The Screening Tomosynthesis Trial with Advanced Reader Methods (STREAM): design and rationale of a population-based breast cancer screening trial.

Objectives: It is uncertain what the effects of introducing digital breast tomosynthesis (DBT) in the Dutch breast cancer screening programme would be on detection, recall, and interval cancers (ICs), while reading times are expected to increase. Therefore, an investigation into the efficiency and cost-effectiveness of DBT screening while optimising reading is required.

Materials and methods: The Screening Tomosynthesis trial with advanced REAding Methods (STREAM) aims to include 17,275 women (age 50-72 years) eligible for breast cancer screening in the Netherlands for two biennial DBT screening rounds to determine the short-, medium-, and long-term effects and acceptability of DBT screening and identify an optimised strategy for reading DBT. The control group will consist of 86,400 women selected from the database of the Dutch breast cancer screening programme screened with digital mammography. The intervention group will undergo DBT examinations only. Four different reading strategies will be evaluated on a subset of first-round screening exams. These four strategies will also be evaluated combined with replacing one of the two readers with AI predictions. The Microsimulation Screening Analysis (MISCAN)-Breast model will be used to estimate the long-term outcomes of DBT screening assuming the best-performing reading method.

Results: The primary outcome measure is the IC and advanced cancer rate at the second round (combined endpoint) in the DBT group compared to the control group. Secondary outcome measures are participation, recall and detection rates, positive predictive value, acceptability, reading method with the best case-based area under the curve and reading time, predicted breast cancer mortality, number of cancers overdiagnosed, and cost-effectiveness.

Key points: Question The short-, medium-, and long-term effects of digital breast tomosynthesis (DBT) imaging in the Dutch breast cancer screening programme are unknown, but essential to decide about implementation. Findings This protocol paper describes the primary endpoint of the STREAM trial: the combined interval and advanced cancer detection rate at the second DBT round. Clinical relevance The STREAM trial is a prospective, non-randomised, population-based study in the Dutch breast cancer screening programme, that aims to evaluate the effects and acceptability of two rounds of DBT screening to determine if DBT can enhance the programme's outcomes.