High Resolution MRI Study for Prostate Cancer

Evaluation of a Novel High-Resolution Diffusion-Weighted MRI Sequence

This high resolution MRI (hrMRI), along with stand MRI (sMRI) will be obtained at baseline and again in approximately 1 year in patients on prostate cancer active surveillance. Changes in lesion size and ADC values will be assessed on the serial studies. This study evaluates the hypothesis that hrMRI will detect changes that sMRI cannot detect and that these changes will correlate with prostate cancer progression as determined on prostate biopsy.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Diagnostic test: high resolution MRI (hrMRI)

Detailed Description

2.0 BACKGROUND AND RATIONALE

Multiparametric MRI Multiparametric MRI combining T2-weighted, diffusion-weighted, and dynamic contrast enhanced (DCE) images is commonly employed for detection and localization of prostate lesions. Diffusion-weighted imaging (DWI) is sensitive to the diffusion of water molecules interacting with surrounding macromolecules. DWI, which provides a quantitative biological parameter called apparent diffusion coefficient (ADC) value, is a robust MRI parameter for differentiating benign and malignant prostate tissue. In fact, the latest version of the Prostate Imaging-Reporting and Data System (PI-RADS) scoring system relies almost exclusively on DWI to identify tumors in the peripheral zone, which is where the vast majority of prostate cancers form. Findings on T2 images are not used to identify cancer, and DCE images are only used to differentiate between some PI-RADS 3 and 4 lesions. In a pilot study of prostate cancer AS, DW-MRI was useful for detecting progression of Gleason score based on changes in ADC value. Tumor size is another important clinical criterion for defining low risk prostate cancer, and tumor size based on DWI has been shown to crudely predict low risk prostate cancer. However, conventional DWI using single-shot echo-planar imaging is unable to detect small tumors, low grade tumors, or small changes in tumor size on serial imaging. Approximately 20% of small, low grade tumors found in men on AS are detected on modern prostate MRI.

High Resolution MRI Investigators introduce a new three-dimensional (3D) high-resolution diffusion-weighted imaging sequence (HR-DWI), which improves image quality while conferring at least a 5-fold improvement in resolution when compared to standard two-dimensional (2D) DWI (S-DWI). This novel 3D DWI technique has been developed by our team and can be applied on existing 1.5T or 3T MRI systems. S-DWI suffers from two important limitations. a) It uses single-shot echo-planar imaging (EPI) for data acquisition, which produces magnetic susceptibility induced streaking artifacts and geometric distortions so that round objects may appear oval. b) The relatively low signal-to-noise ratio and 2D image acquisition with S-DWI limit spatial resolution, which is defined by the minimum distance between two objects required to resolve them uniquely. Our HR-DWI overcomes these limitations by using magnetization prepared, multi-shot, turbo-spin-echo acquisition, which improves signal-to-noise ratio (SNR), spatial resolution, and image quality, and eliminates geometric distortions and streaking artifacts associated with EPI.

Preliminary studies

In preliminary studies assessing the performance of our HR-DWI in a prospective pilot trial of prostate cancer AS patients, the technique could detect tumors not seen on S-DWI and measure ADC, which correlates with grade. This is important because the long-term natural history of small prostate cancers invisible to S-DWI has never been prospectively defined, in part due to lack of adequate imaging technology. In the era of molecular diagnostics and next-generation sequencing, an important step in understanding the biology of these lesions is to develop technologies to image and characterize these lesions. Importance of HR-DWI includes:

• Better imaging will allow these lesions to be monitored serially and targeted for biopsy, providing tissue for both histologic and molecular characterization.
• Higher resolution imaging will better delineate tumor boundaries, which can improve tumor staging and identify margins during partial-gland ablation by cryotherapy or high intensity focused ultrasound (HIFU), which was approved in 2015 by the U.S. FDA.
• Improved imaging resolution will allow for more accurate measurement of tumor size and ADC, and detection of small changes in size or grade over time. Standard prostate DWI has poor resolution; therefore, tumor growth kinetics have never been accepted as clinical criteria for cancer progression while on AS. If tumor growth kinetics or changes in grade determined by ADC prove prognostic, AS can rely less on serial transrectal biopsies, which can lead to serious complications.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age over 18 years
• Patients diagnosed with clinically localized prostate cancer
• Low or Low-intermediate Risk Prostate cancer1 defined as:
• Pre-operative prostate specific antigen (PSA) ≤ 20.0 ng/ml
• Clinical stage cT1 or cT2
• Gleason score 3+3 or 3+4
• Patients choosing AS or already on AS as primary management strategy
• No previous treatment for prostate cancer with radiotherapy, chemotherapy, or hormonal therapy
• No contraindications for gadolinium enhanced MRI

Exclusion Criteria:

• No exclusion criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Paired imaging; Single arm, paired imaging of high resolution MRI (hrMRI) and stand MRI (sMRI)	Diagnostic test: high resolution MRI (hrMRI); high resolution MRI (hrMRI) and standard MRI (sMRI) will be obtained at baseline and again in approximately 1 year in patients on prostate cancer active surveillance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and Specificity of High Resolution Versus Standard MRI in Identifying Adverse Histology	The primary endpoint of the clinical trial was the presence of adverse histology (AH) on prostate biopsy. We defined adverse histology (AH) as either overall Gleason score of 7 or more on any biopsy, or an increase of 3 or more positive cores on serial systematic biopsies. The primary hypothesis was that change in tumor size or apparent diffusion coefficient (ADC) as detected by high resolution MRI (hrMRI) would better predict AH than standard MRI (sMRI). AH histology was a measure intended to capture patients with high Gleason grade component (i.e. Gleason Grade 4 or 5) and patients progressing (e.g. from Gleason Group 1 to Gleason Group 2 or from Gleason Group 2 to Gleason Group 3). The sample size was too small and the followup duration of approximately 12 months was too short to assess only true cancer progression as the endpoint. The presence of AH alone is clinically important since these patients may need close followup and may consider definitive local therapy.	6-12 months after enrollment
Area Under the Receiver Operator Curve of High Resolution Versus Standard MRI in Identifying Adverse Histology	The primary endpoint of the clinical trial was the presence of adverse histology (AH) on prostate biopsy. We defined adverse histology (AH) as either overall Gleason score of 7 or more on any biopsy, or an increase of 3 or more positive cores on serial systematic biopsies. The primary hypothesis was that change in tumor size or apparent diffusion coefficient (ADC) as detected by high resolution MRI (hrMRI) would better predict AH than standard MRI (sMRI). AH histology was a measure intended to capture patients with high Gleason grade component (i.e. Gleason Grade 4 or 5) and patients progressing (e.g. from Gleason Group 1 to Gleason Group 2 or from Gleason Group 2 to Gleason Group 3). The sample size was too small and the followup duration of approximately 12 months was too short to assess only true cancer progression as the endpoint. The presence of AH alone is clinically important since these patients may need close followup and may consider definitive local therapy.	6-12 months after enrollment

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Investigators: Principal Investigator: Hyung L Kim, MD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2017
• Primary Completion (Actual): December 14, 2022
• Study Completion (Actual): December 14, 2022

Study Registration Dates

• First Submitted: September 21, 2017
• First Submitted That Met QC Criteria: September 22, 2017
• First Posted (Actual): September 26, 2017

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: MRI; prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: Pro00049177

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes