Robotic-assisted Esophagectomy vs. Video-Assisted Thoracoscopic Esophagectomy(REVATE) Trial

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

Robotic-assisted Esophagectomy vs. Video-Assisted Thoracoscopic Esophagectomy(REVATE) : a Multicenter Open-label Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03713749
• Other study ID #: 201800322A3C601
• Status: Recruiting
• Phase: N/A
• Start date: October 22, 2018
• Est. completion date: December 22, 2022

Study information

• Verified date: March 2021
• Source: Chang Gung Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will assess the adequacy of nodal dissection along the recurrent laryngeal nerve performed with robot-assisted versus video-assisted thoracoscopic esophagectomy in patients with esophageal squamous cell carcinoma through a prospective multicentre randomized study design.

Description:

Radical lymph node dissection (LND) along the recurrent laryngeal nerve (RLN) is surgically demanding and can be associated with substantial postoperative morbidity. The question as to whether robot-assisted esophagectomy (RE) might be superior to video-assisted thoracoscopic esophagectomy (VATE) for performing LND along the RLN in patients with esophageal squamous cell carcinoma (ESCC) remains open. The investigators will conduct a multicenter, open-label, randomized controlled trial (termed REVATE) enrolling patients with ESCC scheduled to undergo LND along the RLN. Patients will be randomly assigned to either RE or VATE. The primary outcome measure will be the rate of unsuccessful LND along the left RLN, which will be defined as 1) failure to remove lymph nodes along the left RLN or 2) occurrence of left RLN palsy following LND. Secondary outcomes will include the number of successfully removed RLN nodes, postoperative recovery, length of hospital stay, 30- and 90-day mortality, quality of life, and oncological outcomes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 212
• Est. completion date: December 22, 2022
• Est. primary completion date: April 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion criteria

1. Age between 18~80

2. Histologically proven primary intrathoracic esophageal squamous cell carcinoma and will undergo McKeown MIE and bilateral RLN LND.

3. Patients should have a performance status 0, 1 or 2 according to the European Clinical Oncology Group.

4. Surgical resectable(cT1~4a, N0~3, M0)

5. Written informed consent Exclusion criteria are

1. Previous major thoracic surgery rendering minimal invasive approach unfeasible

2. prognosis determining malignancy other than esophageal cancer, inability to undergo curative resection and/or follow-up

3. inability to provide oral or written informed consent.

4. pre-existed vocal cord dysfunction will also be excluded.

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma

Intervention

Device:
• Robot esophagectomy (RE)
Patients in RE group will receive Robotic-assisted surgery in thoracic phase.

Locations

Country	Name	City	State
Taiwan	Chang Gung memorial hospital-Linkou	Taoyuan

Sponsors (3)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital	Shanghai Chest Hospital, Tianjin Medical University Cancer Institute and Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (26)

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Chao YK, Hsieh MJ, Liu YH, Liu HP. Lymph Node Evaluation in Robot-Assisted Versus Video-Assisted Thoracoscopic Esophagectomy for Esophageal Squamous Cell Carcinoma: A Propensity-Matched Analysis. World J Surg. 2018 Feb;42(2):590-598. doi: 10.1007/s00268-017-4179-0. — View Citation

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Li ZG, Zhang XB, Wen YW, Liu YH, Chao YK. Incidence and Predictors of Unsuspected Recurrent Laryngeal Nerve Lymph Node Metastases After Neoadjuvant Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma. World J Surg. 2018 Aug;42(8):2485-2492. doi: 10.1007/s00268-018-4516-y. — View Citation

Low DE, Alderson D, Cecconello I, Chang AC, Darling GE, D'Journo XB, Griffin SM, Hölscher AH, Hofstetter WL, Jobe BA, Kitagawa Y, Kucharczuk JC, Law SY, Lerut TE, Maynard N, Pera M, Peters JH, Pramesh CS, Reynolds JV, Smithers BM, van Lanschot JJ. International Consensus on Standardization of Data Collection for Complications Associated With Esophagectomy: Esophagectomy Complications Consensus Group (ECCG). Ann Surg. 2015 Aug;262(2):286-94. doi: 10.1097/SLA.0000000000001098. — View Citation

