The BARCODE1 Pilot: a feasibility study of using germline single nucleotide polymorphisms to target prostate cancer screening
Authors: Benafif Sarah , Ni Raghallaigh Holly , McGrowder Eva , Saunders Edward J. , Brook Mark N. , Saya Sibel , Rageevakumar Reshma , Wakerell Sarah , James Denzil , Chamberlain Anthony , Taylor Natalie , Hogben Matthew , Benton Barbara , D’Mello Lucia , Myhill Kathryn , Mikropoulos Christos , Bowen‐Perkins Hywel , Rafi Imran , Ferris Michelle , Beattie Andre , Kuganolipava Shophia , Sevenoaks Tamsin , Bower Juliet , Kumar Pardeep , Hazell Steven , deSouza Nandita M. , Antoniou Antonis , Bancroft Elizabeth , Kote‐Jarai Zsofia , Eeles Rosalind 
Published: July 2021

Objectives

To assess the feasibility and uptake of a community‐based prostate cancer (PCa) screening programme selecting men according to their genetic risk of PCa. To assess the uptake of PCa screening investigations by men invited for screening. The uptake of the pilot study would guide the opening of the larger BARCODE1 study recruiting 5000 men.

Subjects and Methods

Healthy males aged 55–69 years were invited to participate via their general practitioners (GPs). Saliva samples were collected via mailed collection kits. After DNA extraction, genotyping was conducted using a study specific assay. Genetic risk was based on genotyping 130 germline PCa risk single nucleotide polymorphisms (SNPs). A polygenic risk score (PRS) was calculated for each participant using the sum of weighted alleles for 130 SNPs. Study participants with a PRS lying above the 90th centile value were invited for PCa screening by prostate magnetic resonance imaging (MRI) and biopsy.

Results

Invitation letters were sent to 1434 men. The overall study uptake was 26% (375/1436) and 87% of responders were eligible for study entry. DNA genotyping data were available for 297 men and 25 were invited for screening. After exclusions due to medical comorbidity/invitations declined, 18 of 25 men (72%) underwent MRI and biopsy of the prostate. There were seven diagnoses of PCa (38.9%). All cancers were low‐risk and were managed with active surveillance.

Conclusion

The BARCODE1 Pilot has shown this community study in the UK to be feasible, with an overall uptake of 26%. The main BARCODE1 study is now open and will recruit 5000 men. The results of BARCODE1 will be important in defining the role of genetic profiling in targeted PCa population screening.

Patient Summary

What is the paper about?

Very few prostate cancer screening programmes currently exist anywhere in the world. Our pilot study investigated if men in the UK would find it acceptable to have a genetic test based on a saliva sample to examine their risk of prostate cancer development. This test would guide whether men are offered prostate cancer screening tests.

What does it mean for patients?

We found that the study design was acceptable: 26% of men invited to take part agreed to have the test. The majority of men who were found to have an increased genetic risk of prostate cancer underwent further tests offered (prostate MRI scan and biopsy). We have now expanded the study to enrol 5000 men. The BARCODE1 study will be important in examining whether this approach could be used for large‐scale population prostate cancer screening.