Robot-Assisted versus Video-Assisted Lobectomy for Early-Stage Non-Small Cell Lung Cancer (RAVAR): Study Protocol of a Prospective, Multicentre, Open-Label, Randomised Controlled Trial

Robot-Assisted versus Video-Assisted Lobectomy for Early-Stage Non-Small Cell Lung Cancer (RAVAR): Study Protocol of a Prospective, Multicentre, Open-Label, Randomised Controlled Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Robot-Assisted versus Video-Assisted Lobectomy for Early-Stage Non-Small Cell Lung Cancer (RAVAR): Study Protocol of a Prospective, Multicentre, Open-Label, Randomised Controlled Trial Teng-Fei Zhu, Mu-Zi Yang, Li Ling, Jun Yi, Zhong-Min Peng, Yong-De Liao, and 22 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5750168/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Video-assisted lobectomy (VAL) and robot-assisted lobectomy (RAL) are recommended standard treatments for early-stage non-small cell lung cancer (NSCLC). Nevertheless, comparisons of long-term survival between VAL and RAL are controversial because of the lack of robust evidence from prospective multicentre randomised controlled trials (RCTs). Method We are conducting a prospective multicentre RCT to evaluate whether RAL is non-inferior to VAL in terms of long-term survival in patients with clinical stage T1-2N0-1M0 (stage I-II) NSCLC who underwent lobectomies (RAVAR study). A total of 1,124 patients will be enrolled from multiple institutions. The primary endpoint is the five-year disease-free survival rate. The secondary endpoints include five-year overall survival and short-term outcomes, such as perioperative complications, length of postoperative hospital stay, operation time, number of dissected lymph nodes, chest tube duration, pain score, and total cost of hospitalisation. The Ethics Committee of the Sun Yat-sen University Cancer Center approved the study protocol in May 2020, and patient enrolment began in August 2020. Approval was obtained from each institutional ethics committee before initiating patient enrolment. Discussion This multicentre RCT compares the long-term outcomes of RAL and VAL in resectable early-stage NSCLC. The expected results of this study will determine whether RAL can achieve satisfactory long-term outcomes that are not inferior to those of VAL in patients with early-stage NSCLC, thereby providing high-level evidence for a minimally invasive approach for these patients. Trial registration The protocol of RAVAR trial was registered in the China Clinical Trials Registry as ChiCTR2000034737 (registration date: July 17, 2020) and ClinicalTrials.gov as NCT06524427 (registration date: July 29, 2024). Date of First Participant Enrollment: August 26, 2020. Non-small cell lung cancer Robotic-assisted thoracoscopic surgery Video-assisted thoracic surgery Multicenter study Randomized controlled trial Background Video-assisted lobectomy (VAL) has gradually replaced open thoracotomy as the preferred surgical technique for early-stage non-small cell lung cancer (NSCLC) because it can reduce surgical trauma and accelerate postoperative recovery [ 1 – 3 ]. Over the last 20 years, robot-assisted lobectomy (RAL) has been increasingly applied in the treatment of early-stage NSCLC because of the advantages of three-dimensional vision and articulated instruments that could overcome the limitations of VAL, and numerous retrospective analyses have demonstrated that robotic surgery may yield better short-term outcomes than video-assisted surgery [ 4 – 9 ]. Therefore, both RAL and VAL are recommended as standard care in the National Comprehensive Cancer Network (NCCN) guidelines for the surgical treatment of early-stage NSCLC [ 10 ]. However, most published studies have focused on the feasibility and safety of RAL, and few have addressed the long-term outcomes, with most of them being retrospective studies [ 11 – 14 ]. To the best of our knowledge, only one randomised controlled trial (RCT) has compared the survival prognosis between RAL and VAL in patients with clinical stage I-III NSCLC, suggesting that the 3-year disease-free survival (DFS) and overall survival (OS) in the RAL group were non-inferior to those in the VAL group [ 15 ]. Unfortunately, this study was a single-centre trial, and the number of cases may not have been adequate to answer this question sufficiently (157 cases for RAL and 163 cases for VAL). To provide high-level evidence to compare the oncological results of RAL and VAL, we initiated a prospective, multicentre RCT to determine whether RAL is non-inferior to VAL in terms of long-term outcomes in patients with clinical stage I-II NSCLC. Methods/design Study design This prospective, multicentre, open-label RCT aims to prove the non-inferiority of RAL over VAL in terms of short- and long-term outcomes in patients with clinical stage I-II NSCLC. Patients in the experimental group (RAL group) will receive RAL for surgical treatment of NSCLC and patients in the control group (VAL group) will receive VAL for surgical treatment of NSCLC. All patients will receive standard anatomical lobectomy combined with systematic mediastinal lymph node dissection (MLND). Study setting This trial is being coordinated by the Department of Thoracic Surgery at the Sun Yat-sen University Cancer Center. A total of 24 distinct hospitals across China mainland have joined this trial. All of these hospitals are well-known hospitals with large volumes in China and are located in South China, Southwest China, Central China, Northeast China, Northwest China, and Southeast China. The selection of such a diverse range of sites will guarantee wide demographic coverage and bolster the applicability of the findings to a broader population. Endpoint The primary endpoint is the 5-year DFS, defined as the time from randomisation to relapse or death from any cause. The secondary endpoints include the 5-year OS, blood loss, conversion rate, perioperative complications, operative death rate, postoperative length of hospital stay, pain score, R0 rate, operative time, number of dissected lymph nodes (LNs), chest tube duration, acesodyne (Grade III) dose, and total cost of hospitalisation. OS is defined as the time from randomisation to death from any cause. Blood loss is defined as the blood loss during surgery. The conversion rate is defined as the proportion of patients who undergo open surgery among all patients who underwent surgery in each group. Perioperative complications are defined as complications that occurred during surgery or within 30 days after surgery among all patients undergoing operations, which will be recorded and classified using the Clavien-Dindo classification system [ 16 ] daily during hospitalisation and surveillance after discharge. The operative death rate is defined as the proportion of patients who die within 30/90 days of surgery among all patients undergoing surgery in each group. The length of the postoperative hospital stay is defined as the time between the date of surgery and discharge. The pain score will be evaluated using a Numerical Rating Scale (NRS) daily during hospitalisation after surgery and during surveillance after discharge. The R0 rate is defined as the proportion of patients who undergo complete resection among all the patients undergoing surgery in each group. Operative time is defined as the total time from skin incision to skin suturing, and the time of each step will be recorded simultaneously during each surgery. The number of dissected LNs will be calculated on the basis of the official postoperative pathological report. The chest tube duration is defined as the time between the date of surgery and chest tube removal. The acesodyne (Grade III) dose is defined as the total amount of analgesic medication, including morphine, pethidine, and fentanyl, used by the patient during the postoperative hospital stay. Total hospitalisation cost is defined as the total cost incurred by the patient from admission to discharge. Eligibility criteria Inclusion criteria Age from 18 to 80 years Patients with blood pressure < 160/100 mmHg, 5.6 < blood glucose level < 11.2 mmol/L, normal functioning of major organs: (1) Goldman index between grade 1 and 2; (2) predicted forced expiratory volume in 1s ≥ 40% and diffusing capacity of the lung for carbon monoxide ≥ 40%; (3) total bilirubin ≤ 1.5 upper limit of normal; (4) alanine aminotransferase/aspartate aminotransferase ≤ 2.5 upper limit of normal; (5) creatinine ≤ 1.25 upper limit of normal and creatinine clearance rate ≥ 60 mL/min The first clinical diagnosis before surgery is NSCLC, which includes adenocarcinoma, squamous cell carcinoma, large-cell carcinoma, and other unknown types Clinical stage T1-2N0-1 (cI-II): Maximum diameter of tumour ≤ 5 cm and short diameter of mediastinal lymph node ≤ 1 cm in thin layer computed tomography Performance status of Eastern Cooperative Oncology Group = 0–1 All relevant examinations completed within 28 days before the operation Patients who understand this study and signed an Informed Consent Form Exclusion criteria Patients undergoing radiotherapy, chemotherapy, targeted therapy, or immunotherapy before surgery Patients with a previous history of other malignancies Patients with secondary primary cancer when enrolled Patients diagnosed as showing pure ground glass opacity (GGO) before surgery Patients diagnosed as showing mixed GGO whose solid part ≤ 50% and maximum diameter of tumour ≤ 2 cm Patients with small cell lung cancer Patients with prior unilateral open thoracic surgical procedures Female patients who are pregnant or breast feeding Patients with interstitial pneumonia, pulmonary fibrosis, or severe emphysema Patients with an active bacterial or fungal infection that is difficult to control Patients with serious psychosis History of severe heart attack, heart failure, myocardial infarction, or angina within the last 6 months Sample size calculation The primary endpoint of this trial is the 5-year DFS. Based on previous studies, the 5-year DFS rate of VAL is 68.0%, with a non-inferiority margin of 8% [ 17 – 19 ], an overall type I error of 0.025 (one-sided), and a power of 0.80. Considering a 10% dropout rate, 562 cases per group were required for a total sample size of 1,124. Randomisation Stratified block randomisation will be performed in this trial. The random number table will be generated by an independent randomisation committee using SPSS (version 25.0; IBM Corp, Armonk, NY, USA) before the start of the study and kept confidential by the investigators and related personnel. After successful enrolment, each included patient will be assigned an opaque envelope, which will be opened by the investigators to assign a random number to the patient. Based on the random number, patients will be randomly assigned to two groups (RAL and VAL groups). The study will be stratified according to the centre and clinical stage (clinical stages I and II). Block sizes of 4, 6, and 8 will be randomly assigned to each centre in a 1:1 ratio. Neither the investigators nor the patients will be blinded to the study treatment. Treatments Standard of surgery All patients will undergo surgery under general anaesthesia with double-lumen endotracheal intubation. RAL will be performed using the Da Vinci Xi/Si Surgical robot system (Intuitive Surgical Inc., USA). VAL can be performed using a single-port, single-utility-port, or multiport surgical approach. All included patients will undergo standard anatomical lobectomy combined with systematic MLND as proposed by the International Association for the Study of Lung Cancer (IASLC) [ 20 ]. According to IASLC guidelines, the criteria for systematic MLND are as follows [ 20 ]: At least three mediastinal lymph node stations and the subcarinal lymph nodes must be examined in all patients. Patients with left-sided NSCLC must undergo examination of level 5/6/7 lymph nodes; those with right-sided NSCLC must undergo examination of level 2R/4R/7 lymph nodes; and those with lower-lobe NSCLC must undergo examination of level 9 lymph nodes. The total number of dissected LNs must be greater than 6, including at least 3 mediastinal LNs, and all lymph nodes and their surrounding tissues within the anatomical landmark must be completely removed. Postoperative therapy Postoperative adjuvant treatment strategies will be determined by each centre based on the relevant clinical guidelines and the patient's wishes. If recurrence or metastasis is identified during follow-up, appropriate treatment protocols will be implemented promptly. If necessary, a multidisciplinary process may be employed to develop a scientific treatment protocol that may include surgical intervention, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. The specific treatment protocol will be established on the basis of the experiences of various centres. Quality control of study To ensure that this clinical trial is conducted strictly in accordance with the protocol, throughout the entire process, clinical researchers must operate in strict compliance with the requirements of the good clinical practice (GCP), ensuring standardized trial procedures, accurate trial data, and reliable research conclusions. Establishment of standard operating procedures (SOP) The lead institution of the project is responsible for the overall design and implementation of the research, establishing SOP for quality control of this clinical trial, forming a multicentre clinical research team, and providing unified training. Prior to the project initiation, training sessions on GCP regulations, clinical protocol explanations, and case report form (CRF) completion will be conducted for all researchers. Evidence related to endpoint events will be assessed and judged by an independent third-party institution to determine whether an endpoint event has occurred. Research nurses Equip the project with research nurses to assist the investigator in implementing the trial, ensuring that the trial is conducted in accordance with the established protocol and GCP regulations. Specific responsibilities include assisting with enrolment, managing subjects, completing CRFs, communication, document archiving, follow-up, financial matters, and cooperating with inspections. Requirements of attending surgeons The trial will include surgeons skilled in performing RAL and VAL who have completed more than 100 RALs and 100 VALs. Intraoperative video recording Investigators must record the whole surgical procedure from start to finish of all enrolled patients in this trial during surgeries. The study coordinator will conduct a central peer review of the surgical procedure every 6 months by checking the intraoperative videos. These surgical videos must be stored on a cloud server and must be kept for at least 5 years after the end of the study. Follow-up All enrolled patients will be scheduled for regular follow-up assessments every 3 months in the first year after surgical treatment, every 6 months in the second to fifth years, and once a year thereafter until death or the end of the study. If new symptoms are identified during follow-up, the patients will be re-examined promptly. The contents of the review include physical examinations, enhanced chest and abdominal CT scans, and tumour marker assessments. In addition, patients’ symptoms need to be tested appropriately. If recurrence or metastasis occurs during the follow-up period, the sites of recurrence and metastasis, related symptoms, and subsequent treatments will be recorded. Data management and storage CRF The CRF is completed by the investigator and should be filled in promptly to ensure accuracy. Generally, the CRF should not be altered; if errors do occur and need correction, the corrections should be signed off. The CRF is issued in triplicate, with copies submitted to the principal investigator, the sponsor, and the collaborating hospital for storage upon completion of the trial. After review by the clinical monitor, the completed CRFs will be used for data entry. The content of the CRF will not be modified thereafter. Establishment of the database Upon receiving the CRFs, the statistician will verify any queries through the investigator, who should respond promptly. The statistician will establish the database in a timely manner, and upon review, the data will be locked by the principal investigator, sponsor, statistician, and clinical monitor. Data security will be ensured, with unauthorized personnel prevented from accessing and modifying the data, and backups of the data will be maintained. Storage of materials The investigator should ensure the complete storage of materials for ready retrieval and inspection. In accordance with GCP principles in China, study-related materials should be retained for a period of over five years by the study party. Data monitoring The Department of Clinical Research of Sun Yat-sen University Cancer Center will independently monitor this trial to evaluate and improve the study progress, data integrity, and patient safety. Research data will be filed on the RDD platform ( www.researchdata.org.cn ) before publication to ensure the authenticity of the data. Statistical analysis The Kaplan-Meier method will be employed to estimate the survival rates for OS and DFS, while the log-rank test will be used to compare survival rates between different groups. Furthermore, to minimise the influence of confounding factors, a multivariate Cox proportional-hazard regression model may also be applied. For categorical variables, including R0 resection rate, conversion rate, complication rate, and surgical mortality, differences between the two groups will be assessed using either the chi-square test or Fisher's exact test. When comparing continuous variables, such as operation time, blood loss, postoperative hospital stays, and chest tube duration, the t-test or Wilcoxon rank-sum test will be employed for two-group comparisons. Discussion In the 1990s, VAL was first used to treat early-stage NSCLC [ 21 ]. Subsequently, several RCTs confirmed that VAL could significantly reduce surgical trauma and accelerate patient recovery while achieving therapeutic effects comparable to those of open surgery [ 1 – 3 ]. Consequently, international clinical guidelines recommend VAL as one of the preferred surgical methods for early-stage NSCLC [ 10 ]. However, VAL has significant drawbacks, such as distorted two-dimensional vision, unavoidable camera shake, easy fatigue for surgeons, and clumsy “chopstick”-like surgical instruments. These limitations significantly hinder the promotion, application, and popularisation of VAL, rendering it incapable of meeting the growing surgical treatment needs of patients with NSCLC. At the beginning of this century, RAL began to be used in the treatment of lung cancer [ 4 ]. The robotic surgical system has a 3D high-definition view, tremor-filtering capability, and surgical instruments with seven degrees of freedom. The rapid development of RAL indicates that robotic surgical systems have broad application prospects in lung cancer surgery. Consequently, RAL, similar to VAL, is recommended by clinical guidelines as the preferred surgical approach for early-stage NSCLC [ 10 ]. However, many issues remain unresolved in the field of RAL. In terms of short-term outcomes, many retrospective studies have demonstrated that RAL is a safe and effective surgical technique. Some studies have even suggested that RAL may achieve superior short-term outcomes than VAL [ 5 – 9 , 22 ]. However, the long-term outcomes of RAL in early-stage NSCLC need to be determined. Numerous retrospective studies have indicated that RAL is comparable to VAL in terms of the long-term survival of patients with resectable NSCLC [ 11 – 14 , 23 ]. Yang et al. included 470 unique patients (172 RALs, 141 VALs, and 157 open lobectomies), and they found that the 5-year DFS of patients who underwent RAL was statistically better than that of those who underwent VAL (P = 0.047). However, this result was not confirmed by multivariate analysis [ 13 ]. Another large-scale multicentre retrospective study including 2789 RALs and 2661 VALs also found that patients with RAL had significantly better OS than those with VAL (P = 0.007) [ 23 ]. However, these studies were limited by their retrospective nature, and prospective RCTs are warranted to confirm the long-term survival comparison between RAL and VAL. The RVlob trial is a single-centre RCT to compare the survival prognosis between RAL and VAL in patients with clinical stage I-III NSCLC [ 15 ]. A total of 320 patients were included in this trial, and the authors reported that RAL is non-inferior to VAL in terms of 3-year DFS and OS [ 15 ]. It should be noted that RVlob trial is a single-center RCT that including clinical stage I-IIIA patients with primary endpoint as 3-year DFS, and the sample size is not large, which should be considered when drawing a definite conclusion. Therefore, we believe that large-scale multicentre RCTs and longer follow-up periods are warranted to determine the long-term outcomes of RAL and VAL in early-stage NSCLC. To the best of our knowledge, the RAVAR study is the largest multicentre RCT to compare the long-term outcomes between RAL and VAL in early-stage NSCLC. The trial will include 1,124 patients with clinical stage I-II NSCLC, with 5-year DFS as the primary endpoint and 5-year OS and short-term outcomes as the secondary endpoints. The expected results will determine whether RAL is non-inferior to VAL in terms of long-term survival in early-stage NSCLC, providing high-level evidence for the surgical treatment of early-stage NSCLC, and thereby improving the standard of care for these patients. Declarations Ethics approval and consent to participate This study is conducted according to the Declaration of Helsinki, relevant Chinese laws and regulations. The Ethics Committee of Sun Yat-Sen University Cancer Center approved this study protocol in May 2020, and the date of first participant enrollment was August 26, 2020. Approval from the institutional review board was obtained before starting patient enrollment in each institution. Written informed consent has been obtained from all enrolled patients. The participating institutions are as follows: Sun Yat-sen University Cancer Center; The First Affiliated Hospital of Nanchang University; The Affiliated Hospital of Qingdao University; General Hospital of Eastern Theater Command; Gansu Provincial People's Hospital; The Second Affiliated Hospital of Air Force Medical University; Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology; The First Affiliated Hospital of Chongqing Medical University; West China Hospital, Sichuan University; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Shenzhen People's Hospital; The First Affiliated Hospital of Zhengzhou University; Shandong Provincial Hospital; Jiangsu Cancer Hospital; Liaoning Cancer Hospital; Guangdong Provincial People's Hospital; Jiangxi Provincial People's Hospital; Sichuan Cancer Hospital; Nanxishan Hospital of Guangxi Zhuang Autonomous Region; Chongqing University Cancer Hospital; The First Affiliated Hospital Of Shandong First Medical University; Qilu Hospital of Shandong University; Shenzhen Third People’s Hospital; The Second Hospital of Lanzhou University. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Funding This study was fully funded by Sun Yat-sen University Clinical Research 5010 Program (2019012). Author Contribution T. Z. and M. Y. wrote the manuscript. M. Y. and H. Y. proposed the concept of the RAVAR study and drafted the protocol design for the study. L. L. contributed to the sample size calculation and randomisation of the protocol, and will undertake the statistical analysis. J. Y., Z. P., Y. L., Y. G., H. L., W. J., Q. X., M. D., Y. W., G. Q., B. J., Y. Q., X. Y., G. W., B. Y., K. Q., M. L., B. L., B. H., R.X., W. Y., N. Z., Z. W., H. T., and H.Y. revised the protocol for the study, and will contribute to subject recruitment for this study. All authors approved the final manuscript. Data Availability Data sharing is not applicable to this article because no datasets had been generated or analyzed at the time of submission. Abbreviations VAL Video-Assisted Lobectomy NSCLC Non-Small Cell Lung Cancer RAL Robot-Assisted Lobectomy NCCN National Comprehensive Cancer Network RCT Randomized Controlled Trial DFS Disease-Free Survival OS Overall Survival MLDN Mediastinal Lymph Node Dissection NRS Numerical Rating Scale GGO Ground Glass Opacity IASLC International Association for the Study of Lung Cancer GCP Good Clinical Practice SOP Standard Operating Procedures CRF Case Report Form References Kirby TJ, Mack MJ, Landreneau RJ, Rice TW. Lobectomy–video-assisted thoracic surgery versus muscle-sparing thoracotomy. A randomized trial. J Thorac Cardiovasc Surg. 1995;109:997–1001. Craig SR, Leaver HA, Yap PL, Pugh GC, Walker WS. Acute phase responses following minimal access and conventional thoracic surgery. Eur J Cardiothorac Surg. 2001;20:455–63. Swanson SJ, Herndon JE 2nd, D'Amico TA, Demmy TL, McKenna RJ Jr., Green MR, et al. 