SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screen-detected breast cancer - a UK phase III randomised multi-centre trial

TPS625 Background: Mammographic screening programmes reduce breast cancer mortality but detect many small tumours with favourable biology which may not progress. These are treated with surgery and adjuvant therapies, but associated morbidities mean there is a need to reduce overtreatment. Minimally invasive treatments such as vacuum-assisted excision (VAE) have been described but there is no prospective randomised evidence to support their routine use. SMALL (ISRCTN 12240119) is designed to establish the feasibility of using VAE to treat small tumours detected within the UK NHS Breast Screening Programme (BSP). Methods: Phase III multicentre randomised trial comparing surgery with VAE for screen-detected good prognosis cancers. Eligibility criteria are age ≥47 years, unifocal grade 1 tumours (maximum diameter 15mm), strongly ER/PR+ve and HER2-ve, with negative axillary staging. Patients are randomised 2:1 to VAE or surgery, with no axillary surgery in the VAE arm. Excision is assessed radiologically, and if incomplete, patients undergo surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm. Co-primary end-points are 1) Non-inferiority comparison of the requirement for a second procedure. 2) Single arm analysis of local recurrence (LR) at 5 years after VAE. Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure, ensuring sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A QuinteT Recruitment Intervention (QRI) is integrated throughout SMALL to optimise recruitment and informed consent. Recruitment challenges are identified by analysing recruiter/patient interviews, audio-recordings of trial discussions, and by review of screening, eligibility and recruitment data and study documentation. Solutions are developed collaboratively, including recruiter feedback and recruitment tips documents. Results: At 10 th February 2023, 231 patients had been recruited from 32 centres, (~45% of eligible patients), with per site recruitment of 0.4-0.5 patients/month. Based on preliminary QRI findings, a recruitment tips document has been circulated (on discussing SMALL, providing balanced information on treatment options and explaining randomisation), with individual recruiter feedback underway and wider feedback planned shortly. Conclusion: SMALL has excellent recruitment to date, confirming feasibility and acceptability, and is expected to have a global impact on treatment of screen-detected breast cancer. Clinical trial information: ISRCTN12240119 .