Neoadjuvant Chemoradiotherapy with Cisplatin Plus Fluorouracil for Borderline Resectable Esophageal Squamous Cell Carcinoma



The optimal treatment strategy for patients with borderline resectable (BR) esophageal squamous cell carcinoma (ESCC), in which tumors grow very close to the adjacent vital organs, remains unclear. This study evaluated the efficacy of neoadjuvant chemoradiotherapy (NACRT) with cisplatin plus fluorouracil (CF) and irradiation (40 Gy) for these patients.


The study cohort included 50 patients with BR-ESCC who received NACRT as the initial treatment and were allocated to one of two groups: patients who achieved curative resection (R0 group) or those who did not (Non-R0 group). The overall survival (OS), relapse-free survival (RFS), and pre-therapeutic predictive factors for Non-R0 were evaluated.


Among the 50 patients, 22 (44%) achieved curative resection clinically. The median OS was significantly better in the R0 group than in the Non-R0 group (2.4 vs 0.8 years; hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.12–0.67; p < 0.01). The independent predictive factors before NACRT for Non-R0 were higher serum SCC antigen level (p < 0.01) and clinical nodal involvement (p = 0.02). In addition, OS was significantly worse for the patients with higher levels of serum SCC antigen than for those with lower levels (p < 0.01).


Curative resection was achieved for about 40% of the patients who received NACRT for BR-ESCC. Therefore, NACRT could be a useful neoadjuvant treatment option for BR-ESCC. However, a higher serum SCC antigen level before NACRT is predictive of treatment failure and poor survival.

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  1. 1.

    GLOBOCAN database. Accessed 8 July 2019.

  2. 2.

    Surveillance, epidemiology, and end results program. Accessed 8 July 2019.

  3. 3.

    Sasaki Y, Tamura M, Koyama R, et al. Genomic characterization of esophageal squamous cell carcinoma: insights from next-generation sequencing. World J Gastroenterol. 2016;22:2284–93.

    CAS  Article  Google Scholar 

  4. 4.

    Ando N, Kato H, Igaki H, et al. 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. 2012;19:68–74.

    Article  Google Scholar 

  5. 5.

    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  Google Scholar 

  6. 6.

    Ohtsu A, Boku N, Muro K, et al. Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus. J Clin Oncol. 1999;17:2915–21.

    CAS  Article  Google Scholar 

  7. 7.

    Kitagawa Y, Uno T, Oyama T, et al. Esophageal cancer practice guidelines 2017, edited by the Japan Esophageal Society: part 2. Esophagus. 2019;16:25–43.

    Article  Google Scholar 

  8. 8.

    Ishida K, Ando N, Yamamoto S, et al. Phase II study of cisplatin and 5-fluorouracil with concurrent radiotherapy in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG)/Japan Clinical Oncology Group Trial (JCOG9516). Jpn J Clin Oncol. 2004;34:615–9.

    Article  Google Scholar 

  9. 9.

    Shinoda M, Ando N, Kato K, et al. Randomized study of low-dose versus standard-dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303). Cancer Sci. 2015;106:407–12.

    CAS  Article  Google Scholar 

  10. 10.

    Burmeister BH, Smithers BM, Gebski V, et al. Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomized controlled phase III trial. Lancet Oncol. 2005;6:659–68.

    Article  Google Scholar 

  11. 11.

    Tepper J, Krasna MJ, Niedzwiecki D, et al. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008;26:1086–92.

    CAS  Article  Google Scholar 

  12. 12.

    Mariette C, Dahan L, Mornex F, et al. Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal cancer: final analysis of randomized controlled phase III trial FFCD 9901. J Clin Oncol. 2014;32:2416–22.

    CAS  Article  Google Scholar 

  13. 13.

    van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.

    Article  Google Scholar 

  14. 14.

    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  Google Scholar 

  15. 15.

    Picus D, Balfe DM, Koehler RE, et al. Computed tomography in the staging of esophageal carcinoma. Radiology. 1983;146:433–8.

    CAS  Article  Google Scholar 

  16. 16.

    Noguchi T, Moriyama H, Wada S, et al. Resection surgery with neoadjuvant chemoradiotherapy improves outcomes of patients with T4 esophageal carcinoma. Dis Esophagus. 2003;16:94–8.

    CAS  Article  Google Scholar 

  17. 17.

    Fujita H, Sueyoshi S, Tanaka T, et al. Prospective non-randomized trial comparing esophagectomy followed by chemoradiotherapy versus chemoradiotherapy followed by esophagectomy for T4 esophageal cancers. J Surg Oncol. 2005;90:209–19.

    Article  Google Scholar 

  18. 18.

    Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649–55.

