# MRI for Prostate Cancer Screening: The ReIMAGINE Study Explained The ReIMAGINE study, published in BMJ Oncology, investigated whether MRI scans could serve as a primary screening tool for prostate cancer, working independently of—or alongside—the traditional PSA blood test. In a group of 303 men aged 50–75 who responded to a general practice (GP) invitation for a prostate health check, 1 in 6 men (16%) had a lesion visible on MRI, and 9.6% were ultimately diagnosed with clinically significant prostate cancer. Strikingly, more than half of the men with clinically significant cancer had PSA levels below the commonly used threshold of 3 ng/mL, meaning the PSA test alone would have missed them. These results suggest that an MRI-led approach to screening could detect more clinically significant cancers while potentially reducing the overdiagnosis and overtreatment associated with PSA-based screening. # MRI for Prostate Cancer Screening: The ReIMAGINE Study Explained ## Table of Contents - Key Points - Why This Research Matters - What We Already Knew: PSA Testing Has Limits - How the Study Was Designed - Who Took Part in the Study - The Screening Procedures: MRI and PSA - Key Finding: Who Responded to the Invitation? - Key Finding: What Did the MRI Scans Show? - Key Finding: PSA Density Results - Key Finding: Cancer Detection After NHS Assessment - Clinical Implications: What This Means for Patients - Study Limitations: What It Couldn't Prove - Future Research and Recommendations - Frequently Asked Questions - Source Information ## Key Points - In a study of 303 men aged 50–75, 1 in 6 had a lesion visible on MRI, and 9.6% were diagnosed with clinically significant prostate cancer. - More than half of men with clinically significant cancer had PSA below 3 ng/mL, so PSA testing alone would have missed them. - Only 1% of screened men were diagnosed with clinically insignificant cancer, compared with about half in PSA-based screening trials. - Response to the invitation was lower among black and Asian men, despite black men having a higher risk of prostate cancer. - The study was a single-centre feasibility study with no long-term follow-up, so it cannot prove that MRI screening reduces deaths. ## Why This Research Matters Prostate cancer is the most common cancer in men in the UK, and the second most common cause of cancer-related death. The UK currently has no formal national screening programme for prostate cancer, yet the country's age-standardised prostate cancer-specific mortality rate is 12.4 per 100,000 population. That is notably higher than other developed nations: the USA has a rate of 8.2 per 100,000, France 8.4, Spain 7.3, and Italy 5.9 per 100,000. The absence of a screening programme means many cancers are found late. However, past attempts at screening have been controversial, because they can cause more harm than good in some men. This study — called ReIMAGINE — was designed to test a new approach: using MRI scans as a primary screening tool, rather than relying on the PSA blood test first. ## What We Already Knew: PSA Testing Has Limits The European Randomised Screening for Prostate Cancer (ERSPC) study demonstrated that organised screening can reduce prostate cancer death rates. Men screened using a PSA threshold of >3 ng/mL, or an abnormal digital rectal examination (DRE), followed by a standard transrectal biopsy, had a 20% reduction in prostate cancer-specific mortality at 16 years of follow-up compared with unscreened men. But this benefit came at a significant price: overdiagnosis. When PSA is used as a triage test and transrectal biopsy as the verification step, roughly half of all detected cancers are low grade — meaning they are unlikely to ever cause symptoms or threaten a man's life. Even so, many men with these low-risk cancers accept radical treatment, exposing them to unnecessary side effects such as urinary incontinence and erectile dysfunction. A large UK Cluster Randomised Trial involving more than 400,000 men, which used a single PSA test, found similar prostate cancer-specific and overall mortality rates between screened men and controls when analysed at 10 years. It did, however, find an increased proportion of men diagnosed with low-risk prostate cancer in the screened group. This problem of overdiagnosis and the associated personal and economic costs of continued monitoring — or "overtreatment" — has been a significant barrier to introducing PSA-based screening programmes. The PROMIS study, conducted in a clinical population of men with raised PSA or abnormal DRE, found that standard transrectal biopsy missed over half of the significant cancers that were visible on MRI. It also showed that MRI lesions scoring 4 out of 5 had a greater than 50% likelihood of harbouring clinically significant cancer, and lesions scoring 5 out of 5 had a greater than 70% likelihood. MRI lesions are positively correlated with higher histological grade and prostate cancer volume. Given that PSA and traditional transrectal biopsy both have significant limitations, the researchers behind ReIMAGINE asked a fundamental question: **How would MRI perform on its own if used in an age-defined — not PSA-defined — population?