Trial Information

MRI and Ultrasound Soft Image Fusion Guided Biopsies Compared to Gold Standard Prostate Biopsies

Biopsy procedures

1. Conventional TRUS biopsy procedure (Gold standard). These patients will first undergo
0-6 TRUS targeted biopsies (TRUS TB) (2 targeted biopsies in up to 3 lesions), directed
towards lesions suspect of prostate cancer seen on TRUS, or detected by DRE
(standard-target). Subsequently, they will undergo a standard random 12 core TRUS
guided biopsy procedure. All biopsies will be performed using the Bruel and Kjaer
ultrasound unit, type 1846, and transrectal transducer No 8531 (New york, United
States). If there for any reason would be desirable to reduce the total number of
biopsies, we will omit random biopsies if targeted biopsies already have been taken at
that specific site.

Two dedicated urologist, (L. M. E. and G. M.), with special interest and experience in
prostate cancer will perform conventional TRUS biopsies according to the protocol, and
according to their previous experience. No effort will be done for these two urologists
to harmonize their biopsy procedures.

2. 3D image documented biopsy (3D IDB) procedure. These patients will first undergo an MRI
examination of the prostate. Possible cancer-suspect areas will be identified and
mapped in 3D. MRI findings with high grade of cancer suspicion will be marked as red
circles with diameter from 6 to 8 mm. MRI finding compatible with low or intermediate
cancer suspicions will be labelled as yellow circles from 6 to 8 mm in the diameter.
The circles will be placed in the centre of MRI findings. A few days later the patients
will first undergo 0-6 targeted biopsies, directed towards possible lesions detected by
MRI, which are transferred (by soft image fusion) to the TRUS images, allowing for TRUS
biopsies directed towards lesions detected by MRI, so-called MRI targeted biopsies (MRI
TB). These biopsies will be used for additional cytological imprints for evaluation of
presence/absence of carcinoma.

Subsequently, they will undergo 12 core random TRUS guided biopsy procedure, using the 3D
IDB software and 3D TRUS equipment (3D IDB random). When performing these random biopsies,
the MRI findings will not be displayed on the US screen.

One dedicated urologist (E. B.) with substantial experience with the 3D IDB procedure will
perform the MRI TB.

Biopsy procedures will be performed in local anaesthesia using 6-10 ml 2% Lidocaine. Using
ultrasound control, local anaesthetic is injected around the prostate using a 22-gauge
spinal needle. Prostate volume is calculated using the standard ellipsoid formula,
multiplying the largest anterioposterior (height), transverse (width) and cephalocaudal
(length) prostate diameters by 0,524.

Biopsies will be performed using 18 gauge spring-loaded needle (Angiotech®). All individual
biopsies cores will be marked and kept in separate glasses for fixation.

Biopsy time defined as time when the TRUS probe is in place is registered in both groups.

MRI examination Patients randomized to the 3D IDB procedure with MRI US fusion, will undergo
examination of the prostate using a 1,5 T MR scanner (Siemens Avanto, Erlangen Germany) with
a body array coil. Total scan time will be approximately 12 minutes.

Siemens Picture Archive Communicating System (PACS) and Nordic ICE® will be used for post
processing analyses. Evaluation of the MRI examinations will be performed by one radiologist
(E. R.).

Patient preparation Warfarin anticoagulant therapy is stopped 3 days before biopsy procedure
and biopsy is not performed if international normalized ratio (INR) value is over 2,0. If
needed, low molecular weight heparin can be administered to the patient. A cleansing enema
is not strictly required. One hour before the biopsy procedure is planned a peroral
antibiotic (Trimethoprim 160 mg, Sulfamethoxazole 800 mg) is administered and additional
dose is taken the following evening.

Assessment of patient tolerance and discomfort will be registered in both groups by visual
analogue score (VAS) pain score questionnaire (10 scores denoting the worst and 0 denoting
no bother).

Cytological procedures Each targeted biopsy will be subject to cytological imprint. These
smears will undergo standard staining and classified as positive or negative according to
presence of carcinoma or not.

Histopathological procedures Routine hematoxylin and eosin (HE) stain of the biopsies will
be performed, and evaluated according to Gleason system (gold standard for histological
evaluation) ranging from 1-5, with 5 being the most aggressive tumour. Gleason score is the
sum of the two dominating Gleason grades, for instance 5+5 for the most aggressive tumour
giving a Gleason score of 10. The biopsies will be marked, in order to evaluate the spatial
distribution of cancer.

The length of the biopsy core and tumour involvement will be measured.

Null hypotheses

1. There is no difference in the overall prostate cancer detection (rate of positive
biopsies) between the group undergoing conventional TRUS biopsy procedure and the group
undergoing 3D IDB MRI TB.

2. There is not higher rate of Gleason grade 4 and 5 in the 3D IDB MRI TB group compared
to the conventional TRUS group.

3. The 3D IDB MRI TB group do not have more prostate cancer than random 3D IDB

4. The MRI TB does not detect more prostate cancer than TRUS TB.

5. Random 3D IDB do not detect more prostate cancer than TRUS random biopsies.

6. The rate of re-biopsies is equal between the two groups.

7. There is no correlation of the cytological and histological results.