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University","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Du","suffix":""},{"id":398341909,"identity":"6240f602-4b96-4721-95c9-21390cfdddc1","order_by":11,"name":"Yun Wang","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Yun","middleName":"","lastName":"Wang","suffix":""},{"id":398341910,"identity":"6d256765-9a19-47f4-bc87-44b4e4dd9606","order_by":12,"name":"Gui-Bin Qiao","email":"","orcid":"","institution":"Guangdong Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Gui-Bin","middleName":"","lastName":"Qiao","suffix":""},{"id":398341911,"identity":"145cad47-22b9-46c7-965e-fcdda5b476db","order_by":13,"name":"Ben-Yuan Jiang","email":"","orcid":"","institution":"Guangdong Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ben-Yuan","middleName":"","lastName":"Jiang","suffix":""},{"id":398341912,"identity":"10c55570-feb0-49c9-a644-dd6d1b16adbe","order_by":14,"name":"Yu Qi","email":"","orcid":"","institution":"First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Qi","suffix":""},{"id":398341913,"identity":"7c9299d0-f920-4c2e-9d2a-3b95f23106fa","order_by":15,"name":"Xiao-Long Yan","email":"","orcid":"","institution":"Second Affiliated Hospital of Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiao-Long","middleName":"","lastName":"Yan","suffix":""},{"id":398341914,"identity":"9e97bdbd-43a5-4272-8b79-3a2100a521f0","order_by":16,"name":"Guang-Suo Wang","email":"","orcid":"","institution":"ShenZhen People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Guang-Suo","middleName":"","lastName":"Wang","suffix":""},{"id":398341915,"identity":"2ad50f00-8f3e-4784-a3bd-44473bb2b7d0","order_by":17,"name":"Ben-Tong Yu","email":"","orcid":"","institution":"First Affiliated Hospital of Nanchang University","correspondingAuthor":false,"prefix":"","firstName":"Ben-Tong","middleName":"","lastName":"Yu","suffix":""},{"id":398341916,"identity":"e16346fd-8815-4e97-80cf-f6cb8fd8d1dc","order_by":18,"name":"Kun Qiao","email":"","orcid":"","institution":"Shenzhen Third People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kun","middleName":"","lastName":"Qiao","suffix":""},{"id":398341917,"identity":"1f039b79-c65a-4955-b582-504c4fcff11c","order_by":19,"name":"Ming Li","email":"","orcid":"","institution":"Jiangsu Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Li","suffix":""},{"id":398341918,"identity":"4ba57a3c-c6aa-40a6-8b8f-140dd3e547bb","order_by":20,"name":"Bin Li","email":"","orcid":"","institution":"Lanzhou University Second Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bin","middleName":"","lastName":"Li","suffix":""},{"id":398341919,"identity":"0429279c-7664-41c0-95c0-b3ef45fba9a8","order_by":21,"name":"Bin Hu","email":"","orcid":"","institution":"Sichuan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bin","middleName":"","lastName":"Hu","suffix":""},{"id":398341920,"identity":"9cefffa7-53db-459b-9285-4b05d9085666","order_by":22,"name":"Rong-Sheng Xiong","email":"","orcid":"","institution":"Nanxishan Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Rong-Sheng","middleName":"","lastName":"Xiong","suffix":""},{"id":398341921,"identity":"dadd53f5-1736-4d00-991e-d386fba67925","order_by":23,"name":"Wei-Ming Yue","email":"","orcid":"","institution":"Qilu Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Wei-Ming","middleName":"","lastName":"Yue","suffix":""},{"id":398341922,"identity":"6f2621cf-a3ae-47ce-903f-ab289386e259","order_by":24,"name":"Ni Zhang","email":"","orcid":"","institution":"Tongji Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ni","middleName":"","lastName":"Zhang","suffix":""},{"id":398341923,"identity":"58b4048f-9a44-47b9-9382-b857bcf87751","order_by":25,"name":"Zhi-Qiang Wang","email":"","orcid":"","institution":"Chongqing University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhi-Qiang","middleName":"","lastName":"Wang","suffix":""},{"id":398341924,"identity":"7b9e5c6d-a446-47bd-8d3d-fc239cfd33d4","order_by":26,"name":"Hui Tian","email":"","orcid":"","institution":"The First Affiliated Hospital Of Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Tian","suffix":""},{"id":398341925,"identity":"d67e2c51-7efc-454e-a607-63b5bf5525c8","order_by":27,"name":"Hao-Xian Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIiWNgGAWjYJACZgYGG9K1pJGu5TAJyg2Onz38urDtvL3B+TOGH34w2OTLOzA/e4BXy5m8NOsZZ24nbriRYyzZw5BmufEAm7kBXi0HcsyMeSpuJxjc4DEDudDAsIGHTQKvlvNvgFoMzoEcRqwWoHse81QcYNwAtA6sRZ6BgBbJG2/MmHnOJCfOvJFWLNljkGZgwMxmhlcL3/kc48+8bXb2fOcPb/zwo8LGQL69+RleLQoHGCDOADJA7gQiQnEk38DA/AHKgIuMglEwCkbBKEABAGBxRUH5kQNYAAAAAElFTkSuQmCC","orcid":"","institution":"Sun Yat-sen University Cancer Center","correspondingAuthor":true,"prefix":"","firstName":"Hao-Xian","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2025-01-02 08:38:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5750168/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5750168/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":94490249,"identity":"95aafcda-991a-48e9-9a4c-92f7fa2803e6","added_by":"auto","created_at":"2025-10-27 17:08:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":768847,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5750168/v1/bfc8b347-0f7c-4b4f-b301-5299cdef3e6f.pdf"},{"id":73305624,"identity":"d00dfe9e-d34f-4d79-b172-d79d1e3ac425","added_by":"auto","created_at":"2025-01-08 16:53:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":144769,"visible":true,"origin":"","legend":"","description":"","filename":"SPIRITFillablechecklistRAVAR.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5750168/v1/f29f4784791edcfdf15d305a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Robot-Assisted versus Video-Assisted Lobectomy for Early-Stage Non-Small Cell Lung Cancer (RAVAR): Study Protocol of a Prospective, Multicentre, Open-Label, Randomised Controlled Trial","fulltext":[{"header":"Background","content":"\u003cp\u003eVideo-assisted lobectomy (VAL) has gradually replaced open thoracotomy as the preferred surgical technique for early-stage non-small cell lung cancer (NSCLC) because it can reduce surgical trauma and accelerate postoperative recovery [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Over the last 20 years, robot-assisted lobectomy (RAL) has been increasingly applied in the treatment of early-stage NSCLC because of the advantages of three-dimensional vision and articulated instruments that could overcome the limitations of VAL, and numerous retrospective analyses have demonstrated that robotic surgery may yield better short-term outcomes than video-assisted surgery [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, both RAL and VAL are recommended as standard care in the National Comprehensive Cancer Network (NCCN) guidelines for the surgical treatment of early-stage NSCLC [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, most published studies have focused on the feasibility and safety of RAL, and few have addressed the long-term outcomes, with most of them being retrospective studies [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. To the best of our knowledge, only one randomised controlled trial (RCT) has compared the survival prognosis between RAL and VAL in patients with clinical stage I-III NSCLC, suggesting that the 3-year disease-free survival (DFS) and overall survival (OS) in the RAL group were non-inferior to those in the VAL group [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Unfortunately, this study was a single-centre trial, and the number of cases may not have been adequate to answer this question sufficiently (157 cases for RAL and 163 cases for VAL).\u003c/p\u003e \u003cp\u003eTo provide high-level evidence to compare the oncological results of RAL and VAL, we initiated a prospective, multicentre RCT to determine whether RAL is non-inferior to VAL in terms of long-term outcomes in patients with clinical stage I-II NSCLC.\u003c/p\u003e"},{"header":"Methods/design","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis prospective, multicentre, open-label RCT aims to prove the non-inferiority of RAL over VAL in terms of short- and long-term outcomes in patients with clinical stage I-II NSCLC. Patients in the experimental group (RAL group) will receive RAL for surgical treatment of NSCLC and patients in the control group (VAL group) will receive VAL for surgical treatment of NSCLC. All patients will receive standard anatomical lobectomy combined with systematic mediastinal lymph node dissection (MLND).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy setting\u003c/h3\u003e\n\u003cp\u003eThis trial is being coordinated by the Department of Thoracic Surgery at the Sun Yat-sen University Cancer Center. A total of 24 distinct hospitals across China mainland have joined this trial. All of these hospitals are well-known hospitals with large volumes in China and are located in South China, Southwest China, Central China, Northeast China, Northwest China, and Southeast China. The selection of such a diverse range of sites will guarantee wide demographic coverage and bolster the applicability of the findings to a broader population.\u003c/p\u003e\n\u003ch3\u003eEndpoint\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint is the 5-year DFS, defined as the time from randomisation to relapse or death from any cause. The secondary endpoints include the 5-year OS, blood loss, conversion rate, perioperative complications, operative death rate, postoperative length of hospital stay, pain score, R0 rate, operative time, number of dissected lymph nodes (LNs), chest tube duration, acesodyne (Grade III) dose, and total cost of hospitalisation.\u003c/p\u003e \u003cp\u003eOS is defined as the time from randomisation to death from any cause. Blood loss is defined as the blood loss during surgery. The conversion rate is defined as the proportion of patients who undergo open surgery among all patients who underwent surgery in each group. Perioperative complications are defined as complications that occurred during surgery or within 30 days after surgery among all patients undergoing operations, which will be recorded and classified using the Clavien-Dindo classification system [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] daily during hospitalisation and surveillance after discharge. The operative death rate is defined as the proportion of patients who die within 30/90 days of surgery among all patients undergoing surgery in each group. The length of the postoperative hospital stay is defined as the time between the date of surgery and discharge. The pain score will be evaluated using a Numerical Rating Scale (NRS) daily during hospitalisation after surgery and during surveillance after discharge. The R0 rate is defined as the proportion of patients who undergo complete resection among all the patients undergoing surgery in each group. Operative time is defined as the total time from skin incision to skin suturing, and the time of each step will be recorded simultaneously during each surgery. The number of dissected LNs will be calculated on the basis of the official postoperative pathological report. The chest tube duration is defined as the time between the date of surgery and chest tube removal. The acesodyne (Grade III) dose is defined as the total amount of analgesic medication, including morphine, pethidine, and fentanyl, used by the patient during the postoperative hospital stay. Total hospitalisation cost is defined as the total cost incurred by the patient from admission to discharge.\u003c/p\u003e\n\u003ch3\u003eEligibility criteria\u003c/h3\u003e\n\u003cp\u003e \u003cb\u003eInclusion criteria\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAge from 18 to 80 years\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients with blood pressure\u0026thinsp;\u0026lt;\u0026thinsp;160/100 mmHg, 5.6\u0026thinsp;\u0026lt;\u0026thinsp;blood glucose level\u0026thinsp;\u0026lt;\u0026thinsp;11.2 mmol/L, normal functioning of major organs: (1) Goldman index between grade 1 and 2; (2) predicted forced expiratory volume in 1s\u0026thinsp;\u0026ge;\u0026thinsp;40% and diffusing capacity of the lung for carbon monoxide\u0026thinsp;\u0026ge;\u0026thinsp;40%; (3) total bilirubin\u0026thinsp;\u0026le;\u0026thinsp;1.5 upper limit of normal; (4) alanine aminotransferase/aspartate aminotransferase\u0026thinsp;\u0026le;\u0026thinsp;2.5 upper limit of normal; (5) creatinine\u0026thinsp;\u0026le;\u0026thinsp;1.25 upper limit of normal and creatinine clearance rate\u0026thinsp;\u0026ge;\u0026thinsp;60 mL/min\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe first clinical diagnosis before surgery is NSCLC, which includes adenocarcinoma, squamous cell carcinoma, large-cell carcinoma, and other unknown types\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eClinical stage T1-2N0-1 (cI-II): Maximum diameter of tumour\u0026thinsp;\u0026le;\u0026thinsp;5 cm and short diameter of mediastinal lymph node\u0026thinsp;\u0026le;\u0026thinsp;1 cm in thin layer computed tomography\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePerformance status of Eastern Cooperative Oncology Group\u0026thinsp;=\u0026thinsp;0\u0026ndash;1\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAll relevant examinations completed within 28 days before the operation\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients who understand this study and signed an Informed Consent Form\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eExclusion criteria\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients undergoing radiotherapy, chemotherapy, targeted therapy, or immunotherapy before surgery\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients with a previous history of other malignancies\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients with secondary primary cancer when enrolled\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients diagnosed as showing pure ground glass opacity (GGO) before surgery\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients diagnosed as showing mixed GGO whose solid part\u0026thinsp;\u0026le;\u0026thinsp;50% and maximum diameter of tumour\u0026thinsp;\u0026le;\u0026thinsp;2 cm\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients with small cell lung cancer\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients with prior unilateral open thoracic surgical procedures\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eFemale patients who are pregnant or breast feeding\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients with interstitial pneumonia, pulmonary fibrosis, or severe emphysema\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients with an active bacterial or fungal infection that is difficult to control\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients with serious psychosis\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eHistory of severe heart attack, heart failure, myocardial infarction, or angina within the last 6 months\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e\n\u003ch3\u003eSample size calculation\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint of this trial is the 5-year DFS. Based on previous studies, the 5-year DFS rate of VAL is 68.0%, with a non-inferiority margin of 8% [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], an overall type I error of 0.025 (one-sided), and a power of 0.80. Considering a 10% dropout rate, 562 cases per group were required for a total sample size of 1,124.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eRandomisation\u003c/h2\u003e \u003cp\u003eStratified block randomisation will be performed in this trial. The random number table will be generated by an independent randomisation committee using SPSS (version 25.0; IBM Corp, Armonk, NY, USA) before the start of the study and kept confidential by the investigators and related personnel. After successful enrolment, each included patient will be assigned an opaque envelope, which will be opened by the investigators to assign a random number to the patient. Based on the random number, patients will be randomly assigned to two groups (RAL and VAL groups). The study will be stratified according to the centre and clinical stage (clinical stages I and II). Block sizes of 4, 6, and 8 will be randomly assigned to each centre in a 1:1 ratio. Neither the investigators nor the patients will be blinded to the study treatment.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTreatments\u003c/h3\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStandard of surgery\u003c/h2\u003e \u003cp\u003eAll patients will undergo surgery under general anaesthesia with double-lumen endotracheal intubation. RAL will be performed using the Da Vinci Xi/Si Surgical robot system (Intuitive Surgical Inc., USA). VAL can be performed using a single-port, single-utility-port, or multiport surgical approach. All included patients will undergo standard anatomical lobectomy combined with systematic MLND as proposed by the International Association for the Study of Lung Cancer (IASLC) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. According to IASLC guidelines, the criteria for systematic MLND are as follows [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAt least three mediastinal lymph node stations and the subcarinal lymph nodes must be examined in all patients.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients with left-sided NSCLC must undergo examination of level 5/6/7 lymph nodes; those with right-sided NSCLC must undergo examination of level 2R/4R/7 lymph nodes; and those with lower-lobe NSCLC must undergo examination of level 9 lymph nodes.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe total number of dissected LNs must be greater than 6, including at least 3 mediastinal LNs, and all lymph nodes and their surrounding tissues within the anatomical landmark must be completely removed.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePostoperative therapy\u003c/h2\u003e \u003cp\u003ePostoperative adjuvant treatment strategies will be determined by each centre based on the relevant clinical guidelines and the patient's wishes. If recurrence or metastasis is identified during follow-up, appropriate treatment protocols will be implemented promptly. If necessary, a multidisciplinary process may be employed to develop a scientific treatment protocol that may include surgical intervention, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. The specific treatment protocol will be established on the basis of the experiences of various centres.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eQuality control of study\u003c/h2\u003e \u003cp\u003eTo ensure that this clinical trial is conducted strictly in accordance with the protocol, throughout the entire process, clinical researchers must operate in strict compliance with the requirements of the good clinical practice (GCP), ensuring standardized trial procedures, accurate trial data, and reliable research conclusions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eEstablishment of standard operating procedures (SOP)\u003c/h2\u003e \u003cp\u003eThe lead institution of the project is responsible for the overall design and implementation of the research, establishing SOP for quality control of this clinical trial, forming a multicentre clinical research team, and providing unified training. Prior to the project initiation, training sessions on GCP regulations, clinical protocol explanations, and case report form (CRF) completion will be conducted for all researchers. Evidence related to endpoint events will be assessed and judged by an independent third-party institution to determine whether an endpoint event has occurred.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eResearch nurses\u003c/h2\u003e \u003cp\u003eEquip the project with research nurses to assist the investigator in implementing the trial, ensuring that the trial is conducted in accordance with the established protocol and GCP regulations. Specific responsibilities include assisting with enrolment, managing subjects, completing CRFs, communication, document archiving, follow-up, financial matters, and cooperating with inspections.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eRequirements of attending surgeons\u003c/h2\u003e \u003cp\u003eThe trial will include surgeons skilled in performing RAL and VAL who have completed more than 100 RALs and 100 VALs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eIntraoperative video recording\u003c/h2\u003e \u003cp\u003eInvestigators must record the whole surgical procedure from start to finish of all enrolled patients in this trial during surgeries. The study coordinator will conduct a central peer review of the surgical procedure every 6 months by checking the intraoperative videos. These surgical videos must be stored on a cloud server and must be kept for at least 5 years after the end of the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eFollow-up\u003c/h2\u003e \u003cp\u003eAll enrolled patients will be scheduled for regular follow-up assessments every 3 months in the first year after surgical treatment, every 6 months in the second to fifth years, and once a year thereafter until death or the end of the study. If new symptoms are identified during follow-up, the patients will be re-examined promptly. The contents of the review include physical examinations, enhanced chest and abdominal CT scans, and tumour marker assessments. In addition, patients\u0026rsquo; symptoms need to be tested appropriately. If recurrence or metastasis occurs during the follow-up period, the sites of recurrence and metastasis, related symptoms, and subsequent treatments will be recorded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eData management and storage\u003c/h2\u003e \u003cdiv id=\"Sec19\" class=\"Section3\"\u003e \u003ch2\u003eCRF\u003c/h2\u003e \u003cp\u003eThe CRF is completed by the investigator and should be filled in promptly to ensure accuracy. Generally, the CRF should not be altered; if errors do occur and need correction, the corrections should be signed off. The CRF is issued in triplicate, with copies submitted to the principal investigator, the sponsor, and the collaborating hospital for storage upon completion of the trial. After review by the clinical monitor, the completed CRFs will be used for data entry. The content of the CRF will not be modified thereafter.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eEstablishment of the database\u003c/h2\u003e \u003cp\u003eUpon receiving the CRFs, the statistician will verify any queries through the investigator, who should respond promptly. The statistician will establish the database in a timely manner, and upon review, the data will be locked by the principal investigator, sponsor, statistician, and clinical monitor. Data security will be ensured, with unauthorized personnel prevented from accessing and modifying the data, and backups of the data will be maintained.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eStorage of materials\u003c/h2\u003e \u003cp\u003eThe investigator should ensure the complete storage of materials for ready retrieval and inspection. In accordance with GCP principles in China, study-related materials should be retained for a period of over five years by the study party.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eData monitoring\u003c/h2\u003e \u003cp\u003eThe Department of Clinical Research of Sun Yat-sen University Cancer Center will independently monitor this trial to evaluate and improve the study progress, data integrity, and patient safety. Research data will be filed on the RDD platform (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.researchdata.org.cn\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.researchdata.org.cn\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) before publication to ensure the authenticity of the data.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec23\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe Kaplan-Meier method will be employed to estimate the survival rates for OS and DFS, while the log-rank test will be used to compare survival rates between different groups. Furthermore, to minimise the influence of confounding factors, a multivariate Cox proportional-hazard regression model may also be applied. For categorical variables, including R0 resection rate, conversion rate, complication rate, and surgical mortality, differences between the two groups will be assessed using either the chi-square test or Fisher's exact test. When comparing continuous variables, such as operation time, blood loss, postoperative hospital stays, and chest tube duration, the t-test or Wilcoxon rank-sum test will be employed for two-group comparisons.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the 1990s, VAL was first used to treat early-stage NSCLC [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Subsequently, several RCTs confirmed that VAL could significantly reduce surgical trauma and accelerate patient recovery while achieving therapeutic effects comparable to those of open surgery [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Consequently, international clinical guidelines recommend VAL as one of the preferred surgical methods for early-stage NSCLC [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, VAL has significant drawbacks, such as distorted two-dimensional vision, unavoidable camera shake, easy fatigue for surgeons, and clumsy \u0026ldquo;chopstick\u0026rdquo;-like surgical instruments. These limitations significantly hinder the promotion, application, and popularisation of VAL, rendering it incapable of meeting the growing surgical treatment needs of patients with NSCLC.\u003c/p\u003e \u003cp\u003eAt the beginning of this century, RAL began to be used in the treatment of lung cancer [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The robotic surgical system has a 3D high-definition view, tremor-filtering capability, and surgical instruments with seven degrees of freedom. The rapid development of RAL indicates that robotic surgical systems have broad application prospects in lung cancer surgery. Consequently, RAL, similar to VAL, is recommended by clinical guidelines as the preferred surgical approach for early-stage NSCLC [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, many issues remain unresolved in the field of RAL. In terms of short-term outcomes, many retrospective studies have demonstrated that RAL is a safe and effective surgical technique. Some studies have even suggested that RAL may achieve superior short-term outcomes than VAL [\u003cspan additionalcitationids=\"CR6 CR7 CR8\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, the long-term outcomes of RAL in early-stage NSCLC need to be determined. Numerous retrospective studies have indicated that RAL is comparable to VAL in terms of the long-term survival of patients with resectable NSCLC [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Yang et al. included 470 unique patients (172 RALs, 141 VALs, and 157 open lobectomies), and they found that the 5-year DFS of patients who underwent RAL was statistically better than that of those who underwent VAL (P\u0026thinsp;=\u0026thinsp;0.047). However, this result was not confirmed by multivariate analysis [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Another large-scale multicentre retrospective study including 2789 RALs and 2661 VALs also found that patients with RAL had significantly better OS than those with VAL (P\u0026thinsp;=\u0026thinsp;0.007) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, these studies were limited by their retrospective nature, and prospective RCTs are warranted to confirm the long-term survival comparison between RAL and VAL. The RVlob trial is a single-centre RCT to compare the survival prognosis between RAL and VAL in patients with clinical stage I-III NSCLC [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A total of 320 patients were included in this trial, and the authors reported that RAL is non-inferior to VAL in terms of 3-year DFS and OS [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. It should be noted that RVlob trial is a single-center RCT that including clinical stage I-IIIA patients with primary endpoint as 3-year DFS, and the sample size is not large, which should be considered when drawing a definite conclusion. Therefore, we believe that large-scale multicentre RCTs and longer follow-up periods are warranted to determine the long-term outcomes of RAL and VAL in early-stage NSCLC.\u003c/p\u003e \u003cp\u003eTo the best of our knowledge, the RAVAR study is the largest multicentre RCT to compare the long-term outcomes between RAL and VAL in early-stage NSCLC. The trial will include 1,124 patients with clinical stage I-II NSCLC, with 5-year DFS as the primary endpoint and 5-year OS and short-term outcomes as the secondary endpoints. The expected results will determine whether RAL is non-inferior to VAL in terms of long-term survival in early-stage NSCLC, providing high-level evidence for the surgical treatment of early-stage NSCLC, and thereby improving the standard of care for these patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eThis study is conducted according to the Declaration of Helsinki, relevant Chinese laws and regulations. The Ethics Committee of Sun Yat-Sen University Cancer Center approved this study protocol in May 2020, and the date of first participant enrollment was August 26, 2020. Approval from the institutional review board was obtained before starting patient enrollment in each institution. Written informed consent has been obtained from all enrolled patients. The participating institutions are as follows: Sun Yat-sen University Cancer Center; The First Affiliated Hospital of Nanchang University; The Affiliated Hospital of Qingdao University; General Hospital of Eastern Theater Command; Gansu Provincial People's Hospital; The Second Affiliated Hospital of Air Force Medical University; Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology; The First Affiliated Hospital of Chongqing Medical University; West China Hospital, Sichuan University; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Shenzhen People's Hospital; The First Affiliated Hospital of Zhengzhou University; Shandong Provincial Hospital; Jiangsu Cancer Hospital; Liaoning Cancer Hospital; Guangdong Provincial People's Hospital; Jiangxi Provincial People's Hospital; Sichuan Cancer Hospital; Nanxishan Hospital of Guangxi Zhuang Autonomous Region; Chongqing University Cancer Hospital; The First Affiliated Hospital Of Shandong First Medical University; Qilu Hospital of Shandong University; Shenzhen Third People\u0026rsquo;s Hospital; The Second Hospital of Lanzhou University.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was fully funded by Sun Yat-sen University Clinical Research 5010 Program (2019012).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eT. Z. and M. Y. wrote the manuscript. M. Y. and H. Y. proposed the concept of the RAVAR study and drafted the protocol design for the study. L. L. contributed to the sample size calculation and randomisation of the protocol, and will undertake the statistical analysis. J. Y., Z. P., Y. L., Y. G., H. L., W. J., Q. X., M. D., Y. W., G. Q., B. J., Y. Q., X. Y., G. W., B. Y., K. Q., M. L., B. L., B. H., R.X., W. Y., N. Z., Z. W., H. T., and H.Y. revised the protocol for the study, and will contribute to subject recruitment for this study. All authors approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData sharing is not applicable to this article because no datasets had been generated or analyzed at the time of submission.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eVAL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eVideo-Assisted Lobectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eNSCLC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eNon-Small Cell Lung Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eRAL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eRobot-Assisted Lobectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eNCCN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eNational Comprehensive Cancer Network\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eRandomized Controlled Trial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eDFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eDisease-Free Survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eOS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eOverall Survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eMLDN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eMediastinal Lymph Node Dissection\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eNRS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eNumerical Rating Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eGGO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eGround Glass Opacity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eIASLC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eInternational Association for the Study of Lung Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eGCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eGood Clinical Practice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eSOP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eStandard Operating Procedures\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8698%;\"\u003e\n \u003cp\u003eCRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1302%;\"\u003e\n \u003cp\u003eCase Report Form\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKirby TJ, Mack MJ, Landreneau RJ, Rice TW. Lobectomy\u0026ndash;video-assisted thoracic surgery versus muscle-sparing thoracotomy. A randomized trial. J Thorac Cardiovasc Surg. 1995;109:997\u0026ndash;1001.