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Definitive Chemoradiotherapy Versus Trimodality Therapy for Resectable Oesophageal Carcinoma: Meta-analyses and Systematic Review of Literature

  • Daan M. VoetenEmail author
  • Chantal M. den Bakker
  • David J. Heineman
  • Johannes C. F. Ket
  • Freek Daams
  • Donald L. van der Peet
Scientific Review

Abstract

Background

Standard therapy for loco-regionally advanced, resectable oesophageal carcinoma is trimodality therapy (TMT) consisting of neoadjuvant chemoradiotherapy and oesophagectomy. Evidence of survival advantage of TMT over organ-preserving definitive chemoradiotherapy (dCRT) is inconclusive. The aim of this study is to compare survival between TMT and dCRT.

Methods

A systematic review and meta-analyses were conducted. Randomised controlled trials and observational studies on resectable, curatively treated, oesophageal carcinoma patients above 18 years were included. Three online databases were searched for studies comparing TMT with dCRT. Primary outcomes were 1-, 2-, 3- and 5-year overall survival rates. Risk of bias was assessed using the Cochrane risk of bias tools for RCTs and cohort studies. Quality of evidence was evaluated according to Grading of Recommendation Assessment, Development and Evaluation.

Results

Thirty-two studies described in 35 articles were included in this systematic review, and 33 were included in the meta-analyses. Two-, three- and five-year overall survival was significantly lower in dCRT compared to TMT, with relative risks (RRs) of 0.69 (95% CI 0.57–0.83), 0.76 (95% CI 0.63–0.92) and 0.57 (95% CI 0.47–0.71), respectively. When only analysing studies with equal patient groups at baseline, no significant differences for 2-, 3- and 5-year overall survival were found with RRs of 0.83 (95% CI 0.62–1.10), 0.81 (95% CI 0.57–1.14) and 0.63 (95% CI 0.36–1.12).

Conclusion

These meta-analyses do not show clear survival advantage for TMT over dCRT. Only a non-significant trend towards better survival was seen, assuming comparable patient groups at baseline. Non-operative management of oesophageal carcinoma patients might be part of a personalised and tailored treatment approach in future. However, to date hard evidence proving its non-inferiority compared to operative management is lacking.

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

268_2018_4901_MOESM1_ESM.docx (505 kb)
Supplementary material 1 (DOCX 504 kb)

References

  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386CrossRefGoogle Scholar
  2. 2.
    Wu PC, Posner MC (2003) The role of surgery in the management of oesophageal cancer. Lancet Oncol 4:481–488CrossRefGoogle Scholar
  3. 3.
    Walsh TN, Noonan N, Hollywood D et al (1996) A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 335:462–467CrossRefGoogle Scholar
  4. 4.
    Hagen P, Hulshof M, Lanschot J et al (2012) Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366:2074–2084CrossRefGoogle Scholar
  5. 5.
    Sjoquist KM, Burmeister BH, Smithers BM et al (2011) Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol 12:681–692CrossRefGoogle Scholar
  6. 6.
    Lester SC, Lin SH, Chuong M et al (2017) A multi-institutional analysis of trimodality therapy for esophageal cancer in elderly patients. Int J Radiat Oncol Biol Phys 98:820–828CrossRefGoogle Scholar
  7. 7.
    Shao MS, Wong AT, Schwartz D et al (2016) Definitive or preoperative chemoradiation therapy for esophageal cancer: patterns of care and survival outcomes. Ann Thorac Surg 101:2148–2154CrossRefGoogle Scholar
  8. 8.
    Suntharalingam M, Moughan J, Coia LR et al (2005) Outcome results of the 1996–1999 patterns of care survey of the national practice for patients receiving radiation therapy for carcinoma of the esophagus. J Clin Oncol 23:2325–2331CrossRefGoogle Scholar
  9. 9.
    Smit JK, Muijs CT, Burgerhof JG et al (2013) Survival after definitive (chemo)radiotherapy in esophageal cancer patients: a population-based study in the north-East Netherlands. Ann Surg Oncol 20:1985–1992CrossRefGoogle Scholar
  10. 10.
    Herskovic A, Martz SM et al (1992) Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 326:1593–1598CrossRefGoogle Scholar
  11. 11.
    Mikhail S, Wei L, Salem ME et al (2017) Outcomes of definitive chemoradiation in patients with esophageal cancer. Dis Esophagus 30:1–7Google Scholar
  12. 12.
    Wong RK, Malthaner RA, Zuraw L et al (2003) Combined modality radiotherapy and chemotherapy in nonsurgical management of localized carcinoma of the esophagus: a practice guideline. Int J Radiat Oncol Biol Phys 55:930–942CrossRefGoogle Scholar
  13. 13.
    Stahl M, Stuschke M, Lehmann N et al (2005) Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 23:2310–2317CrossRefGoogle Scholar
  14. 14.
    Bedenne L, Michel P, Bouché O et al (2007) Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 25:1160–1168CrossRefGoogle Scholar
  15. 15.
    Higgins JP, Altman DG, Gotzsche PC et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928CrossRefGoogle Scholar
  16. 16.
    Higgins JP, Green S (2011) Cochrane handbook for systematic reviews of interventions. The Cochrane Collaboration. Wiley, Chichester. www.cochrane-handbook.org. Accessed 27 Oct 2017
  17. 17.
    Adams R, Morgan M, Mukherjee S et al (2007) A prospective comparison of multidisciplinary treatment of oesophageal cancer with curative intent in a UK cancer network. Eur J Surg Oncol 33:307–313CrossRefGoogle Scholar
  18. 18.
    Algan O, Coia LR, Keller SM et al (1995) Management of adenocarcinoma of the esophagus with chemoradiation alone or chemoradiation followed by esophagectomy: results of sequential nonrandomized phase II studies. Int J Radiat Oncol Biol Phys 32:753–761CrossRefGoogle Scholar
  19. 19.
    Berger B, Stahlberg K, Lemminger A et al (2011) Impact of radiotherapy, chemotherapy and surgery in multimodal treatment of locally advanced esophageal cancer. Oncology 81:387–394CrossRefGoogle Scholar
  20. 20.
    Gemici C, Yaprak G, Batirel HF et al (2016) Radiation field size and dose determine oncologic outcome in esophageal cancer. World J Surg Oncol 14:263.  https://doi.org/10.1186/s12957-016-1024-0 CrossRefGoogle Scholar
  21. 21.
    Haefner MF, Lang K, Verma V et al (2018) Neoadjuvant versus definitive chemoradiotherapy for locally advanced esophageal cancer: outcomes and patterns of failure. Strahlenther Onkol 194:116–124CrossRefGoogle Scholar
  22. 22.
    Hainsworth J, Meluch A, Gray J et al (2007) Concurrent chemoradiation followed by esophageal resection vs chemoradiation alone for localized esophageal cancer. Community Oncol 4:431–439CrossRefGoogle Scholar
  23. 23.
    Hategan M, Cook N, Prewett S et al (2015) Trimodality therapy and definitive chemoradiotherapy for esophageal cancer: a single-center experience and review of the literature. Dis Esophagus 28:612–618CrossRefGoogle Scholar
  24. 24.