** ## How the Study Was Designed The ReIMAGINE study was a prospective, single-centre feasibility study, designed to assess whether a screening approach using both PSA and MRI could work in a community setting. University College London (UCL) was the study sponsor (reference 122665). The study was funded by the Medical Research Council (MRC) (grant number MR/R014043/1) and Cancer Research UK (CRUK), and it was registered at ClinicalTrials.gov under the identifier NCT04063566. A key feature of the funding process was patient and public involvement (PPI). Patients were involved in the planning and design of the research from the outset. They were interviewed by the grant awarding committee alongside two senior researchers, co-developed the screening protocol, and suggested lowering the age of invitation from a proposed higher threshold down to 50, because of concerns about missed significant cancers in younger men. When the study was paused for COVID-19 in April 2020, the PPI group were instrumental in designing modifications to allow recruitment to continue safely, which ultimately led to recruitment finishing ahead of the original planned schedule. ## Who Took Part in the Study Potential participants were identified by searching existing patient databases at eight London GP surgeries. Men aged 50 to 75, who had no prior diagnosis of prostate cancer, were identified and randomly selected for invitation. A single letter explaining the study was sent to each man, inviting him to contact the study team to check eligibility. Eligible men who wanted to take part were offered a screening visit at University College London Hospital Trust. In total, 2,096 men were invited across the eight GP practices. Of those, **457 men (22%) contacted the study team in response to the invitation**. Ultimately, 309 men attended for screening. The number of men screened was limited by the availability of a fixed number of MRI slots, so not all eligible responders were able to participate. ## The Screening Procedures: MRI and PSA The screening visit included the formal consent process. Each man who consented had a PSA blood test and a screening MRI (sMRI). The PSA density — a measure that relates the PSA level to the volume of the prostate gland — was calculated using the prostate volume measured on the MRI. The MRI protocol was designed to be efficient and feasible for a screening setting. It was carried out on a 3 Tesla scanner, with a total scan time of under 20 minutes. The clinical sequences included T2-weighted axial turbo spin echo and diffusion-weighted imaging using a high b value of 2000 s/mm², with an acquisition time of under 10 minutes. Importantly, contrast enhancement was not used, and there were no apparent diffusion coefficient (ADC) sequences — simplifying the scan and making it quicker than a standard diagnostic MRI. Each MRI was scored as positive or negative independently by two radiologists, according to pre-defined criteria. If the two radiologists did not agree on the screening result, a third reviewer was brought in to settle the case. Men were deemed "screen positive" if they had either a positive sMRI or a PSA density above 0.12 ng/mL². This threshold is a recognised clinical marker of increased risk. Screen-negative men were informed of their result and exited the study. Screen-positive men were advised to have a referral for National Health Service (NHS) assessment through an urgent suspected cancer pathway. Biopsies were performed if indicated after multiparametric MRI within a standard NHS pathway, at one of two London hospitals. A transperineal approach was used, with targeted biopsy of the MRI lesion and systematic sampling of the peripheral zones of the prostate. **Clinically significant cancer was defined as any Gleason pattern 4 or above** — a standard definition used to distinguish aggressive cancers from indolent ones. ## Key Finding: Who Responded to the Invitation? Response to the invitation was strongly influenced by age and ethnicity. Multivariable logistic regression analysis showed that older white men were the most likely to respond. Men in the 65–70 age band had the highest acceptance rate, taking note that prostate cancer incidence rises with age. - Men aged 50–55: 19% accepted the invitation - Men aged 55–60: 19% accepted - Men aged 60–65: 25% accepted - Men aged 65–70: 32% accepted - Men aged over 70: 28% accepted The most striking disparity was by ethnicity. Black men had only **one-fifth of the response rate of white men** (odds ratio 0.21 in the univariable model, p<0.001; odds ratio 0.22 in the multivariable model, p<0.001). Asian men also had significantly lower response rates compared with white men (odds ratio 0.32, p<0.001). This matters clinically because black men in the UK are known to have a higher risk of developing and dying from prostate cancer. Deprivation, measured using the Index of Multiple Deprivation (IMD), did not differ between responders and non-responders. The ethnicity distribution of the invited men reflected the ethnicity distribution across London as a whole, meaning the lower response rate among black and Asian