MRI scans improve prostate cancer diagnosis traditionally using blood tests – leading to a major cut in deaths in men over 50

byJoaquim Cardoso

24 de agosto de 2023

14 minute read

the health strategist
multidisciplinary institute

Joaquim Cardoso MSc.

Chief Research and Strategy Officer (CRSO),
Chief Editor and Senior Advisor

August 24, 2023

What is the message?

A new REIMAGINE study reveals that incorporating MRI scans into prostate cancer screening significantly enhances detection accuracy compared to PSA tests alone.

These scans identified serious cancers that would have been missed by the traditional blood tests, even in cases with low PSA scores.

This advancement in screening methodology could potentially lead to a more effective approach for diagnosing prostate cancer and reducing both mortality rates and unnecessary treatments.

One page summary:

In the article published by The National Institute for Health and Care Research (NIHR), the results of the REIMAGINE study demonstrate the effectiveness of magnetic resonance imaging (MRI) scans in improving the accuracy of prostate cancer detection.

This research, financially supported by the Medical Research Council and Cancer Research UK, and backed by prominent institutions including University College London (UCL), University College London Hospitals (UCLH), and King’s College London, employed a combination of MRI scans and prostate-specific antigen (PSA) density to assess the need for additional diagnostic measures within the prevailing NHS procedures.

Key observations from the study encompass the following:

Out of the participants aged between 50 and 75, who underwent both MRI scans and PSA tests, 48 individuals (16%) received positive results from the screening MRI, which indicated the presence of prostate cancer.

Of significant note, half of these cases exhibited PSA scores categorized as ‘low.’ Traditionally, such PSA levels would not trigger supplementary investigations based on existing protocols.

The study’s impact on referral practices is evident, with a notable proportion of individuals with positive MRI outcomes demonstrating PSA levels below the established threshold for triggering referrals. This underscores the potential of MRI scans to identify cases of cancer that might otherwise go unnoticed solely on the basis of PSA tests.

A key implication of the findings is the potential for MRI scans to offer a more reliable means of detecting severe cancers at an early stage. This, in turn, holds the promise of reducing instances of overdiagnosis in situations involving low-risk conditions.

A pertinent issue raised by the study is the disparities observed in response rates to screening invitations among distinct racial groups.

In particular, black men exhibited considerably lower participation rates in comparison to their white counterparts. Addressing this discrepancy is recognized as an essential aspect of future research endeavors.

The upcoming LIMIT trial holds significance as it represents a move towards a broader national prostate cancer screening initiative. This endeavor involves a more extensive and diverse pool of participants and intends to increase the inclusion of black men.

Innovative strategies, such as employing mobile screening units to reach underserved communities, are being considered to enhance participation.

The successful outcome of the LIMIT trial would pave the way for larger-scale national trials before the potential integration of prostate cancer screening into mainstream medical practices.

Professor Mark Emberton, a senior author of the study, emphasized the long-term impact of these findings. He highlighted the potential to substantially reduce the UK’s prostate cancer mortality rate through the establishment of a comprehensive national screening program.

While acknowledging the work required to achieve this goal, the authors express optimism about realizing such a program within the forthcoming 5 to 10 years.

The comprehensive outcomes of the study, documented in BMJ Oncology, underscore its substantive contribution to refining the field of prostate cancer diagnosis and its potential to reshape clinical paradigms.

DEEP DIVE

Prevalence of MRI lesions in men responding to a GP-led invitation for a prostate health check: a prospective cohort study [excerpt]

BMJ Oncology

Caroline M Moore, Elena Frangou, Neil McCartan, Aida Santaolalla, Douglas Kopcke, Giorgio Brembilla, Joanna Hadley Francesco Giganti1, Teresa Marsden, Mieke Van Hemelrijck, Fiona Gong, Alex Freeman, Aiman Haider, Steve Tuck, Nora Pashayan, Thomas Callender, Saran Green, Louise C Brown, Shonit Punwani, and Mark Emberton, on behalf of the Re-Imagine Study group

August 21, 2023

Abstract

Objective

In men with a raised prostate-specific antigen (PSA), MRI increases the detection of clinically significant cancer and reduces overdiagnosis, with fewer biopsies. MRI as a screening tool has not been assessed independently of PSA in a formal screening study. We report a systematic community-based assessment of the prevalence of prostate MRI lesions in an age-selected population.

Methods and analysis

Men aged 50–75 were identified from participating general practice (GP) practices and randomly selected for invitation to a screening MRI and PSA. Men with a positive MRI or a raised PSA density (≥0.12 ng/mL²) were recommended for standard National Health Service (NHS) prostate cancer assessment.

Results

Eight GP practices sent invitations to 2096 men. 457 men (22%) responded and 303 completed both screening tests. Older white men were most likely to respond to the invitation, with black men having 20% of the acceptance rate of white men.

One in six men (48/303 men, 16%) had a positive screening MRI, and an additional 1 in 20 men (16/303, 5%) had a raised PSA density alone. After NHS assessment, 29 men (9.6%) were diagnosed with clinically significant cancer and 3 men (1%) with clinically insignificant cancer.

Two in three men with a positive MRI, and more than half of men with clinically significant disease had a PSA <3 ng/mL.

Conclusions

Prostate MRI may have value in screening independently of PSA. These data will allow modelling of the use of MRI as a primary screening tool to inform larger prostate cancer screening studies.

Introduction

Prostate cancer is the most common cancer, and the second most common cause of cancer-related death, in men in the UK.1 The UK, with no formal screening programme, has a high age-standardised prostate cancer-specific mortality, at 12.4/100 000 population, compared with the USA at 8.2, France 8.4, Spain 7.3 and Italy 5.9.2

The European Randomised Screening study for Prostate Cancer demonstrated that organised screening can reduce prostate cancer mortality, compared with controls, by 20% at 16-year follow-up.3 However, this comes at a significant cost of overdiagnosis. Screening using prostate-specific antigen (PSA) as triage and transrectal biopsy as verification resulted in half of all detected cancers being low grade and unlikely to result in a prostate cancer death but was still associated with acceptance of radical treatment. The Cluster Randomised Trial in over 400 000 men in the UK, using a single PSA test, reported similar prostate cancer-specific and all-cause mortality rates between screened men compared with controls when analysed at 10 years, but an increase in the proportion of men diagnosed with low-risk prostate cancer.4 Overdiagnosis, and the associated personal and economic costs of continued monitoring or ‘overtreatment’, has proved a significant barrier to the introduction of screening programmes based on PSA and standard transrectal biopsy.

A number of studies have shown that, in men with a raised PSA or abnormal digital rectal examination (DRE), an MRI scan between PSA and subsequent biopsy verification reduces unnecessary biopsy, and subsequent diagnosis of indolent disease; and by detecting more clinically significant disease than standard biopsy alone.5–7 Given the known inherent error associated with both PSA and traditional transrectal biopsy, the next question to ask was: ‘How would MRI perform on its own if used in an age defined—not PSA defined—population setting?’

In the PROMIS study, in a clinical population defined by raised PSA or abnormal DRE, it was found that over half of the significant cancers seen on MRI were missed on standard transrectal biopsy.8 MRI lesions scoring 4/5 had >50% likelihood of harbouring clinically significant cancer, and those scoring 5/5 had >70% likelihood of harbouring clinically significant cancer. MRI lesions are positively correlated with higher histological grade and prostate cancer volume.9 The study we report here allowed us to explore the prevalence of MRI lesions in men based on age, not PSA. This knowledge will permit us to both model the performance of an MRI-based screening strategy and design the next stage in exploring its role as a primary screening test.

Objective

To report the prevalence of a positive screening MRI in men who respond to a general practice (GP)-led invitation for prostate cancer screening, to inform future prostate cancer screening strategies.

Materials and methods

Study design

The ReIMAGINE prostate cancer screening study was a prospective single-centre feasibility study designed to assess the feasibility of a screening approach using PSA and MRI.10 University College London (UCL) is the study sponsor (122665). This study is supported by the Medical Research Council (MRC) (grant number MR/R014043/1) and Cancer Research UK (CRUK). The study is registered at ClinicalTrials.gov.

Setting

Participants were selected for invitation by participating GP practices, and the screening procedures (MRI and PSA) were carried out in a single London university hospital.

Participants

Potential participants were identified through screening of existing patient databases at eight London GP surgeries. Men aged 50–75, without a prior prostate cancer diagnosis, were identified and randomly selected for invitation.

Invitation

A letter explaining the study was sent, and men were invited to contact the study group to be assessed for eligibility. Eligible men who were keen to take part, having already received a patient information sheet, were offered a screening visit at University College London Hospital Trust.

Screening assessment

The screening visit included the consent process. Consented men had a PSA blood test, and a screening MRI (sMRI). PSA density was calculated using sMRI-measured prostate volume.

The sMRI consisted of clinical and research-specific T2 exploratory acquisitions, carried out in a 3 Tesla scanner, with a total scan time of <20 min. 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 under 10 min. Contrast enhancement was not used, and there were no apparent diffusion coefficient sequences.

The MRI was scored positive or negative by two radiologists independently, according to pre-defined criteria, with a third reviewer if the two radiologists were not in agreement on the screening result.

