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The Impact of Tumor Regression on Prognosis After Neoadjuvant Chemoradiotherapy in Surgically Treated Esophageal Adenocarcinoma

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

Abstract

Background

The 5-year survival for patients with esophageal carcinoma remains poor despite neoadjuvant therapy and surgery. The eighth American Joint Committee on Cancer (AJCC) staging, based on the neoadjuvant treated TNM (ypTNM) stage of the resection specimen, is used for prognosis. Tumor characteristics such as tumor grade, subtype of adenocarcinoma, and tumor regression scores are not included in this classification. This study aimed to determine the impact of these tumor characteristics on overall survival (OS) and disease-free survival (DFS).

Methods

This retrospective cohort study included 228 patients with esophageal adenocarcinoma. Tumor regression was determined by the Mandard tumor regression (MTR) score. Subtype and grade of adenocarcinoma were confirmed using either the preoperative biopsy or residual tumor tissue after surgery. The MTR was modified to a three-tier classification. The study classified MTR 1 and 2 in one group as a “major response,” with MTR 4 and 5 classified in one group as a “minimal response.”

Results

The median follow-up period was 2.1 years. Combining MTR with AJCC staging did not improve the prognostic value for the prediction of OS. However, the multivariate analysis showed that the prognostic value of AJCC staging for DFS was improved by adding the three-tiered MTR (odds ratio for MTR4+5: 2.46; 95 % confidence interval, 1.07–5.67). Grade or subtype correlated with neither OS nor DFS in the univariate analyses and did not improve the prognostic value of the AJCC staging.

Conclusion

Neither adenocarcinoma subtype nor grade influenced OS or DFS. However, the eighth AJCC staging combined with a three-tier MTR provided a better prognostic tool for DFS in esophageal adenocarcinoma treated with esophagectomy after neoadjuvant chemoradiotherapy.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. https://doi.org/10.3322/caac.21492.

    Article  PubMed  Google Scholar 

  2. van Putten M, de Vos-Geelen J, Nieuwenhuijzen GAP, et al. Long-term survival improvement in oesophageal cancer in the Netherlands. Eur J Cancer. 2018;94:138–47. https://doi.org/10.1016/j.ejca.2018.02.025.

    Article  PubMed  Google Scholar 

  3. Khan OA, Alexiou C, Soomro I, Duffy JP, Morgan WE, Beggs FD. Pathological determinants of survival in node-negative oesophageal cancer. Br J Surg. 2004;91:1586–91. https://doi.org/10.1002/bjs.4778.

    Article  CAS  PubMed  Google Scholar 

  4. Shapiro J, van Lanschot JJB, Hulshof MCCM, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomized controlled trial. Lancet Oncol. 2015;16:1090–8. https://doi.org/10.1016/S1470-2045(15)00040-6.

    Article  PubMed  Google Scholar 

  5. Noble F, Nolan L, Bateman AC, et al. Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus. World J Gastroenterol. 2013;19:9282–93. https://doi.org/10.3748/wjg.v19.i48.9282.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Tomasello G, Ghidini M, Barni S, Passalacqua R, Petrelli F. Overview of different available chemotherapy regimens combined with radiotherapy for the neoadjuvant and definitive treatment of esophageal cancer. Expert Rev Clin Pharmacol. 2017;10:649–60. https://doi.org/10.1080/17512433.2017.1313112.

    Article  CAS  PubMed  Google Scholar 

  7. Rice TW, Patil DT, Blackstone EH. 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice. Ann Cardiothorac Surg. 2017;6:119–30. https://doi.org/10.21037/acs.2017.03.14.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma: an attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49. https://doi.org/10.1111/apm.1965.64.1.31.

    Article  CAS  PubMed  Google Scholar 

  9. Vošmik M, Laco J, Sirák I, et al. Histopathologic features are more important prognostic factors than primary tumour location in gastro-oesophageal adenocarcinoma treated with preoperative chemoradiation and surgery. Pathol Oncol Res. 2018;24:373–83. https://doi.org/10.1007/s12253-017-0253-z.

    Article  CAS  PubMed  Google Scholar 

  10. Spoerl S, Novotny A, Al-Batran SE, et al. Histopathological regression predicts treatment outcome in locally advanced esophagogastric adenocarcinoma. Eur J Cancer. 2018;90:26–33. https://doi.org/10.1016/j.ejca.2017.11.020.

    Article  PubMed  Google Scholar 

  11. van der Kaaij RT, Snaebjornsson P, Voncken FEM, et al. The prognostic and potentially predictive value of the Laurén classification in oesophageal adenocarcinoma. Eur J Cancer. 2017;76:27–35. https://doi.org/10.1016/j.ejca.2017.01.031.

