The role of targeted MRI-ultrasound fusion biopsies of the prostate in patients suspected for prostate cancer

Prostate cancer (PCa) is the most commons cancer among men over 40 years.
Standard diagnostics for men suspected to have prostate cancer encompass 10-12
ultrasound-guided random biopsies of the prostate in a fixed manner. This
method is known to have several shortcomings such as detection of clinically
insignificant cancers, false-negative results and the need for repeated
biopsies in case of negative results. Multi-parametric magnetic resonance
imaging (MP-MRI) of the prostate is an evolving imaging method that allows
accurate visualization of prostate cancer. By fusing these images with
transrectal ultrasound images, targeted biopsies can be performed. These
MRI-ultrasound fusion biopsies are reported to diagnose more clinically
relevant prostate cancers (with a higher Gleason score). Therefore
MRI-ultrasound fusion biopsies have the potential to reduce overtreatment of
patients. However, random biopsies are shown to diagnose more cases of prostate
cancer and optimal clinical application of targeted biopsies has not yet been
determined. Also inclusion criteria for Active Surveillance have not yet been
determined. Unfortunately, studies until now have not been performed with
uniform definitions according to EAU guidelines or have not applied de PIRADS
classification system. Furthermore, negative MP-MRI ruled out prostate
biopsies. Therefore, a good comparison between MP-MRI, MRI-ultrasound fusion
biopsies and random biopsies has not been performed yet.


It is clear that a more targeted approach is necessary to improve detection of
clinically significant prostate cancer and to reduce overtreatment.
Furthermore, new definitions for inclusion for *Active Surveillance* follow-up
are necessary with this new imaging modality. This study aims to make a full
comparison between random biopsies versus MRI-ultrasound targeted biopsies in
respect of inclusion for Active Surveillance but also number of prostate
cancers diagnosed.


Hypothesis:

MRI-ultrasound fusion biopsies will detect more clinically relevant tumours
(I.e. higher Gleason score) when compared to random biopsies.



References:


1) JAMA. 2015;313(4):390-7


2) Curr Opin Urol. 2013;23(1):43-50


3) Eur Urol. 2012;62(5):902-9


4) World J Urol. 2014;32(4):847-58

The objective of this study is to improve the treatment of prostate cancer. By
more accurately diagnosing both clinically significant and insignificant
prostate cancer, treatment strategies will improve. This accounts for active
treatment like radical prostatectomy (less understaging) but alsof for Active
Surveillance (less overtreatment). Furthermore, this study aims to lower
patients' burden by ultimatly reducing the number of biopsies needed.


Researchquestions:

Can random prostate biopsies be safely replaced by MRI-ultrasound fusion
biopsies without missing cancers that according to the current definition of
Active Surveillance need active treatment?

Will MRI-ultrasound fusion prostate biopsies detect clinically relevant
prostate cancers that demand active treatment and would otherwise be included
in Active Surveillance according to random biopsies alone?

Can MRI-ultrasound fusion prostate biopsies reduce the amount of false Active
Surveillance follow-up?

Can MRI-ultrasound fusion prostate biopsies improve the amount of true Active
Surveillance follow-up?

Will MRI-ultrasound fusion prostate biopsies reduce the amount of patients'
burden in both diagnosing (less biopsies) and treatment (less overtreatment)?

We will perform a observational diagnostic study in which two different methods
for taking prostate biopsies within the same patient will be compared.

Inclusion and MRI
Patients, referred for prostate biopsies, will be informed by their urologist
about the study. If the urologist together witht the patient decides that the
patient will undergo prostate biopsies and the patient is included in the
study, the patient will undergo prostate biopsies within 14 days. Before the
biopsies a mpMRI will be made. A dedicated UG-radiologist will look at the
MRI-scan and draw Regions of Interest (ROIs) if prostate cancer is suspected
(PIRADS ((Prostate Imaging Reporting and Data System)) >2).

Biopsies
Patients will undergo 10 standardized ultrasound guided biopsies, 5 biopsies on
each side. Each biopsy will be marked with an ink color before it is enclosed
in a formaline-filled jar. This way, the specific location of each biopsy is
known for the investigator by its color. In the same session, the mpMRI will be
fused with the ultrasound images so that two additional biopsies can be taken
from the ROI. If no ROI is drawn by the radiologist two random additional
biopsies will be taken. These biopsies will also be marked with ink and each
enclosed in one of the two jars (left or right side prostate). Each jar will
contain 6 biopsies with 6 different colors, linked to a specific location or
ROI only known by the investigator.

Pathological examination
The two jars with the marked biopsies will be analyzed and examined by a
pathologist who is blind for the color marking. Each biopsy will receive a
Gleason score if applicable. Any positive biopsies will be named together with
their color so that the investigator can link the biopsy to a specific location.

Revision
The results of the mpMRI and biopsies will be reported to the patient by their
own urologist. All biopsies will be used for therapy decision making and
therefore this study can benefit the diagnosis of the participating patient as
well.

Both MRI-ultrasound fusion biopsies as well as random biopsies will be taken in
the same session without removal of the rectal probe. Two additional biopsies
will be taken, thereby reducing patients' risk and burden.