USPIO-enhanced and Diffusion-weighted MRI for the Detection of Pelvic Lymph Node Metastases

Study Overview
=================
Brief Summary
-----------------
Preoperative detection of lymph node metastases in patients with prostate or bladder cancer is crucial for selection of the appropriate treatment strategy (surgery, androgen deprivation with/or without radiation therapy or chemotherapy) and thus for patient prognosis. Until now CT or MRI have been the modalities of choice for preoperative staging procedures. However, current morphological assessment of lymph nodes based on size and shape is unable to detect smaller metastases or liable to give false positive results on lymph nodes with reactive hyperplasia. We hypothesize that USPIO-enhanced MRI combined with DW-MRI will be able to detect pelvic lymph node metastases preoperatively with high sensitivity and specificity.

Official Title
-----------------
Noninvasive Detection of Clinically Occult Lymph Node Metastases in Prostate and Bladder Cancer Evaluated by USPIO-Enhanced MRI and Diffusion-Weighted MRI: A Histopathological Correlation

Conditions
-----------------
Prostate Cancer, Bladder Cancer

Intervention / Treatment
-----------------
* Other: Imaging: diffusion-weighted MRI
* Other: Sinerem (USPIO) enhanced MRI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with histologically proven prostate cancer (T1-2N0M0 Gleason score 6-10) scheduled for radical prostatectomy or patients with histologically proven bladder cancer (T1-3bN0M0G3) scheduled for cystectomy Written informed consent to participate in this trial. Exclusion Criteria: Patients with contraindications for MRI (e.g. pacemaker, metal implants, claustrophobia). Patients in a critical cardiovascular state, with risk of decompensation after administration of the USPIO contrast agent. Patients with hemochromatosis or an allergy to dextran or iron compounds. Pregnant or breast-feeding women. Patients who have received gadolinium complexes within 2 days or iron oxide particles within 7 days before MRI. Patients who underwent chemotherapy or radiotherapy before surgery. Patients whose degree of cooperation is incompatible with carrying out the study. Patients with contraindications to Glucagon administration.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: A<br>Diffusion-weighted MRI | Other: Imaging: diffusion-weighted MRI<br>* Diffusion-weighted MRI of the entire pelvis to detect lymph node metastases<br>|
| Other: B<br>Sinerem (USPIO)- enhanced MRI | Other: Sinerem (USPIO) enhanced MRI<br>* USPIO (Sinerem) will be administered intravenously immediately after the first MR examination at a dose of 2.6 mg Fe/kg body weight diluted in 100 ml of saline (optimal dose according to: (9, 10)) during a period of about 30 minutes under medical supervision. Postcontrast MR imaging will be performed 24-36 hours after contrast medium injection.<br>* Other names: SINEREM;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Discrimination of N positive (N+) vs. N negative (N0) patients (prostate and bladder cancer) using diffusion-weighted imaging, USPIO enhancement and both. |  | 1 year | 
| Preoperative localization of all suspected positive nodes in accordance to the predefined regions on both sides and in comparison with histopathology. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Node-by-node analysis of USPIO-enhanced and DW-MRI positive lymph nodes with histopathology. |  | 2-3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prostate cancer, Bladder cancer, Pelvic lymph node metastases, Diffusion-weighted MRI, Sinerem (USPIO)-enhanced MRI, Imaging influence on surgery, Noninvasive detection of pelvic lymph node metastases, Influence of imaging protocol on surgical outcome