Prostate Cancer Secondary Screening in Sapienza and Policlinico Umberto I

Prostate Cancer (Diagnosis) Clinical Trial

— ProSa-I  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04803188
• Other study ID #: 5996
• Status: Enrolling by invitation
• Phase: N/A
• Start date: September 21, 2020
• Est. completion date: September 2022

Study information

• Verified date: March 2021
• Source: University of Roma La Sapienza
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 710
• Est. completion date: September 2022
• Est. primary completion date: September 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 40 Years to 69 Years

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Prostate Cancer (Diagnosis)
• Prostatic Neoplasms

Intervention

Diagnostic Test:
• Magnetic Resonance
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.

Locations

Country	Name	City	State
Italy	Sapienza University of Rome	Rome	Roma

Sponsors (1)

Lead Sponsor	Collaborator
University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

References & Publications (13)

Boesen L, Nørgaard N, Løgager V, Balslev I, Bisbjerg R, Thestrup KC, Winther MD, Jakobsen H, Thomsen HS. Assessment of the Diagnostic Accuracy of Biparametric Magnetic Resonance Imaging for Prostate Cancer in Biopsy-Naive Men: The Biparametric MRI for Det — View Citation

Eldred-Evans D, Burak P, Connor MJ, Day E, Evans M, Fiorentino F, Gammon M, Hosking-Jervis F, Klimowska-Nassar N, McGuire W, Padhani AR, Prevost AT, Price D, Sokhi H, Tam H, Winkler M, Ahmed HU. Population-Based Prostate Cancer Screening With Magnetic Res — View Citation

Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA; Grading Committee. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposa — View Citation

Jambor I, Boström PJ, Taimen P, Syvänen K, Kähkönen E, Kallajoki M, Perez IM, Kauko T, Matomäki J, Ettala O, Merisaari H, Kiviniemi A, Dean PB, Aronen HJ. Novel biparametric MRI and targeted biopsy improves risk stratification in men with a clinical suspi — View Citation

Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, Briganti A, Budäus L, Hellawell G, Hindley RG, Roobol MJ, Eggener S, Ghei M, Villers A, Bladou F, Villeirs GM, Virdi J, Boxler S, Robert G, Singh PB, Venderink W, Hadaschik B — View Citation

Knaapila J, Jambor I, Ettala O, Taimen P, Verho J, Perez IM, Kiviniemi A, Pahikkala T, Merisaari H, Lamminen T, Saunavaara J, Aronen HJ, Syvänen KT, Boström PJ. Negative Predictive Value of Biparametric Prostate Magnetic Resonance Imaging in Excluding Sig — View Citation

Matoso A, Epstein JI. Defining clinically significant prostate cancer on the basis of pathological findings. Histopathology. 2019 Jan;74(1):135-145. doi: 10.1111/his.13712. Review. — View Citation

Mottet N, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, Fanti S, Fossati N, Gandaglia G, Gillessen S, Grivas N, Grummet J, Henry AM, van der Kwast TH, Lam TB, Lardas M, Liew M, Mason MD, Moris L, Oprea-Lager DE, van der Poel — View Citation

Nam RK, Wallis CJ, Stojcic-Bendavid J, Milot L, Sherman C, Sugar L, Haider MA. A Pilot Study to Evaluate the Role of Magnetic Resonance Imaging for Prostate Cancer Screening in the General Population. J Urol. 2016 Aug;196(2):361-6. doi: 10.1016/j.juro.201 — View Citation

Panebianco V, Barchetti G, Simone G, Del Monte M, Ciardi A, Grompone MD, Campa R, Indino EL, Barchetti F, Sciarra A, Leonardo C, Gallucci M, Catalano C. Negative Multiparametric Magnetic Resonance Imaging for Prostate Cancer: What's Next? Eur Urol. 2018 J — View Citation

Turkbey B, Rosenkrantz AB, Haider MA, Padhani AR, Villeirs G, Macura KJ, Tempany CM, Choyke PL, Cornud F, Margolis DJ, Thoeny HC, Verma S, Barentsz J, Weinreb JC. Prostate Imaging Reporting and Data System Version 2.1: 2019 Update of Prostate Imaging Repo — View Citation

Wegelin O, Exterkate L, van der Leest M, Kummer JA, Vreuls W, de Bruin PC, Bosch JLHR, Barentsz JO, Somford DM, van Melick HHE. The FUTURE Trial: A Multicenter Randomised Controlled Trial on Target Biopsy Techniques Based on Magnetic Resonance Imaging in — View Citation

Welch HG, Albertsen PC. Reconsidering Prostate Cancer Mortality - The Future of PSA Screening. N Engl J Med. 2020 Apr 16;382(16):1557-1563. doi: 10.1056/NEJMms1914228. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Stratification according to outcome	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
Other	Comparison of different positive screening tests	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
Other	Comparison of different combination of screening tests	Comparison of the different combination of screening tests in terms of detection rate, non-clinically significant and clinically significant cancer detection rate.	2 years
Primary	Diagnosis of prostate cancer with non-contrast MRI	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	Percentage of men with a positive PSA screening test	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