Skip to main content

Advertisement

Log in

Novel pathological staging for patients with locally advanced esophageal squamous cell carcinoma undergoing neoadjuvant chemotherapy followed by surgery

  • Original Article
  • Published:
Esophagus Aims and scope Submit manuscript

Abstract

Background

The aim of the present study was to clarify an appropriate staging system for patients with locally advanced esophageal squamous cell carcinoma (LAESCC) after neoadjuvant chemotherapy (NAC) prior to surgery.

Methods

A total of 388 patients with clinical stage II or III LAESCC who had undergone NAC followed by an esophagectomy with three-field lymphadenectomy were retrospectively reviewed.

Results

The relapse-free survival (RFS) curves plotted using ypN grading and ypTNM staging both monotonically decreased as the classification number increased, and the groups were more clearly separated than when the Japanese Classification (JC) was applied. A multivariate analysis of relapse free survival (RFS) suggested that ypN (HR = 2.911, P < 0.001), lymphovascular invasion (LVI) (HR = 2.608, P < 0.001) were independent factors associated with OS. The LVI+/ypN+ group had a significantly poorer outcome than the other groups (P < 0.001). The 5-year RFS rates for patients with ypStage IIIA or higher among the LVI-negative cases and ypStage II or higher among the LVI-positive cases were around 0.6 or under. The novel pathological staging which was based on the present results was proposed and RFS curves of each novel stage suggested the suitability of these staging for our cohort.

Conclusions

The present results suggest that a novel pathological staging system using the ypTNM classification, in which the supraclavicular lymph node was regarded as a regional lymph node and the presence of LVI was included as a category, was appropriate for patients with LAESCC after NAC prior to surgery.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ohashi S, Miyamoto S, Kikuchi O, et al. Recent advances from basic and clinical studies of esophageal squamous cell carcinoma. Gastroenterology. 2015;149:1700–15.

    Article  Google Scholar 

  2. 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 

  3. Watanabe M, Tachimori Y, Oyama T, et al. Comprehensive registry esophageal cancer in Japan, 2013. Esophagus. 2021;18:1–24.

    Article  Google Scholar 

  4. 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—JCOG9204. J Clin Oncol. 2003;21:4592–6.

    Article  Google Scholar 

  5. 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 

  6. Vermorken JB, Remenar E, van Herpen C, et al. Cisplatin, fluorouracil and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007;357:1695–704.

    Article  CAS  Google Scholar 

  7. van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325Study Group. J Clin Oncol. 2006;24:4991–7.

    Article  Google Scholar 

  8. Chiarion-Sileni V, Corti L, Roul A, et al. Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer. Br J Cancer. 2007;96:432–8.

    Article  CAS  Google Scholar 

  9. 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.

    Article  CAS  Google Scholar 

  10. Makino T, Yamasaki M, Tanaka K, et al. Treatment and clinical outcome of clinical T4 esophageal cancer: a systematic review. Ann Gastroenterol Surg. 2018;3:169–80.

    Article  Google Scholar 

  11. 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. https://doi.org/10.1007/s00268-019-05000-3.

    Article  PubMed  Google Scholar 

  12. 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 radiotherapy with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer (JCOG 1109, NExT study). Jpn J Clin Oncol. 2013;43:752–5.

    Article  Google Scholar 

  13. Rice TW, Ishwaran H, Hofstetter WL, Kelsen DP, Apperson-Hansen C, Blackstone EH, et al. Recommendation for pathologic staging (pTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals. Dis Esophagus. 2016;29:897–905.

    Article  CAS  Google Scholar 

  14. Japan Esophageal Society. Japanese classification of esophageal cancer, 11th edition: part I. Esophagus. 2017;14:1–36.

    Article  Google Scholar 

  15. Rice TW, Ishwaran H, Kelsen DP, Hofstetter WL, Apperson-Hansen C, Blackstone EH, et al. Recommendation for neoadjuvant pathologic staging (ypTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals. Dis Esophagus. 2016;29:906–12.

    Article  Google Scholar 

  16. Oguma J, Ozawa S, Koyanagi K, Kazuno A, Yamamoto M, Ninomiya Y, et al. Prognostic significance of pathological tumor response and residual nodal metastasis in patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy followed by surgery. Esophagus. 2019;16:395–401.

    Article  Google Scholar 

  17. Kadota T, Hatogai K, Yano T, et al. Pathological tumor regression grade of metastatic tumors in lymph node predicts prognosis in esophageal cancer patients. Cancer Sci. 2018;109:2046–55.

    Article  CAS  Google Scholar 

  18. Yokota T, Ando N, Igaki H, et al. Prognostic factors in patients receiving neoadjuvant 5-fluorouracil plus cisplatin for advanced esophageal cancer (JCOG9907). Oncology. 2015;89:143–51.

    Article  CAS  Google Scholar 

  19. Burt BM, Groth SS, Sada YH, et al. Utility of adjuvant chemotherapy after neoadjuvant chemoradiation and esophagectomy for esophageal cancer. Ann Surg. 2017;266:297–304.

    Article  Google Scholar 

  20. Mokdad AA, Yopp AC, Polanco PM, et al. Adjuvant chemotherapy vs postoperative observation following preoperative chemoradiotherapy and resection in gastroesophageal cancer. JAMA Oncol. 2018;4:31–8.

    Article  Google Scholar 

  21. 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 

  22. Rice TW, Patil DT, Blackstone EH. 8th edition AJCC/UICC staging of cancer of the esophagus and esophagogastric junction: application to clinical practice. Ann Cardiothorac Surg. 2017;6:119–30.

    Article  Google Scholar 

  23. Udagawa H, Ueno M, Shinohara H, et al. The importance of grouping of lymph node stations and rationale of three-field lymphoadenectomy for thoracic esophageal cancer. J Surg Oncol. 2012;106:742–7.

    Article  Google Scholar 

  24. Tachimori Y, Ozawa S, Numasawa H, et al. Efficacy of lymph node dissection by node zones according to tumor location for esophageal squamous cell carcinoma. Esophagus. 2016;13:1–7.

    Article  Google Scholar 

  25. Hatogai K, Fujii S, Kojima T, et al. Prognostic significance of tumor regression grade for patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy followed by surgery. J Surg Oncol. 2016;113:390–6.

    Article  Google Scholar 

  26. Mori D, Yamasaki F, Shibaki M, et al. Lateral peritumoral lymphatic vessel invasion can predict lymph node metastasis in esophageal squamous cell carcinoma. Mod Pathol. 2007;20:694–700.

    Article  Google Scholar 

  27. Tomita N, Matsumoto T, Hayashi T, et al. Lymphatic invasion according to D2–40 immunostaining is a strong predictor of nodal metastasis in superficial squamous cell carcinoma of the esophagus: Algorithm for risk of nodal metastasis based on lymphatic invasion. Pathol Int. 2008;58:282–7.

    Article  Google Scholar 

  28. Oguma J, Ozawa S, Kazuno A, et al. Prognostic impact of lymphovascular invasion in lymph node negative-superficial esophageal squamous cell carcinoma. Dis Esophagus. 2019. https://doi.org/10.21037/jtd.2018.05.170.

    Article  PubMed  Google Scholar 

  29. Lagarde SM, Phillips AW, Navidi M, et al. The presence of lymphovascular and perineural infiltration after neoadjuvant therapy and oesophagectomy identifies patients at high risk for recurrence. Br J Cancer. 2015;113:1427–33.

    Article  CAS  Google Scholar 

  30. Chen WH, Huang YL, Chao YK, et al. Prognostic significance of lymphovascular invasion in patients with esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy. Ann Surg Oncol. 2015;22:338–43.

    Article  Google Scholar 

  31. Daiko H, Kato K. Updates in the 8th edition of the TNM staging system for esophagus and esophagogastric junction cancer. Jpn J Clin Oncol. 2020;50:847–51.

    Article  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hiroyuki Daiko.

Ethics declarations

Conflict of interest

All authors declare no conflict of interest.

Ethical statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and its later versions. This article does not contain any studies with human or animal subjects performed by any author(s).

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

10388_2021_891_MOESM1_ESM.pptx

Supplementary file1 Supplemental Figure 1 Relapse free survival curves for all patients according to ypN-grading (ypTNM classification) (A) and pN-grading (JCEC) (B). The curves were calculated using the Kaplan–Meier method. Supplemental Figure 2 Relapse free survival curves for all patients assuming that supraclavicular lymph node was regarded as regional lymph node according to ypTNM staging. The curves were calculated using the Kaplan–Meier method. * The number of patients were changed after re-staging (PPTX 255 kb)

Supplementary file2 (DOCX 26 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oguma, J., Ishiyama, K., Kurita, D. et al. Novel pathological staging for patients with locally advanced esophageal squamous cell carcinoma undergoing neoadjuvant chemotherapy followed by surgery. Esophagus 19, 214–223 (2022). https://doi.org/10.1007/s10388-021-00891-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10388-021-00891-5

Keywords

Navigation