NIHR Signal MRI scan before biopsy could detect more prostate cancer

Published on 7 March 2017

In men with a raised prostate specific antigen (PSA) blood test, which can be a sign of prostate cancer, MRI scanning before standard biopsy could allow more targeted biopsies and increase diagnosis of medium and high-risk prostate cancer.

In this NIHR-funded study, 576 men with suspected prostate cancer received a multi-parametric (MP)-MRI scan in addition to transrectal ultrasound-guided (TRUS) biopsy. They also had template mapping (TPM) biopsy of the entire prostate to reliably diagnose cancer.

Neither MP-MRI scan nor TRUS-biopsy were entirely accurate. However, if MP-MRI is used as an initial test, followed by TRUS-biopsy targeted at areas identified on the scan, 18% more cancers could be detected than by TRUS biopsy alone. It may also help avoid unnecessary TRUS-biopsy (and its associated complications) in 27% of men without prostate cancer or with low risk cancer that is unlikely to grow or spread.

Some hospitals already carry out MP-MRI as a triage test to guide further biopsy. If cost-effective, routine MP-MRI scan before biopsy could improve prostate cancer diagnosis across the UK.

Why was this study needed?

Prostate cancer is the most common cancer in men and will affect one in eight UK men at some point in their lives. There were 11,287 prostate cancer deaths in 2014.

Men presenting with possible prostate symptoms often have a digital rectal examination and PSA blood test. If doctor and patient decide that further tests are needed, the usual option is TRUS-biopsy. However, TRUS-biopsy can be unreliable, missing half of the medium and high risk cancers while identifying low-risk cancers that may not have caused problems. It can also carry risks such as infection.

One option is to perform a MP-MRI scan before the biopsy. This combines information on prostate volume and structure to identify fast growing cancers while overlooking lower risk disease. This study aimed to see if MP-MRI is reliable enough to be used as a triage step to help doctors decide if further biopsy is needed.

What did this study do?

The Prostate MRI Imaging Study (PROMIS) was a multicentre UK cohort including 576 men with clinical suspicion of prostate cancer.

All men underwent both a MP-MRI scan and standard TRUS-biopsy in addition to TPM-biopsy. TPM-biopsy samples tissue across the entire prostate and is able to reliably diagnose prostate cancer and was therefore the “gold standard” against which both MP-MRI and TRUS-biopsy could be compared for accuracy.

TPM-biopsy was performed before TRUS-biopsy; therefore the swelling and tissue disruption caused by the first test may have affected the accuracy of the subsequent TRUS-biopsy. A further limitation is that the researchers could not investigate whether using the MRI results improved TRUS-biopsy accuracy.

What did it find?

  • Forty per cent of men (230 of 576) were found to have clinically significant prostate cancer on TPM-biopsy. This was defined as a Gleason score of 4 + 3 or more, or a maximum cancer core length involvement of 6mm or more in any location. This indicates prostate cancer of medium to high risk of progression.
  • MP-MRI scan had higher accuracy at detecting clinically significant cancer among those who had it when compared with TPM-biopsy. MP-MRI scan would correctly identify 93% of cases, known as the sensitivity (95% confidence interval [CI] 88 to 96%) compared to 48% for TRUS-biopsy (95% CI 42 to 55%). Therefore TRUS-biopsy would miss more cases.
  • TRUS-biopsy was better at correctly excluding clinically significant cancer in men who did not have cancer or had low risk cancer. This is indicated by higher specificity of 96%, (95% CI 94 to 98%) than 41% for MP-MRI (95% CI 36 to 46%). Thus MP-MRI would give more “false positive” results.
  • The positive predictive value of MP-MRI of 51%, (95% CI 46 to 56%) was lower than 90% for TRUS-biopsy (95% CI 83 to 94%). This means that only half of men with a positive MP-MRI scan actually had clinically significant prostate cancer, whereas most men with positive TRUS-biopsy had clinically significant disease.
  • The negative predictive value however, was higher for MP-MRI scan at 89%, (95% CI 83 to 94%) compared to 74% for TRUS-biopsy (95% CI 69 to 78%). This means that 26% of men with negative TRUS-biopsy had in fact got clinically significant cancer, whereas MP-MRI was falsely negative in only 11% of cases.
  • A scenario using MP-MRI as a triage assessment, where only men with a suspicious MP-MRI go on to have a biopsy, would avoid 27% of men having biopsy and reduce the number of low-risk cancer diagnoses by 5%. If MP-MRI was followed by biopsy targeted to the suspect lesions, they estimated that this could help diagnose 18% more cases of clinically significant cancer than the standard method of TRUS-biopsy alone assuming this technique would be 100% accurate. Relying on an MP-MRI scan could miss 5% of cancers, though it is not clear if these would be picked up by a subsequent biopsy.

