In-vivo focal prostate imaging with confocal laser endomicroscopy and optical coherence tomography

The current limitations in prostate cancer diagnostics lead to over- and
undertreatment for a significant fraction of patients. Confocal Laser
Endomicroscopy (CLE) and Optical Coherence Tomography (OCT) are focal imaging
modalities with potential for in-vivo prostate imaging. We anticipate that
integrating focal imaging with MRI/TRUS fusion will further improve prostate
cancer detection and provides a real-time histopathological three-dimensional
representation of the tumor lesions.

Objective procedure 1:
To assess the technical feasibility and safety of in-vivo focal imaging with
CLE and OCT.

Objective procedure 2:
Primary Objective:
To identify and define characteristics of prostate cancer on CLE and OCT and
compare this with histology.

Secondary Objective(s):
- To develop the first steps towards an in-vivo CLE and OCT image atlas of the
prostate (benign glands, cystous atrophy, regular atrophy, stroma, malignant
tissue using the Gleason score, inflammation, fat)
- To assess procedure related adverse events of in-vivo focal imaging by use of
Common Terminology Criteria for Adverse Events
- To detect lymph node metastasis (ex-vivo) with CLE after extended pelvic
lymph node dissection

This is an investigator-initiated, prospective in-vivo safety and feasibility
study with two procedures.

Procedure 1:
Patients that are indicated for transperineal template mapping biopsies (TTMB)
are included for procedure 1 and will receive transperineal CLE or OCT
measurements prior to TTMB.
Procedure 1 is to test the technical feasibility and safety of in-vivo focal
imaging with CLE and OCT. Only if transperineal CLE or OCT measurements are
possible, we proceed with procedure 2.

Procedure 2:
Patients scheduled for a robot-assisted laparoscopic prostatectomy (RALP) will
be included in procedure 2 and receive transperineal CLE or OCT measurements
prior to their surgery. Results will be correlated with histology by
correlating biopsies during the TTMB procedure or with RALP the measurement
trajectory will be marked. After the RALP, the prostate will be cut exactly
through the measurement trajectory for whole mount coupes.
In high-risk of high-intermediate-risk patients receiving an extended pelvic
lymph node dissection with the RALP, ex-vivo CLE measurements will be
performed.

Transperineal SFR and CLE measurements will be performed directly prior to the
surgery procedure or prior to the TTMB. In case of surgery, intraprostatic
plastic IV cannulas will be placed for histopathology correlation. Ex-vivo CLE
measurements will be performed and if applicable ex-vivo CLE measurements will
be performed in lymph nodes after extend pelvic lymph node dissection.

For patients included in this feasibility study there is no direct benefit.
However, the results of this study are important for patients in the future,
diagnosed with prostate cancer. Previous in-vivo studies OCT did not report any
adverse events. Previous studies of CLE combined with intravenous
administration of fluorescein haven proven to be safe. Patients with a known
allergic reaction to fluorescein cannot participate in this study. Both
modalities are performed by needle guidance with the same diameter as a normal
prostate biopsy gun. Two sterile cannulas, for marking the measurement
trajectory, will stay in the prostate during the surgery and will be removed
when the prostate is removed. The cannulas harbor a small increased risk for
infection . However, antibiotic prophylaxis is administered as standard of care
2 hour prior surgery to reduce the risk of infection. The estimated prolonged
time of the procedure is approximately 30 minutes. Standard care and
pathological evaluation as stated by the internal protocol will not be affected
in this study.