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The Effect of Neoadjuvant Therapy on Esophagectomy for cT2N0M0 Esophageal Adenocarcinoma

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

Abstract

Background

For cT2N0M0 esophageal adenocarcinomas, the effects of neoadjuvant chemoradiotherapy (NT) on surgical outcomes and the oncological benefits to the patients are debatable. In this study, we investigated the optimal management for cT2N0M0 adenocarcinoma (1) assessing the perioperative impact of NT on esophagectomy and (2) evaluating the oncologic effect of NT in a homogeneous group of patients with clinical stage IIA. We hypothesized that NT does not negatively affect perioperative outcomes and provides an oncologic benefit to selected patients with cT2N0M0 disease.

Methods

The National Cancer Database was queried (2010–2019) for patients with cT2N0M0 esophageal adenocarcinoma undergoing esophagectomy. After propensity-matching to adjust for differences in patient and tumor characteristics, we compared postoperative outcomes (logistic regression) and survival (Kaplan–Meier and Cox regression) among those who underwent NT vs upfront surgery (S).

Results

This study included 3413 patients, of whom 2359 (69%) received NT, and 1054 (31%) S. In contrast to those who underwent S, in the matched cohort, patients treated with NT had comparable conversion rates (8% vs11.1%, p = 0.06), length of stay (9 vs 10 days, p = 0.078), unplanned readmission (5.4% vs 8.8%, p = 0.109), and 30- (3.9% vs 3.7%, p = 0.90) and 90-day mortality (5.7% vs 4.7%, p = 0.599). In addition, NT associated with improved survival in patients with cT2N0M0 tumors > 5 cm (HR 0.30, 95% CI 0.17–0.36).

Conclusions

NT does not appear to increase technical complexity or to adversely affect postoperative outcomes after esophagectomy. Furthermore, minimally invasive esophagectomy is feasible following NT, with comparable conversion rates to those who had upfront surgery. Lastly, NT was selectively associated with improved survival in patients with cT2N0M0 esophageal cancer.

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References

  1. van der Sluis PC, Schizas D, Liakakos T, van Hillegersberg R. Minimally invasive esophagectomy. Dig Surg. 2020;37(2):93–100. https://doi.org/10.1159/000497456.

    Article  PubMed  Google Scholar 

  2. Wei B, D’Amico TA. Thoracoscopic versus robotic approaches: advantages and disadvantages. Thoracic Surg Clin. 2014;24:177–88.

    Article  Google Scholar 

  3. Zingg U, Smithers BM, Gotley DC, Smith G, Aly A, Clough A, et al. Factors associated with postoperative pulmonary morbidity after esophagectomy for cancer. Ann Surg Oncol. 2011;18:1460–8.

    Article  PubMed  Google Scholar 

  4. Shapiro J, Van Lanschot JJB, Hulshof MC, van Hagen P, van Berge Henegouwen MI, Wijnhoven BP, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. The Lancet Oncology. 2015;16:1090–8.

    Article  PubMed  Google Scholar 

  5. Tang H, Tan L, Shen Y, Wang H, Lin M, Feng M, et al. CMISG1701: a multicenter prospective randomized phase III clinical trial comparing neoadjuvant chemoradiotherapy to neoadjuvant chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0-1M0)(NCT03001596). BMC Cancer. 2017;17:1–8.

    Article  CAS  Google Scholar 

  6. Wang H, Tang H, Fang Y, Tan L, Yin J, Shen Y, et al. Morbidity and mortality of patients who underwent minimally invasive esophagectomy after neoadjuvant chemoradiotherapy vs neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma: a randomized clinical trial. JAMA Surgery. 2021;156:444–51.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kim JY, Hofstetter WL. Esophagectomy after chemoradiation: who and when to operate. Semin Thoracic Cardiovasc Surg. 2012;24:288–93. https://doi.org/10.1053/j.semtcvs.2012.10.005.

    Article  Google Scholar 

  8. Franko J, Voynov G, Goldman CD. Esophagectomy timing after neoadjuvant therapy for distal esophageal adenocarcinoma. Ann Thoracic Surg. 2016;101:1123–30.

    Article  Google Scholar 

  9. Berlth F, Hadzijusufovic E, Mann C, Fetzner UK, Grimminger P. Minimal invasive Ösophagektomie für maligne Tumore der Speiseröhre. Therapeutische Umschau. 2022;79:181–7.