What does current guidance say on this issue?

The 2014 NICE Prostate Cancer guideline recommends that doctors discuss abnormal physical examination and blood PSA results with men, along with their medical history and risk factors, to help them decide whether to proceed to biopsy. This should include discussion of the risks and benefits of the procedure.

NICE recommend considering MP-MRI for men with a negative TRUS biopsy (10 to 12 core samples) in helping to determine if another biopsy is needed, but do not recommend MP-MRI before biopsy. However, some hospitals have already started performing an MP-MRI scan before deciding whether to do a biopsy. The NICE guideline is currently being updated and is due to be published in January 2019.

What are the implications?

The higher sensitivity of MP-MRI compared with TRUS-biopsy means that it would miss fewer cases of cancer. Therefore, MP-MRI as a triage test could help guide more targeted biopsies to increase the detection of high risk cancers.

Initial MP-MRI may also prevent unnecessary biopsies and reduce detection of prostate cancers that are at low risk of progression. However, this strategy may miss some cases.

NICE will need to evaluate the cost effectiveness of MP-MRI before it could be recommended as a routine triage step. The technology is already in place in some hospitals, but the costs of widespread introduction and staff training would need to be considered.

Citation and Funding

Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017;389(10071):815-22.

The PROMIS study was funded by the National Institute for Health Research- Health Technology Assessment Programme (HTA) (project number 09/22/67) and partly funded by UCLH/UCL Biomedical Research Centre and The Royal Marsden and Institute for Cancer Research Biomedical Research Centre.

Bibliography

Cancer Research UK. Prostate cancer mortality statistics. London: Cancer Research UK; 2014.

NICE. Guidance on prostate cancer: diagnosis and management. CG175. London: National Institution for Health and Care Excellence; 2014.

Prostate Cancer UK. About prostate cancer. London: Prostate Cancer UK; 2016.

Prostate Cancer UK. Frequently asked questions about prostate cancer. London: Prostate Cancer UK; 2016.

Prostate Cancer UK. Introduction to prostate tests. London: Prostate Cancer UK; 2016.

Prostate Cancer UK. Prostate biopsy. London: Prostate Cancer UK; 2016.

Why was this study needed?

Prostate cancer is the most common cancer in men and will affect one in eight UK men at some point in their lives. There were 11,287 prostate cancer deaths in 2014.

Men presenting with possible prostate symptoms often have a digital rectal examination and PSA blood test. If doctor and patient decide that further tests are needed, the usual option is TRUS-biopsy. However, TRUS-biopsy can be unreliable, missing half of the medium and high risk cancers while identifying low-risk cancers that may not have caused problems. It can also carry risks such as infection.

One option is to perform a MP-MRI scan before the biopsy. This combines information on prostate volume and structure to identify fast growing cancers while overlooking lower risk disease. This study aimed to see if MP-MRI is reliable enough to be used as a triage step to help doctors decide if further biopsy is needed.

What did this study do?

The Prostate MRI Imaging Study (PROMIS) was a multicentre UK cohort including 576 men with clinical suspicion of prostate cancer.

All men underwent both a MP-MRI scan and standard TRUS-biopsy in addition to TPM-biopsy. TPM-biopsy samples tissue across the entire prostate and is able to reliably diagnose prostate cancer and was therefore the “gold standard” against which both MP-MRI and TRUS-biopsy could be compared for accuracy.

TPM-biopsy was performed before TRUS-biopsy; therefore the swelling and tissue disruption caused by the first test may have affected the accuracy of the subsequent TRUS-biopsy. A further limitation is that the researchers could not investigate whether using the MRI results improved TRUS-biopsy accuracy.

What did it find?

