Clinical trial NCT04803188: Prostate Cancer Secondary Screening in Sapienza and Policlinico Umberto I
Official title: A Randomized Controlled Trial on the Role of Magnetic Resonance Imaging for Prostate Cancer Screening
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Prostate Cancer (Diagnosis)
Keywords: Prostate Cancer
Screening
Non-contrast MRI
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
First posted: 2021-03-17
Enrollment: 710
Sex: MALE
Minimum age (years): 40
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Diagnosis of prostate cancer with non-contrast MRI
timeFrame: 24 months
Secondary outcomes:
measure: Percentage of men with a positive PSA screening test
timeFrame: 2 years
Other outcomes:
measure: Stratification according to outcome
timeFrame: 2 years
measure: Comparison of different positive screening tests
timeFrame: 2 years
measure: Comparison of different combination of screening tests
timeFrame: 2 years
Locations:
city: Rome
country: Italy
facility: Sapienza University of Rome
state: Roma
Study officials:
affiliation: University of Roma La Sapienza
name: Valeria Panebianco, MD
role: PRINCIPAL_INVESTIGATOR
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