Predicting Prostate Biopsy Results With Biomarkers and mpMRI. (ProBioM)

March 22, 2023 updated by: Torben Brøchner Pedersen

Developing a Multivariable Diagnostic Prediction Model for Prostate Biopsy Outcome Using Biomarkers and mpMRI as Prediction Variables in Biopsy naïve Men.

Current standard prostate biopsy techniques, used to definitively diagnose prostate cancer (PC), utilises an ultrasound guided biopsy approach, that offers unsatisfactory specificity and sensitivity for clinical significant PC. This often leads to harmful unnecessary biopsies. To improve the overall detection of clinical significant PC, multiparametric magnetic resonance imaging (mpMRI) has emerged as a new technique that might be useful in selecting the appropriate patient for biopsy. Nevertheless, mpMRI fail to detect cancer in some circumstances and the exact role of mpMRI is undetermined. Currently, the majority of PC is diagnosed either incidentally or by unsystematic screening with prostate specific antigen (PSA). PSA suffers from being an organ specific, but cancer unspecific serum biomarker. PSA testing may neither rule out or confirm the presence of prostate cancer. Newer biomarkers have shown promise in curbing some of this sensitivity and specificity gap, but still needs refinement.

In the present study, the investigators will use mpMRI and a new set of urine and plasma biomarkers in combination, prior to performing standard biopsies in order to develop a prediction model for the biopsy outcome. If proven successful the model would offer excellent risk stratification and possibly mitigating the need for biopsies.

Study Overview

Detailed Description

Background Prostate cancer (PC) remains a significant cause of morbidity and death among men in Denmark and the rest of the western world. Over 4,500 PC cases are diagnosed every year being the second most common malignancy among men in Denmark. With increasing life expectancy, the incidence of PC is projected to increase. Pivotal to the successful treatment of prostate cancer is establishing an early diagnosis. Localised PC is potentially curable and current curative treatment options have shown efficacy in reducing cancer related mortality.

TRUS biopsies:

Transrectal ultrasound guided prostate biopsies (TRUS biopsies) are conducted routinely for histopathological confirmation in cases of suspected PC. Indication for prostate biopsies include elevated Prostate Specific Antigen (PSA) levels or palpable tumour on digital rectal examination. TRUS biopsies is associated with morbidity in the form of infection, haematuria, rectal bleeding and discomfort. Some of these complications may require hospital admission and can be life threatening.

Current standard biopsy regimes include 10 to 14 systemic biopsy cores taken from the peripheral zone of the prostate. The majority of PC involve the posterior peripheral zone of the prostate readily available for biopsies. The remaining PC are isolated to the transition-, central- and anterior zone of the prostate which are not routinely biopsied on systemic biopsies. Thus, anteriorly located cancers may not be sampled with routine investigations and TRUS biopsies may yield false negative results. As the biopsies are taken randomly throughout the gland, significant cancers located in the peripheral zone will in some cases be missed.

Biomarkers and liquid biopsies:

PSA testing has been widely adopted and more cancers are being detected in Denmark due to unsystematic screening with PSA. PSA is a glycoprotein of the human kallikrein family, and elevated serum concentrations are associated to PC. It is organ specific but not cancer specific, therefore other causes may elevate values, including benign prostatic hyperplasia, prostatitis, urinary tract infections and bladder outlet obstruction. To distinguish prostate cancer from other causes of PSA elevation and to confirm the diagnosis, TRUS biopsies are currently the standard diagnostic test.

A range of novel biomarkers has been proposed to overcome the limitations of PSA's low specificity. Few of these biomarkers have been implemented in clinical practise. In a recently published study, Albitar et al, using a panel of urine and plasma biomarkers, where able to predict biopsy outcomes with a positive predictive value of 90% and negative predictive value of 89% tolerating some low grade cancers (Gleason score < 7). This idea has been disseminated as liquid biopsies.

mpMRI of the prostate: Multiparametric magnetic resonance imaging (mpMRI) of the prostate has emerged as a new technology with the ability to detect PC. Especially in the setting of previously negative TRUS biopsies, mpMRI can provide important additional information enabling targeting of biopsies towards suspected PC lesions. Nevertheless, a PC negative mpMRI may fail to detect cancers in 43% of cases and miss 16% of PCs classified as clinical significant. Thus a negative mpMRI will currently still mandate systemic biopsies. Therefore, novel approaches are needed to better direct biopsies and select patient for biopsies.

Aim

The aim of the current project is to study the following issues:

Assessing the value of prebiopsy mpMRI combined with liquid biopsies in biopsy naive men in predicting biopsy results and possible deriving a diagnostic predictive model.

Assessment of the performance of TRUS mpMRI fusion guided biopsies vs. systemic biopsies combined with liquid biopsies.

Confirming the value of liquid biopsies and investigating its relation to tumour grade and volume.

Study Type

Interventional

Enrollment (Actual)

261

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Odense, Denmark, 5000
        • Odense University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  1. Able to provide informed written consent.
  2. PSA < 20.
  3. Referred for prostate biopsy.

Exclusion Criteria::

  1. Previously diagnosed with prostate cancer.
  2. Active use of anticoagulant (excluding platelet inhibitors) or other contraindication for prostate biopsies.
  3. Previously undergone prostate biopsies.
  4. Inability to undergo mpMRI scan (pacemaker , claustrophobia, impaired renal function, allergy towards contrast agent etc)
  5. Any, previous or current, therapy for benign prostate hyperplasia including surgery or medical therapy (except alpha adrenal blockers).
  6. They withdraw their consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard care
Study subject will undergo sampling of plasma and urine biomarkers.
Study subjects will undergo urine and plasma biomarker testing prior to standard biopsy
Experimental: Magnetic Resonance Imaging.
Prior to biopsies a magnetic resonance imaging scan will be performed.
Study subjects will undergo urine and plasma biomarker testing prior to standard biopsy
Study subjects will undergo urine and plasma biomarker testing and mpMRI prior to biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Detection of clinical significant cancer.
Time Frame: 1 month
Positive biopsies with a Gleason grade > 7.
1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Detection rate of any cancers
Time Frame: 1 month
Positive biopsies, any Gleason grade.
1 month

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Health Related Quality of Life
Time Frame: Baseline, 24 hour, 1 month and 12 months
Assessed utilizing the EuroQoL EQ-5D-5L questionnaire (comprising 5 questions with a score from 1 to 5 each and a visual analogue scale from 0 to 100).
Baseline, 24 hour, 1 month and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Lars Lund, DMsc, Odense University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 5, 2018

Primary Completion (Actual)

July 1, 2021

Study Completion (Actual)

June 1, 2022

Study Registration Dates

First Submitted

August 21, 2018

First Submitted That Met QC Criteria

November 2, 2018

First Posted (Actual)

November 5, 2018

Study Record Updates

Last Update Posted (Actual)

March 23, 2023

Last Update Submitted That Met QC Criteria

March 22, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Prostate Cancer

Clinical Trials on Urine and plasma biomarkes.

3
Subscribe