Clinical trial NCT02380027: PRostate Evaluation for Clinically Important Disease: Sampling Using Image-guidance Or Not?
Official title: A Randomized Control Trial of Magnetic Resonance Imaging-targeted Biopsy Compared to Standard Trans-rectal Ultrasound Guided Biopsy for the Diagnosis of Prostate Cancer in Men Without Prior Biopsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Neoplasm
Keywords: Prostate biopsy
MRI
transrectal
Detection
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
name: University Hospital, Lille
name: Radboud University Medical Center
name: London North West Healthcare NHS Trust
name: Royal Free Hospital NHS Foundation Trust
name: Sunnybrook Health Sciences Centre
name: University College London Hospitals
name: University Ghent
name: Helsinki University Central Hospital
name: Jewish General Hospital
name: University of Roma La Sapienza
name: Göteborg University
name: Erasmus Medical Center
name: Hunter Holmes Mcguire Veteran Affairs Medical Center
name: University Hospital Heidelberg
name: University Hospital, Aachen
name: Hampshire Hospitals NHS Foundation Trust
name: Princess Alexandra Hospital NHS Trust
name: San Raffaele University Hospital, Italy
name: M.D. Anderson Cancer Center
name: University Hospital Southampton NHS Foundation Trust
name: University of Oulu
name: The Whittington Hospital NHS Trust
name: University Hospital of Cologne
name: Mayo Clinic
name: Centro de Urologia Argentina
name: Weill Medical College of Cornell University
name: University of Chicago
name: University Hospital, Bordeaux
First posted: 2015-03-05
Enrollment: 500
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: This evaluates the detection rates of prostate cancer by MRI-targeted prostate biopsy compared to standard 12-core trans-rectal ultrasound guided (TRUS) prostate biopsy. Each participant will be randomly allocated to one of the biopsy tests.

We hypothesise that MRI-targeted biopsy will detect no fewer clinically significant cancers than TRUS biopsy but will detect fewer clinically insignificant prostate cancers than TRUS biopsy.

Detailed description: The classical pathway for the diagnosis of prostate cancer is trans-rectal ultrasound guided (TRUS) biopsy of the prostate following a raised PSA. This is currently the mainstay for prostate cancer diagnosis in the majority of centres. It has many advantages and can be performed routinely under local anaesthetic in an outpatient setting. However it does have some limitations, including the over-diagnosis of insignificant cancer and the under-diagnosis of significant cancer.

An alternative pathway for the diagnosis of prostate cancer in men with raised prostate specific antigen (PSA) is to perform a multi-parametric MRI to localize cancer and to use this information to influence conduct of a subsequent biopsy, known as an MRI-targeted biopsy. MRI-targeted biopsy has been shown in preliminary studies to detect a similar amount of clinically significant cancer to TRUS-biopsy but may have several advantages, for example in reducing the number of men who require biopsy.

This randomized controlled trial aims to assess the detection rate of clinically significant and clinically insignificant cancer of MRI-targeted biopsy compared to standard 12-core TRUS biopsy in men referred with clinical suspicion of prostate cancer who have had no prior prostate biopsy.

A 'clinically insignificant cancer' is cancer which is unlikely to progress or affect a man's life expectancy and therefore does not warrant treatment. However when diagnosed with insignificant cancer a large proportion of patients request treatment in case a more significant cancer is present. A prostate cancer detection pathway that finds significant cancers while avoiding the diagnosis of insignificant cancer is a major unmet need.

The potential implications of this trial include:

* A redefining of the prostate cancer diagnostic pathway
* A reduction in the number of patients undergoing prostate biopsy
* A reduction in the number of biopsy cores taken per patient
* A reduction in biopsy-related sepsis, pain and other side effects
* A reduction in the over-diagnosis of clinically insignificant prostate cancer
* A reduction of the economic burden of diagnosing and treating prostate cancer

Eligibility criteria: Inclusion Criteria:

1. Men at least 18 years of age referred with clinical suspicion of prostate cancer who have been advised to have a prostate biopsy
2. Serum PSA ≤ 20ng/ml within the previous 3 months
3. Suspected stage ≤ T2 on rectal examination (organ-confined prostate cancer) within the previous 3 months
4. Fit to undergo all procedures listed in protocol
5. Able to provide written informed consent

Exclusion Criteria:

1. Prior prostate biopsy
2. Prior treatment for prostate cancer
3. Contraindication to MRI (e.g. claustrophobia, pacemaker, estimated glomerular filtration rate ≤ 50mls/min)
4. Contraindication to prostate biopsy
5. Men in whom artifact would reduce the quality of the MRI
6. Previous hip replacement surgery, metallic hip replacement or extensive pelvic orthopaedic metal work
7. Unfit to undergo any procedures listed in protocol

Primary outcomes:
measure: Proportion of men with clinically significant detected
timeFrame: When histology results available, at an expected average of 30 days post-biopsy
Secondary outcomes:
measure: Proportion of men in MRI arm who avoid biopsy
timeFrame: When MRI results available, at an expected average of 30 days post-MRI
measure: Proportion of men with MRI score 3, 4 or 5 who have no clinically significant cancer detected
timeFrame: When histology results available, at an expected average of 30 days post-biopsy
measure: Proportion of men who go on to definitive treatment for prostate cancer
timeFrame: After treatment decision, at an expected average of 30 days post-biopsy
measure: Cancer core length of the most involved biopsy core (maximum cancer core length)
timeFrame: When histology results available, at an expected average of 30 days post-biopsy
measure: Proportion of men with post-biopsy adverse events
timeFrame: 30 days post biopsy
measure: EQ-5D-5L Quality of Life scores
timeFrame: Baseline, 24 hours post intervention and 30 days post intervention
measure: Proportion of men undergoing Radical prostatectomy who have Gleason grade upgrading
timeFrame: An expected average of 90 days post-biopsy
measure: Cost per diagnosis of cancer
timeFrame: 30 days post-biopy
measure: Proportion of men with clinically insignificant detected
timeFrame: When histology results available, at an expected average of 30 days post-biopsy
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: University College Hospitals
Study officials:
affiliation: University College Hospital London and University College London
name: Caroline Moore, MD FRCS
role: STUDY_CHAIR
affiliation: University College Hospital London and University College London
name: Mark Emberton, MD FRCS
role: STUDY_CHAIR
References:
citation: Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, Briganti A, Budaus L, Hellawell G, Hindley RG, Roobol MJ, Eggener S, Ghei M, Villers A, Bladou F, Villeirs GM, Virdi J, Boxler S, Robert G, Singh PB, Venderink W, Hadaschik BA, Ruffion A, Hu JC, Margolis D, Crouzet S, Klotz L, Taneja SS, Pinto P, Gill I, Allen C, Giganti F, Freeman A, Morris S, Punwani S, Williams NR, Brew-Graves C, Deeks J, Takwoingi Y, Emberton M, Moore CM; PRECISION Study Group Collaborators. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med. 2018 May 10;378(19):1767-1777. doi: 10.1056/NEJMoa1801993. Epub 2018 Mar 18.
citation: Kasivisvanathan V, Jichi F, Klotz L, Villers A, Taneja SS, Punwani S, Freeman A, Emberton M, Moore CM. A multicentre randomised controlled trial assessing whether MRI-targeted biopsy is non-inferior to standard transrectal ultrasound guided biopsy for the diagnosis of clinically significant prostate cancer in men without prior biopsy: a study protocol. BMJ Open. 2017 Oct 12;7(10):e017863. doi: 10.1136/bmjopen-2017-017863.