Study protocol for VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer, a UK multicentre randomised controlled trial with an internal pilot (the VIOLET study)

Abstract

IntroductionLung cancer is a leading cause of cancer deaths worldwide and surgery remains the main treatment for early stage disease. Prior to the introduction of video-assisted thoracoscopic surgery (VATS), lung resection for cancer was undertaken through an open thoracotomy. To date, the evidence base supporting the different surgical approaches is based on non-randomised studies, small randomised trials and is focused mainly on short-term in-hospital outcomes.Methods and analysisThe VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer study is a UK multicentre parallel group randomised controlled trial (RCT) with blinding of outcome assessors and participants (to hospital discharge) comparing the effectiveness, cost-effectiveness and acceptability of VATS lobectomy versus open lobectomy for treatment of lung cancer. We will test the hypothesis that VATS lobectomy is superior to open lobectomy with respect to self-reported physical function 5 weeks after randomisation (approximately 1 month after surgery). Secondary outcomes include assessment of efficacy (hospital stay, pain, proportion and time to uptake of chemotherapy), measures of safety (adverse health events), oncological outcomes (proportion of patients upstaged to pathologic N2 (pN2) disease and disease-free survival), overall survival and health related quality of life to 1 year. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment.Ethics and disseminationThis trial has been approved by the UK (Dulwich) National Research Ethics Service Committee London. Findings will be written-up as methodology papers for conference presentation, and publication in peer-reviewed journals. Many aspects of the feasibility work will inform surgical RCTs in general and these will be reported at methodology meetings. We will also link with lung cancer clinical studies groups. The patient and public involvement group that works with the Respiratory Biomedical Research Unit at the Brompton Hospital will help identify how we can best publicise the findings.Trial registration number ISRCTN13472721

Video‐assisted thoracoscopic surgery as the gold standard for lung cancer surgery

“…36,37 Although the final paper has yet to be published, the VIOLET investigators reported that in this trial of 503 patients with early-stage lung cancer from nine UK centres randomly assigned to receive lobectomy by VATS (n = 247) or open thoracotomy (n = 256), VATS patients had significantly better outcomes than thoracotomy patients in terms of less pain on post-operative day 2 (VATS pain score 3 vs thoracotomy 4), fewer in-hospital complications (32.8% vs 44.3%) and shorter hospital stays (4 vs 5 days). 36,37 Powerful though these latest randomized trials were, they merely reconfirmed what was already shown since the 1990s. Today, it is recognized by many thoracic surgeons that future randomized trials are likely to be increasingly difficult to conduct because the benefits of VATS have been so well demonstrated through years of clinical practice that equipoise may no longer exist in much of the thoracic surgery community, and patients themselves may refuse to be recruited for randomization if they may end up allocated to receive open thoracotomy.…”

“…70,71 The fact that some good RCT can still emerge in the field of lung cancer surgery testifies to the strong desire of thoracic surgeons to strive for high-quality evidence despite these daunting obstacles. [35][36][37] However, when RCT prove unfeasible or have reached a 'glass ceiling' due to the above-mentioned limitations, the value of welldesigned and rigorously performed cohort studies should not be dismissed. 39,70,71 The accumulation of a large volume of meticulously documented experience in operating patients around the world provides robust data informing surgical practice.…”

“…Even at 1 year after surgery, patients who had VATS experienced fewer episodes of moderate‐to‐severe pain than those receiving thoracotomy ( P < 0·0001), and reported better quality of life (QoL; P = 0·014). Most recently, the results of the VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer (VIOLET) study, a UK multicentre randomized controlled trial (RCT), were reported 36,37 . Although the final paper has yet to be published, the VIOLET investigators reported that in this trial of 503 patients with early‐stage lung cancer from nine UK centres randomly assigned to receive lobectomy by VATS ( n = 247) or open thoracotomy ( n = 256), VATS patients had significantly better outcomes than thoracotomy patients in terms of less pain on post‐operative day 2 (VATS pain score 3 vs thoracotomy 4), fewer in‐hospital complications (32.8% vs 44.3%) and shorter hospital stays (4 vs 5 days) 36,37 .…”

Robotic versus open and video-assisted thoracoscopic surgery approaches for lobectomy

“…Nevertheless, they found no difference between VATS and thoracotomy for postoperative Grade 3 and 4 adverse events, and quality of life according to the European Organisation for Research and Treatment of Cancer 30-item quality of life questionnaire (QLC-C30) (P = 0.13). More recently, the first results of the randomized controlled VIOLET study [41] confirmed better shortterm outcomes after lobectomy by VATS than by open surgery.…”

Electronic Patient-Reported Outcomes After Thoracic Surgery: Toward Better Remote Management of Perioperative Symptoms

“…This prospective, longitudinal study is one of the few to use validated, disease-specific survey instruments to study this population. 2 , 3 Until the results of the UK-based VIOLET trial (comparing the impact of VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy) are available, 4 this study provides the most contemporary information on HRQOL trajectory after lung cancer surgery. Importantly, the authors show HRQOL continues to suffer and residual symptoms persist at 1 year after minimally invasive lung cancer surgery.…”