Skip to main content
SpringerLink
Log in
Book cover

Esophageal Squamous Cell Carcinoma pp 233–251Cite as

Neoadjuvant and Adjuvant Therapy

  • Chapter
  • First Online:

  • 432 Accesses

Abstract

Most clinicians today are conscious of the necessity of a multimodality approach with surgery as the mainstay to improve the outcome of esophageal cancer victims. What results of clinical trials are available in Western countries are not applicable to clinical practice related to esophageal cancer in Asia, because of considerable East–West differences in this field. In Japan, the emphasis in surgical adjuvant therapy for patients with squamous cell carcinoma shifted from postoperative radiotherapy in the 1980s to postoperative chemotherapy, including cisplatin as a key drug in the 1990s. Later, the optimal timing for perioperative adjuvant therapy returned to preoperative treatment in the late 2000s, based on the results of a JCOG study (JCOG9907) comparing preoperative chemotherapy using cisplatin and 5-fluorouracil (CF) with postoperative chemotherapy. A meta-analysis consisting of 12 randomized controlled trials comparing preoperative chemoradiotherapy vs. surgery alone showed a significant survival benefit of preoperative chemoradiotherapy in both histologic types, squamous cell carcinoma, and adenocarcinoma. While a recent meta-analysis consisting of six randomized controlled trials in patients with resectable squamous cell carcinoma comparing preoperative chemotherapy vs. surgery alone or postoperative chemotherapy using CF showed a borderline survival benefit of preoperative chemotherapy and suggested its worthy of reinvestigation. Next, the clinical question of which is better, preoperative aggressive chemotherapy or preoperative chemoradiotherapy, still requires resolution. The JEOG three-arm randomized controlled trial is in progress to confirm the superiority of DCF (CF plus docetaxel) and the superiority of chemoradiotherapy in overall survival over CF as preoperative therapy for locally advanced esophageal squamous cell carcinoma. Clinical trials incorporating molecular-targeted therapeutics including immune-checkpoint inhibitors into multimodality treatment for esophageal cancer have started to define their efficacy.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Ando N, Ozawa S, Kitagawa Y, et al. Improvement in the results of surgical treatment of advanced squamous esophageal carcinoma during 15 consecutive years. Ann Surg. 2000;232:225–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Akiyama H, Tsurumaru M, Udagawa H, et al. Radical lymph node dissection for cancer of the thoracic esophagus. Ann Surg. 1994;220:364–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mariette C, Piessen G, Triboulet JP. Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. Lancet Oncol. 2007;8:545–53.

    Article  PubMed  Google Scholar 

  4. Law S, Wong J. Changing disease burden and management issues for esophageal cancer in the Asia-Pacific region. J Gastroenterol Hepatol. 2002;17:374–81.

    Article  PubMed  Google Scholar 

  5. Fukuda H. Development of cancer cooperative group in Japan. Jpn J Clin Oncol. 2010;40:881–90.

    Article  PubMed  Google Scholar 

  6. Ando N. Progress in multidisciplinary treatment for esophageal cancer in Japan as reflected in JCOG studies. Esophagus. 2011;8:151–7.

    Article  Google Scholar 

  7. Kitagawa Y, Uno T, Oyama T, et al. Esophageal cancer practice guidelines 2017 edited by the Japan esophageal society: part 1. Esophagus. 2019;16:1–24.

    Article  PubMed  Google Scholar 

  8. Akakura I, Nakamura Y, Kakegawa T, et al. Surgery of carcinoma of the esophagus with preoperative radiation. Chest. 1970;57:47–57.

    Article  CAS  PubMed  Google Scholar 

  9. Cooperative Clinical Study Group for Esophageal Carcinoma. Multidisciplinary treatment for esophageal carcinoma. Jpn J Clin Oncol. 1983;13:417–24.

    Google Scholar 

  10. Kasai M. Surgical treatment for carcinoma of the esophagus. J Jpn Surg Soc. 1980;81:845–53.

    Google Scholar 

  11. Iizuka T, Ide H, Kakegawa T, et al. Preoperative radioactive therapy for esophageal carcinoma randomized evaluation trial in eight institutions. Chest. 1988;93:1054–8.

    Article  CAS  PubMed  Google Scholar 

  12. Japanese Esophageal Oncology Group. A comparison of chemotherapy and radiotherapy as adjuvant treatment to surgery for esophageal carcinoma. Chest. 1993;104:203–7.

    Article  Google Scholar 

  13. Ando N, Iizuka T, Kakegawa T, et al. A randomized trial of surgery with and without chemotherapy for localized squamous carcinoma of the thoracic esophagus: the Japan clinical oncology group study. J Thorac Cardiovasc Surg. 1997;114:205–9.

    Article  CAS  PubMed  Google Scholar 

  14. Ando N, Iizuka T, Ide H, et al. Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan clinical oncology group study-JCOG 9204. J Clin Oncol. 2003;24:4592–6.

