Detection of ISUP≥2 Prostate Cancers Using Multiparametric MRI: Prospective Multicenter Comparison of the PI-RADS Score and an Artificial Intelligence System (CHANGE)

Multiparametric MRI of the prostate is recommended before each prostate biopsy. It identifies suspicious areas which will then be the subject of targeted biopsies. However, MRI suffers from low specificity and moderate inter-reader reproducibility, including with the use of the PI-RADS version 2.1 score.

We are developing, within the framework of RHU PERFUSE, a computer-aided diagnosis system (CAD) for the detection of ISUP ≥2 cancers. This system has been trained on a database of patients who had prostate MRI and prostatectomy at the Hospices Civils de Lyon and performed well on a database of patients who had prostate MRI before biopsy at the Hopices civils de Lyon.

However, one of the weaknesses of artificial intelligence systems is their low robustness when tested on MRI images from different manufacturers or institutions.

The goal of the CHANGE study is to build a prospective multicenter cohort of patients who underwent prostate multiparametric MRI followed by systematic and targeted prostate biopsies. The cohort will be used for the final external validation of the CAD developed in PERFUSE.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Biological: Blood sample; Other: Follow up questionnaire; Diagnostic test: Human reading of prostate MR images (PI-RADSv2.1).

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Olivier ROUVIERE, Pr; Phone Number: +33 4 72 11 61 70; Email: olivier.rouviere@chu-lyon.fr
• Study Contact Backup: Name: Adeline MANSUY, PhD; Phone Number: +33 4 72 11 51 70; Email: adeline.mansuy@chu-lyon.fr

Study Locations

• France
  • Bordeaux, France, 33076
    • Not yet recruiting
    • Department of radiology and urology, CHU Pellegrin
    • Contact: Clément Marcellin, Dr; Phone Number: +33 5 56 79 55 99; Email: clement.marcelin@chu-bordeaux.fr
    • Sub-Investigator: Franck Bladou, Pr
  • Grenoble, France, 38043
    • Not yet recruiting
    • Department of urology and Radiology, CHU Grenoble Alpes
    • Contact: Bénedicte Guillaume, Dr; Phone Number: +33 4 76767984; Email: bguillaume@chu-grenoble.fr
    • Sub-Investigator: Gaelle Fiard, MD
  • Lille, France, 59037
    • Not yet recruiting
    • Department of radiology and urology, CHU de Lille
    • Contact: Philippe Puech, Pr; Phone Number: +33 3 20 44 61 91; Email: philippe.puech@chru-lille.fr
    • Sub-Investigator: Arnauld Villers, Pr
  • Lyon, France, 69003
    • Recruiting
    • Department of radiology and urology, Hôpital Edouard Herriot
    • Contact: Olivier Rouvière, Pr; Phone Number: +33 4 72 11 61 67; Email: olivier.rouviere@chu-lyon.fr
    • Sub-Investigator: Sébastien Crouzet, Pr
  • Lyon, France, 69007
    • Not yet recruiting
    • Department of radiology and urology, Hôpital Saint Joseph Saint Luc
    • Contact: Favie Bratan, MD; Phone Number: +33 4 78 61 88 00; Email: fbratan@ch-stjoseph-stluc-lyon.fr
    • Sub-Investigator: Nicolas Arfi, MD
  • Marseille, France, 13003
    • Not yet recruiting
    • Department of Radiology and Urology, Hopital Européen Marseille
    • Contact: Marc ANDRE, MD
    • Sub-Investigator: Antoine Van Hove, MD
  • Marseille, France, 13273
    • Not yet recruiting
    • Department of Radiology and Urology, Institut Paoli-Calmettes Marseille
    • Contact: Serge Brunelle, MD; Phone Number: +33 4 91 22 34 19; Email: brunelles@ipc.unicancer.fr
    • Sub-Investigator: Jochen Walz, MD
  • Montpellier, France, 34070
    • Not yet recruiting
    • Department of Urology, Clinique Beausoleil Montpellier
    • Contact: Grégoire Poinas, Dr; Phone Number: +33 4 67 459365; Email: g.poinas@languedoc-mutualite.fr
  • Montpellier, France, 34090
    • Not yet recruiting
    • Department of urology and Radiology
    • Contact: Ingrid Millet, Pr; Phone Number: +33 6 78 88 71 74; Email: i-millet@chu-montpellier.fr
    • Sub-Investigator: Rodolphe Thuret, Pr
  • Nantes, France, 44800
    • Not yet recruiting
    • Department Urology, Clinique urologique Nantes Atlantis
    • Contact: Eric Potiron, MD; Phone Number: +33 2 28 03 04 44; Email: ep@cliniqueuro.com
  • Paris, France, 75013
    • Not yet recruiting
    • Department of radiology and urology, Hôpital la Pitié Salpêtrière
    • Contact: Raphaele renardpenna, Pr; Phone Number: +33 1 42 17 82 15; Email: raphaele.renardpenna@aphp.fr
    • Sub-Investigator: Pierre Mozer, Pr
  • Paris, France, 75015
    • Not yet recruiting
    • Department of radiology, Hôpital Necker
    • Contact: jean-michel correas, Pr; Phone Number: +33 1 44 49 41 40; Email: jean-michel.correas@aphp.fr
  • Pierre-Bénite, France, 69310
    • Not yet recruiting
    • Department of urology and radiology, CHLS
    • Contact: Paul Moldovan, MD; Phone Number: +33 4 72 11 12 31; Email: paul-cezar.moldovan@chu-lyon.fr
    • Sub-Investigator: Alain Ruffion, Pr
  • Quint Fonsegrives, France, 31130
    • Not yet recruiting
    • Department of Urology, Quint Fonsegrives
    • Contact: Guillaume Ploussard, MD/PhD; Phone Number: +33 5 32 02 72 02; Email: gploussard@capio.fr
  • Saint-Etienne, France, 42055
    • Not yet recruiting
    • Department of urology, CHU de Saint-Étienne Hôpital Nord
    • Contact: Nicolas Mottet-Auselot, Pr; Phone Number: +33 4 77 82 83 31; Email: nicolas.mottet@chu-st-etienne.fr
    • Sub-Investigator: Remi Grange, Dr
  • Strasbourg, France, 67000
    • Not yet recruiting
    • Department of Radiology and Urology, Nouvel Hôpital Civil - CHU de Strasbourg
    • Contact: Catherine Roy, Pr; Phone Number: +33 3 69 55 07 31; Email: catherine.roy@chru-strasbourg.fr
    • Sub-Investigator: Thibault Tricard, Pr
  • Toulouse, France, 231059
    • Not yet recruiting
    • Department of Radiology adn Urology, Institut Universitaire du Cancer ,Toulouse
    • Contact: aziza richard, MD; Phone Number: +33 5 31 15 60 60; Email: aziza.richard@iuct-oncopole.fr
    • Sub-Investigator: bernard malavaud, Pr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men over 18 years of age
• Patient with clinical suspicion of prostate cancer referred for a multiparametric MRI of the prostate before a first series of biopsies or before new biopsies after one or more series of negative biopsies
• PSA ≤ 30 ng / ml
• Clinical stage ≤ T2c
• Affiliation or beneficiary of a social security scheme

