Clinical trial NCT03979573: Prospective Evaluation of Mp-MRI, MR-guided Biopsy, and Molecular Markers for Active Surveillance of Prostate Cancer
Official title: Prospective Phase II Trial Evaluating Multiparametric MRI, Radiomics, MR-guided Biopsy, and Molecular Markers for Active Surveillance of Patients With Low- and Intermediate-Risk Prostate Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Prostate Cancer
Keywords: Prospective Study
Multiparametric MRI
Radiomics
MR-guided Biopsy
Molecular Markers
Active Surveillance
Prostate Cancer
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
First posted: 2019-06-07
Enrollment: 90
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective' Single-Arm, Phase-II Study
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Reduction of the discontinuation of Active Surveillance (AS)
timeFrame: 24 months
Secondary outcomes:
measure: Value of MRI (ADC) regarding aggressiveness
timeFrame: 36 months
measure: Detectionrates of targeted (FUS-GB) versus systematic (TRUS-GB) biopsies
timeFrame: 36 months
measure: Detectionrates of targeted (FUS-GB) versus systematic (TRUS-GB) biopsies
timeFrame: 36 months
measure: Correlation of clinical parameters with Gleason score progression or MRI quantified progression
timeFrame: 36 months
measure: Correlation of clinical parameters with Gleason score progression or MRI quantified progression
timeFrame: 36 months
measure: Correlation of clinical parameters with Gleason score progression or MRI quantified progression
timeFrame: 36 months
measure: Patient compliance to recommended MRI-based observation
timeFrame: 36 months
measure: Patient compliance to recommended MRI-based observation
timeFrame: 36 months
measure: Evaluation of Resolve DWI
timeFrame: 36 months
measure: Evaluation of Resolve DWI
timeFrame: 36 months
measure: Evaluation of Resolve DWI
timeFrame: 36 months
measure: Evaluation of Resolve DWI
timeFrame: 36 months
Other outcomes:
Locations:
city: Dusseldorf
country: Germany
facility: University Düsseldorf, Medical Faculty
state: NRW
Study officials:
affiliation: University Düsseldorf, Medical Faculty; Department of Diagnostic and Interventional Radiology
name: Lars Schimmöller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Düsseldorf, Medical Faculty; Department of Urology
name: Christian Arsov, MD
role: PRINCIPAL_INVESTIGATOR
References: