Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): primary results of a prospective two-arm study

Gregory Bruce Mann; Anita Rohini Skandarajah; Nicholas Zdenkowski; Janemary Hughes; Allan Park; Dennis Petrie; Karinna Saxby; Sean M Grimmond; Anand Murugasu; Andrew J Spillane; Boon H Chua; Heath Badger; Helen Braggett; Val Gebski; Arlene Mou; John P Collins; Allison K Rose

doi:10.1016/S0140-6736(23)02476-5

Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): primary results of a prospective two-arm study

Lancet. 2024 Jan 20;403(10423):261-270. doi: 10.1016/S0140-6736(23)02476-5. Epub 2023 Dec 5.

Authors

Gregory Bruce Mann¹, Anita Rohini Skandarajah², Nicholas Zdenkowski³, Janemary Hughes⁴, Allan Park⁴, Dennis Petrie⁵, Karinna Saxby⁶, Sean M Grimmond⁷, Anand Murugasu⁴, Andrew J Spillane⁸, Boon H Chua⁹, Heath Badger³, Helen Braggett³, Val Gebski¹⁰, Arlene Mou¹¹, John P Collins², Allison K Rose¹²

Affiliations

¹ The Royal Melbourne Hospital, Parkville, VIC, Australia; The Royal Women's Hospital, Parkville, VIC, Australia; Breast Cancer Trials, Newcastle, NSW, Australia; Department of Surgery, The University of Melbourne, Parkville, VIC, Australia. Electronic address: bruce.mann@mh.org.au.
² The Royal Melbourne Hospital, Parkville, VIC, Australia; Department of Surgery, The University of Melbourne, Parkville, VIC, Australia.
³ Breast Cancer Trials, Newcastle, NSW, Australia.
⁴ The Royal Melbourne Hospital, Parkville, VIC, Australia.
⁵ Centre for Health Economics, Monash University, Caulfield East, VIC, Australia.
⁶ Centre for Health Economics, Monash University, Caulfield East, VIC, Australia; Melbourne Institute of Applied Economic and Social Research, Parkville, VIC, Australia.
⁷ The University of Melbourne Centre for Cancer Research, Parkville, VIC, Australia.
⁸ University of Sydney, Wollstonecraft, NSW, Australia; Mater Hospital, Wollstonecraft, NSW, Australia.
⁹ UNSW Medicine & Health, The University of New South Wales, Sydney, NSW, Australia.
¹⁰ NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
¹¹ The Royal Melbourne Hospital, Parkville, VIC, Australia; Department of Radiology, The University of Melbourne, Parkville, VIC, Australia.
¹² The Royal Melbourne Hospital, Parkville, VIC, Australia; The Royal Women's Hospital, Parkville, VIC, Australia; Department of Radiology, The University of Melbourne, Parkville, VIC, Australia.

PMID: 38065194
DOI: 10.1016/S0140-6736(23)02476-5

Abstract

Background: Adjuvant breast radiotherapy as a standard component of breast-conserving treatment for early cancer can overtreat many women. Breast MRI is the most sensitive modality to assess local tumour burden. The aim of this study was to determine whether a combination of MRI and pathology findings can identify women with truly localised breast cancer who can safely avoid radiotherapy.

Methods: PROSPECT is a prospective, multicentre, two-arm, non-randomised trial of radiotherapy omission in patients selected using preoperative MRI and postoperative tumour pathology. It is being conducted at four academic hospitals in Australia. Women aged 50 years or older with cT1N0 non-triple-negative breast cancer were eligible. Those with apparently unifocal cancer had breast-conserving surgery (BCS) and, if pT1N0 or N1mi, had radiotherapy omitted (group 1). Standard treatment including excision of MRI-detected additional cancers was offered to the others (group 2). All were recommended systemic therapy. The primary outcome was ipsilateral invasive recurrence rate (IIRR) at 5 years in group 1. Primary analysis occurred after the 100th group 1 patient reached 5 years follow-up. Quality-adjusted life-years (QALYs) and cost-effectiveness of the PROSPECT pathway were analysed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000810011).

Findings: Between May 17, 2011, and May 6, 2019, 443 patients with breast cancer underwent MRI. Median age was 63·0 years. MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%). Of 201 group 1 patients who had BCS without radiotherapy, the IIRR at 5 years was 1·0% (upper 95% CI 5·4%). In group 1, one local recurrence occurred at 4·5 years and a second at 7·5 years. In group 2, nine patients had mastectomy (2% of total cohort), and the 5-year IIRR was 1·7% (upper 95% CI 6·1%). The only distant metastasis in the entire cohort was genetically distinct from the index cancer. The PROSPECT pathway increased QALYs by 0·019 (95% CI 0·008-0·029) and saved AU$1980 (95% CI 1396-2528) or £953 (672-1216) per patient.

Interpretation: PROSPECT suggests that women with unifocal breast cancer on MRI and favourable pathology can safely omit radiotherapy.

Funding: Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation.

Publication types

Clinical Trial
Multicenter Study

MeSH terms

Aged
Breast Neoplasms* / diagnostic imaging
Breast Neoplasms* / radiotherapy
Breast Neoplasms* / surgery
Female
Humans
Magnetic Resonance Imaging
Mastectomy
Mastectomy, Segmental / methods
Middle Aged
Neoplasm Recurrence, Local / pathology
Neoplasm Staging
Prospective Studies
Radiotherapy, Adjuvant
Victoria