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCraig SR, Leaver HA, Yap PL, Pugh GC, Walker WS. Acute phase responses following minimal access and conventional thoracic surgery. Eur J Cardiothorac Surg. 2001;20:455\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSwanson SJ, Herndon JE 2nd, D'Amico TA, Demmy TL, McKenna RJ Jr., Green MR, et al. Video-assisted thoracic surgery lobectomy: report of CALGB 39802\u0026ndash;a prospective, multi-institution feasibility study. J Clin Oncol. 2007;25:4993\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMelfi FM, Menconi GF, Mariani AM, Angeletti CA. Early experience with robotic technology for thoracoscopic surgery. Eur J Cardiothorac Surg. 2002;21:864\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark BJ, Flores RM, Rusch VW. Robotic assistance for video-assisted thoracic surgical lobectomy: technique and initial results. J Thorac Cardiovasc Surg. 2006;131:54\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCerfolio RJ, Bryant AS, Skylizard L, Minnich DJ. Initial consecutive experience of completely portal robotic pulmonary resection with 4 arms. J Thorac Cardiovasc Surg. 2011;142:740\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKent M, Wang T, Whyte R, Curran T, Flores R, Gangadharan S. Open, video-assisted thoracic surgery, and robotic lobectomy: review of a national database. Ann Thorac Surg. 2014;97:236\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiang H, Liang W, Zhao L, Chen D, Zhang J, Zhang Y, et al. Robotic versus video-assisted lobectomy/segmentectomy for lung cancer: a Meta-analysis. Ann Surg. 2018;268:254\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNelson DB, Mehran RJ, Mitchell KG, Rajaram R, Correa AM, Bassett RL Jr., et al. Robotic-assisted lobectomy for non-small cell lung cancer: a comprehensive institutional experience. Ann Thorac Surg. 2019;108:370\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNCCN Clinical Practice. Guidelines in Non-Small Cell Lung Cancer Version 6.2020.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark BJ, Melfi F, Mussi A, Maisonneuve P, Spaggiari L, Da Silva RK, et al. Robotic lobectomy for non-small cell lung cancer (NSCLC): long-term oncologic results. J Thorac Cardiovasc Surg. 2012;143:383\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCerfolio RJ, Ghanim AF, Dylewski M, Veronesi G, Spaggiari L, Park BJ. The long-term survival of robotic lobectomy for non-small cell lung cancer: A multi-institutional study. J Thorac Cardiovasc Surg. 2018;155:778\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang HX, Woo KM, Sima CS, Bains MS, Adusumilli PS, Huang J, et al. Long-term survival based on the surgical approach to lobectomy for clinical stage I non-small cell lung cancer: comparison of robotic, video-assisted thoracic surgery, and thoracotomy lobectomy. Ann Surg. 2017;265:431\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTasoudis PT, Diehl JN, Merlo A, Long JM. Long-term outcomes of robotic versus video-assisted pulmonary lobectomy for non-small cell lung cancer: systematic review and meta-analysis of reconstructed patient data. J Thorac Dis. 2023;15:5700\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNiu Z, Cao Y, Du M, Sun S, Yan Y, Zheng Y, et al. Robotic-assisted versus video-assisted lobectomy for resectable non-small-cell lung cancer: the RVlob randomized controlled trial. EClinicalMedicine. 2024;74:102707.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDindo 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;240:205\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamirez PT, Frumovitz M, Pareja R, Lopez A, Vieira M, Ribeiro R, et al. Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer. N Engl J Med. 2018;379:1895\u0026ndash;904.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStevenson AR, Solomon MJ, Lumley JW, Hewett P, Clouston AD, Gebski VJ, et al. Effect of laparoscopic-assisted resection vs open resection on pathological outcomes in rectal cancer: the ALaCaRT randomized clinical trial. JAMA. 2015;314:1356\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDarling GE, Allen MS, Decker PA, Ballman K, Malthaner RA, Inculet RI, et al. Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030 Trial. J Thorac Cardiovasc Surg. 2011;141:662\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRusch VW, Asamura H, Watanabe H, Giroux DJ, Rami-Porta R, Goldstraw P. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009;4:568\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLewis RJ. The role of video-assisted thoracic surgery for carcinoma of the lung: wedge resection to lobectomy by simultaneous individual stapling. Ann Thorac Surg. 1993;56:762\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePatel YS, Baste JM, Shargall Y, Waddell TK, Yasufuku K, Machuca TN, et al. Robotic lobectomy is cost-effective and provides comparable health utility scores to video-assisted lobectomy: early results of the RAVAL trial. Ann Surg. 2023;278:841\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKent MS, Hartwig MG, Valli\u0026egrave;res E, Abbas AE, Cerfolio RJ, Dylewski MR, et al. Pulmonary open, robotic, and thoracoscopic lobectomy (PORTaL) study: survival analysis of 6646 cases. Ann Surg. 2023;277:1002\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Non-small cell lung cancer, Robotic-assisted thoracoscopic surgery, Video-assisted thoracic surgery, Multicenter study, Randomized controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-5750168/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5750168/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eVideo-assisted lobectomy (VAL) and robot-assisted lobectomy (RAL) are recommended standard treatments for early-stage non-small cell lung cancer (NSCLC). Nevertheless, comparisons of long-term survival between VAL and RAL are controversial because of the lack of robust evidence from prospective multicentre randomised controlled trials (RCTs).\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eWe are conducting a prospective multicentre RCT to evaluate whether RAL is non-inferior to VAL in terms of long-term survival in patients with clinical stage T1-2N0-1M0 (stage I-II) NSCLC who underwent lobectomies (RAVAR study). A total of 1,124 patients will be enrolled from multiple institutions. The primary endpoint is the five-year disease-free survival rate. The secondary endpoints include five-year overall survival and short-term outcomes, such as perioperative complications, length of postoperative hospital stay, operation time, number of dissected lymph nodes, chest tube duration, pain score, and total cost of hospitalisation. The Ethics Committee of the Sun Yat-sen University Cancer Center approved the study protocol in May 2020, and patient enrolment began in August 2020. Approval was obtained from each institutional ethics committee before initiating patient enrolment.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e \u003cp\u003eThis multicentre RCT compares the long-term outcomes of RAL and VAL in resectable early-stage NSCLC. The expected results of this study will determine whether RAL can achieve satisfactory long-term outcomes that are not inferior to those of VAL in patients with early-stage NSCLC, thereby providing high-level evidence for a minimally invasive approach for these patients.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e \u003cp\u003eThe protocol of RAVAR trial was registered in the China Clinical Trials Registry as ChiCTR2000034737 (registration date: July 17, 2020) and ClinicalTrials.gov as NCT06524427 (registration date: July 29, 2024). Date of First Participant Enrollment: August 26, 2020.\u003c/p\u003e","manuscriptTitle":"Robot-Assisted versus Video-Assisted Lobectomy for Early-Stage Non-Small Cell Lung Cancer (RAVAR): Study Protocol of a Prospective, Multicentre, Open-Label, Randomised Controlled Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-08 16:45:51","doi":"10.21203/rs.3.rs-5750168/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a89be93a-bd7d-4b24-ab22-fa716ca928e8","owner":[],"postedDate":"January 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T15:05:42+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-08 16:45:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5750168","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5750168","identity":"rs-5750168","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}