Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY): protocol of a prospective, multicentre, observational study

Abstract

Introduction: Recurrence rate following radical therapy for lung cancer remains high, potentially reflecting occult metastatic disease, and better staging tools are required. Minimal pleural effusion (mini-PE) is associated with particularly high recurrence risk and is defined as an ipsilateral pleural collection (<1/3 hemithorax on chest radiograph), which is either too small to safely aspirate fluid for cytology using a needle, or from which fluid cytology is negative. Thoracoscopy (local anaesthetic thoracoscopy (LAT) or video-assisted thoracoscopic surgery (VATS)) is the gold-standard diagnostic test for pleural malignancy in patients with larger symptomatic effusions. Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY) will prospectively evaluate thoracoscopic staging in lung cancer associated-mini-PE for the first time.

Methods and analysis: STRATIFY is a prospective multicentre observational study. Recruitment opened in January 2020. The primary objective is to determine the prevalence of detectable occult pleural metastases (OPM). Secondary objectives include assessment of technical feasibility and safety, and the impact of thoracoscopy results on treatment plans, overall survival and recurrence free survival. Inclusion criteria are (1) suspected/confirmed stages I-III lung cancer, (2) mini-PE, (3) Performance Status 0-2 (4), radical treatment feasible if OPM excluded, (5) ≥16 years old and (6) informed consent. Exclusion criteria are any metastatic disease or contraindication to the chosen thoracoscopy method (LAT/VATS). All patients have LAT or VATS within 7 (±5) days of registration, with results returned to lung cancer teams for treatment planning. Following an interim analysis, the sample size was reduced from 96 to 50, based on a lower-than-expected OPM rate. An MRI substudy was removed in November 2022 due to pandemic-related site setup/recruitment delays. These also necessitated a no-cost recruitment extension until October 2023.

Ethics and dissemination: Protocol approved by the West of Scotland Research Ethics Committee (Ref: 19/WS/0093). Results will be published in peer-reviewed journals and presented at international meetings.

Trial registration number: ISRCTN13584097.

Keywords: Lung Cancer; Pleural Disease; Thoracic Surgery.

Figure 1

Minimal pleural effusion (mini-PE) examples. Both panels show axial plane CT images in patients with non-small cell lung cancer (NSCLC). (A) A T2b N1 M0 (stage 2A) NSCLC with associated Mini-PE (red arrows). Based on retrospective data, the HR for death in this case is 2.24 relative to T2b N1 without Mini-PE. (B) A T3 N1 M0 (stage 2B) NSCLC without Mini-PE. Both patients have potentially radically treatable disease (circled).

Figure 2

Study flow chart summarising the design and major study interventions. CT, Computed Tomography; LAT, local anaesthetic thoracoscopy; MDT, multidisciplinary team; mini-PE, minimal pleural effusion; NSCLC, non-small cell lung cancer; OPM, occult pleural metastases; PET-CT, Positron Emission Tomography-Computed Tomography; RT, radiotherapy; VATS, Video Assisted Thoracoscopic Surgery.