Clinical trial NCT02485379: Assessment of Prostate MRI Before Prostate Biopsies
Official title: Improvement in the Detection of Aggressive Prostate Cancer by Targeted Biopsies Using Multiparametric MRI Findings
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prostate Cancer
Keywords: Prostate cancer
Multiparametric MRI
Prostate biopsy
Targeted biopsy
Comparative study
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2015-06-30
Enrollment: 275
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Background: Prostate cancer is difficult to detect using ultrasound. As a result, in case of suspicion of prostate cancer based on digital rectal examination (DRE) or Prostate Specific Antigen (PSA) level, it is currently recommended to perform "blinded" systematically distributed biopsies with 10-18 samples obtained from predefined locations in the gland.

These so-called systematic biopsies (SB) may lead to improper patient management by (i) missing clinically significant cancer, especially in the anterior half of the gland that tends to be undersampled, (ii) inducing chance detection of clinically insignificant cancer foci that may result in overtreatments, (iii) undersampling the tumor foci and thus underestimating their volume and aggressiveness.

Multiparametric Magnetic Resonance Imaging (mp-MRI) has yielded promising results in detecting aggressive (Gleason ≥7) prostate cancers. Several monocenter studies showed that targeted biopsies (TB) based on mp-MRI findings could detect significantly more aggressive cancers, reduce the diagnosis of clinically insignificant cancers, and better evaluate the aggressiveness of detected cancers than SB. However, these monocenter studies only provide low-level evidence and three recent independent reviews of literature concluded that there was a need for a robust multicenter trial evaluating the diagnostic yield of TB as compared to SB. This is particularly important since many academic and private centers in France already perform mp-MRI before prostate biopsy in daily routine. Therefore the risk is that this approach becomes the norm without being properly evaluated and it is crucial and urgent to perform a controlled multicentric study to provide high-level evidence as to whether mp-MRI should or should not be obtained before prostate biopsy.

One controlled multicentric study has been published recently in which SB and TB had been obtained by two different operators in 95 patients. TB yielded a significantly higher detection rate for all prostate cancers (69% vs 59%, p=0.033) and for clinically significant cancers (67% vs 52%, p=0.0011). However, this study was limited by the fact that patients with negative mp-MRI were not included.

Research hypotheses: There is currently no robust multicenter trial comparing prostate TB based on mp-MRI findings versus the current standard of care (SB). We propose a multicentre prospective trial comparing the results of SB and TB performed in the same patients by two independent operators. Our hypothesis is that TB detects aggressive (Gleason ≥7) cancers in a significantly higher percentage of patients than SB.

Main objective: To compare the percentage of patients with "clinically significant cancer" (using definition A, i.e. cancer with Gleason score ≥7) detected by SB versus TB.


Eligibility criteria: Inclusion Criteria:

* Patient referred for prostate mp-MRI before a first set of prostate biopsies, with a planned time interval of less than 3 months between MRI and biopsies
* Age ≤75 years
* PSA level ≤20 ng/mL
* Clinical stage ≤T2c
* Patient insured under the French social security system or beneficiary of an equivalent regime

Exclusion Criteria:

* Contraindication to transrectal biopsy
* Contraindication to MRI
* History of hip prosthesis
* History of androgen deprivation therapy
* Patients with history of prostate cancer diagnosed on TURP
* Patients with history of pelvic radiation therapy (whatever the reason)
* Patient deprived of freedom following a court or administrative order
* Patient under guardianship or under legal guardianship

Primary outcomes:
measure: Detection of "clinically significant cancer" (using definition A, i.e. Gleason ≥7 cancers) in at least one core of SB or TB.
timeFrame: Between 1 and 4 months after the enrollment
Secondary outcomes:
measure: To compare the percentage of patients with "clinically significant cancer" (using definition B, i.e. any Gleason ≥7 cancer or Gleason 6 cancer with at least one sample with ≥6 mm of cancer) detected by SB and TB.
timeFrame: Between 1 and 4 months after the enrollment
measure: To compare the percentage of patients with "clinically significant cancer" (using definition C, i.e. any Gleason ≥7 (4+3) cancer)
timeFrame: Between 1 and 4 months after the enrollment
measure: To compare the percentage of patients with "clinically insignificant cancer" (defined as a Gleason ≤6 cancer with ≤2 positive samples and <3 mm of cancer on the positive samples) detected by SB and TB.
timeFrame: Between 1 and 4 months after the enrollment
measure: To compare the percentage of patients with Gleason ≥7 cancer detected by SB and TB in different subgroups
timeFrame: Between 1 and 4 months after the enrollment
measure: To compare the percentage of patients detected by TB and by SB+TB with "clinically significant cancer" (using definitions A, B and C) and "clinically insignificant" cancer.
timeFrame: Between 1 and 4 months after the enrollment
measure: To compare the percentage of patients with "clinically significant cancer" (using definitions A, B and C) detected by the 2 optional US-guided biopsies and by the regular 12 systematic biopsies.
timeFrame: Between 1 and 4 months after the enrollment
measure: To evaluate the percentage of patients with overall cancer and with "clinically significant cancer" (using definitions A, B and C) on SB and who had a negative MRI
timeFrame: Between 1 and 4 months after the enrollment
measure: To evaluate the percentage of patients with overall cancer and "clinically significant cancer" (using definitions A, B and C) on SB and who had a positive MRI in the sextant(s) that were positive on SB.
timeFrame: Between 1 and 4 months after the enrollment
measure: To evaluate the percentage of patients with discordant results (Gleason score, maximum length of invasion) between the local pathological analysis and between the central pathological review.
timeFrame: Between 1 and 4 months after the enrollment
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin - CHU de Bordeaux
city: Grenoble
country: France
facility: Hôpital Michallon - CHU de Grenoble
city: Lille
country: France
facility: Hôpital Huriez - CHU de Lille
city: Lille
country: France
facility: Hôpital Privé La Louvière
city: Lille
country: France
facility: CLIMAL (Centre Libéral Imagerie Médicale Agglomération Lille)
city: Lyon Cedex 03
country: France
facility: Hôpital Edouard Herriot
city: Lyon
country: France
facility: Centre Hospitalier St Joseph St Luc
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nantes
country: France
facility: Clinique Jules Verne
city: Paris
country: France
facility: Hopital Pitie Salpetriere
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Necker
city: Pierre Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Saint-Etienne
country: France
facility: CHU de Saint-Etienne
city: Saint-Priest-en-Jarez
country: France
facility: IRMAS
city: St Herblain
country: France
facility: Clinique Urologique Nantes Atlantis
city: Strasbourg
country: France
facility: Nouvel Hopital Civil - CHU de Strasbourg
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole - CHU de Toulouse
city: Vandoeuvre-les-Nancy
country: France
facility: CHU Nancy Brabois
Study officials:
References:
citation: Rouviere O, Puech P, Renard-Penna R, Claudon M, Roy C, Mege-Lechevallier F, Decaussin-Petrucci M, Dubreuil-Chambardel M, Magaud L, Remontet L, Ruffion A, Colombel M, Crouzet S, Schott AM, Lemaitre L, Rabilloud M, Grenier N; MRI-FIRST Investigators. Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study. Lancet Oncol. 2019 Jan;20(1):100-109. doi: 10.1016/S1470-2045(18)30569-2. Epub 2018 Nov 21.