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The Impact of Pathological Tumor Regression and Nodal Status on Survival and Systemic Disease in Patients Undergoing Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Although tumor regression and nodal status are reported to be useful prognostic factors for patients with oesophageal cancer who are treated with neoadjuvant chemoradiotherapy, the clinical effects of those factors remain to be explained fully in neoadjuvant chemotherapy. Additionally, factor predictive of systemic disease after neoadjuvant therapy remain unexplored.

Methods

The impact of pathological tumor regression and the number of involved lymph nodes on survival and the occurrence of systemic disease were examined in 405 patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy,

Results

Among the 405 patients studied, 96 (23.7%) achieved good response, whereas 309 (76.3%) were classified as poor response to neoadjuvant chemotherapy. Systemic disease occurred in 136 patients (34.6%) of 393 patients who underwent curative esophagectomy. The number of involved lymph nodes and pathological tumor regression were associated with survival and the occurrence of systemic disease. Multivariate analysis showed that the number of involved lymph nodes was identified as an independent factor associated with both survival and the occurrence of systemic disease, together with the latest AJCC ypstage. However, tumor regression was not found to be an independent factor associated with survival and systemic disease in multivariate analysis.

Conclusions

Posttreatment nodal status rather than pathological tumor regression seems to be useful for predicting prognosis and the occurrence of systemic disease in patients with esophageal squamous cell carcinoma who underwent neoadjuvant chemotherapy. Additional systemic therapy may be needed in patients with several involved lymph nodes remaining after neoadjuvant therapy.

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References

  1. 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. 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  PubMed  CAS  Google Scholar 

  3. 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  PubMed  Google Scholar 

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

    Article  Google Scholar 

  5. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.

    Article  PubMed  CAS  Google Scholar 

  6. Miyata H, Yamasaki M, Miyazaki Y, et al. Clinical importance of supraclavicular lymph node metastasis after neoadjuvant chemotherapy for esophageal squamous cell carcinoma. Ann Surg. 2015;262:280–5.

    Article  PubMed  Google Scholar 

  7. Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29:1715–21.

    Article  PubMed  CAS  Google Scholar 

  8. Bekkar S, Gronnier C, Renaud F, et al. Multicentre study of neoadjuvant chemotherapy for stage I and II oesophageal cancer. Br J Surg. 2016;103:855–62.

    Article  PubMed  CAS  Google Scholar 

  9. Burmeister BH, Thomas JM, Burmeister EA, et al. Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial. Eur J Cancer. 2011;47:354–60.

    Article  PubMed  Google Scholar 

  10. Klevebro F, Alexandersson von Döbeln G, 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  PubMed  CAS  Google Scholar 

  11. Hoeppner J, Lordick F, Brunner T, et al. Prospective randomized controlled multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (NCT02509286). BMC Cancer. 2016;16:503.

    Article  PubMed  PubMed Central  CAS  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 (JCOG1109, NExT study). Jpn J Clin Oncol. 2013;43:752–5.

    Article  PubMed  Google Scholar 

  13. Berger AC, Farma J, Scott WJ, et al. Complete response to neoadjuvant chemoradiotherapy in esophageal carcinoma is associated with significantly improved survival. J Clin Oncol. 2005; 23: 4330–6.

    Article  PubMed  Google Scholar 

  14. Chirieac LR, Swisher SG, Ajani JA, et al. Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation. Cancer 2005; 103: 1347–55.

    Article  PubMed  Google Scholar 

  15. Schneider PM, Baldus SE, Metzger R, et al. Histomorphologic tumor regression and lymph node metastases determine prognosis following neoadjuvant radiochemotherapy for esophageal cancer. Implication for response classification. Ann Surg. 2005;5:684–92.

    Google Scholar 

  16. Reynolds JV, Muldoon C, Hollywood D, et al. Long-term outcomes following neoadjuvant chemoradiotherapy for esophageal cancer. Ann Surg. 2007;245:707–16.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mariette C, Piessen G, Briez N, et al. The number of metastatic lymph nodes and the ratio between metastatic and examined lymph nodes are independent prognostic factors in esophageal cancer regardless of neoadjuvant chemoradiation or lymphadenectomy extent. Ann Surg. 2008;247:365–71.

    Article  PubMed  Google Scholar 

  18. Koen Talsma A, Shapiro J, Looman CW, et al. Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival. Ann Surg. 2014;260:786–92.

