Prospective Evaluation of Mp-MRI, MR-guided Biopsy, and Molecular Markers for Active Surveillance of Prostate Cancer

NCT ID: NCT03979573

Last Updated: 2019-06-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-01
• Study Completion Date: 2021-09-30

Brief Summary

Active Surveillance (AS) is a treatment option in patients with favorable risk prostate cancer. According to the current guidelines patients are monitored by prostate specific antigen (PSA) testing (every 3 months) and regular re-biopsies. Due to histological reclassification and/or patient noncompliance a high number of patients discontinue AS. Nonetheless, because of an increasing number of diagnosed early stage tumors overdiagnosis and overtreatment of patients has become a major clinical problem. Therefore AS is a promising and important tool for patients with low and intermediate risk prostate cancer.

Multiparametric MRI (mp-MRI) in combination with radiomics analysis, MR-guided biopsies, and molecular markers are promising tools to optimize patient selection and observation during AS.

This prospective, single arm, multicenter phase II study evaluates mp-MRI, radiomics, MR-guided biopsies and molecular markers for AS with the primary endpoint of reducing discontinuation based on histologic reclassification.

At the end of this study the results may allow defining a MRI-based pathway to identify and monitor patients suitable for AS supported by radiomics. Thus, the high rate of discontinuation due to misclassification at initial diagnosis will be reduced.

Additionally, this strategy will allow reducing over-treatment of clinically insignificant PCA, and on the other hand, increasing early treatment of higher-risk disease. Monitoring by mp-MRI will reduce the number of prostate biopsies and cores per patient during AS, and thus increase the patient compliance. Finally, such a strategy will reduce the economic burden of treating insignificant prostate cancer.

Detailed Description

This prospective multicenter phase II study evaluates multiparametric MRI (mp-MRI), radiomics and MR-guided biopsies for Active Surveillance (AS) of men with low- and intermediate-risk prostate cancer (PCA) with the primary endpoint of reducing the rate of discontinuation of AS based on histologic reclassification in an observation period of 24 months.

Men with low- or intermediate-risk PCA diagnosed by mp-MRI followed by an MR/ultrasound fusion-guided biopsy (FUS-GB) plus systematic ultrasound-guided biopsy (SB) will be included in this study.

During the study observation period PSA values will be obtained every 3 months. After having obtained three values PSA doubling times (PSA-DT) will be calculated at every visit. In case of PSA-DT <3 years patients will get a repeat mp-MRI and in case of MRI progression a repeat targeted FUS-GB plus SB will be performed. In case of a Gleason score upgrading by the targeted biopsy the patient will discontinue AS and get treatment. In cases of stable MRI or stable Gleason score the patient will continue with PSA controls every 3 months.

In addition all patients with stable PSA values will undergo a mp-MRI after 12 months. If this MRI demonstrates progression the protocol proceeds as mentioned above for patients with PSA-increase. At the end of study (24 months after enrollment), all patients will receive another mp-MRI and FUS-GB+SB.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Intervention Arm

• PSA testing
• Multiparametric MRI (mp-MRI)
• Radiomics
• MR-guided biopsy (MR-guided and systematic US-guided)
• Molecular Markers (Histological analysis of biopsy cores)

Group Type: OTHER

Multiparametric MRI

Intervention Type: DIAGNOSTIC_TEST

Multiparametric prostate MRI (mp-MRI)

Radiomics

Intervention Type: DIAGNOSTIC_TEST

Radiomics analyses will consist of image intensity normalization, image coregistration and resampling, radiomic feature extraction, combination with clinical and molecular parameters, feature extraction and machine learning, model testing on validation and test cohorts and comparison to existing clinical risk models.

MR-guided Biopsy

Intervention Type: DIAGNOSTIC_TEST

MR-guided targeted prostate biopsies as well as systematic TRUS-guided biopsies (at least 12 cores) will be performed on a fusion-guided biopsy system. The biopsy cores can either be obtained transrectal or transperineal.

Molecular Markers

Intervention Type: DIAGNOSTIC_TEST

Molecular markers will be analyzed on the initial and final targeted and systematic biopsy cores. The molecular panel consists of a methylation-specific PCR and a set of highly selected markers that can be detected by immunohistochemistry. The resulting data will be prospectively recorded to enable a retrospective analysis of the prognostic value.

Interventions

Multiparametric MRI

Multiparametric prostate MRI (mp-MRI)

Intervention Type: DIAGNOSTIC_TEST

Radiomics

Radiomics analyses will consist of image intensity normalization, image coregistration and resampling, radiomic feature extraction, combination with clinical and molecular parameters, feature extraction and machine learning, model testing on validation and test cohorts and comparison to existing clinical risk models.

Intervention Type: DIAGNOSTIC_TEST

MR-guided Biopsy

MR-guided targeted prostate biopsies as well as systematic TRUS-guided biopsies (at least 12 cores) will be performed on a fusion-guided biopsy system. The biopsy cores can either be obtained transrectal or transperineal.

Intervention Type: DIAGNOSTIC_TEST

Molecular Markers

Molecular markers will be analyzed on the initial and final targeted and systematic biopsy cores. The molecular panel consists of a methylation-specific PCR and a set of highly selected markers that can be detected by immunohistochemistry. The resulting data will be prospectively recorded to enable a retrospective analysis of the prognostic value.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Patients with a Gleason score of 3+3=6 or 3+4=7a and ≤ 33% of positive biopsy cores verified by an at least 12 core systematic prostate biopsy (SB)
• Organ-confined disease (≤cT2a), note: tumor-positive biopsies in both lobes with non-palpable tumor are rated as cT1c
• PSA value ≤10 ng/ml

Exclusion Criteria

• Gleason score ≥4+3=7b or a Gleason score 3+4=7a with positive biopsy cores >33% of all cores in SB
• PSA >10 ng/ml
• Patients not able to give informed consent
• Contraindication to mp-MRI
• Contraindication to prostate biopsy

• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lars Schimmöller, MD

Role: PRINCIPAL_INVESTIGATOR

University Düsseldorf, Medical Faculty; Department of Diagnostic and Interventional Radiology

Christian Arsov, MD

Role: PRINCIPAL_INVESTIGATOR

University Düsseldorf, Medical Faculty; Department of Urology

Locations

University Düsseldorf, Medical Faculty

Düsseldorf, North Rhine-Westphalia, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Lars Schimmöller, MD

Role: CONTACT

Lars.Schimmoeller@med.uni-duesseldorf.de

+49 211-81-08505

Christian Arsov, MD

Role: CONTACT

Christian.Arsov@med.uni-duesseldorf.de

+49 211-81-08607

Facility Contacts

Almut Diem

Role: primary

diem@med.uni-duesseldorf.de

+49 211-8119353

Other Identifiers

5941R

Identifier Type: -

Identifier Source: org_study_id