    Article  Google Scholar 

  15. Kleinberg L, Forastiere A. Chemoradiation in the management of esophageal cancer. J Clin Oncol. 2007;25:4110–7.

    Article  CAS  PubMed  Google Scholar 

  16. Ando N, Kato H, Shinoda M, et al. A randomized trial of postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus neoadjuvant chemotherapy for localized squamous cell carcinoma of the thoracic esophagus (JCOG 9907). Ann Surg Oncol. 2012;19:68–74.

    Article  PubMed  Google Scholar 

  17. Hirao M, Ando N, Tsujinaka T, et al. Japan esophageal oncology group/Japan clinical oncology group: influence of preoperative chemotherapy for advanced thoracic esophageal squamous cell carcinoma on perioperative complications. Br J Surg. 2011;98:1735–41.

    Article  CAS  PubMed  Google Scholar 

  18. Tsukada Y, Higashi T, Shimada H, et al. The use of neoadjuvant therapy for resectable locally advanced thoracic esophageal squamous cell carcinoma in an analysis of 5016 patients from 305 designated cancer care hospitals in Japan. Int J Clin Oncol. 2017;23:81–91.

    Article  PubMed  Google Scholar 

  19. Hara H, Tahara M, Daiko H, et al. Phase II feasibility study of preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for esophageal squamous cell carcinoma. Cancer Sci. 2013;104:1455–60.

    Article  CAS  PubMed  Google Scholar 

  20. Nakamura K, Kato K, Igaki H, et al. Three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel, cisplatin plus 5-FU (DCF) versus radiation therapy with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer (JCOG1109, NExT study). Jpn J Clin Oncol. 2013;43:752–5.

    Article  PubMed  Google Scholar 

  21. Pouliquen X, Levard H, Hay JM, et al. 5-fluorouracil and cisplatin therapy after palliative surgical resection of squamous cell carcinoma of the esophagus. A multicenter randomized trial. French associations for surgical research. Ann Surg. 1996;223:127–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lee J, Lee KE, Im YH, et al. Adjuvant chemotherapy with 5-fuorouracil and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma. Ann Thorac Surg. 2005;80:1170–5.

    Article  PubMed  Google Scholar 

  23. Zhang SS, Yang H, Xie X, et al. Adjuvant chemotherapy versus surgery alone for esophageal squamous cell carcinoma: a meta-analysis of randomized controlled trials and nonrandomized studies. Dis Esophagus. 2014;27:574–84.

    Article  PubMed  Google Scholar 

  24. Law S, Fok M, Chow S, et al. Preoperative chemotherapy versus surgical therapy alone for squamous cell carcinoma of the esophagus: a prospective randomized trial. J Thorac Cardiovasc Surg. 1997;114:210–7.

    Article  CAS  PubMed  Google Scholar 

  25. Ancona E, Ruol A, Santi S, et al. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma. Final report of randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer. 2001;91:2165–74.

    Article  CAS  PubMed  Google Scholar 

  26. Kelsen DP, Ginsberg R, Pajak TF, et al. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998;339:1979–84.

    Article  CAS  PubMed  Google Scholar 

  27. Kelsen DP, Winter KA, Gunderson LL, et al. Long-term results of RTOG trial 8911 (USA intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer. J Clin Oncol. 2007;25:3719–25.

    Article  PubMed  Google Scholar 

  28. Medical Research Council Oesophageal Cancer Working Party. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet. 2002;359:1727–33.

    Article  Google Scholar 

  29. Allum WH, Stenning SP, Bancewicz J, et al. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 2009;27:5062–7.

    Article  PubMed  Google Scholar 

  30. Zheng Y, Li Y, Liu X, et al. Reevaluation of neoadjuvant chemotherapy for esophageal squamous cell carcinoma A meta – analysis of randomized controlled trials over the past 20 years. Medicine. 2015;94:e1102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Almhanna K, Strosberg JR. Multimodality approach for locally advanced esophageal cancer. World J Gastroenterol. 2012;18:5679–87.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Merkow RP, Bilimoria KY, McCarter MD, et al. Use of multimodality neoadjuvant therapy for esophageal cancer in the United States: assessment of 987 hospitals. Ann Surg Oncol. 2012;19:357–64.

    Article  PubMed  Google Scholar 

  33. Pennathur A, Gibson MK, Jobe BA, et al. Oesophageal carcinoma. Lancet. 2013;381:400–12.

    Article  PubMed  Google Scholar 

  34. Bedenne L, Vincent J, Jouve JL. Is surgery always necessary in esophageal cancer? Esophagus. 2011;8:3–7.

    Article  Google Scholar 

  35. Apinop C, Puttisak P, Preecha N. A prospective study of combined therapy in esophageal cancer. Hepato-Gastroenterology. 1994;41:391–3.

    CAS  PubMed  Google Scholar 

  36. Bosset JF, Gignoux M, Triboulet JP, et al. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med. 1997;337:161–7.

    Article  CAS  PubMed  Google Scholar 

  37. Le Price E, Etienne PL, Meunier B, et al. A randomized study of chemotherapy, radiation therapy, and surgery versus surgery for localized squamous cell carcinoma of the esophagus. Cancer. 1994;73:1779–84.

    Article  Google Scholar 

  38. Nygaard K, Hagen S, Hansen HS, et al. Preoperative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of preoperative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer. World J Surg. 1992;16:1104–9.

    Article  CAS  PubMed  Google Scholar 

  39. Lee JL, Park SI, Kim SB, et al. A single institutional phase III trial of preoperative chemotherapy with hyperfractionation radiotherapy plus surgery versus surgery alone for resectable esophageal squamous cell carcinoma. Ann Oncol. 2004;15:947–54.

    Article  CAS  PubMed  Google Scholar 

  40. Yang H, Liu H, Chen Y, et al. Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus (NEOCRTEC5010): a phase III multicenter, randomized, open-label clinical trial. J Clin Oncol. 2018;36:2796–803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Shapiro J, van Lanschot JJB, Hulshof MCCM, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for esophageal or junctional cancer (CROSS): long-term results of a randomized controlled trial. Lancet Oncol. 2015;16:1090–8.

    Article  PubMed  Google Scholar 

  42. Wijnhoven BPL, van Lanschot JJB, Tilanus HW, et al. Neoajuvant chemoradiotherapy for esophageal cancer: a review of meta-analyses. World J Surg. 2009;33:2606–14.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.

    Article  PubMed  Google Scholar 

  44. Gebski V, Burmeister B, Smithers BM, et al. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007;8:226–34.

    Article  CAS  PubMed  Google Scholar 

  45. Hamilton E, Vohra RS, Griffiths EA. What is the best neoadjuvant regimen prior to oesophagectomy: chemotherapy or chemoradiotherapy? Int J Surg. 2014;12:196–9.

    Article  PubMed  Google Scholar 

  46. Klevebro F, Alexandersson von Dobeln G, Wang N, et al. A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol. 2016;27:660–7.

    Article  CAS  PubMed  Google Scholar 

  47. Pasquali S, Yim G, Vohra RS, et al. Survival after neoadjuvant and adjuvant treatments compared to surgery alone for resectable esophageal carcinoma A network meta-analysis. Ann Surg. 2017;265:481–91.

    Article  PubMed  Google Scholar 

  48. Kitajima M, Kitagawa Y. Surgical treatment of esophageal cancer - the advent of the era of individualization. N Engl J Med. 2002;347:1705–8.

    Article  PubMed  Google Scholar 

  49. Takeuchi H, Kitagawa Y. Sentinel node navigation surgery in esophageal cancer. Ann Gastroenterol Surg. 2019;3:7–13.

    Article  PubMed  Google Scholar 

  50. Forastiere AA. Multimodality treatment of esophagus cancer: current status and future perspectives in the United States. Esophagus. 2010;7:1–6.

    Article  Google Scholar 

  51. Gibson MK, Abraham SC, Wu TT, et al. Epidermal growth factor receptor, p 53 mutation and pathological response predict survival in patients with locally advanced esophageal cancer treated with preoperative chemoradiotherapy. Clin Cancer Res. 2003;9:6461–8.

    CAS  PubMed  Google Scholar 

  52. Okumura H, Uchikado Y, Setoyama T, et al. Biomarkers for predicting the response of esophageal squamous cell carcinoma to neoadjuvant chemoradiation therapy. Surg Today. 2014;44:421–8.

    Article  CAS  PubMed  Google Scholar 

  53. Ruhstaller T, Pless M, Dietich D, et al. Cetuximab in combination with chemoradiotherapy before surgery in patients with resectable, locally advanced esophageal carcinoma: a prospective, multicenter phase IB/II trial (SAKK 75/06). J Clin Oncol. 2011;29:626–31.

    Article  CAS  PubMed  Google Scholar 

  54. Shah MA, Jhawer M, Ilson DH, et al. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011;29:868–74.

    Article  CAS  PubMed  Google Scholar 

  55. Crosby T, Hurt CN, Falk S, et al. Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicenter, phase 2/3 randomised trial. Lancet Oncol. 2013;14:627–37.

    Article  CAS  PubMed  Google Scholar 

  56. Kudo T, Hamamoto Y, Kato K, et al. Nivolumab treatment for oesophageal squamous cell carcinoma: an open-label, multicenter, phase 2 trial. Lancet Oncol. 2017;18:631–9.

    Article  CAS  PubMed  Google Scholar 

  57. Doi T, Piha-Paul SA, Jalal SI, et al. Safety and antitumor activity of the anti-programmed death-1 antibody pembrolizumab in patients with advanced esophageal carcinoma. J Clin Oncol. 2017;36:61–7.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, International Goodwill Hospital, Yokohama, Japan

    Nobutoshi Ando

Authors
  1. Nobutoshi Ando
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nobutoshi Ando .

Editor information

Editors and Affiliations

  1. International Goodwill Hospital, Yokohama, Japan

    Nobutoshi Ando

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ando, N. (2020). Neoadjuvant and Adjuvant Therapy. In: Ando, N. (eds) Esophageal Squamous Cell Carcinoma. Springer, Singapore. https://doi.org/10.1007/978-981-15-4190-2_14

Download citation

  • DOI: https://doi.org/10.1007/978-981-15-4190-2_14

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-4189-6

  • Online ISBN: 978-981-15-4190-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation