Predicting Prostate Biopsy Results With Biomarkers and mpMRI.
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): mpMRI; Urine and plasma biomarkes.
Intervention type(s): Diagnostic Test; Diagnostic Test
Intervention description(s): Study subjects will undergo urine and plasma biomarker testing and mpMRI prior to biopsy; Study subjects will undergo urine and plasma biomarker testing prior to standard biopsy
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Study subjects will be randomized in a 1:7 fashion between
Standard biopsies + biomarkers and
Biomarkers + mpMRI and Standard / mpMRI targeted biopsies.
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Biomarkers; Magnetic Resonance Imaging; Diagnostic