Added Value of Preoperative Contrast Enhanced Mammography in Staging of Malignant Breast Lesions (PROCEM): A Randomized Controlled Trial.

Background Contrast-enhanced mammography (CEM) is increasingly used in breast cancer diagnostics; however, randomized trials assessing the added value of CEM in preoperative staging of breast cancer beyond digital mammography, digital breast tomosynthesis, and US are lacking. Purpose To assess the added value of CEM for preoperative breast cancer staging in a randomized controlled trial. Materials and Methods This prospective randomized controlled trial (Added Value of Preoperative Contrast Enhanced Mammography in Staging of Malignant Breast Lesions) enrolled women diagnosed with early-stage breast cancer eligible for primary surgery at two breast centers in Sweden. Participants were randomized 1:1 to preoperative CEM or control from November 2020 through April 2024. The primary outcome was a 10% change in treatment due to preoperative CEM findings. Secondary outcomes included differences in reoperation and mastectomy rates between groups and accuracy of malignant extent estimation with CEM, mammography/tomosynthesis, and US using histopathologic extent as the reference, assessed with Bland-Altman statistics and concordance analysis. Subgroup analyses were performed according to menopausal status, breast density, histopathologic type of cancer, lesion size, and presence of microcalcifications at baseline imaging. Results In total, 415 participants (median age, 66 years; IQR, 56-73 years) completed the trial: 202 in the CEM group and 213 in the control group. Treatment was changed in 17 of 202 participants (8.4%; 95% CI: 5.3, 13.1) based on CEM findings. No evidence of differences was observed between the CEM and control groups with regard to mastectomy (17% [35 of 202] vs 18% [39 of 213]; P = .78) or reoperation (7.9% [16 of 202] vs 10% [22 of 213]; P = .39) rates. CEM showed the closest agreement with histopathologic malignant extent (bias, 3.5 mm), outperforming mammography and/or tomosynthesis (4.8 mm) and US (10.7 mm) overall and in nine of 10 predefined subgroups, except for ductal carcinoma in situ. Conclusion This trial did not meet its primary end point of a 10% treatment change; however, preoperative CEM improved malignant extent estimation. ClinicalTrials.gov: NCT04437602 © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Mesurolle and El Khoury in this issue.