PROCEM; A prospective randomized trial on the added value of preoperative contrast-enhanced mammography in staging of malignant breast lesions

Abstract Introduction Contrast enhanced mammography (CEM) is an alternative to MRI in preoperative staging of breast cancer above digital mammography/tomosynthesis (DM/DBT) and ultrasound (US). This is the first prospective randomized trial assessing the additional value of CEM preoperatively. Method In total 440 breast cancer patients, eligible for primary surgery, were randomized 1:1 to preoperative CEM or not (control) at two sites. Primary endpoint was treatment change. Secondary endpoints included reoperation, mastectomy rates and extent estimation with DM/DBT, US and CEM compared to postoperative histologic extent as reference. Subgroup analyses were made according to menopausal status, breast density and type of cancer. Result 202 (CEM) and 213 (control) participants fulfilled the trial. For 17 participants (8.4%) treatment changed. Eleven patients received more extensive surgery, five had findings of contralateral cancer and one had neoadjuvant treatment instead. Menopausal status, breast density and type of cancer were the same in change/no change groups. Mastectomy rate (p = 0.777) and reoperation rate were identical (p = 0.387) between CEM/control. Surgery type and reoperation rate differed between study sites, despite similar cohort characteristics. Extent estimation was superior with CEM compared to DM/DBT and US, (using Bland-Altman and concordance analyses), overall and for both ductal and lobular cancers, pre- and postmenopausal women and low density breasts. Discussion This prospective randomized trial did not meet its primary endpoint but suggests that all breast cancer patients might benefit from preoperative CEM for improved extent estimation. Confidence in the method is essential to translate CEM findings into clinically relevant treatment changes.