Prostate Cancer Secondary Screening in Sapienza and Policlinico Umberto I (ProSa-I)

March 16, 2021 updated by: Valeria Panebianco, University of Roma La Sapienza

A Randomized Controlled Trial on the Role of Magnetic Resonance Imaging for Prostate Cancer Screening

Prostate Cancer (PCa) screening is still a controversial topic in the urology community, this is mostly linked to the low specificity of Prostate Specific Antigen (PSA) value. Screening with total PSA value has cause overdiagnosis of clinically insignificant prostate cancer (ciPCa) for many years, with lack of survival improvement. Non-contrast MRI, on the other hand, has become one of the most promising MRI applications, as it is a more sensitive test able to perform clinically significant PCa early detection. With this background the primary endpoint was to investigate the role of non-contrast MRI (without injection of paramagnetic contrast medium), as a secondary prevention test for the early diagnosis of prostate cancer, comparing it with the serum PSA test, in a randomized fashion.

Study Overview

Status

Enrolling by invitation

Intervention / Treatment

Detailed Description

ENDPOINTS Primary endpoint To investigate the role of non-contrast Magnetic Resonance Imaging (MRI), as a secondary prevention test for the early diagnosis of prostate cancer (PCa), comparing it with the serum PSA test.

Secondary endpoints

  1. Assess the percentage of men with a positive PSA screening test, defined as > 4 ng/ml and > 2.5 ng/ml in patients with family history of PCa (father and/or sibling).
  2. Evaluation of the percentage of men with positive MRI and MRI targeted biopsy results stratified according to: absence of neoplasm, non-clinically significant neoplasm (ISUP 1) and clinically significant neoplasm (ISUP> 1), compared with PSA test and serum biomarkers (optional).
  3. Comparison of the percentages of participants with PCa and with clinically significant PCa, according to the different positive screening tests.
  4. Comparison of the different screening tests combinations in terms of PCa detection rate, both for non-clinically significant and clinically significant cancer.

STUDY DESIGN

Design:

Single center, prospective, interventional randomized controlled trial Duration: 2 years Evaluation of the effectiveness of the primary outcome: the evaluation of the effectiveness non-contrast MRI for the PCa detection will be based on MRI-guided biopsy targeted on the areas described and classified as biparametric Prostate Imaging-Reporting and Data System (bPI-RADS) ≥3 (scored according to the biparametric evaluation).

The reference standard for the diagnosis of prostate cancer will be the Magnetic Resonance Imaging - Transrectal Ultrasound (MRI-TRUS) guided targeted biopsy, which will be performed at a maximum of 4 weeks from MRI.

In order to evaluate the diagnostic accuracy of non-contrast MRI the diagnostic performance variables (sensitivity, specificity, accuracy, positive and negative predictive value, area under the curve and receiver operating characteristic curves) will be calculated.

For the statistical analysis of the effectiveness, only those participants who have undergone prostate biopsy as planned by the operator will be included.

In addition, the interreader agreement between two radiologists responsible for the analysis of MRI images, with 10 and 8 years of experience in urogenital imaging, respectively, will be evaluated. The agreement between the two radiologists will be calculated using the weighted Cohen's k statistic.

Evaluation of secondary outcomes: the evaluation of the effectiveness of secondary outcomes will be verified by evaluating the same statistical variables of diagnostic accuracy implemented for the primary purpose.

Safety evaluation: the safety of the procedure will be determined by assessing the incidence and severity of adverse events, defined as complications related to the procedure recorded from the first treatment and during the entire duration of the follow-up (2 years).

Participants in the study:

Enrollment: 710 men will be enrolled and blindly randomized in two different arms. Arm a) 355 patients will perform MRI with a bi-parametric approach (without contrast medium) regardless their PSA value; Arm b) 355 patients will perform MRI with a bi-parametric approach (without contrast medium) only when PSA is elevated.

Patients with positive MRI defined as bPI-RADS ≥3, will undergo MRI-directed targeted prostate biopsy.

