VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer, a multi-centre randomised controlled trial with an internal pilot. The VIOLET Study

DESIGN: Parallel group randomised controlled trial (RCT) with an internal pilot phase. Progression to phase 2 will depend on meeting defined success criteria in Phase 1. Phase 1 is necessary to establish processes for recruitment and to develop a study manual and measure of surgical expertise for participation in phase 2. The full RCT will evaluate the effectiveness, cost effectiveness and acceptability of minimal access VATS vs. conventional open lobectomy for lung cancer. Study participants will be randomised in a 1:1 ratio to VATS or open surgery and followed to 1-year. SETTING: Phase 1 will be conducted in 5 centres; Brompton, Bristol, Liverpool, Harefield & Middlesbrough. Qualitative research will be applied to both phases of the study to optimise recruitment. In-depth interviews with recruiters (surgeons and nurses) will discuss the study design, views about the procedures, and approaches to recruitment. Audio-recorded recruitment consultations and patient interviews will be conducted and analysed to identify communication difficulties, optimise information provision and ensure fully informed consent. Phase 2 will extend the study to a further 5 centres. TARGET POPULATION: Adults with early stage lung cancer suitable for both minimal access and open surgery. INCLUSION / EXCLUSION CRITERIA: Eligible patient with be adults, able to provide written informed consent, undergoing lobectomy for the treatment of known or suspected primary lung cancer with a peripheral tumour beyond a lobar orifice in TNM8 stage cT1-3 (by size criteria, equivalent to TNM7 stage cT1a-2b) or cT3 (by virtue of 2 nodules in the same lobe), N0-1 and M0 or undergoing frozen section biopsy with the intention to proceed with lobectomy or bilobectomy if primary lung cancer with a peripheral tumour beyond a lobar orifice in TNM8 stage cT1-3 (by size criteria, equivalent to TNM7 stage cT1a-2b) or cT3 (by virtue of 2 nodules in the same lobe), N0-1 and M0 is confirmed. Patients must have disease suitable for both VATS & open surgery, to be considered eligible. Patients who have a previous malignancy that influences life expectancy, in whom robotic surgery is planned or those having pneumonectomy or non-anatomic resection (e.g. wedge dissection) are not eligible to participate. HEALTH TECHNOLOGIES BEING ASSESSED: Video assisted thoracoscopic surgery (VATS) lobectomy and conventional open lobectomy. MEASUREMENT OF COST & OUTCOMES: Primary outcome is the physical function at 5 weeks measured using EORTC QLQ-C30 quality-of-life questionnaire, chosen because it is a patient-centred outcome that will reflect the anticipated earlier recovery with VATS lobectomy and has been used in other minimal access surgery trials (nephrectomy, colorectal, oesophageal). The 5 week timing was chosen to capture the early benefits of minimal access surgery on recovery. Secondary outcomes will include generic and disease specific patient-reported outcomes (EORTC QLQ-C30, QLQ-LC-13, EQ5D), overall and disease-free survival, adverse events, economic evaluation and utility, uptake of adjuvant treatment, pathologic up-staging, the proportion of patients who undergo complete resection during the procedure and the proportion of patients who experience prolonged incision pain. SAMPLE SIZE: 498 patients will provide 90% power to test the hypothesis that minimal access surgery leads to greater physical function than open surgery (5% sig. level), assuming an improvement of 0.25 standard deviations is clinically important and allowing for 20% dropout at 1 year. We will recruit about 162 participants in phase 1 and 498 by the end of phase 2. Project timetable including recruitment rate: Study will run over 69 months: 6m set-up; 45m recruitment (phase 1: 21m; phase 2: 24m), 12m follow-up on all participants; 6m analysis and report. We anticipate an average 20 eligible patients/m in phase 1 and that 30% will be recruited initially, increasing to 50% within 6m of study start at each centre. EXPERTISE IN THE TEAM: The team has surgeons, trialists, health economists and patients. MRC Trials Methodology Hub members provide qualitative expertise and expertise in RCTs in surgery.