Exclusion Criteria:

• Men over 80 years of age
• PSA> 30 ng / ml
• Stage T3 or T4 on digital rectal examination
• Previous prostate biopsy performed within 12 months
• History of prostate cancer diagnosed by biopsy or endourethral resection.
• History of pelvic radiotherapy regardless of the cause.
• History of total or focal treatment for prostate cancer.
• History of hormone therapy
• MRI performed more than 3 months before biopsy
• Prostate MRI performed on a machine other than the center's machines accredited for the study.
• Presence of a hip prosthesis
• Contraindication to performing an MRI
• Contraindication to performing prostate biopsy
• Patient subject to a legal protection measure or deprived of liberty
• Subject participating or having participated in interventional medical research with an exclusion period still in progress
• Misunderstanding of the French language

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Prospective multicenter cohort; Constitution of a prospective multicenter cohort of 420 patients with suspected prostate cancer that will undergo prostate multiparametric MRI followed by systematic and targeted biopsy. When available (i.e., at the end of the RHU PERFUSE program, November 2022), the final version of the CAD will be used retrospectively to assess the risk that the prostate/targeted lesions harbor ISUP ≥2 cancer. In addition, a blood sample will be taken in all patients before the biopsy to assess the performance of the PHI index in predicting the presence of ISUP ≥2 cancer at systematic and targeted biopsy (ancillary study, secondary objective).