Men were deemed screen positive if they had a positive sMRI or a PSA density of >0.12 ng/mL².11 Screen negative men were informed of their result, and exited the study. Screen positive men were told of their screening result, and recommended to have a referral for National Health Service (NHS) assessment on an urgent suspected cancer pathway. Biopsies were carried out if indicated after multiparametric MRI within a standard NHS pathway. The biopsies were done according to local practice at one of two London hospitals. A transperineal approach was used, with targeting of the MRI lesion and systematic sampling of the peripheral zones. They were followed up for the outcome of this assessment. They exited the study at this point, but gave permission for data to be collected from their standard of care NHS assessment. Clinically significant cancer was defined as any Gleason pattern 4 or above.

Patient and public involvement (PPI)

Patients were involved in the planning and design of the research, and were interviewed with two senior researchers by the grant awarding committee, a key step in the process. Patients co-developed the screening protocol and suggested lowering the age of invitation to 50, due to concerns of 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 continued recruitment with COVID-19-safety measures, leading to recruitment ahead of the original planned schedule.

Statistical analysis

Data were accessed via the UCL Research Electronic Data Capture (REDCap) service. STATA V.16.1 was used throughout the analysis.

Age was reported within 5-year bands. Ethnicity was presented across broad categories. Summary statistics were used to describe data; mean (range, SD) or median (IQR) for continuous variables or n (%) for categorical variables. Proportions were reported alongside 95% CIs. Univariable and multivariable logistic regression was used to explore baseline characteristics in relation to acceptance rates and screening results. Results are presented as ORs with 95% CIs. ORs of higher than 1 indicate greater association between a baseline variable and the outcome; when the variable is categorical, the OR is interpreted with respect to the reference category which is stated in each case. Significance is assessed at the 5% level.

Partial postcodes and in particular postcode sectors were collected for all invited participants. GeoConvert12 was used to obtain full postcodes and subsequently Index of Multiple Deprivation (IMD) scores for each postcode. The IMD scores were then averaged and mapped back to the collected postcode sectors. Census data from 2011 were used.

Role of the funding source

The MRC and CRUK had no role in the study design, data collection, data analysis, data interpretation or writing of the report. CM and EF had full access to the data and CM had final responsibility for the decision to submit for publication.

Results

Response to the screening invitation

Two thousand and ninety-six men were invited across eight GP practices, and 457 men (22%) contacted the study team in response to the invitation. Of these, 309 men attended for screening (figure 1). 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.

Baseline characteristics are shown in table 1. The mean age of recruited participants was 61.9 (range 50–77) and median PSA was 1.2 ng/mL (IQR 0.7–2.2).

Characteristics of responders versus non-responders

Logistic regression results show that age and ethnicity are both associated with response to screening invitation, with older white men the most likely to respond. Multivariable logistic regression showed that black men had one-fifth the response rate of white men. IMD did not vary between responders and non-responders (table 2). The ethnicity distribution of invited men reflected the ethnicity distribution across London (table 3).

Results of screening tests

Prevalence of a positive MRI

Of 303 men who had an sMRI, 48 men (16%) had a lesion which was deemed screen positive (figure 1). Their median PSA was 1.2 ng/mL (IQR 0.7–2.2). Thirty-two of these 48 men (67%) had a PSA below 3 ng/mL (figure 2). None of the 13 black men in the study had a positive MRI (online supplemental table A1). Logistic regression by age, ethnicity and IMD showed that older age and Asian or other ethnicity were associated with a higher likelihood of a positive MRI (online supplemental table A2).

PSA density results

Of the 255 men with a negative MRI, 16 men (5%) had a PSA density of >0.12 ng/mL², and were also recommended to have an NHS referral for further assessment. Three of these 16 men (19%) had a PSA below 3 ng/mL. Logistic regression showed that PSA density was significantly higher in black and Asian men, and in men aged 65–70 (online supplemental table A3).

Referral for NHS assessment

Sixty-four of 303 men (21%) had either a positive screening MRI or a raised PSA density and were recommended for further assessment via the NHS. These referrals and assessments were done according to local GP practice preference and were outside of the study protocol. Men consented for these data to be collected.

Outcome of NHS assessment

Of the 48 men with a positive screening MRI, 25 (52%) had clinically significant cancer, and 2 men (4%) had clinically insignificant cancer. The full biopsy characteristics, MRI lesion volume and PSA of all men with detected cancers are shown in online supplemental table A4.

The biopsy characteristics of the cancers detected in 17 men with a positive screening MRI and a PSA <3 ng/mL included 2 Gleason 3+3 cancers, 13 Gleason 3+4 cancers, with a mean cancer core length (MCCL) of 7 mm, 1 Gleason 4+3 (3mm MCCL) and 1 Gleason 4+5 (9mm MCCL) (online supplemental table A4).

Of the 25 men with a positive MRI and clinically significant cancer, 15 had a PSA <3 ng/mL.

Of the additional 16 men who had a negative MRI but a raised PSA density, 4 men (25%) had clinically significant cancer and 1 man (6%) had a clinically insignificant cancer.

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.