James is a 69 year old man, fit and well with no symptoms. He comes to see you, worried. ‘I’d like a prostate check. I had one of those PSA tests last year, which did put my mind at rest at the time. But I’ve just seen on the news that those tests miss loads of cancers, and that an MRI scan is much better. Please can I have one?’
You understand his concern. Prostate cancer is a serious disease, the most common cancer, and the second most common cause of cancer death in males in the UK Cancer Research UK. The lack of a national screening programme has been a longstanding source of controversy amongst clinicians and frustration for worried patients like James.
So, can we reassure James that his normal PSA was a good enough test? No, not completely as the UK National Screening Council found that PSA does not meet the requirements of a screening tool because it is too unreliable at detecting cancer that needs treatment. NHS patient information quotes both a significant false negative rate (misses cancer in 1/7) and a high false positive rate ( no cancer identified in ¾ of positive PSA tests)
Enter the ReIMAGINE study, published in BMJ Oncology in August 2023. This asks whether MRI could be used for age defined, rather than PSA defined, prostate cancer screening.
The idea for MRI as a screening test follows from its success as a diagnostic tool in men with a raised PSA. MRI is now used as an interim step between abnormal PSA or DRE and biopsy. It reduces the need for biopsies in those without cancer, reduces ‘overdiagnosis’ of clinically insignificant cancer and guides biopsy for those that need it.
So, MRI is very helpful for investigation of a raised PSA and diagnosis of clinically significant prostate cancer but how does MRI perform as a screening test? ReIMAGINE was a prospective cohort study based out of 8 GP practices in London. 2096 men aged 50-75yrs were randomly invited for a ‘prostate health check’, comprising of a screening MRI and PSA test. There was a 22% response rate (457 men), the low pick up rate partially due to pandemic restrictions. Men with a positive MRI or PSA density (³0.12ng/mL2) were referred in on standard NHS pathways to assess for cancer.
What were the results? A surprisingly high proportion of one in six men (16%) had a positive screening MRI (43/303). An additional one in twenty men had a positive PSA density alone. 29 men (9.6%) went on to be diagnosed with ‘clinically significant’ cancer, defined as any Gleason pattern 4 or above. The most striking finding was that more than half the men with ‘clinically significant’ disease had a normal PSA value (<3ng/mL) and would have been missed by PSA alone.
So, no surprise at all that in this study MRI plus PSA performs better than PSA alone for screening. But does that mean that MRI should be used for a screening programme? Not necessarily and certainly not yet. Despite the positive media headlines, the authors themselves state that their findings show that MRI ‘may have value in screening independent of PSA’ but it will need further evaluation in a much larger UK population and for much longer to assess whether it could reduce prostate cancer mortality whilst reducing overdiagnosis and associated overtreatment. This is before you even look at the cost effectiveness, with the high costs needed for MRI scanning and associated staffing and infrastructure. Other research is exploring other ways of delivering MRI screening, including the LIMIT study which is looking at the feasibility of a 5 minute prostate MRI in a lorry in the community. This kind of novel intervention may have the potential to shift the goalposts, but it will be years before we have a definitive answer.
In the meantime, what about James and his worry that he may have prostate cancer despite the negative PSA test? We can acknowledge that the results of this study revealing cancers in men with normal PSA levels is potentially concerning, however, we can explain to him that this was a small feasibility screening study and that much more research is needed to evaluate these findings further and it is certainly not in national guidance to proceed to an MRI scan. James has no symptoms so we should continue to the PCRMP Guidance on testing for asymptomatic men, and for symptomatic men we should continue to follow NICE NG12 guidance based on age adjusted PSA levels and DRE findings with appropriate safety netting and follow up. We also need to remember the importance of family history and ethnicity –black men have a higher risk of prostate cancer but in the ReIMAGINE study they were much less likely to take up the invitation for screening.
In conclusion, despite the headlines, a screening MRI for prostate cancer (or a diagnostic one for a man with a normal PSA) is very unlikely to be an NHS option any time soon but it will be interesting to see how this story develops over the next few years.