Study Type

Interventional

Enrollment (Anticipated)

710

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Roma
      • Rome, Roma, Italy, 00185
        • Sapienza University of Rome

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 69 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion criteria:

  • Males aged between 49-69 years (from the age of 40 for those with family history of prostate cancer) at the time of enrollment
  • Life expectancy greater than or equal to 10 years
  • Sufficient understanding of the Italian language for written and verbal understanding of the information for enrollment in the Trial and for the process of obtaining informed consent.
  • Patient with the ability to understand and want, able to express informed consent and to perform all the visits and procedures required by the study

Exclusion criteria:

  • General contraindications to MRI
  • Previous history of prostate cancer, prostate biopsy or treatment for prostate cancer
  • Any contraindications to prostate biopsy, such as severe coagulation abnormalities (INR> 1.5), active urinary tract infection and acute prostatitis (NIH category I, II and III).
  • Dementia or altered mental status that would prohibit understanding or granting informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A: patients will perform non-contrast MRI
A: 355 patients will perform non-contrast MRI regardless their serum PSA value

Screening MRI examinations will be performed on an MRI General Electric (GE) 3 Tesla MRI using a 32-channel phased array pelvic coil. The imaging protocol will include: T2-weighted morphological and diffusion-weighted functional sequences.

All images will be reviewed by two radiologists experienced in urogenital imaging, who will be blinded to the patients' medical history. Both radiologists in charge will then assign a PI-RADS score (1 to 5) to each lesion for bi-parametric MRI, representing the likelihood of a clinically significant prostate lesion. For the generation of the overall PI-RADS score assigned to each lesion, the PI-RADS score algorithm for non-contrast MRI described in the PI-RADS version 2.1 recommendations will be applied. Lesions scored as bPI-RADS superior or equal than 3 will be directed to MRI-TRUS guided targeted biopsy.

Experimental: B: patients will perform non-contrast MRI
B: 355 patients will perform non-contrast MRI when serum PSA value is increased (>4 ng/ml or 2.5 ng/ml if positive family history)

Screening MRI examinations will be performed on an MRI General Electric (GE) 3 Tesla MRI using a 32-channel phased array pelvic coil. The imaging protocol will include: T2-weighted morphological and diffusion-weighted functional sequences.

All images will be reviewed by two radiologists experienced in urogenital imaging, who will be blinded to the patients' medical history. Both radiologists in charge will then assign a PI-RADS score (1 to 5) to each lesion for bi-parametric MRI, representing the likelihood of a clinically significant prostate lesion. For the generation of the overall PI-RADS score assigned to each lesion, the PI-RADS score algorithm for non-contrast MRI described in the PI-RADS version 2.1 recommendations will be applied. Lesions scored as bPI-RADS superior or equal than 3 will be directed to MRI-TRUS guided targeted biopsy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnosis of prostate cancer with non-contrast MRI
Time Frame: 24 months
To investigate the role of MRI with a bi-parametric approach (without injection of paramagnetic contrast medium), as a secondary prevention test for the early diagnosis of prostate cancer, comparing it with the serum PSA test.
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of men with a positive PSA screening test
Time Frame: 2 years
To assess the percentage of men with a positive PSA screening test, defined as > 4 ng/ml and > 2.5 ng/ml in patients with family history of prostate cancer (father and/or sibling).
2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Stratification according to outcome
Time Frame: 2 years
To evaluate the percentage of men with positive non-contrast MRI stratified according to: absence of neoplasm, non-clinically significant neoplasm (ISUP 1) and clinically significant neoplasm (ISUP> 1), compared with the tests of the PSA and serum biomarkers (optional).
2 years
Comparison of different positive screening tests
Time Frame: 2 years
Comparison of the percentages of participants with the different positive screening tests. Comparison of the same in the subpopulation of patients with clinically significant neoplasia (ISUP> 1).
2 years
Comparison of different combination of screening tests
Time Frame: 2 years
Comparison of the different combination of screening tests in terms of detection rate, non-clinically significant and clinically significant cancer detection rate.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Valeria Panebianco, MD, University of Roma La Sapienza

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 21, 2020

Primary Completion (Anticipated)

September 1, 2021

Study Completion (Anticipated)

September 1, 2022

Study Registration Dates

First Submitted

March 11, 2021

First Submitted That Met QC Criteria

March 16, 2021

First Posted (Actual)

March 17, 2021

Study Record Updates

Last Update Posted (Actual)

March 17, 2021

Last Update Submitted That Met QC Criteria

March 16, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Other Study ID Numbers

  • 5996 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

all individual participant data that underlie results in a publication

IPD Sharing Time Frame

Starting in January 2022, will be available for 6 months after publication

IPD Sharing Access Criteria

The access will be granted to any researcher who will contact the principal investigator via email, upon reasonable request

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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