men was not simply because fewer men from these groups were invited. It is worth noting that not all men who responded could actually be scanned. MRI slots were limited by fixed funding, and men were allocated on a "first come, first served" basis. ## Key Finding: What Did the MRI Scans Show? Of the 303 men who completed both screening tests (the MRI and the PSA test), the mean age was 61.9 years (range 50–77, standard deviation 7.23 years). The median PSA was 1.2 ng/mL (interquartile range 0.7–2.2), and the median prostate volume was 29 mL. The median PSA density was 0.04 ng/mL² (interquartile range 0.03–0.06). The central finding of the study: **One in six men (48 of 303, 16%) had a positive screening MRI** — meaning a lesion was visible that warranted further investigation. Even more notable was the relationship between MRI findings and PSA levels. Of the 48 men with a positive MRI, **32 men (67%) had a PSA below 3 ng/mL** — a level that would typically be considered "normal" and would not trigger further investigation under traditional PSA-based screening protocols. These men would have been falsely reassured if they had been screened with PSA alone. It is also worth noting that none of the 13 black men in the study had a positive MRI, although the small numbers mean this result should be interpreted cautiously. Logistic regression adjusting for age, ethnicity, and deprivation showed that older age and Asian or other ethnicity were associated with a higher likelihood of a positive MRI. ## Key Finding: PSA Density Results PSA density is calculated by dividing the PSA level by the prostate volume. A higher PSA density suggests that the PSA is coming from cancer tissue rather than from benign prostate enlargement. In this study, a PSA density of >0.12 ng/mL² was considered a positive screening result, even if the MRI was negative. Of the 255 men with a negative MRI, **16 men (5%) had a raised PSA density** of >0.12 ng/mL² and were therefore also recommended for an NHS referral for further assessment. Three of these 16 men (19%) had a PSA below 3 ng/mL, again illustrating that relying on an absolute PSA threshold can miss some men at risk. PSA density was significantly higher in black and Asian men, and in men aged 65–70, compared with other groups. These differences reflect known variations in PSA levels and prostate size across different populations. ## Key Finding: Cancer Detection After NHS Assessment A total of 64 of the 303 screened men (21%) had either a positive screening MRI or a raised PSA density. These men were recommended for further assessment through the NHS cancer pathway, which was carried out according to local GP practice preference and outside of the study protocol. The results of that assessment were sobering and encouraging at the same time. **Among the 48 men with a positive screening MRI:** - 25 men (52%) were found to have clinically significant prostate cancer after biopsy - 2 men (4%) had clinically insignificant cancer - 21 men (44%) had no cancer detected on biopsy **Among the 16 men who had a negative MRI but a raised PSA density:** - 4 men (25%) were found to have clinically significant cancer - 1 man (6%) had clinically insignificant cancer In total, **29 of the 303 screened men (9.6%) were diagnosed with clinically significant prostate cancer**, and 3 men (1%) were diagnosed with clinically insignificant cancer. This means that fewer than 1% of all screened men were "overdiagnosed" with low-risk disease — a striking contrast to the overdiagnosis rates seen with traditional PSA-based screening, where half of detected cancers are low grade. Perhaps the most clinically important finding relates to PSA thresholds. Of the 25 men with a positive MRI and clinically significant cancer, **15 men (60%) had a PSA below 3 ng/mL**. More than half of the men with significant disease would have been missed by a PSA-based screening strategy that uses the conventional threshold of >3 ng/mL for biopsy referral. In a detailed analysis of the 17 men with a positive MRI and a PSA below 3 ng/mL, the biopsy results included: - 2 Gleason 3+3 cancers (low-risk) - 13 Gleason 3+4 cancers with a mean cancer core length (MCCL) of 7 mm - 1 Gleason 4+3 cancer with a 3 mm MCCL - 1 Gleason 4+5 cancer with a 9 mm MCCL The Gleason 4+5 cancer is particularly notable, as a Gleason pattern 5 represents a highly aggressive form of the disease that carries a substantial risk of progression and death if left untreated. ## Clinical Implications: What This Means for Patients These findings have significant implications for how prostate cancer screening might be conducted in the future. MRI as a triage test — used between a raised PSA or abnormal DRE and a biopsy — has been recommended in UK guidelines since 2018. It is now also recommended in the European Association of Urology guidelines and by the American Urology Association. But this study goes a step further, exploring whether MRI could be the primary screening test itself. The key takeaways for patients are clear: - **The PSA test is not enough on its own.