    Article  PubMed  Google Scholar 

  12. van der Kaaij RT, Koemans WJ, van Putten M, et al. A population-based study on intestinal and diffuse type adenocarcinoma of the oesophagus and stomach in the Netherlands between 1989 and 2015. Eur J Cancer. 2020;130:23–31. https://doi.org/10.1016/j.ejca.2020.02.017.

    Article  PubMed  Google Scholar 

  13. Kim T, Grobmyer SR, Smith R, et al. Esophageal cancer: the five year survivors. J Surg Oncol. 2011;103:179–83. https://doi.org/10.1002/jso.21784.

    Article  PubMed  Google Scholar 

  14. Hou X, Gu YK, Liu XW, et al. The impact of tumor cell differentiation on survival of patients with resectable esophageal squamous cell carcinomas. Ann Surg Oncol. 2015;22:1008–14. https://doi.org/10.1245/s10434-014-4067-x.

    Article  PubMed  Google Scholar 

  15. Mandard A-M, Dalibard F, Mandard J-C, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73:2680–6. https://doi.org/10.1002/1097-0142(19940601)73:11%3c2680::AID-CNCR2820731105%3e3.0.CO;2-C.

    Article  CAS  PubMed  Google Scholar 

  16. Karamitopoulou E, Thies S, Zlobec I, et al. Assessment of tumor regression of esophageal adenocarcinomas after neoadjuvant chemotherapy. Am J Surg Pathol. 2014;38:1551–6. https://doi.org/10.1097/pas.0000000000000255.

    Article  PubMed  Google Scholar 

  17. Hölscher AH, Drebber U, Schmidt H, Bollschweiler E. Prognostic classification of histopathologic response to neoadjuvant therapy in esophageal adenocarcinoma. Ann Surg. 2014;260:779–85. https://doi.org/10.1097/SLA.0000000000000964.

    Article  PubMed  Google Scholar 

  18. Puetz K, Bollschweiler E, Semrau R, Mönig SP, Hölscher AH, Drebber U. Neoadjuvant chemoradiation for patients with advanced oesophageal cancer: which response grading system best impacts prognostic discrimination? Histopathology. 2019;74:731–43. https://doi.org/10.1111/his.13811.

    Article  PubMed  Google Scholar 

  19. Zhu Y, Sun Y, Hu S, et al. Comparison of five tumor regression grading systems for gastric adenocarcinoma after neoadjuvant chemotherapy: a retrospective study of 192 cases from National Cancer Center in China. BMC Gastroenterol. 2017;17:1–18. https://doi.org/10.1186/s12876-017-0598-5.

    Article  CAS  Google Scholar 

  20. 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. https://doi.org/10.1097/SLA.0b013e3182a66588.

    Article  PubMed  Google Scholar 

  21. Maag-darm-leverartsen V Van. Oesofaguscarcinoom Inhoudsopgave. Published online 2010:1–12. Accessed 8 July 2021.

  22. Ryan R, Gibbons D, Hyland JMP, et al. Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology. 2005;47:141–6. https://doi.org/10.1111/j.1365-2559.2005.02176.x.

    Article  CAS  PubMed  Google Scholar 

  23. Sarbia M. The histological appearance of oesophageal adenocarcinoma: an analysis based on 215 resection specimens. Virchows Arch. 2006;448:532–8. https://doi.org/10.1007/s00428-006-0168-7.

    Article  PubMed  Google Scholar 

  24. Polkowski W, Van Sandick JW, Offerhaus GJA, et al. Prognostic value of Lauren classification and c-erbB-2 oncogene overexpression in adenocarcinoma of the esophagus and gastroesophageal junction. Ann Surg Oncol. 1999;6:290–7. https://doi.org/10.1007/s10434-999-0290-2.

    Article  CAS  PubMed  Google Scholar 

  25. van Hagen P, Hulshof MCCM, van Lanschot JJB, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84. https://doi.org/10.1056/nejmoa1112088.

    Article  PubMed  Google Scholar 

  26. 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. https://doi.org/10.1016/S1470-2045(11)70142-5.

    Article  PubMed  Google Scholar 

  27. Zhao X, Ren Y, Hu Y, Cui N, Wang X, Cui Y. Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or the gastroesophageal junction: a meta-analysis based on clinical trials. PloS One. 2018;13:1–19. https://doi.org/10.1371/journal.pone.0202185.

    Article  CAS  Google Scholar 

  28. Deng HY, Wang WP, Wang YC, et al. Neoadjuvant chemoradiotherapy or chemotherapy? A comprehensive systematic review and meta-analysis of the options for neoadjuvant therapy for treating oesophageal cancer. Eur J Cardiothorac Surg. 2017;51:421–31. https://doi.org/10.1093/ejcts/ezw315.

