The feasibility of risk-stratified screening as routine practice in the NHS Breast Screening Programme in England: the PROCAS2 research programme

Background Screening for breast cancer produces benefits through cancers being detected earlier, thereby reducing premature deaths and the need for more intensive treatment. As with all screening, it can also produce harms such as false-positive screening test results. One way to improve the ratio of benefits to harms is through risk stratification. The main potential benefits of risk-stratified screening are via identifying women who are currently unaware that they are at increased risk and who can be offered more frequent screening and medicines for breast cancer prevention. However, it is unclear if these benefits would materialise in routine practice, whether additional harms would materialise and whether risk stratification is cost-effective. Objectives Our aims were to develop a risk-stratification system, BC-Predict, and to evaluate its feasibility when delivered as part of the National Health Service Breast Screening Programme. Specific objectives were to: (1) automate BC-Predict informatics systems and integrate into National Health Service Breast Screening Programme; (2) optimise to be acceptable to women who were offered it and healthcare professionals delivering it; (3) assess feasibility of BC-Predict, including estimates of benefits and harms; (4) identify likely cost-effectiveness and (5) engage key stakeholders to consider how risk stratification should be taken forward. Design and methods The PROCAS2-Collator software was created to control the workflow of BC-Predict, and qualitative methods were used to develop patient-facing materials, care pathways and study procedures. The main feasibility study involved women being offered BC-Predict as part of routine National Health Service Breast Screening Programme, with a comparison group of standard National Health Service Breast Screening Programme. Setting and participants The BC-Predict was offered at seven screening sites (three screening centres), with the comparison standard National Health Service Breast Screening Programme organised by two sites (one screening centre), within North West England. Participants were all women offered the National Health Service Breast Screening Programme at participating sites, with nested qualitative work with healthcare providers from the same screening centres. Intervention The BC-Predict risk-stratification system, offered to women when invited to the National Health Service Breast Screening Programme, calculated the 10-year risk based on the Tyrer–Cuzick model and produced risk feedback letters after negative screening test results were received. Women at high risk (≥ 8% 10-year risk) or moderate risk (≥ 5% to < 8% 10-year risk) were thereby encouraged to make telephone appointments to discuss prevention and early detection options. Main outcome measures Uptake of BC-Predict and subsequent prevention and early detection offers. BC-Predict was costed using a National Health Service perspective, and a decision-analytic model-based cost-effectiveness analysis was technically verified with validation. Results The BC-Predict was offered to 19,464 women, where 14,661 women attended screening (60.7%). Only 2429 women (12.5%) who were eligible took up the offer of BC-Predict. Uptake was substantially higher when women were personally approached at the study site: 137/263 (52.1%). Attendance at the telephone risk appointments offered was also lower than expected: 80/197 (40.6%) of high-risk and 68/379 (17.9%) of moderate-risk women. Of those who took up risk appointments, 105/148 (71%) women received a prescription for preventive medication and 63/80 (79%) accepted additional mammography. The cost-effectiveness analysis indicated that risk-based screening using self-reported risk factors and mammographic density provided 0.004 incremental quality-adjusted life-years per woman screened at an additional cost of £42 when compared to the current NHSBSP using 3-yearly screening (incremental cost-effectiveness ratio of £10,500 per QALY). Comparing this ICER with a cost-effectiveness threshold of £20,000 per QALY, suggests that replacing the current NHSBSP with risk-based screening could be a good use of the NHS budget. A nested questionnaire study found no effects on general anxiety or cancer-related worry for women who were offered BC-Predict. Thematic analyses of qualitative interviews revealed women were positive about BC-Predict, with only transient increases in worry reported by high-risk women. Healthcare professionals who were involved with the implementation were generally enthusiastic about the risk-stratified screening. The agenda-setting meeting identified a consensual view that risk-stratified screening is likely to happen eventually and that there is a need to develop plans to prepare for it. Limitations The study was not randomised and was dramatically impacted by the COVID-19 pandemic, with uptake of the study and of risk appointments in those identified as moderate or high risk almost certainly affected. As such, generalisability of the results will need to be reassessed after the results from the My Personalised Breast Screening trial are available. Conclusions The present work suggests that risk-stratified screening for breast cancer is feasible, acceptable and likely to be a cost-effective use of the healthcare budget. Key stakeholders at all stages viewed risk-stratified screening as generally desirable and inevitable. Future work The My Personalised Breast Screening trial has recruited over 50,000 women to examine the effectiveness of risk-stratified screening at preventing later-stage (2+) breast cancers. It is timely to consider information technology and workforce needs now and how best to engage women, especially those who are currently underserved by the existing National Health Service Breast Screening Programme. Study registration This study is registered as clinicaltrials.gov NCT04359420. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme (NIHR award ref.: RP-PG-1214-20016) and is published in full in Programme Grants for Applied Research ; Vol. 13, No. 13. See the NIHR Funding and Awards website for further award information.