Luketich JD, Pennathur A, Awais O, Levy RM, Keeley S, Shende M, Christie NA, Weksler B, Landreneau RJ, Abbas G, Schuchert MJ, Nason KS. Outcomes after minimally invasive esophagectomy: review of over 1000 patients. Ann Surg. 2012 Jul;256(1):95-103. doi: 10.1097/SLA.0b013e3182590603. — View Citation

Mizutani M, Murakami G, Nawata S, Hitrai I, Kimura W. Anatomy of right recurrent nerve node: why does early metastasis of esophageal cancer occur in it? Surg Radiol Anat. 2006 Aug;28(4):333-8. Epub 2006 May 23. — View Citation

Noshiro H, Iwasaki H, Kobayashi K, Uchiyama A, Miyasaka Y, Masatsugu T, Koike K, Miyazaki K. Lymphadenectomy along the left recurrent laryngeal nerve by a minimally invasive esophagectomy in the prone position for thoracic esophageal cancer. Surg Endosc. 2010 Dec;24(12):2965-73. doi: 10.1007/s00464-010-1072-4. Epub 2010 May 22. — View Citation

Park SY, Kim DJ, Yu WS, Jung HS. Robot-assisted thoracoscopic esophagectomy with extensive mediastinal lymphadenectomy: experience with 114 consecutive patients with intrathoracic esophageal cancer. Dis Esophagus. 2016 May;29(4):326-32. doi: 10.1111/dote.12335. Epub 2015 Feb 26. — View Citation

Rice TW, Ishwaran H, Ferguson MK, Blackstone EH, Goldstraw P. Cancer of the Esophagus and Esophagogastric Junction: An Eighth Edition Staging Primer. J Thorac Oncol. 2017 Jan;12(1):36-42. doi: 10.1016/j.jtho.2016.10.016. Epub 2016 Oct 31. — View Citation

Sato Y, Kosugi S, Aizawa N, Ishikawa T, Kano Y, Ichikawa H, Hanyu T, Hirashima K, Bamba T, Wakai T. Risk Factors and Clinical Outcomes of Recurrent Laryngeal Nerve Paralysis After Esophagectomy for Thoracic Esophageal Carcinoma. World J Surg. 2016 Jan;40(1):129-36. — View Citation

Suda K, Ishida Y, Kawamura Y, Inaba K, Kanaya S, Teramukai S, Satoh S, Uyama I. Robot-assisted thoracoscopic lymphadenectomy along the left recurrent laryngeal nerve for esophageal squamous cell carcinoma in the prone position: technical report and short-term outcomes. World J Surg. 2012 Jul;36(7):1608-16. doi: 10.1007/s00268-012-1538-8. — View Citation

Tachimori Y, Ozawa S, Numasaki H, Matsubara H, Shinoda M, Toh Y, Udagawa H, Fujishiro M, Oyama T, Uno T; Registration Committee for Esophageal Cancer of the Japan Esophageal Society. Efficacy of lymph node dissection by node zones according to tumor location for esophageal squamous cell carcinoma. Esophagus. 2016;13:1-7. Epub 2015 Nov 17. — View Citation

Udagawa H, Ueno M, Shinohara H, Haruta S, Kaida S, Nakagawa M, Tsurumaru M. The importance of grouping of lymph node stations and rationale of three-field lymphoadenectomy for thoracic esophageal cancer. J Surg Oncol. 2012 Nov;106(6):742-7. doi: 10.1002/jso.23122. Epub 2012 Apr 13. — View Citation

van der Sluis PC, Ruurda JP, van der Horst S, Verhage RJ, Besselink MG, Prins MJ, Haverkamp L, Schippers C, Rinkes IH, Joore HC, Ten Kate FJ, Koffijberg H, Kroese CC, van Leeuwen MS, Lolkema MP, Reerink O, Schipper ME, Steenhagen E, Vleggaar FP, Voest EE, Siersema PD, van Hillegersberg R. Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer, a randomized controlled trial (ROBOT trial). Trials. 2012 Nov 30;13:230. doi: 10.1186/1745-6215-13-230. — View Citation

van der Sluis PC, Ruurda JP, Verhage RJ, van der Horst S, Haverkamp L, Siersema PD, Borel Rinkes IH, Ten Kate FJ, van Hillegersberg R. Oncologic Long-Term Results of Robot-Assisted Minimally Invasive Thoraco-Laparoscopic Esophagectomy with Two-Field Lymphadenectomy for Esophageal Cancer. Ann Surg Oncol. 2015 Dec;22 Suppl 3:S1350-6. doi: 10.1245/s10434-015-4544-x. Epub 2015 May 29. — View Citation

Weijs TJ, Seesing MF, van Rossum PS, Koëter M, van der Sluis PC, Luyer MD, Ruurda JP, Nieuwenhuijzen GA, van Hillegersberg R. Internal and External Validation of a multivariable Model to Define Hospital-Acquired Pneumonia After Esophagectomy. J Gastrointest Surg. 2016 Apr;20(4):680-7. doi: 10.1007/s11605-016-3083-5. Epub 2016 Feb 16. — View Citation

