Prospective Assessment of Image Registration for the Diagnosis of Prostate Cancer

Each biopsy session would be preceded by mpMRI, which would be delineated and assigned a
degree of suspicion by a radiologist (see above).The PI-RADS scoring system will be used to
assign a degree of suspicion to regions of interest within the prostate. A second reader
will independently score the RSI on a Likert scale, blinded to the other MRI data. The
regions of interest will be delineated using software developed by Eigen in collaboration
with a study co-author (D.M.), now commercially available and in use by the UCLA team for
the past 2 years (ProFuse, Eigen).The RSI data will be integrated with the standard mpMRI
data and any change in scoring or presence of additional lesions, determined by RSI, will be
quantified. For men with a MR-visible target of PI-RADS score 3 or more, irrespective of RSI
score, the biopsy session would then proceed in an ordered routine, as follows:

1. Conventional ultrasound-guided 12-core systematic biopsy would be performed first. This
portion will be performed without operator knowledge of the MRI report, i.e., the
urologist will be blinded to possible tumor location and use the method in standard
practice throughout the U.S. for many years.

2. Next a targeted biopsy would be performed using visual guidance (cognitive fusion),
under the supervision of a radiologist specializing in prostate MRI. The radiologist
will be in the biopsy suite and help the urologist direct needle at location of region
of interest in the prostate seen on MRI. Three directed biopsy cores will be obtained.

3. Third, a targeted biopsy using Artemis device fusion of MRI and ultrasound images would
be performed. The prostate will be scanned and the MRI region of interest (target)
brought into the 3D model via device fusion. Targeted biopsy will be performed by
taking three cores of tissue from the target area, visualized as a 3D region in the
fusion device.

Biopsy sites to be dictated by geometric guides (12 point pattern vs visual direction of
radiologist vs fusion target), not chosen arbitrarily.

The above biopsy schema will not require any more procedure time or samples taken than
fusion biopsy as performed under IRB approval at our institution for the last five years.
Additional cores will be required for the visual biopsy method, but no biopsy cores will be
obtained from secondary targets. Most patients exhibit secondary targets. An analysis of
data from past 2 years demonstrated that the chance of a secondary target showing
significant cancer, not present in a primary target, is less than 1%. Therefore, secondary
targets will not be sampled, as cores are instead taken from primary targets using the two
methods. In 200 men undergoing initial biopsy, an average of 17 +/- 3 S.D. cores/patient has
been obtained. In the present proposal, 18 cores will be taken. Thus, the number of
cores/patient in this trial will not substantially exceed the number that has been routinely
taken in our practice in the past.

A sampling method of three directed cores per target was chosen as a compromise between what
is clinically feasible and a statistical ideal of taking additional cores for significant
cancer detection in lower grade targets.

The cognitive biopsy will require approximately 90 seconds of additional time, but this
added time will be more than compensated by the reduced time obtained from excluding
secondary targets. The overall biopsy schema should require no more (and probably less) than
the 15-20 minutes/procedure as in the past. Biopsies will be performed by an experienced
team, which has been working together since 2009.

Inclusion Criteria:

- Men undergoing a first-time prostate biopsy driven by PSA elevation to rule out
cancer.

- PSA 2.5 - 20 ng/mL

- Prostate volume 20 - 100 cc

- No prior ablation or TURP

- Able to tolerate MRI

- T1c suspect

- Signed informed consent

Exclusion Criteria:

- Any prior prostate biopsy

- Active bleeding disorder or concurrent use of coumadin or any other anticoagulant,
unless anticoagulation can be temporarily stopped for at least 7 days before and 7
days after the biopsy

- Any prostate ablative procedure, including transurethral resection,
photovaporization, or electrovaporization

- Any contraindication to MRI (contrast allergy, severe claustrophobia,
MRI-incompatible prosthesis) ,

- Palpable prostate mass lesion (i.e., Stage >T1c suspected)

- Any condition that would preclude the subject from getting the required biopsy as
stated in the protocol