    Article  PubMed  CAS  Google Scholar 

  19. Bedenne L, Michel P, Bouché O, et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol. 2007;25:1160–8.

    Article  PubMed  CAS  Google Scholar 

  20. Kelsen DP, Winter KA, Gunderson LL, et al. A random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer. J Clin Oncol. 2007 20;25:3719–25.

    Article  Google Scholar 

  21. Oppedijk V, van der Gaast A, van Lanschot JJ, et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol. 2014;32:385–91.

    Article  PubMed  Google Scholar 

  22. 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.

    Article  PubMed  CAS  Google Scholar 

  23. Miyata H, Yamasaki M, Takahashi T, et al. Relevance of 18F-fluorodeoxyglucose positron emission tomography-positive lymph nodes after neoadjuvant chemotherapy for squamous cell oesophageal cancer. Br J Surg 2013;100:1490–7.

    Article  PubMed  CAS  Google Scholar 

  24. Miyata H, Yano M, Doki Y, et al. A prospective trial for avoiding cervical lymph node dissection for thoracic esophageal cancers, based on intra-operative genetic diagnosis of micrometastasis in recurrent laryngeal nerve chain nodes. J Surg Oncol. 2006;93:477–84.

    Article  PubMed  Google Scholar 

  25. Japanese Society for Esophageal Diseases: Guidelines for the clinical and pathologic studies on carcinoma of the esophagus (ed 10). Tokyo, Japan, Kanehara Syuppan, 2007.

  26. Miyata H, Yamasaki M, Takiguchi S, et al. Prognostic value of endoscopic biopsy findings after induction chemoradiotherapy with and without surgery for esophageal cancer. Ann Surg. 2011;253:279–84.

    Article  PubMed  Google Scholar 

  27. Brierley J, Gospodarowicz M, Wittekind C. TNM Classification of Malignant Tumours eighth edition. Oxford: Wiley, 2017.

    Google Scholar 

  28. Amin MB, Edge SB, Greene FL, et al. AJCC Cancer Staging Manual, 8th edn. New York: Springer, 2017.

    Book  Google Scholar 

  29. Peyre CG, Hagen JA, DeMeester SR, et al. The number of lymph nodes removed predicts survival in esophageal cancer: an international study on the impact of extent of surgical resection. Ann Surg. 2008;248:549–56.

    Article  PubMed  Google Scholar 

  30. Smyth EC, Fassan M, Cunningham D, et al. Effect of pathologic tumor response and nodal status on survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial. J Clin Oncol. 2016;34:2721–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Schmidt T, Sicic L, Blank S, et al. Prognostic value of histopathological regression in 850 neoadjuvantly treated oesophagogastric adenocarcinomas. Br J Cancer. 2014;110:1712–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Mandard AM, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathological correlations. Cancer 1994;73:2680–6.

    CAS  Google Scholar 

  33. Donohoe CL, O’Farrell NJ, Grant T, et al. Classification of pathologic response to neoadjuvant therapy in esophageal and junctional cancer: assessment of existing measures and proposal of a novel 3-point standard. Ann Surg. 2013;258:784–92.

    Article  PubMed  Google Scholar 

  34. Robb WB, Dahan L, Mornex F, et al. Impact of neoadjuvant chemoradiation on lymph node status in esophageal cancer: post hoc analysis of a randomized controlled trial. Ann Surg. 2015;261:902–8.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Hiroshi Miyata MD, Koji Tanaka MD, Tomoki Makino MD, Makoto Yamasaki MD, Yasuhiro Miyazaki MD, Tsuyoshi Takahashi MD, Yukinori Kurokawa MD, Kiyokazu Nakajima MD, Shuji Takiguchi MD, Masaki Mori MD & Yuichiro Doki MD

  2. Department of Pathology, Graduate School of Medicine, Osaka University, Osaka, Japan

    Eiichi Morii MD

  3. Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan

    Hiroshi Miyata MD

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  1. Hiroshi Miyata MD
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  2. Koji Tanaka MD
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  3. Tomoki Makino MD
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  4. Makoto Yamasaki MD
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  5. Yasuhiro Miyazaki MD
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  6. Tsuyoshi Takahashi MD
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Correspondence to Hiroshi Miyata MD.

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Miyata, H., Tanaka, K., Makino, T. et al. The Impact of Pathological Tumor Regression and Nodal Status on Survival and Systemic Disease in Patients Undergoing Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 25, 2409–2417 (2018). https://doi.org/10.1245/s10434-018-6507-5

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  • DOI: https://doi.org/10.1245/s10434-018-6507-5

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