  Overall survival  HR 1.31, 95% CI 1.02–1.69; P = 0.036  Okuno et al. (2017), Int J Clin Oncol, Japan [9] Cohort study (level 3)  131 patients with oesophageal cancer undergoing chemoradiotherapy (stenosis group: 61 patients; non-stenosis group: 70 patients) Stenosis definition: patients who experienced dysphagia or patients whose primary lesions were too narrow for an endoscopy to be performed  Median survival time  Stenosis group: 9.9 months vs non-stenosis group: 16.0 months (P = 0.001)   Definition of stenosis included dysphagia, which is different from other papers, and, therefore, may be less robust  Overall survival  HR 2.01, 95% CI 1.29–3.14; P = 0.002  CI: confidence interval; HR: hazard ratio. RESULTS In 1997, Hiele et al. [2] explored the relationship between endoscopic ultrasound (EUS) findings and outcomes of patients with tumours of the oesophagus or oesophagogastric junction for the first time. They found that patients with oesophageal stenosis that could not be passed by EUS yielded significantly shorter median survival time than those whose stenosis could be passed (10 and 20 months, respectively; P = 0.02), indicating that oesophageal stenosis had a negative impact on the prognosis of oesophageal cancer patients. Mariette et al. [3] also explored the value of EUS as a predictor of long-term survival in oesophageal cancer patients treated with surgery, and they found that the median survival time of patients with oesophageal stenosis was significantly shorter than that of patients without stenosis (23 and 54 months, respectively; P = 0.004). Their study indicated that oesophageal stenosis was significantly correlated with poor survival of oesophageal cancer patients. However, Morgan et al. [4] conducted a study especially focusing on the prognostic value of failure to cross oesophageal cancer by EUS. Although there was shorter median survival in patients with oesophageal stenosis when compared to those without (10 and 24 months, respectively), this was not significant (P = 0.105). However, there were only 12 patients with oesophageal stenosis in their study population with 411 patients. In 2013, du Rieu et al. [5] explored the recurrence risk of oesophageal cancer patients after oesophagectomy. They found that patients with oesophageal stenosis had significantly lower 5-year recurrence-free survival than patients without (31.8% and 77.9%, respectively; P < 0.0001). Moreover, in the multivariate analysis of recurrence risk, they found that oesophageal stenosis was a significant prognostic factor associated with an increased risk of local relapse [hazard ratio (HR) 3.36, 95% confidence interval (CI) 1.68–6.72; P = 0.001]. Clavier et al. [6] explored the prognostic factors of oesophageal cancer patients treated with definitive chemoradiotherapy and found that there was no significant difference of overall survival time between patients with oesophageal stenosis and those without (16.6 and 24.3 months, respectively; P = 0.12). However, they found that oesophageal stenosis was significantly correlated with poor recurrence-free survival of oesophageal cancer patients (HR 1.35, 95% CI 1.05–1.75; P = 0.021). Recently, Cho et al. [7] explored the role of EUS non-traversability in patients with oesophageal cancer treated with multimodality therapy. They found that patients with oesophageal stenosis yielded significantly lower 5-year survival rate than patients without (30.8% and 49.3%, respectively; P = 0.023) and oesophageal stenosis was a significant prognostic factor of poor overall survival of oesophageal cancer patients treated with multimodality therapy (HR 2.47, 95% CI 1.37–4.46; P = 0.003). Yang et al. [8] conducted a similar study in patients treated with oesophagectomy and also found that patients with oesophageal stenosis yielded significantly lower 5-year survival rate than patients without (27.7% and 40.5%, respectively; P < 0.001), and oesophageal stenosis was a significant prognostic factor of poor overall survival of oesophageal cancer patients (HR 1.31, 95% CI 1.02–1.69; P = 0.036). Okuno et al. [9] also confirmed that oesophageal stenosis was significantly correlated with poor survival of oesophageal cancer patients treated with chemoradiotherapy (HR 2.01, 95% CI 1.29–3.14; P = 0.002). However, their definition of stenosis differed from previous studies by defining both patients who experienced dysphagia and patients whose primary lesions were too narrow for an endoscopy to be performed as stenosis. CLINICAL BOTTOM LINE Oesophageal stenosis is a predictor of poor median, overall and recurrence-free survival in patients with oesophageal cancer. This remains the case whether treated with surgical resection, chemoradiotherapy or palliative treatment. ACKNOWLEDGEMENTS We thank the great efforts of Ralph William White from the James Cook University Hospital, Middlesbrough, UK. Conflict of interest: none declared. REFERENCES 1 Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact CardioVasc Thorac Surg  2003; 2: 405– 9. Google Scholar CrossRef Search ADS PubMed  2 Hiele M, De Leyn P, Schurmans P, Lerut A, Huys S, Geboes K et al.   Relation between endoscopic ultrasound findings and outcome of patients with tumors of the esophagus or esophagogastric junction. Gastrointest Endosc  1997; 45: 381– 6. Google Scholar CrossRef Search ADS PubMed  3 Mariette C, Balon JM, Maunoury V, Taillier G, Van Seuningen I, Triboulet JP. Value of endoscopic ultrasonography as a predictor of long-term survival in oesophageal carcinoma. Br J Surg  2003; 90: 1367– 72. 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Interactive CardioVascular and Thoracic Surgery – Oxford University Press

Published: Mar 30, 2018

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