  • Forty per cent of men (230 of 576) were found to have clinically significant prostate cancer on TPM-biopsy. This was defined as a Gleason score of 4 + 3 or more, or a maximum cancer core length involvement of 6mm or more in any location. This indicates prostate cancer of medium to high risk of progression.
  • MP-MRI scan had higher accuracy at detecting clinically significant cancer among those who had it when compared with TPM-biopsy. MP-MRI scan would correctly identify 93% of cases, known as the sensitivity (95% confidence interval [CI] 88 to 96%) compared to 48% for TRUS-biopsy (95% CI 42 to 55%). Therefore TRUS-biopsy would miss more cases.
  • TRUS-biopsy was better at correctly excluding clinically significant cancer in men who did not have cancer or had low risk cancer. This is indicated by higher specificity of 96%, (95% CI 94 to 98%) than 41% for MP-MRI (95% CI 36 to 46%). Thus MP-MRI would give more “false positive” results.
  • The positive predictive value of MP-MRI of 51%, (95% CI 46 to 56%) was lower than 90% for TRUS-biopsy (95% CI 83 to 94%). This means that only half of men with a positive MP-MRI scan actually had clinically significant prostate cancer, whereas most men with positive TRUS-biopsy had clinically significant disease.
  • The negative predictive value however, was higher for MP-MRI scan at 89%, (95% CI 83 to 94%) compared to 74% for TRUS-biopsy (95% CI 69 to 78%). This means that 26% of men with negative TRUS-biopsy had in fact got clinically significant cancer, whereas MP-MRI was falsely negative in only 11% of cases.
  • A scenario using MP-MRI as a triage assessment, where only men with a suspicious MP-MRI go on to have a biopsy, would avoid 27% of men having biopsy and reduce the number of low-risk cancer diagnoses by 5%. If MP-MRI was followed by biopsy targeted to the suspect lesions, they estimated that this could help diagnose 18% more cases of clinically significant cancer than the standard method of TRUS-biopsy alone assuming this technique would be 100% accurate. Relying on an MP-MRI scan could miss 5% of cancers, though it is not clear if these would be picked up by a subsequent biopsy.

What does current guidance say on this issue?

The 2014 NICE Prostate Cancer guideline recommends that doctors discuss abnormal physical examination and blood PSA results with men, along with their medical history and risk factors, to help them decide whether to proceed to biopsy. This should include discussion of the risks and benefits of the procedure.

NICE recommend considering MP-MRI for men with a negative TRUS biopsy (10 to 12 core samples) in helping to determine if another biopsy is needed, but do not recommend MP-MRI before biopsy. However, some hospitals have already started performing an MP-MRI scan before deciding whether to do a biopsy. The NICE guideline is currently being updated and is due to be published in January 2019.

What are the implications?

The higher sensitivity of MP-MRI compared with TRUS-biopsy means that it would miss fewer cases of cancer. Therefore, MP-MRI as a triage test could help guide more targeted biopsies to increase the detection of high risk cancers.

Initial MP-MRI may also prevent unnecessary biopsies and reduce detection of prostate cancers that are at low risk of progression. However, this strategy may miss some cases.

NICE will need to evaluate the cost effectiveness of MP-MRI before it could be recommended as a routine triage step. The technology is already in place in some hospitals, but the costs of widespread introduction and staff training would need to be considered.

Citation and Funding

Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017;389(10071):815-22.

The PROMIS study was funded by the National Institute for Health Research- Health Technology Assessment Programme (HTA) (project number 09/22/67) and partly funded by UCLH/UCL Biomedical Research Centre and The Royal Marsden and Institute for Cancer Research Biomedical Research Centre.

Bibliography

Cancer Research UK. Prostate cancer mortality statistics. London: Cancer Research UK; 2014.

NICE. Guidance on prostate cancer: diagnosis and management. CG175. London: National Institution for Health and Care Excellence; 2014.

Prostate Cancer UK. About prostate cancer. London: Prostate Cancer UK; 2016.

Prostate Cancer UK. Frequently asked questions about prostate cancer. London: Prostate Cancer UK; 2016.

Prostate Cancer UK. Introduction to prostate tests. London: Prostate Cancer UK; 2016.

Prostate Cancer UK. Prostate biopsy. London: Prostate Cancer UK; 2016.

Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study

Published on 20 January 2017

H Ahmed, A El-Shater Bosaily, L Brown, R Gabe, R Kaplan, M Parmar, Y Collaco-Moraes, K Ward, R Hindley, A Freeman, A Kirkham, R Oldroyd, C Parker, M Emberton, and the PROMIS study group