    CAS  Article  Google Scholar 

  19. 19.

    Forrest LM, McMillan DC, McArdle CS, Angerson WJ, Dunlop DJ. Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small cell lung cancer. Br J Cancer. 2003;89:1028–30.

    CAS  Article  Google Scholar 

  20. 20.

    Yodying H, Matsuda A, Miyashita M, et al. Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer: a systematic review and meta-analysis. Ann Surg Oncol. 2016;23:646–54.

    Article  Google Scholar 

  21. 21.

    Common Terminology Criteria for Adverse Events (CTCAE) v 5.0. Accessed 18 August 2019.

  22. 22.

    Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.

    Article  Google Scholar 

  23. 23.

    Youden WJ. Index for rating diagnostic tests. Cancer. 1950;3:32–5.

    CAS  Article  Google Scholar 

  24. 24.

    Yokota T, Hatooka S, Ura T, et al. Docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy for locally advanced borderline-resectable T4 esophageal cancer. Anticancer Res. 2011;31:3535–41.

    CAS  PubMed  Google Scholar 

  25. 25.

    Watanabe M, Baba Y, Yoshida N, et al. Outcomes of preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil followed by esophagectomy in patients with resectable node-positive esophageal cancer. Ann Surg Oncol. 2014;21:2838–44.

    Article  Google Scholar 

  26. 26.

    Takeuchi M, Kawakubo H, Mayanagi S, et al. The benefits of docetaxel plus cisplatin and 5-fluorouracil induction therapy in conversion to curative treatment for locally advanced esophageal squamous cell carcinoma. World J Surg. 2019;43:2006–15.

    Article  Google Scholar 

  27. 27.

    Yokota T, Kato K, Hamamoto Y, et al. Phase II study of chemoselection with docetaxel plus cisplatin and 5-fluorouracil induction chemotherapy and subsequent conversion surgery for locally advanced unresectable oesophageal cancer. Br J Cancer. 2016;115:1328–34.

    CAS  Article  Google Scholar 

  28. 28.

    Terada M, Hara H, Daiko H, et al. Phase III study of tri-modality combination therapy with induction docetaxel plus cisplatin and 5-fluorouracil versus definitive chemoradiotherapy for locally advanced unresectable squamous cell carcinoma of the thoracic esophagus (JCOG1510: TRIANgLE). Jpn J Clin Oncol. (2019).

    Article  PubMed  Google Scholar 

  29. 29.

    Torre GC. SCC antigen in malignant and nonmalignant squamous lesions. Tumour Biol. 1998;19:517–26.

    CAS  Article  Google Scholar 

  30. 30.

    Shimada H, Nabeya Y, Okazumi S, et al. Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma. Surgery. 2003;133:486–94.

    Article  Google Scholar 

  31. 31.

    Okamura A, Watanabe M, Mine S, et al. Failure of neoadjuvant chemotherapy for resectable esophageal squamous cell carcinoma. Dis Esophagus. 2017;30:1–8.

    CAS  Article  Google Scholar 

  32. 32.

    Hamamoto Y, Nojima M, Aoki Y, et al. Inter-evaluator heterogeneity of clinical diagnosis for locally advanced esophageal squamous cell carcinoma. Esophagus. 2017;14:324–32.

    Article  Google Scholar 

  33. 33.

    Yokota T, Yasuda T, Kato H. et al. Concordance of clinical diagnosis of T classification among physicians for locally advanced unresectable thoracic esophageal cancer. Int J Clin Oncol. 2018;23:73–80.

    Article  Google Scholar 

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Correspondence to Akihiko Okamura MD, PhD.

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All authors declare no conflicts of interests for this article. Conflicts of interests outside this work are as follows; Kensei Yamaguchi played Consulting or Advisory Role for Bristol-Myers Squibb Japan and Daiichi Sankyo, and received Speakers’ Bureau from Chugai Pharma, Merck Serono, Bristol-Myers Squibb Japan, Takeda, Taiho Pharmaceutical, Lilly, Ono Pharmaceutical, Sanofi and Daiichi Sankyo. Kensei Yamaguchi’s institution (Department of Gastroenterological Medicine, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research) received research funding from MSD Oncology, Ono Pharmaceutical, Dainippon Sumitomo Pharma, Taiho Pharmaceutical, Daiichi Sankyo, Lilly, Gilead Sciences, Yakult Honsha, Chugai Pharma, Boehringer Ingelheim and Eisai.

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Suzuki, T., Okamura, A., Watanabe, M. et al. Neoadjuvant Chemoradiotherapy with Cisplatin Plus Fluorouracil for Borderline Resectable Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 27, 1510–1517 (2020).

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