    Article  PubMed  Google Scholar 

  10. Mitzman B, Lutfi W, Wang C-H, Krantz S, Howington JA, Kim K-W. Minimally Invasive Esophagectomy Provides Equivalent Survival to Open Esophagectomy: An Analysis of the National Cancer Database. Sem Thoracic Cardiovasc Surg. 2017;29:244–53. https://doi.org/10.1053/j.semtcvs.2017.03.007.

    Article  Google Scholar 

  11. Tapias LF, Mathisen DJ, Wright CD, Wain JC, Gaissert HA, Muniappan A, et al. Outcomes with open and minimally invasive Ivor Lewis esophagectomy after neoadjuvant therapy. Ann Thoracic Surg. 2016;101:1097–103.

    Article  Google Scholar 

  12. Bograd AJ, Molena D. Minimally invasive esophagectomy. Curr Probl Surg. 2021;58:100984–100984.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Mariette C, Markar SR, Dabakuyo-Yonli TS, Meunier B, Pezet D, Collet D, et al. Hybrid minimally invasive esophagectomy for esophageal cancer. N Engl J Med. 2019;380:152–62.

    Article  PubMed  Google Scholar 

  14. Kamel MK, Sholi AN, Rahouma M, Harrison SW, Lee B, Stiles BM, et al. National trends and perioperative outcomes of robotic oesophagectomy following induction chemoradiation therapy: a National Cancer Database propensity-matched analysis. Eur J Cardio-Thoracic Surg. 2021;59:403–8.

    Article  Google Scholar 

  15. Halpern AL, Friedman C, Torphy RJ, Al-Musawi MH, Mitchell JD, Scott CD, et al. Conversion to open surgery during minimally invasive esophagectomy portends worse short-term outcomes: an analysis of the National Cancer Database. Surg Endosc. 2020;34:3470–8. https://doi.org/10.1007/s00464-019-07124-y.

    Article  PubMed  Google Scholar 

  16. Ben-David K, Rossidis G, Zlotecki RA, Grobmyer SR, Cendan JC, Sarosi GA, et al. Minimally invasive esophagectomy is safe and effective following neoadjuvant chemoradiation therapy. Ann Surg Oncol. 2011;18:3324–9.

    Article  PubMed  Google Scholar 

  17. Sihag S, Kosinski AS, Gaissert HA, Wright CD, Schipper PH. Minimally invasive versus open esophagectomy for esophageal cancer: a comparison of early surgical outcomes from the society of thoracic surgeons national database. Ann Thorac Surg. 2016;101:1281–9. https://doi.org/10.1016/j.athoracsur.2015.09.095.

    Article  PubMed  Google Scholar 

  18. Zhang JQ, Hooker CM, Brock MV, Shin J, Lee S, How R, et al. Neoadjuvant chemoradiation therapy is beneficial for clinical stage T2 N0 esophageal cancer patients due to inaccurate preoperative staging. Ann Thorac Surg. 2012;93:429–37.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Stiles BM, Mirza F, Coppolino A, Port JL, Lee PC, Paul S, et al. Clinical T2–T3N0M0 esophageal cancer: the risk of node positive disease. Ann Thorac Surg. 2011;92:491–8. https://doi.org/10.1016/j.athoracsur.2011.04.004.

    Article  PubMed  Google Scholar 

  20. Deng W, Yang J, Ni W, Li C, Chang X, Han W, et al. Postoperative radiotherapy in pathological T2–3N0M0 thoracic esophageal squamous cell carcinoma: interim report of a prospective, phase III, randomized controlled study. The Oncologist. 2020;25:e701–8.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Denlinger CS, Matkowskyj KA, Mulcahy MF. Gastric and esophageal cancers: guidelines updates. JNCCN J Natl Compr Cancer Netw. 2021;19:639–43.

    Article  Google Scholar 

  22. Bilimoria KY, Stewart AK, Winchester DP, Ko CY. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol. 2008;15:683–90.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Huang Y, Chang J, Guo X, Zhang C, Ji W, Zhou S, et al. Induction chemotherapy increases efficacy and survival rate of patients with locally advanced esophageal squamous cell carcinoma. Front Oncol. 2022;12:1067838. https://doi.org/10.3389/fonc.2022.1067838.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Vadhwana B, Zosimas D, Lykoudis P, Phen H, Martinou M, Khoo D. Tumour length as an independent prognostic factor in resectable oesophageal carcinoma. Annals. 2020;102:185–90. https://doi.org/10.1308/rcsann.2019.0147.