The Lancet , 2017

Background Men with high serum prostate specific antigen usually undergo transrectal ultrasound-guided prostate biopsy (TRUS-biopsy). TRUS-biopsy can cause side-effects including bleeding, pain, and infection. Multi-parametric magnetic resonance imaging (MP-MRI) used as a triage test might allow men to avoid unnecessary TRUS-biopsy and improve diagnostic accuracy. Methods We did this multicentre, paired-cohort, confirmatory study to test diagnostic accuracy of MP-MRI and TRUS-biopsy against a reference test (template prostate mapping biopsy [TPM-biopsy]). Men with prostate-specific antigen concentrations up to 15 ng/mL, with no previous biopsy, underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy. The conduct and reporting of each test was done blind to other test results. Clinically significant cancer was defined as Gleason score ≥4 + 3 or a maximum cancer core length 6 mm or longer. This study is registered on ClinicalTrials.gov, NCT01292291. Findings Between May 17, 2012, and November 9, 2015, we enrolled 740 men, 576 of whom underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy. On TPM-biopsy, 408 (71%) of 576 men had cancer with 230 (40%) of 576 patients clinically significant. For clinically significant cancer, MP-MRI was more sensitive (93%, 95% CI 88–96%) than TRUS-biopsy (48%, 42–55%; p<0·0001) and less specific (41%, 36–46% for MP-MRI vs 96%, 94–98% for TRUS-biopsy; p<0·0001). 44 (5·9%) of 740 patients reported serious adverse events, including 8 cases of sepsis. Interpretation Using MP-MRI to triage men might allow 27% of patients avoid a primary biopsy and diagnosis of 5% fewer clinically insignificant cancers. If subsequent TRUS-biopsies were directed by MP-MRI findings, up to 18% more cases of clinically significant cancer might be detected compared with the standard pathway of TRUS-biopsy for all. MP-MRI, used as a triage test before first prostate biopsy, could reduce unnecessary biopsies by a quarter. MP-MRI can also reduce over-diagnosis of clinically insignificant prostate cancer and improve detection of clinically significant cancer. Funding PROMIS is funded by the UK Government Department of Health, National Institute of Health Research–Health Technology Assessment Programme, (Project number 09/22/67). This project is also supported and partly funded by UCLH/UCL Biomedical Research Centre and The Royal Marsden and Institute for Cancer Research Biomedical Research Centre and is coordinated by the Medical Research Council Clinical Trials Unit (MRC CTU) at UCL. It is sponsored by University College London (UCL).

Gleason score indicates how aggressive the prostate cancer is and how likely it is to spread. When biopsy samples are examined in the laboratory the cells are graded 1 to 5. Grades 1 and 2 are not cancer, while 3, 4 and 5 are cancer cells with increasing level of abnormality. The two most common Gleason grades are combined to give an overall score. For example clinically significant cancer in this study was defined as a score of at least 4 + 3 or 7. NICE define localised prostate cancer as low risk if the score is 6 or less, medium risk is 7 and high risk 8 to 10.

Expert commentary

This was a fine study which compared MP-MRI, TRUS and TPM biopsy in prostate cancer diagnosis. Limitations include the assumption that “targeted biopsy” would pick up 100% of cancers in abnormal MP-MRI areas but this was not tested. This group has transformed how MP-MRI is used in diagnosis of prostate cancer. Men should undergo pre-biopsy MP-MRI. The data suggest this is to target biopsy, rather than to advise men with negative MP-MRI to safely avoid a biopsy – this would be unwise and premature as MP-MRI missed 17 significant cancers.

David E Neal, Senior Visiting Fellow and Professor Emeritus of Surgical Oncology, University of Cambridge, Department of Oncology, Addenbrooke's Hospital

Expert commentary

Men with persistently raised PSA levels are at substantial risk of having prostate cancer that may cause them harm. Standard diagnostic biopsy methods without image localisation of the likely cancer area only detect about a half of these cancers. MP-MRI scans before a biopsy can identify more than 90% and so could promote patient care. The challenge for the NHS is to improve access to already busy MRI scanners, radiologic training, and to invest in targeted biopsy methods so that MRI cancer suspicious areas be accurately detected and sampled.  These investments could be effective in the current economic climate because fewer men will undergo biopsies, there would be greater certainty about the absence of harmful cancer, and fewer unnecessary treatments that cause more harm than good will be undertaken.

Professor Anwar Padhani, Consultant Radiologist, Mount Vernon Cancer Centre, Northwood; Executive Chair, International Cancer Imaging Society

Expert commentary

Prostate cancer diagnosis has been limited by reliance on random prostate biopsies rather than initial imaging to diagnose. They are recognised to over diagnose ‘insignificant’ cancer (cancer that is unlikely to cause ill health and can lead to over treatment), miss many significant cancers and can cause significant side effects.  The PROMIS trial has shown that the latest MRI imaging is better at identifying significant prostate cancer whilst reducing the need for biopsy. If these results can be translated into clinical practice they could revolutionise/modernise the prostate cancer diagnostic pathway and remove a key obstacle to prostate cancer screening.

Professor Robert Huddart, Reader and Honorary Consultant in Clinical Oncology, The Royal Marsden

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