Discussion
Summary of results
In response to a single paper invitation for screening, 457 of 2096 men (22%) responded. Older men were more likely to respond to the invitation, and multivariable logistic regression showed that black men had one-fifth the response to invitation compared with white men. Not all men who responded to the invitation were able to take part, as funding limited the number of available MRI slots, and men were allocated on a ‘first come, first served’ basis.
Of 303 men who had both screening tests, 64 (21%) screened positive and were recommended for referral for further NHS assessment, outside of the study. One in 6 men (48 of 303, 16%) had a screen positive MRI, and an additional 1 in 20 men (16 of 303, 5%) tested positive on PSA density alone. Two-thirds (32/48) of men with a screen positive MRI had a PSA below 3 ng/mL, and over half of men (15/25) with a positive MRI and clinically significant cancer had a PSA below 3 ng/mL.
After NHS assessment outside of the study, 29 of 303 screened men (9.6%) had clinically significant disease and 3 of 303 men (1%) had clinically insignificant disease.
Limitations of the study
This feasibility study was carried out in a small sample of men across a number of different London GP practices, nominated as research active practices by Noclor, a research support service for primary care. As the scanning centre was based in London, it was not practical for invitations to be sent more widely. A single paper invitation was sent. Formal UK screening programmes would also include more general measures such as advertising campaigns which are likely to increase recruitment. The ethnicity distribution of invited men was reflective of the ethnicity distribution of London as a whole (table 3).
The study started prior to the COVID-19 pandemic, paused recruitment from April to August 2020, and then restarted. At the time, many people were avoiding visits to healthcare facilities, and our PPI panel developed a number of strategies to address the COVID-19 concerns of potential participants.13 These strategies included a dedicated cleaning schedule between patients, ensuring that the participant did not come into contact with other participants, or hospital patients during their visit, and that private transport by car was funded for participants. Even so, the response to the invitation is likely to have been impacted by the pandemic.
Study participation was completed when the results of the screening tests were given, with further assessment, including biopsy if needed, done via the usual NHS pathway. This follows the pattern of formal screening programmes in breast, colorectal and cervical cancer in the UK, although differs from other prostate cancer screening studies which included biopsy within the study protocol.
Clinical implications
MRI as a triage test between a raised PSA or an abnormal DRE, and a biopsy, has been recommended in UK guidelines since 2018.14 15 It is now also recommended in the European Association of Urology guidelines,16 and by the American Urology Association17
In clinical practice, we recognise that the PSA test has limitations in the identification of men at risk for prostate cancer. MRI may allow us an alternative way to assess prostate cancer risk in men in the community. Normative data on the prevalence of MRI lesions in an age-defined systematically recruited community-based population has not been previously reported. The PROSTAGRAM study used MRI, ultrasound and PSA to assess men, but had a mixed approach to recruitment using both invitation via GP practices and some approaches directly to the black community in London.18 Nam and colleagues in Toronto recruited men to an MRI-based screening assessment using a newspaper advert, and responders may not be representative of the population who would be invited for screening using formal healthcare-based mechanisms.19
The finding in this report is that 2 in 3 men with a positive screening MRI have a PSA <3 ng/mL is a sobering one because MRI lesions are positively associated with clinically significant cancer.
Using MRI to detect cancers can allow pick up of significant lesions before the PSA has begun to rise, and so offer an opportunity for early detection. It could lead to ‘overdetection’ of cancers that will not become clinically relevant in a patient’s lifetime. Subsequent screening of the same men after an appropriate time interval would enable us to see whether this high prevalence on first screen is balanced by lower detection on re-screening.
In traditional PSA triage-based screening, these men would have tested negative and have been reassured. This observation might explain why a single PSA-based screening confers so little impact on prostate cancer-specific and all-cause mortality. The more recent work of Eklund and colleagues used a PSA cut-off of 1.6 ng/mL for further assessment, and this may be a more appropriate approach,7 although the use of PSA and MRI as independent risk assessment tools should be explored further in a larger screening study.
Future research
This study has been carried out in a hospital-based setting, at a single university hospital. A screening programme would need to be delivered at specialised screening centres, where consistent high quality acquisition and reporting would need to be achieved.20 Future research would need to assess the feasibility of a community-based MRI delivery programme, with use of a mobile MRI scanner, such as those used in some breast screening programmes.
A response rate of 22% for a single paper-based invitation, during a global pandemic when people were discouraged from attending healthcare settings, is likely to increase in non-pandemic times. The differential response rate, based on age and ethnicity, needs to be addressed. In terms of age, those most likely to respond were those in the 65–70 age band, which has a higher prostate cancer incidence than younger men. In terms of ethnicity, black men were the least likely to respond to an invitation, but have a higher risk of prostate cancer than white men.
In an ideal situation, the likelihood of response to a screening invitation would be proportionate to the risk of disease in that group. A recent model-based analysis, based on USA SEER data, suggested that increasing the intensity of PSA screening in black men between the ages of 45 and 70 would lead to a greater mortality reduction, and limited overdiagnosis, compared with historical general population screening.21 In order to design a screening study which targets men at highest risk of prostate cancer, a variety of approaches may be needed. A recent initiative by Orchid, a UK-based men’s health charity explored ways to engage black and Afro-Caribbean men either diagnosed or at risk of prostate cancer.22 Successful approaches including raising awareness among men and women in the community through roadshows and dedicated materials including a short film, and z-cards with relevant information. It also included increasing awareness among healthcare professionals about the increased risk of prostate cancer in black men.
Further screening studies would need to incorporate other prostate cancer risk assessment approaches including non-imaging biomarkers, to assess the most efficient screening approach in the UK population. Given the incomplete overlap of the risk profiles generated by PSA and MRI, we would encourage each to be used in further research, to assess whether a stepwise approach can be adopted.