Doubling cascade testing uptake for hereditary cancer syndromes: Results from a cluster randomized controlled trial of a registry-aided outreach approach.

11007 Background: Cascade genetic testing for at-risk relatives (ARR) is the most critical strategy for cancer prevention in families with hereditary cancer syndromes. Affected ARR can benefit from increased awareness and frequent screening to ensure cancers are detected at an early, treatable stage. Locally, uptake is persistently low at 6-13%, reflecting a prominent clinical gap. The current standard of care, which relies on passive proband-dependent communication to disseminate genetic information to ARR, is highly inefficient. We hypothesized that a novel, structured, registry-aided outreach model would improve the uptake rate of cascade testing in Singapore, and thus conducted a trial to address the effectiveness of this approach. Methods: We conducted a cluster randomized controlled trial at the National Cancer Centre Singapore comparing two arms. (1) Control arm: Proband-dependent communication. (2) Experimental arm: Proband-dependent communication with systematic outreach to ARR, facilitated by a family registry and executed by trained genetics personnel. This solution shares the burden of disseminating genetic results, ensuring ARR receive accurate information from a healthcare professional. The primary endpoint was the proportion of at-risk first-degree relatives who completed cascade genetic testing. Results: A total of 150 probands from unique families and 386 ARR were recruited from February 2022 to March 2025 in National Cancer Centre Singapore. In the experimental arm, 78/196 relatives (39.8%) attended pre-test genetic counselling compared to 38/190 relatives (20.0%) in the control arm. In the experimental arm, 71/196 relatives (36.2%) proceeded with cascade testing after pre-test counselling, whilst 37/190 relatives (19.5%) in the control arm underwent cascade testing. In our study, with the addition of the novel registry-aided outreach approach, the percentage of relatives who attend the pre-test genetic counselling session doubled, whilst those who eventually had cascade testing increased by 86%, demonstrating its clear superiority over the passive proband-dependent approach. Conclusions: Our trial proves that a systematic, healthcare professional-driven, registry-aided outreach is an effective strategy to overcome the barriers in cascade testing. The registry-aided outreach approach is a feasible, successful and scalable solution to the low uptake of cascade testing in Singapore. Implementing this approach is essential for realizing the full potential of genetic medicine to prevent cancers in high-risk families with hereditary cancer syndromes.