Skip to main content

Advertisement

SpringerLink
Log in

Safety and Feasibility of Robot-Assisted Minimally Invasive Esophagectomy (RAMIE) with Three-Field Lymphadenectomy and Neoadjuvant Chemoradiotherapy in Patients with Resectable Esophageal Cancer and Cervical Lymph Node Metastasis

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

Abstract

Background

In the West, patients with cervical lymph node metastasis of resectable esophageal cancer at diagnosis are generally precluded from curative treatment. This study prospectively explored the safety and feasibility of neoadjuvant chemoradiotherapy followed by robot-assisted minimally invasive esophagectomy (RAMIE) with three-field lymphadenectomy for these patients.

Methods

Between 2015 and 2021, patients with resectable thoracic esophageal cancer and cervical lymph node metastasis were recruited nationwide in the Netherlands. Patients without interval metastasis following neoadjuvant chemoradiotherapy and good physical condition underwent RAMIE with bilateral three-field lymphadenectomy. Safety was predefined as ≤50% Clavien-Dindo grade ≥3b postoperative complications.

Results

Neoadjuvant chemoradiotherapy was administered to 29 patients (19 (66%) adenocarcinoma and 10 (34%) squamous cell carcinoma). After restaging, nine (31%) patients were excluded (interval metastasis, clinical deterioration, or withdrawn consent). RAMIE was performed in 20 patients (R0-rate 95%). A median of 42 [range 21–71] lymph nodes were resected of which 13 [range 2–35] were cervical. Only 1 (5%) patient had an unexpected contralateral cervical lymph node metastasis. Complications grade ≥3b occurred in 50%. Most frequent complications of any grade were recurrent laryngeal nerve palsy (45%) and pneumonia (40%). Overall survival at 1 year was 85% and quality of life at 6 months was comparable to esophageal cancer patients treated with curative intent.

Conclusions

RAMIE with three-field lymphadenectomy following neoadjuvant chemoradiotherapy for patients with resectable esophageal cancer presenting with cervical lymph node metastasis is feasible in a Western population. Because contralateral cervical metastasis is rare, a unilateral neck dissection would suffice in the majority of cases.

Clinical Trial.gov Identifier: NCT02426879.

Dutch trial register Identifier: NTR 4552.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660. (Epub 2021 Feb 4).

    Article  PubMed  Google Scholar 

  2. Omloo JM, Lagarde SM, Hulscher JB, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the mid/distal esophagus: five-year survival of a randomized clinical trial. Ann Surg. 2007;246(6):992–1000; discussion 1000-1. https://doi.org/10.1097/SLA.0b013e31815c4037.

  3. AJCC cancer staging manual, 6th edn. Chicago: Springer; 2002.

  4. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual. 7th edn. New York: Springer; 2010.

    Google Scholar 

  5. Rice TW, Kelsen DP, Blackstone EH, et al. Esophagus and esophagogastric junction. In: MB Amin, SB Edge, FL Greene, et al., editors. AJCC cancer staging manual. 8th edn. New York: Springer; 2017. p. 185–202.

    Chapter  Google Scholar 

  6. Sakata K. Uber die Lymphgefasse des oesophagus und uber seine regionalen. Lymphdrusen mit berucksichtigung der Verbreitung des Karcinoms. Mitt Grenzbeg Med Chizg. 1903;11:634–56.

  7. Li B, Hu H, Zhang Y, et al. Three-field versus two-field lymphadenectomy in transthoracic oesophagectomy for oesophageal squamous cell carcinoma: short-term outcomes of a randomized clinical trial. Br J Surg. 2020;107(6):647–54. https://doi.org/10.1002/bjs.11497. (Epub 2020 Feb 28).

    Article  CAS  PubMed  Google Scholar 

  8. Okamura A, Watanabe M, Kozuki R, et al. Supraclavicular and celiac metastasis in squamous cell carcinoma of the middle thoracic esophagus. Langenbecks Arch Surg. 2018;403(8):977–84. https://doi.org/10.1007/s00423-018-1722-x. (Epub 2018 Oct 25).

    Article  PubMed  Google Scholar 

  9. Tachimori Y, Ozawa S, Numasaki H, et al. Supraclavicular node metastasis from thoracic esophageal carcinoma: a surgical series from a Japanese multi-institutional nationwide registry of esophageal cancer. J Thorac Cardiovasc Surg. 2014;148(4):1224–9. https://doi.org/10.1016/j.jtcvs.2014.02.008. (Epub 2014 Feb 10).

    Article  PubMed  Google Scholar 

  10. Matsuda S, Takeuchi H, Kawakubo H, et al. Three-field lymph node dissection in esophageal cancer surgery. J Thorac Dis. 2017;9(Suppl 8):S731–40. https://doi.org/10.21037/jtd.2017.03.171??

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ma GW, Situ DR, Ma QL, et al. Three-field vs two-field lymph node dissection for esophageal cancer: a meta-analysis. World J Gastroenterol. 2014;20(47):18022–30. https://doi.org/10.3748/wjg.v20.i47.18022.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Li B, Zhang Y, Miao L, et al. Esophagectomy with three-field versus two-field lymphadenectomy for middle and lower thoracic esophageal cancer: long-term outcomes of a randomized clinical trial. J Thorac Oncol. 2021;16(2):310–7. https://doi.org/10.1016/j.jtho.2020.10.157. (Epub 2020 Dec 8).

    Article  PubMed  Google Scholar 

  13. Wen J, Chen D, Zhao T, Chen J, Zhao Y, Liu D, Wang W, Xu X, Fan M, Chen C, Chen Y. Should the clinical significance of supraclavicular and celiac lymph node metastasis in thoracic esophageal cancer be reevaluated? Thorac Cancer. 2019;10(8):1725–35. https://doi.org/10.1111/1759-7714.13144. (Epub 2019 Jul 10).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yamashita M, Takenaka HY, Nakagawa K. Semi-radical chemoradiotherapy for 53 esophageal squamous cell carcinomas with supraclavicular lymph node metastasis in a single institutional retrospective study. Hepatogastroenterology. 2014;61(135):1971–8.

    PubMed  Google Scholar 

  15. The Declaration of Helsinki. Available at: https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/. Accessed Sept 8, 2021.

  16. The Good Clinical Practice Guidelines. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002874.pdf. Accessed 8 Sept 2021.

  17. van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84. https://doi.org/10.1056/NEJMoa1112088.

    Article  PubMed  Google Scholar 

  18. McCulloch P, Altman DG, Campbell WB, et al. No surgical innovation without evaluation: the IDEAL recommendations. Lancet. 2009;374(9695):1105–12. https://doi.org/10.1016/S0140-6736(09)61116-8.

    Article  PubMed  Google Scholar 

  19. Van der Sluis PC, Ruurda JP, van der Horst S, et al. Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer, a randomized controlled trial (ROBOT trial). Trials. 2012;13:230. https://doi.org/10.1186/1745-6215-13-230.

    Article  PubMed  PubMed Central  Google Scholar 

  20. van Hillegersberg R, Seesing MF, Brenkman HJ, et al. Robot-assisted minimally invasive esophagectomy. Chirurg. 2017;88(Suppl 1):7–11. https://doi.org/10.1007/s00104-016-0200-7.

    Article  PubMed  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(2):205–13. https://doi.org/10.1097/01.sla.0000133083.54934.ae.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Low DE, Alderson D, Cecconello I, et al. International consensus on standardization of data collection for complications associated with esophagectomy: Esophagectomy Complications Consensus Group (ECCG). Ann Surg. 2015;262(2):286–94. https://doi.org/10.1097/SLA.0000000000001098.

    Article  PubMed  Google Scholar 

  23. Slankamenac K, Graf R, Barkun J, et al. The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg. 2013;258(1):1–7. https://doi.org/10.1097/SLA.0b013e318296c732.

    Article  PubMed  Google Scholar 

  24. Mandard AM, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73(11):2680–6. https://doi.org/10.1002/1097-0142(19940601)73:11<2680::aid-cncr2820731105>3.0.co;2-c

  25. van Workum F, Verstegen MHP, Klarenbeek BR, et al. Intrathoracic vs cervical anastomosis after totally or hybrid minimally invasive esophagectomy for esophageal cancer: a randomized clinical trial. JAMA Surg. 2021;156(7):601–10. https://doi.org/10.1001/jamasurg.2021.1555.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Schröder W, Raptis DA, Schmidt HM, et al. Anastomotic techniques and associated morbidity in total minimally invasive transthoracic esophagectomy: results from the EsoBenchmark Database. Ann Surg. 2019;270(5):820–6. https://doi.org/10.1097/SLA.0000000000003538.