    Article  PubMed  Google Scholar 

  29. Von Döbeln GA, Klevebro F, Jacobsen AB, et al. Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or gastroesophageal junction: long-term results of a randomized clinical trial. Dis Esophagus. 2019;32:1–11. https://doi.org/10.1093/dote/doy078.

    Article  Google Scholar 

  30. van Hootegem SJM, Smithers BM, Gotley DC, et al. The impact of signet ring cell differentiation on outcome in patients with esophageal and gastroesophageal junction adenocarcinoma. Ann Surg Oncol. 2019;26:2375–84. https://doi.org/10.1245/s10434-019-07322-x.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Hagens E, Tukanova K, Jamel S, et al. Prognostic relevance of lymph node regression on survival in esophageal cancer: a systematic review and meta-analysis. Published online 2021:1–11. https://doi.org/10.1093/dote/doab021.

  32. 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. Science. 2016. https://doi.org/10.1200/JCO.2015.65.7692.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Depypere L, Moons J, Lerut T, et al. Neoadjuvant chemoradiation treatment followed by surgery for esophageal cancer: there is much more than the Mandard tumor regression score. Acta Chir Belg. 2016;116:149–55. https://doi.org/10.1080/00015458.2016.1212500.

    Article  CAS  PubMed  Google Scholar 

  34. Verlato G, Zanoni A, Tomezzoli A, et al. Response to induction therapy in oesophageal and cardia carcinoma using Mandard tumour regression grade or size of residual foci. Br J Surg. 2010;97:719–25. https://doi.org/10.1002/bjs.6949.

    Article  CAS  PubMed  Google Scholar 

  35. Yuan Y, Ma G, Hu X, Huang Q. Evaluating the eighth edition TNM staging system for esophageal cancer among patients receiving neoadjuvant therapy: a SEER study. Cancer Med. 2020;9:4648–55. https://doi.org/10.1002/cam4.2997.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Allum WH, Stenning SP, Bancewicz J, Clark PI, Langley RE. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 2009;27:5062–7. https://doi.org/10.1200/JCO.2009.22.2083.

    Article  PubMed  Google Scholar 

  37. Depypere L, Lerut T, Moons J, et al. Isolated local recurrence or solitary solid organ metastasis after esophagectomy for cancer is not the end of the road. Dis Esophagus. 2017;30:1–8. https://doi.org/10.1111/dote.12508.

    Article  CAS  PubMed  Google Scholar 

  38. Lou F, Sima CS, Adusumilli PS, et al. Esophageal cancer recurrence patterns and implications for surveillance. J Thorac Oncol. 2013;8:1558–62. https://doi.org/10.1097/01.JTO.0000437420.38972.fb.

    Article  PubMed  PubMed Central  Google Scholar 

  39. 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. https://doi.org/10.1097/SLA.0000000000001954.

    Article  PubMed  Google Scholar 

  40. Mokdad AA, Yopp AC, Polanco PM, et al. Adjuvant chemotherapy vs postoperative observation following preoperative chemoradiotherapy and resection in gastroesophageal cancer a propensity score-matched analysis. JAMA Oncol. 2018;4:31–8. https://doi.org/10.1001/jamaoncol.2017.2805.

    Article  PubMed  Google Scholar 

  41. Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021;384:1191–203. https://doi.org/10.1056/nejmoa2032125.

    Article  CAS  PubMed  Google Scholar 

  42. Turgeman I, Ben-Aharon I. Evolving treatment paradigms in esophageal cancer. Ann Transl Med. 2021;9:903–918. https://doi.org/10.21037/atm.2020.03.110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Ziekenhuisgroep Twente, Almelo, The Netherlands

    D. J. Crull MD, M. J. van Det MD, PhD & E. A. Kouwenhoven MD, PhD

  2. Department of Pathology, LabPon, Hengelo, The Netherlands

    M. C. H. Hogenes MD, PhD

  3. Department of Medical Oncology, Ziekenhuisgroep Twente, Almelo, The Netherlands

    R. Hoekstra MD, PhD

  4. Department of Radiation Oncology, Medisch Spectrum Twente, Enschede, The Netherlands

    E. M. Hendriksen MD

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Crull, D.J., Hogenes, M.C.H., Hoekstra, R. et al. The Impact of Tumor Regression on Prognosis After Neoadjuvant Chemoradiotherapy in Surgically Treated Esophageal Adenocarcinoma. Ann Surg Oncol 29, 3658–3666 (2022). https://doi.org/10.1245/s10434-022-11336-3

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