SMALL: open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer-protocol for a phase III randomised multicentre trial

Kenneth Elder; Charlotte Coles; David Dodwell; Beatrix Elsberger; Jessica Foster; Claire Gaunt; Julia R Henderson; Iain Lyburn; Claire Mabena; Jenna Morgan; Zohal Nabi; Sangeetha Paramasivan; Sarah Pinder; Sarah Pirrie; Shelley Potter; Tracy Roberts; Nisha Sharma; Elizabeth Southgate; Hilary Stobart; Amruta Talwalkar; Sian Taylor-Phillips; William Teh; Elliot Turner; Daniel Rea; Matthew G Wallis; Stuart McIntosh

doi:10.1136/bmjopen-2025-099702

SMALL: open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer-protocol for a phase III randomised multicentre trial

Kenneth Elder
, Charlotte Coles
, David Dodwell
, Beatrix Elsberger
, Jessica Foster
, Claire Gaunt
, Julia R Henderson
, Iain Lyburn
, Claire Mabena
, Jenna Morgan
, Zohal Nabi
, Sangeetha Paramasivan
, Sarah Pinder
, Sarah Pirrie
, Shelley Potter
, Tracy Roberts
, Nisha Sharma
, Elizabeth Southgate
, Hilary Stobart
, Amruta Talwalkar

Sian Taylor-Phillips, William Teh, Elliot Turner, Daniel Rea, Matthew G Wallis, Stuart McIntosh^*

^*Corresponding author for this work

Cancer Research UK Clinical Trials Unit

Research output: Contribution to journal › Article › peer-review

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Abstract

INTRODUCTION: Mammographic screening identifies many women with small breast cancers with favourable biological features, which have an excellent prognosis. Some of these may never have become clinically apparent without screening and are commonly described as 'overdiagnosed' cancers. Despite this, all patients with screen-detected cancers are currently treated with surgical excision and sentinel lymph node biopsy, although this may represent overtreatment. There is, therefore, a need for less invasive approaches to reduce treatment burden for patients while maintaining current excellent oncological outcomes. Vacuum-assisted excision (VAE) may represent such an alternative treatment approach, and the SMALL ( Open Surgery versus Minimally invasive-vacuum Assisted excision for smaLL screen-detected breast cancer) trial aims to investigate the use of VAE for the safe de-escalation of surgical treatment for such excellent prognosis invasive breast cancers.

METHODS: SMALL is a prospective, multicentre, randomised phase III trial of VAE versus surgery in patients with small, biologically favourable screen-detected invasive breast cancer. SMALL has an innovative hybrid design with coprimary endpoints. These include a randomised non-inferiority comparison of surgical re-excision rates following initial treatment, and a single-arm analysis of local recurrence at 5 years following VAE. Secondary outcomes include complication rates, overall survival, quality of life and a health economic analysis. The trial includes a QuinteT Recruitment Intervention to support recruitment.

ETHICS AND DISSEMINATION: Ethical approval was obtained from the Office for Research Ethics (Northern Ireland) for all UK sites. Results will be submitted for publication in a peer-reviewed journal, presented, shared with patient partners and with relevant professional organisations to inform future guideline development for the management of screen-detected breast cancer.

TRIAL REGISTRATION NUMBER: ISRCTN12240119.

Original language	English
Article number	e099702
Number of pages	7
Journal	BMJ Open
Volume	15
Issue number	4
DOIs	https://doi.org/10.1136/bmjopen-2025-099702
Publication status	Published - 8 Apr 2025

Bibliographical note

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Humans
Breast Neoplasms/surgery
Female
Vacuum
Minimally Invasive Surgical Procedures/methods
Prospective Studies
Early Detection of Cancer
Randomized Controlled Trials as Topic
Multicenter Studies as Topic
Mammography
Clinical Trials, Phase III as Topic
Neoplasm Recurrence, Local

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10.1136/bmjopen-2025-099702Licence: Creative Commons: Attribution (CC BY)

ElderK2025SMALLFinal published version, 585 KBLicence: Creative Commons: Attribution (CC BY)

SMALL:A phase III, randomised, multi-centre trial addressing overtreatment of small, screen-detected breast cancer by comparing standard surgery with minimally invasive vacuum-assisted excision
Gaunt, C. (Co-Investigator), Pirrie, S. (Co-Investigator), Rea, D. (Principal Investigator) & Roberts, T. (Co-Investigator)
NIHR EVALUATION, TRIALS AND STUDIES COORDINATING CENTRE
1/10/18 → 30/06/29
Project: Other Government Departments

Cite this

Elder, K., Coles, C., Dodwell, D., Elsberger, B., Foster, J., Gaunt, C., Henderson, J. R., Lyburn, I., Mabena, C., Morgan, J., Nabi, Z., Paramasivan, S., Pinder, S., Pirrie, S., Potter, S., Roberts, T., Sharma, N., Southgate, E., Stobart, H., ... McIntosh, S. (2025). SMALL: open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer-protocol for a phase III randomised multicentre trial. BMJ Open, 15(4), Article e099702. https://doi.org/10.1136/bmjopen-2025-099702

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title = "SMALL: open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer-protocol for a phase III randomised multicentre trial",

abstract = "INTRODUCTION: Mammographic screening identifies many women with small breast cancers with favourable biological features, which have an excellent prognosis. Some of these may never have become clinically apparent without screening and are commonly described as 'overdiagnosed' cancers. Despite this, all patients with screen-detected cancers are currently treated with surgical excision and sentinel lymph node biopsy, although this may represent overtreatment. There is, therefore, a need for less invasive approaches to reduce treatment burden for patients while maintaining current excellent oncological outcomes. Vacuum-assisted excision (VAE) may represent such an alternative treatment approach, and the SMALL ( Open Surgery versus Minimally invasive-vacuum Assisted excision for smaLL screen-detected breast cancer) trial aims to investigate the use of VAE for the safe de-escalation of surgical treatment for such excellent prognosis invasive breast cancers. METHODS: SMALL is a prospective, multicentre, randomised phase III trial of VAE versus surgery in patients with small, biologically favourable screen-detected invasive breast cancer. SMALL has an innovative hybrid design with coprimary endpoints. These include a randomised non-inferiority comparison of surgical re-excision rates following initial treatment, and a single-arm analysis of local recurrence at 5 years following VAE. Secondary outcomes include complication rates, overall survival, quality of life and a health economic analysis. The trial includes a QuinteT Recruitment Intervention to support recruitment.ETHICS AND DISSEMINATION: Ethical approval was obtained from the Office for Research Ethics (Northern Ireland) for all UK sites. Results will be submitted for publication in a peer-reviewed journal, presented, shared with patient partners and with relevant professional organisations to inform future guideline development for the management of screen-detected breast cancer.TRIAL REGISTRATION NUMBER: ISRCTN12240119.",

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author = "Kenneth Elder and Charlotte Coles and David Dodwell and Beatrix Elsberger and Jessica Foster and Claire Gaunt and Henderson, \{Julia R\} and Iain Lyburn and Claire Mabena and Jenna Morgan and Zohal Nabi and Sangeetha Paramasivan and Sarah Pinder and Sarah Pirrie and Shelley Potter and Tracy Roberts and Nisha Sharma and Elizabeth Southgate and Hilary Stobart and Amruta Talwalkar and Sian Taylor-Phillips and William Teh and Elliot Turner and Daniel Rea and Wallis, \{Matthew G\} and Stuart McIntosh",

note = "{\textcopyright} Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.",

year = "2025",

month = apr,

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doi = "10.1136/bmjopen-2025-099702",

language = "English",

volume = "15",

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Elder, K, Coles, C, Dodwell, D, Elsberger, B, Foster, J, Gaunt, C, Henderson, JR, Lyburn, I, Mabena, C, Morgan, J, Nabi, Z, Paramasivan, S, Pinder, S, Pirrie, S, Potter, S, Roberts, T, Sharma, N, Southgate, E, Stobart, H, Talwalkar, A, Taylor-Phillips, S, Teh, W, Turner, E , Rea, D, Wallis, MG & McIntosh, S 2025, 'SMALL: open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer-protocol for a phase III randomised multicentre trial', BMJ Open, vol. 15, no. 4, e099702. https://doi.org/10.1136/bmjopen-2025-099702

TY - JOUR

T1 - SMALL

T2 - open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer-protocol for a phase III randomised multicentre trial

AU - Elder, Kenneth

AU - Coles, Charlotte

AU - Dodwell, David

AU - Elsberger, Beatrix

AU - Foster, Jessica

AU - Gaunt, Claire

AU - Henderson, Julia R

AU - Lyburn, Iain

AU - Mabena, Claire

AU - Morgan, Jenna

AU - Nabi, Zohal

AU - Paramasivan, Sangeetha

AU - Pinder, Sarah

AU - Pirrie, Sarah

AU - Potter, Shelley

AU - Roberts, Tracy

AU - Sharma, Nisha

AU - Southgate, Elizabeth

AU - Stobart, Hilary

AU - Talwalkar, Amruta

AU - Taylor-Phillips, Sian

AU - Teh, William

AU - Turner, Elliot

AU - Rea, Daniel

AU - Wallis, Matthew G

AU - McIntosh, Stuart

PY - 2025/4/8

Y1 - 2025/4/8

N2 - INTRODUCTION: Mammographic screening identifies many women with small breast cancers with favourable biological features, which have an excellent prognosis. Some of these may never have become clinically apparent without screening and are commonly described as 'overdiagnosed' cancers. Despite this, all patients with screen-detected cancers are currently treated with surgical excision and sentinel lymph node biopsy, although this may represent overtreatment. There is, therefore, a need for less invasive approaches to reduce treatment burden for patients while maintaining current excellent oncological outcomes. Vacuum-assisted excision (VAE) may represent such an alternative treatment approach, and the SMALL ( Open Surgery versus Minimally invasive-vacuum Assisted excision for smaLL screen-detected breast cancer) trial aims to investigate the use of VAE for the safe de-escalation of surgical treatment for such excellent prognosis invasive breast cancers. METHODS: SMALL is a prospective, multicentre, randomised phase III trial of VAE versus surgery in patients with small, biologically favourable screen-detected invasive breast cancer. SMALL has an innovative hybrid design with coprimary endpoints. These include a randomised non-inferiority comparison of surgical re-excision rates following initial treatment, and a single-arm analysis of local recurrence at 5 years following VAE. Secondary outcomes include complication rates, overall survival, quality of life and a health economic analysis. The trial includes a QuinteT Recruitment Intervention to support recruitment.ETHICS AND DISSEMINATION: Ethical approval was obtained from the Office for Research Ethics (Northern Ireland) for all UK sites. Results will be submitted for publication in a peer-reviewed journal, presented, shared with patient partners and with relevant professional organisations to inform future guideline development for the management of screen-detected breast cancer.TRIAL REGISTRATION NUMBER: ISRCTN12240119.

AB - INTRODUCTION: Mammographic screening identifies many women with small breast cancers with favourable biological features, which have an excellent prognosis. Some of these may never have become clinically apparent without screening and are commonly described as 'overdiagnosed' cancers. Despite this, all patients with screen-detected cancers are currently treated with surgical excision and sentinel lymph node biopsy, although this may represent overtreatment. There is, therefore, a need for less invasive approaches to reduce treatment burden for patients while maintaining current excellent oncological outcomes. Vacuum-assisted excision (VAE) may represent such an alternative treatment approach, and the SMALL ( Open Surgery versus Minimally invasive-vacuum Assisted excision for smaLL screen-detected breast cancer) trial aims to investigate the use of VAE for the safe de-escalation of surgical treatment for such excellent prognosis invasive breast cancers. METHODS: SMALL is a prospective, multicentre, randomised phase III trial of VAE versus surgery in patients with small, biologically favourable screen-detected invasive breast cancer. SMALL has an innovative hybrid design with coprimary endpoints. These include a randomised non-inferiority comparison of surgical re-excision rates following initial treatment, and a single-arm analysis of local recurrence at 5 years following VAE. Secondary outcomes include complication rates, overall survival, quality of life and a health economic analysis. The trial includes a QuinteT Recruitment Intervention to support recruitment.ETHICS AND DISSEMINATION: Ethical approval was obtained from the Office for Research Ethics (Northern Ireland) for all UK sites. Results will be submitted for publication in a peer-reviewed journal, presented, shared with patient partners and with relevant professional organisations to inform future guideline development for the management of screen-detected breast cancer.TRIAL REGISTRATION NUMBER: ISRCTN12240119.

KW - Humans

KW - Breast Neoplasms/surgery

KW - Female

KW - Vacuum

KW - Minimally Invasive Surgical Procedures/methods

KW - Prospective Studies

KW - Early Detection of Cancer

KW - Randomized Controlled Trials as Topic

KW - Multicenter Studies as Topic

KW - Mammography

KW - Clinical Trials, Phase III as Topic

KW - Neoplasm Recurrence, Local

U2 - 10.1136/bmjopen-2025-099702

DO - 10.1136/bmjopen-2025-099702

M3 - Article

C2 - 40204306

SN - 2044-6055

VL - 15

JO - BMJ Open

JF - BMJ Open

IS - 4

M1 - e099702

ER -

SMALL: open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancer-protocol for a phase III randomised multicentre trial

Abstract

Bibliographical note

UN SDGs

Keywords

Access to Document

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Projects

SMALL:A phase III, randomised, multi-centre trial addressing overtreatment of small, screen-detected breast cancer by comparing standard surgery with minimally invasive vacuum-assisted excision

Cite this