    Article  CAS  Google Scholar 

  25. Song Z, Wang J, Lin B, Zhang Y. Analysis of the tumor length and other prognosis factors in pT1-2 node-negative esophageal squamous cell carcinoma in a Chinese population. World J Surg Oncol. 2012;10:273. https://doi.org/10.1186/1477-7819-10-273.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Griffiths EA, Brummell Z, Gorthi G, Pritchard SA, Welch IM. Tumor length as a prognostic factor in esophageal malignancy: Univariate and multivariate survival analyses. J Surg Oncol. 2006;93:258–67. https://doi.org/10.1002/jso.20449.

    Article  PubMed  Google Scholar 

  27. Yendamuri S, Swisher SG, Correa AM, Hofstetter W, Ajani JA, Francis A, et al. Esophageal tumor length is independently associated with long-term survival. Cancer. 2009;115:508–16. https://doi.org/10.1002/cncr.24062.

    Article  PubMed  Google Scholar 

  28. Mariette C, Dahan L, Mornex F, Maillard E, Thomas P-A, Meunier B, 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. JCO. 2014;32:2416–22. https://doi.org/10.1200/JCO.2013.53.6532.

    Article  CAS  Google Scholar 

  29. Mu Y, Wang H, He T, Xu L. The impact of radiation dose on preoperative neoadjuvant chemoradiotherapy effects for patients with locally advanced squamous cell esophageal carcinoma: a propensity score-matched retrospective study. J Immunol Res. 2022;2022:7581799. https://doi.org/10.1155/2022/7581799.

    Article  Google Scholar 

  30. Liu X-H, Hu Y, Li K-K, Wang Y-J, Jiang Y-G, Guo W. Intraoperative conversion does not affect the oncological outcomes of minimally invasive esophagectomy for treatment of esophageal cancer. Surg Endosc. 2018;32:4517–26.

    Article  PubMed  Google Scholar 

  31. Sancheti M, Fernandez F. Management of T2 esophageal cancer. Surg Clin. 2012;92:1169–78.

    Google Scholar 

  32. Speicher PJ, Ganapathi AM, Englum BR, Hartwig MG, Onaitis MW, D’Amico TA, et al. Induction therapy does not improve survival for clinical stage T2N0 esophageal cancer. J Thorac Oncol. 2014;9:1195–201. https://doi.org/10.1097/JTO.0000000000000228.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Perez Holguin RA, Olecki EJ, Stahl KA, Wong WG, Vining CC, Dixon MEB, et al. Management of clinical T2N0 esophageal and gastroesophageal junction adenocarcinoma: What is the optimal treatment? J Gastrointest Surg. 2022;26:2050–60. https://doi.org/10.1007/s11605-022-05441-7.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiovascular and Thoracic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, NY, USA

    Jorge Humberto Rodriguez-Quintero MD, Rajika Jindani MD, Mostafa Elbahrawy MD, PhD, Marc Vimolratana MD, Neel P. Chudgar MD & Brendon M. Stiles MD

  2. Department of Cardiothoracic Surgery, University of Rochester Medical Center, Rochester, NY, USA

    Mohamed K. Kamel MD

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  1. Jorge Humberto Rodriguez-Quintero MD
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  3. Rajika Jindani MD
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Correspondence to Brendon M. Stiles MD.

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Disclosures

Dr. Stiles: Medtronic, AstraZeneca, Genentech, Pfizer, Arcus Biosciences, Bristol Myers Squib, BMS Foundation, Gala Therapeutics, Merck, and the Lung Cancer Research Foundation. The rest of the authors have no conflicts of interest to disclose.

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Supplementary file1 (DOCX 31 kb)

10434_2023_14441_MOESM2_ESM.jpg

Supplementary Fig. 1. Sensitivity analysis to determine the tumor size cutoff for subgroups in the survival analysis (JPG 28 kb)

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Rodriguez-Quintero, J.H., Kamel, M.K., Jindani, R. et al. The Effect of Neoadjuvant Therapy on Esophagectomy for cT2N0M0 Esophageal Adenocarcinoma. Ann Surg Oncol 31, 228–238 (2024). https://doi.org/10.1245/s10434-023-14441-z

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