Primary results of ANZ 1002: Post-operative radiotherapy omission in selected patients with early breast cancer trial (PROSPECT) following pre-operative breast MRI.

Abstract

572 Background: Selective use of radiotherapy (RT) after surgery for early breast cancer (EBC) has been an elusive goal. The role of breast MRI in localised EBC is controversial. We aimed to determine if preoperative MRI could identify patients with EBC in whom the ipsilateral invasive recurrence (IIR) rate was sufficiently low without RT, such that RT might be safely omitted. Here we report primary and secondary outcomes, and imaging/biopsy findings for occult lesions. Methods: PROSPECT is a prospective single-arm study. Criteria for omission of RT included age at least 50, nil/minimal or mild Background Parenchymal Enhancement (BPE) on MRI, unifocal pT1N0 cancer, not Triple Negative (TNBC), no LVI. All patients who underwent PROSPECT MRI were included in the analysis. Imaging findings on MMG, US and MRI were documented and all biopsies were recorded. Pathology of lesions identified by MRI was described. The primary outcome was the IIR at 5 years of those treated without RT. An IIR rate of 5% or less was considered acceptable. The protocol specified primary analysis occurred after the 100th patient reached 5 years follow up in May 2021. Results: Between 9/2011 and 5/2019, 443 patients had MRI after diagnosis. BPE was nil/minimal or mild in 344 patients. MRI detected 194 occult lesions in 144 (33%) patients; 139 (72%) were ipsilateral. 61 MMG/US occult malignant lesions - 36 invasive and 25 DCIS - were identified in 48 patients (11% of total cohort). Of 38 ipsilateral lesions in 32 patients (7% of total cohort), 23 were DCIS, 4 were T1a, 7 T1b and 4 T1c. 201 patients were treated on trial without RT. The median age was 63 years (range: 50 to 84), median tumour size 11 mm (range: 2 to 20), grade 1 (104), grade 2 (86) or grade 3 (11). The rate of IIR at 5 years was 1% (1/101). There were 2 IIRs at 4.6 and 7.7 years follow up, 1 regional recurrence, and 1 patient with both a regional and distant recurrence with 1 breast cancer death. There was 1 contralateral (CL) breast cancer, 1 CL DCIS, 2 other cancer diagnoses and 1 death from other causes. Of 242 patients undergoing MRI but not in the main study, median age was 63 range: 50-80, median tumour size, 13mm (range: 4-145). 9 underwent mastectomy (2% of total cohort). Followup is complete for 235. There was 3 IIR, 3 CL primary and no distant metastases or breast cancer deaths. Conclusions: Breast MRI in selected, low risk patients identified occult malignancy in 11% of patients. At a median of 5 years follow up the IIR and other breast cancer events was very low. This suggests that local recurrences may be due to occult breast cancers, and MRI may allow the identification of truly localised cancers for which radiation may be safely omitted. The event rate for the entire cohort was very low, suggesting that identification of occult malignancy in apparently unifocal EBC is beneficial. Confirmatory trials are needed. Clinical trial information: 12610000810011.

Contrast-enhanced mammography (CEM) versus MRI for breast cancer staging: detection of additional malignant lesions not seen on conventional imaging

“…While the effect of detection of the additional cancers on the surgical plan is not evaluated in this paper, the ability of preoperative imaging to differentiate unifocal from multifocal or multicentric breast cancer has important implications, for both patient treatment and prognosis [19,20]. Multicentric disease is often considered a contraindication to breast-conserving surgery; however, the ability of CEM or MRI to exclude multifocal/ multicentric disease is a further important question as it may allow some women to avoid the morbidity of whole breast radiotherapy [21]. malignant disease.…”

Is de-escalation of treatment by omission of radiotherapy associated with fear of cancer recurrence in women with early breast cancer? An exploratory study

“…Participants enrolled in PROSPECT (ANZ-1002) [ 11 ] were approached. Women assessed as eligible for de-escalation following local staging with MRI and surgery who omitted RT comprised Group A of our sample; women deemed ineligible for de-escalation post-MRI and surgery who underwent RT comprised Group B.…”

“…Of the 443 patients registered for PROSPECT, 201 were treated on study without RT. The primary outcome of PROSPECT was reported in 2022, showing a very low rate of recurrence [ 11 ].…”

Reply to G.B. Mann et al and S. Sorscher

“…Mann et al 2 highlight their PROSPECT trial, also published in December 2023, which evaluated whether magnetic resonance imaging (MRI) can improve selection of patients for radiotherapy omission by identifying mammographically occult synchronous malignant lesions that might lead to local recurrence. PROSPECT enrolled 443 women age 50 years and older with apparently unifocal stage I non–triple-negative breast cancer to preoperative MRI and biopsy of any additional suspicious lesions.…”