Effectiveness of hybrid digital breast tomosynthesis/digital mammography compared to digital mammography in women presenting for routine screening at Maroondah BreastScreen: Study protocol for a co-designed, non-randomised prospective trial

Background: Digital breast tomosynthesis (DBT) for breast cancer screening has been shown in international trials to increase cancer detection compared with mammography; however, results have varied across screening settings, and currently there is limited and conflicting evidence on interval cancer rates (a surrogate for screening effectiveness). Australian pilot data also indicated substantially longer screen-reading time for DBT posing a barrier for adoption. There is a critical need for evidence on DBT to inform its role in Australia, including evaluation of potentially more feasible models of implementation, and quantification of screening outcomes by breast density which has global relevance. Methods: This study is a prospective trial embedded in population-based Australian screening services (Maroondah BreastScreen, Eastern Health, Victoria) comparing hybrid screening comprising DBT (mediolateral oblique view) and digital mammography (cranio-caudal view) with standard mammography screening in a concurrent group attending another screening site. All eligible women aged >= 40 years attending the Maroondah service for routine screening will be enrolled (unless they do not provide verbal consent and opt-out of hybrid screening; are unable to provide consent; or where a 'pushback' image on hybrid DBT cannot be obtained). Each arm will enrol 20,000 women. The primary outcomes are cancer detection rate (per 1000 screens) and recall rate (percentage). Secondary outcomes include 'opt-out' rate; cohort characteristics; cancer characteristics; assessment outcomes; screen-reading time; and interval cancer rate at 24-month follow-up. Automated volumetric breast density will be measured to allow stratification of outcomes by mammographic density. Stratification by age and screening round will also be undertaken. An interim analysis will be undertaken after the first 5000 screens in the intervention group. Discussion: This is the first Australian prospective trial comparing hybrid DBT/mammography with standard mammography screening that is powered to show differences in cancer detection. Findings will inform future implementation of DBT in screening programs world-wide and provide evidence on whether DBT should be adopted in the broader BreastScreen program in Australia or in subgroups of screening participants. Trial registration: The trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR, ACTRN12623001144606, https://www.anzctr.org.au/). Registration will be updated to reflect trial progress and protocol amendments.