    Article  PubMed  Google Scholar 

  27. Chen SY, Yue CY, Zhou SH, et al. Three-field lymphadenectomy in minimally invasive esophagectomy for squamous cell carcinoma. Ann Thorac Surg. 2021;112(3):928–34. https://doi.org/10.1016/j.athoracsur.2020.09.022. (Epub 2020 Nov 3).

    Article  PubMed  Google Scholar 

  28. Donker M, Straver ME, Wesseling J, et al. Marking axillary lymph nodes with radioactive iodine seeds for axillary staging after neoadjuvant systemic treatment in breast cancer patients: the MARI procedure. Ann Surg. 2015;261(2):378–82. https://doi.org/10.1097/SLA.0000000000000558.

    Article  PubMed  Google Scholar 

  29. Meta-analysis of health-related quality of life after minimally invasive versus open oesophagectomy for oesophageal cancer.

  30. Kroese TE, Goense L, van Hillegersberg R, et al. Detection of distant interval metastases after neoadjuvant therapy for esophageal cancer with 18F-FDG PET(/CT): a systematic review and meta-analysis. Dis Esophagus. 2018;31(12). doi: https://doi.org/10.1093/dote/doy055.

  31. Goense L, Ruurda JP, Carter BW, et al. Prediction and diagnosis of interval metastasis after neoadjuvant chemoradiotherapy for oesophageal cancer using 18F-FDG PET/CT. Eur J Nucl Med Mol Imaging. 2018;45(10):1742–51. https://doi.org/10.1007/s00259-018-4011-6. (Epub 2018 Apr 16).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Al-Batran SE, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393(10184):1948–57. https://doi.org/10.1016/S0140-6736(18)32557-1. (Epub 2019 Apr 11).

    Article  PubMed  Google Scholar 

  33. Al-Batran SE, Haag GM, Ettrich TJ, et al. Final results and subgroup analysis of the PETRARCA randomized phase II AIO trial: perioperative trastuzumab and pertuzumab in combination with FLOT versus FLOT alone for HER2-positive resectable esophagogastric adenocarcinoma. Ann Oncol. 2020;31:S4.

    Google Scholar 

  34. Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021;384(13):1191–203. https://doi.org/10.1056/NEJMoa2032125.

    Article  CAS  PubMed  Google Scholar 

  35. van den Ende T, de Clercq NC, van Berge Henegouwen MI, et al. Neoadjuvant chemoradiotherapy combined with atezolizumab for resectable esophageal adenocarcinoma: a single-arm phase II feasibility trial (PERFECT). Clin Cancer Res. 2021;27(12):3351–9. https://doi.org/10.1158/1078-0432.CCR-20-4443. (Epub 2021 Jan 27).

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

This trial would not have succeeded without the participation of all Dutch Specialists who referred their patients with esophageal cancer and a cervical lymph node metastasis.

Author information

Authors and Affiliations

  1. Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands

    S. van der Horst MSc, T. J. Weijs MD, PhD, J. P. Ruurda MD, PhD & R. van Hillegersberg MD, PhD

  2. Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands

    W. W. Braunius MD, PhD

  3. Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands

    S. Mook MD, PhD & P. S. N. van Rossum MD, PhD

  4. Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands

    N. Haj Mohammed MD, PhD

  5. Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands

    L. Brosens MD, PhD

  6. Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands

    B. L. A. M. Weusten MD, PhD

Authors
  1. S. van der Horst MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. J. Weijs MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. W. Braunius MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Mook MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. Haj Mohammed MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L. Brosens MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. S. N. van Rossum MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. B. L. A. M. Weusten MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J. P. Ruurda MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. R. van Hillegersberg MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. van Hillegersberg MD, PhD.

Ethics declarations

Disclosures

None.

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.

Supplementary file1 (JPG 162 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

van der Horst, S., Weijs, T.J., Braunius, W.W. et al. Safety and Feasibility of Robot-Assisted Minimally Invasive Esophagectomy (RAMIE) with Three-Field Lymphadenectomy and Neoadjuvant Chemoradiotherapy in Patients with Resectable Esophageal Cancer and Cervical Lymph Node Metastasis. Ann Surg Oncol 30, 2743–2752 (2023). https://doi.org/10.1245/s10434-022-12996-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-022-12996-x

Search

Navigation