    Hennequin C, Gayet B, Sauvanet A et al (2001) Impact on survival of surgery after concomitant chemoradiotherapy for locally advanced cancers of the esophagus. Int J Radiat Oncol Biol Phys 49:657–664CrossRefGoogle Scholar
  25. 25.
    Hofheinz RD, Raab B, Mai S et al (2004) Impact of chemoradiotherapy-induced anemia on survival in uniformly staged patients with locally advanced squamous cell carcinoma of the esophagus. Onkologie 27:462–466Google Scholar
  26. 26.
    Hsu FM, Lin CC, Lee JM et al (2008) Improved local control by surgery and paclitaxel-based chemoradiation for esophageal squamous cell carcinoma: results of a retrospective non-randomized study. J Surg Oncol 98:34–41CrossRefGoogle Scholar
  27. 27.
    Javle MM, Nwogu CE, Donohue KA et al (2006) Management of locoregional stage esophageal cancer: a single center experience. Dis Esophagus 19:78–83CrossRefGoogle Scholar
  28. 28.
    Jingu K, Matsushita H, Takeda K et al (2013) Results of chemoradiotherapy for stage I esophageal cancer in medically inoperable patients compared with results in operable patients. Dis Esophagus 26:522–527CrossRefGoogle Scholar
  29. 29.
    Kapoor R, Bansal A, Kumar S et al (2016) Factors influencing compliance to radical treatment of middle thoracic esophageal cancer: an audit from a regional cancer centre. Indian J Palliat Care 22:288–294CrossRefGoogle Scholar
  30. 30.
    Kim JH, Choi EK, Kim SB et al (2001) Preoperative hyperfractionated radiotherapy with concurrent chemotherapy in resectable esophageal cancer. Int J Radiat Oncol Biol Phys 50:1–12CrossRefGoogle Scholar
  31. 31.
    Lin JW, Hsu CP, Yeh HL et al (2018) The impact of pathological complete response after neoadjuvant chemoradiotherapy in locally advanced squamous cell carcinoma of esophagus. J Chin Med Assoc 81:18–24CrossRefGoogle Scholar
  32. 32.
    Liu S, Qiu B, Luo G et al (2017) TNM staging matched-pair comparison of surgery after neoadjuvant chemoradiotherapy, surgery alone and definitive chemoradiotherapy for thoracic esophageal squamous cell carcinoma. J Cancer 8:683–690CrossRefGoogle Scholar
  33. 33.
    Morita M, Toh Y, Saeki H et al (2012) Clinical significance of chemoradiotherapy and surgical resection for cT4 esophageal cancer. Anticancer Res 32:3275–3282Google Scholar
  34. 34.
    Myslivecek M, Neoral C, Vrba R et al (2012) The value of (1)(8)F-FDG PET/CT in assessment of metabolic response in esophageal cancer for prediction of histopathological response and survival after preoperative chemoradiotherapy. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 156:171–179CrossRefGoogle Scholar
  35. 35.
    Nagata M, Yamamoto H, Takiguchi N et al (2006) Neoadjuvant chemoradiotherapy followed by esophagectomy versus definitive chemoradiotherapy in resectable stage II/III (T1-3N0, 1M0) esophageal squamous cell carcinoma. Esophagus 3:105–111CrossRefGoogle Scholar
  36. 36.
    Naik KB, Liu Y, Goodman M et al (2017) Concurrent chemoradiotherapy with or without surgery for patients with resectable esophageal cancer: an analysis of the National Cancer Data Base. Cancer 123:3476–3485CrossRefGoogle Scholar
  37. 37.
    Nakamura T, Ota M, Ohki T et al (2011) Induction chemoradiotherapy followed by esophagectomy for advanced squamous cell carcinoma of the esophagus. Esophagus 8:89–95CrossRefGoogle Scholar
  38. 38.
    Piessen G, Messager M, Mirabel X et al (2013) Is there a role for surgery for patients with a complete clinical response after chemoradiation for esophageal cancer? An intention-to-treat case-control study. Ann Surg 258:793–799CrossRefGoogle Scholar
  39. 39.
    Sheil F, Donohoe CL, King S et al (2017) Outcomes for esophageal squamous cell carcinoma treated with curative intent in a western cohort: should multimodal therapy be the gold standard? World J Surg 42:1485–1495.  https://doi.org/10.1007/s00268-017-4289-8 CrossRefGoogle Scholar
  40. 40.
    Shridhar R, Chuong MD, Weber J et al (2012) Outcomes of definitive or preoperative IMRT chemoradiation for esophageal cancer. J Radiat Oncol 1:347–354CrossRefGoogle Scholar
  41. 41.
    Shridhar R, Freilich J, Hoffe SE et al (2014) Single-institution retrospective comparison of preoperative versus definitive chemoradiotherapy for adenocarcinoma of the esophagus. Ann Surg Oncol 21:3744–3750CrossRefGoogle Scholar
  42. 42.
    Smith GL, Smith BD, Buchholz TA et al (2009) Patterns of care and locoregional treatment outcomes in older esophageal cancer patients: the SEER-Medicare Cohort. Int J Radiat Oncol Biol Phys 74:482–489CrossRefGoogle Scholar