** More than half of the men in this study with clinically significant cancer — and two-thirds of men with a positive MRI — had PSA below 3 ng/mL. If PSA had been used alone as a triage test, these cancers would not have been detected. - **MRI can detect significant cancers early.** One in six men had a lesion visible on MRI, and of those who went on to have a biopsy, more than half had clinically significant cancer. - **Overdiagnosis may be dramatically reduced.** Only 1% of screened men were diagnosed with clinically insignificant cancer, compared with roughly half of all cancers detected in PSA-based screening trials being low grade. - **An MRI result must be combined with clinical judgement.** The 4% of men with a negative MRI but raised PSA density still had a 25% chance of harbouring clinically significant cancer, so MRI alone was not perfect in this study. The researchers note that a widely used approach at the time of the study was to offer further assessment when PSA was >3 ng/mL. Given their findings, they reference the work of Eklund and colleagues, who used a PSA cut-off of 1.6 ng/mL for further assessment. The ReIMAGINE team suggests that the use of PSA and MRI as independent risk assessment tools deserves further exploration in a larger screening study. ## Study Limitations: What It Couldn't Prove It is important to understand this study's limitations before drawing broad conclusions. This was a feasibility study, carried out in a relatively small sample of men from a number of London GP practices that had been nominated as research-active. Because the scanning centre was based in London, it was not practical to send invitations more widely. The response rate of 22% is also a concern. A single paper invitation was sent, without the general advertising and awareness campaigns that formal UK screening programmes typically include. Moreover, the study was severely affected by the COVID-19 pandemic, which paused recruitment from April to August 2020. At that time, many people were avoiding healthcare settings entirely, and it is likely that the pandemic materially reduced the response rate. Several other limitations deserve attention: - **Selection bias:** Men who respond to a screening invitation may be healthier, more health-conscious, or have different risk profiles than non-responders. Notably, older white men were more likely to respond, and black men — who have a higher risk of prostate cancer — had only one-fifth the response rate of white men. - **Actual screening numbers were limited:** Not all men who responded could be scanned because funding limited the number of available MRI slots. This could introduce additional bias. - **Single-centre design:** The MRI scans were performed and read at a single London university hospital, and the study setting was hospital-based. A true screening programme would need to be delivered across multiple centres, in specialised screening facilities, with machines of consistent high quality. - **No long-term follow-up:** The study assessed only the outcome of the immediate NHS assessment. It did not determine whether detecting these cancers actually reduces prostate cancer mortality over time — the ultimate measure of any screening programme's value. - **Biopsy decisions were outside the study protocol:** Men who screened positive were assessed and biopsied through the standard NHS pathway, according to local GP practice preference. This introduces variability in how and whether biopsies were performed. It is also important to note that the study ended when screening test results were provided. Further assessment, including biopsy, was done via the usual NHS pathway — following the same pattern as UK screening programmes for breast, colorectal, and cervical cancer, but differing from some other prostate cancer screening studies that included biopsy within the study protocol. ## Future Research and Recommendations Despite these limitations, the ReIMAGINE study provides crucial normative data on the prevalence of MRI lesions in an age-defined, systematically recruited community population — data that have not been previously reported. This information will allow researchers to model the performance of an MRI-based screening strategy and design the next stage of research into MRI's role as a primary screening test. The researchers make several recommendations for future work: 1. **Evaluate MRI-led screening in a larger UK population.** The next step is to assess whether an MRI-led approach can maintain the 20% reduction in prostate cancer mortality seen with formal PSA-based screening, while reducing overdiagnosis and overtreatment. 1. **Explore community-based MRI delivery.** A screening programme would need to be delivered at specialised screening centres with consistent high-quality image acquisition and reporting. The use of mobile MRI scanners — similar to those used in some breast screening programmes — should be assessed. 1. **Address differential response rates.** The fact that older white men were most likely to respond, while black men were least likely to respond despite having the highest risk of prostate cancer, needs to be actively addressed. In an ideal screening programme, the likelihood of response should be proportionate to the risk of disease in that group. A recent model-based analysis of USA SEER data suggested that increasing the intensity of PSA screening in black men between the ages of 45 and 65 could help reduce disparities. 1. **Consider repeat screening intervals.** The high prevalence of lesions on first screen might be balanced by lower detection on re-screening. Repeated screening of the same men after an appropriate interval would help answer this question. The response rate of 22% was achieved during a global pandemic when people were actively discouraged from attending healthcare settings. A single paper invitation, without repeated reminders or public health campaigns, achieved a level of uptake that the researchers believe is likely to increase in non-pandemic times. For individual men, the message from this study is that PSA testing alone has significant blind spots. A man with a PSA below 3 ng/mL can still harbour an aggressive prostate cancer — and in this study, more than half of men with clinically significant disease fell into that category. While the ReIMAGINE findings do not yet support widespread MRI screening outside of research settings, they strengthen the case for discussing prostate cancer risk with a doctor, particularly for men in higher-risk groups such as black men and those with a family history of prostate cancer. The study's conclusion is clear: prostate MRI may have value in screening independently of PSA, and these data will inform larger prostate cancer screening studies designed to find the optimal balance between catching significant cancers early and avoiding the harms of overdiagnosis. ## Frequently Asked Questions ### What was the ReIMAGINE study? It was a prospective, single-centre feasibility study that tested whether MRI scans could be used as a primary screening tool for prostate cancer, either alone or alongside the PSA blood test. It involved 303 men aged 50–75 who responded to a GP invitation for a prostate health check. The study was funded by the Medical Research Council and Cancer Research UK. ### Who was eligible to take part in the ReIMAGINE study? Men aged 50 to 75 who had no prior diagnosis of prostate cancer were identified from eight London GP surgeries and randomly selected for invitation. A single letter invited them to contact the study team to check eligibility. In total, 2,096 men were invited, 457 responded, and 309 attended for screening. ### What did the screening involve? Each man who consented had a PSA blood test and a screening MRI. The MRI was done on a 3 Tesla scanner, took under 20 minutes, and did not use contrast dye. PSA density was calculated using prostate volume measured on the MRI. Men were considered screen positive if the MRI was positive or PSA density was above 0.12 ng/mL². ### Does the ReIMAGINE study prove MRI screening saves lives? No. The study assessed only the immediate NHS assessment after screening. It did not determine whether detecting these cancers reduces prostate cancer mortality over time. The researchers say the findings do not yet support widespread MRI screening outside of research settings, and larger studies are needed. ### If my PSA is below 3 ng/mL but I'm still worried about prostate cancer, when should I get a second opinion? A PSA below 3 ng/mL does not rule out significant disease. Among men with a positive screening MRI and clinically significant prostate cancer, 60% had a PSA under 3 ng/mL, and two-thirds of men with a positive MRI had PSA below that level. A second opinion is worth seeking when PSA alone has been used to reassure you, when MRI findings and PSA density give conflicting results, or when a raised PSA density above 0.12 ng/mL² has not led to further assessment. Diagnostic Detectives Network provides independent expert second opinions. ## Source Information **Original article title:** Prevalence of MRI lesions in men Reimagine study Emberton **Authors:** Caroline M Moore, Elena Frangou, Neil McCartan, Aida Santaolalla, Douglas Kopcke, Giorgio Brembilla, Joanna Hadley, Francesco Giganti, Teresa Marsden, Mieke Van Hemelrijck, Fiona Gong, Alex Freeman, Aiman Haider, Steve Tuck, Nora Pashayan, Thomas Callender, Saran Green, Louise C Brown, Shonit Punwani, Mark Emberton, on behalf of the ReIMAGINE Study group. **Journal:** BMJ Oncology, 2023; Volume 2, article e000057. Published online 21 August 2023. doi:10.1136/bmjonc-2023-000057 **Trial registration:** ClinicalTrials.gov identifier NCT04063566 **Funding:** Medical Research Council (grant number MR/R014043/1) and Cancer Research UK. *This patient-friendly article is based on peer-reviewed research. It is intended for informational purposes only and does not constitute medical advice. Men with questions about prostate cancer screening should consult their healthcare provider.* --- Publisher: Diagnostic Detectives Network (https://diagnosticdetectives.com) — independent multi-expert medical second opinions, worldwide, private-pay. Author byline: Anton Titov, MD, PhD. Contact: https://diagnosticdetectives.com/pages/contact Canonical page: https://diagnosticdetectives.com/products/mri-for-prostate-cancer-screening-the-reimagine-study-explained