PS5-09-12: Small: open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer - a UK phase III randomised multi-centre trial

Background: Mammographic screening programmes reduce breast cancer mortality but detect many small good-prognosis tumours which may not progress. Screen-detected cancers are currently treated with standard surgery and adjuvant therapies, with associated morbidities. There is a need to reduce overtreatment of good prognosis tumours and numerous studies are evaluating omission of radiotherapy in low-risk disease. However, there is little evidence for surgical de-escalation, although percutaneous minimally invasive treatment approaches have been described. Vacuum-assisted excision (VAE) is in widespread use for management of lesions of uncertain malignant potential and benign lesions. SMALL (ISRCTN 12240119) aims to determine the feasibility of using this approach to treat small invasive tumours detected within the UK NHS Breast Screening Programme. Methods: SMALL is a phase III multicentre RCT comparing standard surgery with VAE for screen-detected cancers. Main eligibility criteria are age ≥47 years, unifocal grade 1 tumours with 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. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are1. Non-inferiority comparison of the requirement for a second procedure following excision2. Single arm analysis of local recurrence (LR) at 5 years following VAE Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures 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%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A novel feature of SMALL is integration of a QuinteT Recruitment Intervention (QRI), which aims to optimise recruitment to the study. Recruitment challenges are identified by analysing recruiter/patient interviews and audio-recordings of trial discussions, and by review of trial screening logs, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Results: SMALL opened in December 2019. Recruitment halted in 2020 for 5 months due to COVID-19. At 9th July 2025, 49 centres are open, with 640 patients randomised. The randomisation rate is approximately 45%, and per site recruitment rate is 0.4-0.5 patients/month. Drawing from QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on providing balanced information about treatments, encouraging recruiters to engage with patient preferences, and explaining randomisation). Individual recruiter feedback is ongoing, and wider feedback is being delivered across sites via recruitment training workshops. Patient interviews are ongoing to explore patient views and experiences of the trial. Conclusion: SMALL continues to have excellent recruitment, is expected to complete recruitment in 2026 and have a global impact on treatment of breast cancer within mammographic screening programmes. SMALL is funded by the UK NIHR HTA programme award 17/42/32

Citation

McIntosh et al (2026). PS5-09-12: Small: open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer-a UK phase III randomised multi-centre trial. Clinical Cancer Research, 32(4_Supplement), PS5-09.

DOI

10.1158/1557-3265.SABCS25-PS5-09-12

URI

https://hdl.handle.net/20.500.14709/1500

License

Free access to article on publisher's webpage. Click DOI.

Usage rights

Free access to article on publisher's webpage. Click DOI.