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

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 center dot 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 center dot 0% (upper 95% CI 5 center dot 4%). In group 1, one local recurrence occurred at 4 center dot 5 years and a second at 7 center dot 5 years. In group 2, nine patients had mastectomy (2% of total cohort), and the 5 -year IIRR was 1 center dot 7% (upper 95% CI 6 center dot 1%). The only distant metastasis in the entire cohort was genetically distinct from the index cancer. The PROSPECT pathway increased QALYs by 0 center dot 019 (95% CI 0 center dot 008-0 center dot 029) and saved AU$1980 (95% CI 1396-2528) or 953 pound (672-1216) per patient. Interpretation: PROSPECT suggests that women with unifocal breast cancer on MRI and favourable pathology can safely omit radiotherapy.