Biological: Blood sample; Measurement of PHI Index; Other: Follow up questionnaire; 3 years after inclusion; Diagnostic test: Human reading of prostate MR images (PI-RADSv2.1).; The PI-RADSv2.1 score will be compared to systematic and targeted biopsy findings (primary objective) and 3-year follow-up (secondary objective)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the non-inferiority of the AUC of the final CAD developed in the PERFUSE program for the detection of ISUP ≥2 cancers, as compared to that of the PI-RADSv2.1 score (human reading), at per-patient analysis.	AUC of the final CAD and of the PI-RADS version 2.1 score for the detection of ISUP ≥2 cancers on systematic and targeted biopsies performed after MRI, at per-patient analysis. A priori-defined non-inferiority margin: 5 percentage points.	Through recruitment completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the specificities of the CAD and of the PI-RADSv2.1 score for the detection of ISUP ≥2 cancers at per-patient, per-lobe and per-lesion analysis.	Specificity of the final CAD and of the PI-RADSv2.1 score for the detection of ISUP ≥2 cancers on systematic and targeted biopsies performed after MRI (per-patient, per-lobe and per-lesion analysis).	Through recruitment completion, an average of 2 years
Comparison of the sensitivities of the CAD and of the PI-RADSv2.1 score for the detection of ISUP ≥2 cancers at per-patient, per-lobe and per-lesion analysis .	Sensitivity of the final CAD and of the PI-RADSv2.1 score for the detection of ISUP ≥2 cancers on systematic and targeted biopsies performed after MRI (per-patient, per-lobe and per-lesion analysis)	Through recruitment completion, an average of 2 years
Comparison of the AUCs of the final CAD and of the PI-RADSv2.1 score for predicting the diagnosis of ISUP ≥2 cancer within 3 years, at per-patient analysis.	AUC of the final CAD and the PI-RADSv2.1 score for predicting the diagnosis of ISUP ≥2 cancer within 3 years of follow-up, at per-patient analysis.	Through recruitment completion, an average of 2 years
Comparison of the sensitivities and specificities of the final CAD and the PI-RADSv2.1 score for predicting the diagnosis of ISUP ≥2 cancer within 3 years, at per-patient analysis.	Sensitivity and specificity of the final CAD and the PI-RADSv2.1 score for predicting the diagnosis of ISUP ≥2 cancer within 3 years of follow-up, at per-patient analysis.	Through study completion, an average of 5 years
Assessment of the impact of biopsy setting, magnetic field strength, human reader's experience, biopsy guidance technique and prostate volume on the AUC of the CAD and the PI-RADSv2.1 scores for the detection of ISUP cancers ≥2, at per-patient analysis.	Analysis of the effect of biopsy setting, magnetic field strength, reader's experience, biopsy guidance technique and prostate volume on the AUC of the final CAD and the PI-RADv2.1, at per-patient analysis.	Through recruitment completion, an average of 2 years
Comparison of the AUC of the PHI index to that of the final CAD and of the PI-RADSv2.1 score for the detection of ISUP ≥2 cancers, at per-patient analysis.	AUC of the PHI index for the detection of cancers ISUP ≥2 on systematic and targeted biopsies performed after MRI, at per-patient analysis.	Through recruitment completion, an average of 2 years
Estimation of the number of biopsies avoided and the number of ISUP cancers ≥2 missed for the following diagnostic strategies:	Number of biopsies avoided and number of ISUP cancers ≥2 missed according to the strategies described below: PHI index then, if positive, MRI and biopsies regardless of the MRI result (MRI used only to guide targeted biopsies).; PHI index then, if positive, MRI then, if positive, targeted biopsies.; Biopsy only if MRI positive; no PHI index.; MRI then, if positive, PHI index then, if positive, targeted biopsies.; MRI then, if negative, PHI index; biopsy for patients with a positive MRI or with a negative MRI but a positive PHI index; PHI index and MRI for all patients; biopsy if positive PHI index AND positive MRI.; PHI index and MRI for all patients; biopsy if positive PHI OR positive MRI.	Through recruitment completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Olivier ROUVIERE, Pr, Service d'imagerie, pavillon B Hôpital Edouard Herriot

Publications and helpful links

General Publications

• Rouviere O, Souchon R, Lartizien C, Mansuy A, Magaud L, Colom M, Dubreuil-Chambardel M, Debeer S, Jaouen T, Duran A, Rippert P, Riche B, Monini C, Vlaeminck-Guillem V, Haesebaert J, Rabilloud M, Crouzet S. Detection of ISUP >/=2 prostate cancers using multiparametric MRI: prospective multicentre assessment of the non-inferiority of an artificial intelligence system as compared to the PI-RADS V.2.1 score (CHANGE study). BMJ Open. 2022 Feb 9;12(2):e051274. doi: 10.1136/bmjopen-2021-051274.

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2021
• Primary Completion (Estimated): June 15, 2026
• Study Completion (Estimated): June 15, 2026

Study Registration Dates

• First Submitted: January 18, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): February 1, 2021

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: MRI; prostate cancer; Artificial Intelligence; Prostate biopsy; Computer-aided diagnosis system
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 69HCL20_0769

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After publication of the results of the trial, the CHANGE cohort will be made partially accessible to other investigators wishing to test a CAD system aimed at detecting/localizing prostate cancer on MR images while respecting patient information. Request for access to pseudonymized data will be reviewed by the Trial Steering Committee that will grant access or not. To gain access, requestors will be required to sign a data access agreement. Of note, investigators will have access only to the MR images and not to the histological findings. After analysis of the CHANGE MR images by their CAD system, the investigator will be requested to send the results to the Hospices Civils de Lyon. The comparison between the CAD findings and the targeted and systematic biopsy findings will be made by the Hospices Civils de Lyon that will then inform the investigator of the CAD diagnostic performance.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No