Abstract PO4-18-09: SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screen-detected breast cancer – a UK phase III randomised multi-centre trial
Authors: McIntosh Stuart , Coles Charlotte , Dodwell David , Elder Kenneth , Foster Jessica , Gaunt Claire , Kirkham Amanda , Lyburn Iain , Paramasivan Sangeetha , Morgan Jenna , Pinder Sarah , Potter Shelley , Roberts Tracy , Sharma Nisha , Stobart Hilary , Southgate Elizabeth , Taylor-Phillips Sian , Wallis Matthew , Rea Daniel 
Published: May 2024

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 to support 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) is designed 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 randomised trial 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 are:

1. Non-inferiority comparison of the requirement for a second procedure following excision

2. 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 the 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, but recruitment halted in 2020 for 5 months due to COVID-19. At 6th July 2023, 39 centres are open, with 300 patients randomised from 32 of these, with a randomisation rate of approximately 45%, and a per site recruitment rate of 0.4-0.5 patients/month. Despite the pandemic, SMALL achieved the internal pilot feasibility targets and continues to recruit to the main study, with estimated completion of recruitment in June 2025.

Drawing from preliminary 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 has commenced and wider feedback is being delivered across sites via recruitment training workshops.

Conclusion:

Despite pandemic-related challenges, SMALL has excellent recruitment to date and is expected to 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 Format: Stuart McIntosh, Charlotte Coles, David Dodwell, Kenneth Elder, Jessica Foster, Claire Gaunt, Amanda Kirkham, Iain Lyburn, Sangeetha Paramasivan, Jenna Morgan, Sarah Pinder, Shelley Potter, Tracy Roberts, Nisha Sharma, Hilary Stobart, Elizabeth Southgate, Sian Taylor-Phillips, Matthew Wallis, Daniel Rea. SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screen-detected breast cancer – a UK phase III randomised multi-centre trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-09.