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Zhou C, Zhang L, Wang H, Ma X, Shi B, Chen W, He J, Wang K, Liu P, Ren Y. Superiority of Minimally Invasive Oesophagectomy in Reducing In-Hospital Mortality of Patients with Resectable Oesophageal Cancer: A Meta-Analysis. PLoS One. 2015 Jul 21;10(7):e0132889. doi: 10.1371/journal.pone.0132889. eCollection 2015. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of unsuccessful LND along the left RLN	Regardless of the presence of hoarseness, vocal cord function will be assessed by an experienced otolaryngologist using a nexile laryngoscope within one week of surgery. RLN palsy will be classified according to the following variables: site (unilateral versus bilateral); duration (temporary [i.e., recovering within 6 months] versus permanent [i.e. not recovering within 6 months]); and type of treatment required (type I: no therapy required; type II: injury requiring an elective surgical procedure; type III: injury requiring an urgent surgical procedure)	Till 6 months postoperatively
Secondary	The number of nodes removed along the right and left RLN	number of lymph node removed	The pathological analysis will be finished within 2 weeks.
Secondary	Post esophagectomy pneumonia rate	Post esophagectomy pneumonia is defined according to the Revised Uniform Pneumonia Score which includes temperature[°C](Range = 36.1 and = 38.4 =0, = 36.0 and = 38.5=1); leukocyte count [×1000/uL](= 4.0 and = 11.0=0, <4.0 or >11.0=1); and pulmonary radiography(Range No infiltrate=0, Diffused or patchy infiltrate=1, Well-circumscribed infiltrate=2). A sum score of 2 points or higher, of which at least 1 point is assigned because of infiltrative findings on pulmonary radiography, indicates the presence of pneumonia.	Duration of hospital stay, an expected average of 2~3 weeks
Secondary	Rate of major postoperative complication	Complication grade: modified Clavien-Dindo classification (MCDC) grade 2-4 Major complications (MCDC grade 2-4) Including: myocardial infarction, anastomotic leakage (clinical or radiologic diagnosis), anastomotic stenosis, chylothorax (chylous leakage, presence of chylous in chest tubes or indication start medium chain triglycerides containing tube feeding, gastric tube necrosis (proven by gastroscopy), pulmonary embolus, deep vein thrombosis.; Minor complications (MCDC grade 1) Including: wound infections, pleural effusions, delayed gastric emptying	Duration of hospital stay, an expected average of 2~3 weeks
Secondary	In hospital, 30 day and 90 day mortality	Death occurred during the same hospitalization , within 30 and 90 days after surgery	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks and within 30 days or 90 days
Secondary	R0 resection rate	Microscopically negative proximal/distal and circumferential margin	The pathological analysis will be finished within 2 weeks.
Secondary	Operation time(thoracic phase)	thoracic phase operation time(minutes)	Day of surgery
Secondary	Operation time(abdominal)	abdominal phase operation time(minutes)	Day of surgery
Secondary	Total operation time	total surgical time (expressed in minutes)	Day of surgery
Secondary	Unexpected events and complications occurring during surgery	massive hemorrhage, perforation of other organs	Day of surgery, up to 24 hours after surgery.
Secondary	Blood loss during surgery	blood loss during surgery (expressed in mL per phase)	Day of surgery, up to 24 hours after surgery.
Secondary	Rate of thoracotomy conversion	Number of patients requiring conversion to thoracotomy and related reasons	Day of surgery, up to 24 hours after surgery.
Secondary	Length of mechanical ventilator use after surgery	expressed in minutes	Participants will be followed for the duration of hospital stay, an expected average of 2~3 weeks
Secondary	Length of intensive care unit stay after surgery	expressed in hours	Participants will be followed for the duration of hospital stay, an expected average of 2~3 weeks
Secondary	Length of postoperative hospital stay	expressed in days , calculated from the date of surgery to date of discharge	Participants will be followed for the duration of hospital stay, an expected average of 2~3 weeks
Secondary	Re-intubation rate	Need for re-intubation after extubation	Participants will be followed for the duration of hospital stay, an expected average of 2~3 weeks
Secondary	Re-entry ICU rate	Need to transfer back from ward to ICU after surgery	Participants will be followed for the duration of hospital stay, an expected average of 2~3 weeks
Secondary	Overall survival rate	From date of surgery until the date of death from any cause	Assessed 24/36/60 months after surgery
Secondary	Disease free survival rate	From date of surgery until the date of first documented recurrence	Assessed up to 24/36/60 months after surgery
Secondary	Hospital Anxiety and Depression Scale (HADS)	The HADS aims to measure symptoms of anxiety and depression and consists of 14 items,seven items for the anxiety subscale and seven for the depression subscale. The questionnaire responses were analysed in the light of the results of this estimation of the severity of both anxiety and of depression. This enabled a reduction of the number of items in the questionnaire to just seven reflecting anxiety and seven reflecting depression.(Of the seven depression items five reflected aspects of reduction in pleasure response). Each item had been answered by the patient on a four point (0-3) response category so the possible scores ranged from 0 to 21 for anxiety and 0 to 21 for depression. a score of 0 to 7 for either subscale could be regarded as being in the normal range, a score of 11 or higher indicating probable presence ('caseness') of the mood disorder and a score of 8 to 10 being just suggestive of the presence of the respective state.	pre-operative < 5 days and 4 weeks, 3/6 months and yearly up to 5 years post-operatively.
Secondary	European Organisation for Research and Treatment of Cancer(EORTC) QLQ-C30 , QLQ-OES18	The EORTC QLQ-C30 incorporates a range of QOL issues in five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea/vomiting), a global health/QOL scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The EORTC QLQ-OES18 contains four symptom scales (dysphagia, eating disorders, reflux, and pain) and six single items (difficulty swallowing saliva, choking, dry mouth, taste disorder, cough, and speech-related issues). Each question has four response choices ranging from 1 (not at all) to 4 (very much), except for the global QOL scale, which has seven response options ranging from 1 (very poor) to 7 (excellent). All questionnaire responses are linearly transformed to scores from 0 to 100.	pre-operative < 5 days and 4 weeks, 3/6 months and yearly up to 5 years post-operatively.