  43. 43.
    Wang H, Ryu J, Gandara D et al (2007) A phase II study of paclitaxel, carboplatin, and radiation with or without surgery for esophageal cancer. J Thorac Oncol 2:153–157CrossRefGoogle Scholar
  44. 44.
    Taketa T, Xiao L, Sudo K et al (2013) Propensity-based matching between esophagogastric cancer patients who had surgery and who declined surgery after preoperative chemoradiation. Oncology 85:95–99CrossRefGoogle Scholar
  45. 45.
    Xi M, Liao Z, Hofstetter WL et al (2017) 18F-FDG PET response after induction chemotherapy can predict who will benefit from subsequent esophagectomy after chemoradiotherapy for esophageal adenocarcinoma. J Nucl Med 58:1756–1763CrossRefGoogle Scholar
  46. 46.
    Yap WK, Chang YC, Tseng CK et al (2017) Predictive value of nodal maximum standardized uptake value of pretreatment [18F]fluorodeoxyglucose positron emission tomography imaging in patients with esophageal cancer. Dis Esophagus 30:1–10CrossRefGoogle Scholar
  47. 47.
    Yen YC, Chang JH, Lin WC et al (2017) Effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma receiving definitive radiotherapy or concurrent chemoradiotherapy through intensity-modulated radiation therapy techniques. Cancer 123:2043–2053CrossRefGoogle Scholar
  48. 48.
    Liao Z, Zhang Z, Jin J et al (2004) Esophagectomy after concurrent chemoradiotherapy improves locoregional control in clinical stage II or III esophageal cancer patients. Int J Radiat Oncol Biol Phys 60:1484–1493CrossRefGoogle Scholar
  49. 49.
    Vellayappan BA, Soon YY, Ku GY et al (2017) Chemoradiotherapy versus chemoradiotherapy plus surgery for esophageal cancer. Cochrane Database Syst Rev.  https://doi.org/10.1002/14651858.cd010511.pub2 Google Scholar
  50. 50.
    Best LM, Mughal M, Gurusamy KS (2016) Non-surgical versus surgical treatment for oesophageal cancer. Cochrane Database Syst Rev.  https://doi.org/10.1002/14651858.cd011498.pub2 Google Scholar
  51. 51.
    Mendenhall WM, Sombeck MD, Parsons JT et al (1994) Management of cervical esophageal carcinoma. Semin Radiat Oncol 4:179–191CrossRefGoogle Scholar
  52. 52.
    Ajani JA, D’Amico TA, Almhanna K et al (2015) Esophageal and esophagogastric junction cancers, version 1.2015. J Natl Compr Netw 13:194–227CrossRefGoogle Scholar
  53. 53.
    van der Wielen N, Straatman J, Cuesta MA et al (2018) Short-term outcomes in minimally invasive versus open gastrectomy: the differences between East and West. A systematic review of the literature. Gastric Cancer 21:19–30CrossRefGoogle Scholar
  54. 54.
    Arnold M, Soerjomataram I, Ferlay J et al (2015) Global incidence of oesophageal cancer by histological subtype in 2012. Gut 64:381–387CrossRefGoogle Scholar
  55. 55.
    Ando N, Kato H, Igaki H et al (2012) A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol 19:68–74CrossRefGoogle Scholar
  56. 56.
    Koeter M, van Putten M, Verhoeven RHA et al (2018) Definitive chemoradiation or surgery in elderly patients with potentially curable esophageal cancer in the Netherlands: a nationwide population-based study on patterns of care and survival. Acta Oncol 57:1–9CrossRefGoogle Scholar
  57. 57.
    Jamel S, Markar SR (2017) Salvage esophagectomy: safe therapeutic strategy? J Thorac Dis 9:s799–s808CrossRefGoogle Scholar
  58. 58.
    Swisher SG, Moughan J, Komaki RU et al (2017) Final results of NRG oncology RTOG 0246: an organ-preserving selective resection strategy in esophageal cancer patients treated with definitive chemoradiation. J Thorac Oncol 12:368–374CrossRefGoogle Scholar
  59. 59.
    Uberoi GS, Uberoi AS, Bhutani MS (2017) Endoscopic and imaging predictors of complete pathologic response after chemoradiation for esophageal cancer. Curr Gastroenterol Rep 19:57CrossRefGoogle Scholar
  60. 60.
    Noordman BJ, Shapiro J, Spaander MC et al (2015) Accuracy of detecting residual disease after cross neoadjuvant chemoradiotherapy for esophageal cancer (preSANO Trial): rationale and protocol. JMIR Res Protoc 4:e79CrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2019

Authors and Affiliations

  • Daan M. Voeten
    • 1
    Email author
  • Chantal M. den Bakker
    • 1
  • David J. Heineman
    • 1
  • Johannes C. F. Ket
    • 2
  • Freek Daams
    • 1
  • Donald L. van der Peet
    • 1
  1. 1.Department of Gastrointestinal SurgeryVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Medical LibraryVrije UniversiteitAmsterdamThe Netherlands

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