European Multicenter Validation of PCaVision: A Head-to-Head Diagnostic Accuracy Study Comparing Multiparametric Transrectal Ultrasound to MRI for Clinically Significant Prostate Cancer Detection

NCT ID: NCT06935487

Last Updated: 2025-04-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 806 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2027-05-31

Brief Summary

The goal of this clinical trial is to learn if a new ultrasound-based imaging method (PCaVision) can accurately detect clinically significant prostate cancer in adult men (18 years and older) who are either undergoing initial evaluation or are already in active surveillance for prostate cancer. The main questions it aims to answer are:

• Does PCaVision detect clinically significant prostate cancer as accurately as MRI?
• Can some men safely avoid prostate biopsies based on PCaVision imaging results?

Researchers will compare PCaVision-guided biopsies to MRI-guided biopsies to see if PCaVision performs as well as MRI in identifying aggressive prostate cancers.

Participants will:

• Undergo both an MRI and a PCaVision ultrasound scan
• Receive targeted prostate biopsies based on any suspicious areas found in either scan
• Possibly have follow-up visits to monitor for biopsy-related side effects

Detailed Description

Rationale The incidence of prostate cancer (PCa) has increased over the years. To diagnose PCa, histopathological confirmation is required. Different diagnostic pathways are currently available. Systematic biopsies have long been the cornerstone in the diagnostic work-up of men suspected of prostate cancer. However, systematic biopsies can lead to under-diagnosis of clinically significant prostate cancer (csPCa), and each biopsy is associated with the risk of infection and other side effects.

In the magnetic resonance imaging (MRI) pathway, targeted biopsies are only performed when suspicious lesions are detected on MRI. The MRI pathway purposely detects fewer clinically insignificant prostate cancers (ciPCa), but has an increased sensitivity for csPCa and improved localization accuracy of suspicious regions. The MRI-based strategy is now recommended as the first-line investigation. However, reported sensitivities and specificities for MRI vary widely between studies, which can be attributed to differences in MRI equipment, study design, reference standard quality, and inter-observer variability. Moreover, MRI has limited availability and is a time-consuming and expensive imaging modality.

Transrectal ultrasound (TRUS), which is widely available, more cost-effective, and familiar to urologists, may offer a valid alternative. In an ultrasound-based diagnostic pathway, 3D contrast-enhanced ultrasound (CEUS) combined with contrast ultrasound dispersion imaging (CUDI) focuses on detecting angiogenetic changes in the microvascular architecture to localize lesions suspicious for PCa, followed by targeted biopsies for histological confirmation.

PCaVision is a software package designed to support the diagnosis of csPCa by integrating 3D B-mode, 3D Shear Wave Elastography (SWE), and 4D CEUS scans. The PCaVision algorithm was trained on a cohort of 252 patients using prostatectomy pathology as the reference standard, and 83 "negative" patients (no suspicious MRI lesions or positive prostate biopsies). Internal validation showed a sensitivity and specificity of 0.82 and 0.82, respectively. These results led to a first prospective clinical investigation in the Netherlands to demonstrate non-inferiority compared to the MRI-based pathway (NCT06281769). That initial prospective trial aimed to compare the two diagnostic pathways in biopsy-naïve patients under tightly controlled conditions (e.g., 3T MRI, transperineal biopsies, and cognitive or fusion targeting using MIM software). These conditions, however, are not generalizable across Europe, where 1.5T and 3T MRI are used interchangeably, both transperineal and transrectal biopsy approaches are employed, and various fusion systems are in use. Additionally, the previous study excluded patients in active surveillance (AS) and those with prior negative biopsies, who represent a substantial portion of the demand for PCa diagnosis and biopsy guidance.

The objective of the European head-to-head trial described in this protocol is to compare the diagnostic accuracy of two different imaging pathways for detecting csPCa in a broader, more generalizable European setting: (1) the PCaVision-targeted biopsy pathway and (2) the MRI-targeted biopsy pathway. The trial aims to demonstrate the non-inferiority of the PCaVision pathway compared to the MRI pathway in two cohorts: (1) biopsy-naïve and prior negative patients and (2) patients undergoing active surveillance. A fully paired design will be used. The updated PCaVision version 1.1 will be employed in this study, incorporating enhancements to reduce unusable scans and improve diagnostic accuracy and user experience.

Objective

The primary objective is to demonstrate the non-inferiority of csPCa detection in targeted biopsies guided by PCaVision imaging (PCaVision pathway) compared to targeted biopsies guided by MRI (MRI pathway) in two distinct patient cohorts:

1. Biopsy-naïve and prior-negative patients

2. Patients under active surveillance (AS) Clinically significant PCa (csPCa) is defined as International Society of Urological Pathology (ISUP) Grade Group (GG) ≥ 2 in any biopsy core obtained from a lesion.

The secondary objectives include:

1. Comparing the proportion of participants in whom targeted biopsies could be safely omitted in the PCaVision pathway versus the MRI pathway. Safe omission is defined as no lesions identified for targeted biopsy by PCaVision and no csPCa detected by MRI-targeted or systematic biopsies.

2. Conducting the same diagnostic comparison across different definitions of csPCa, including:

• ISUP ≥ 3
• ISUP ≥ 2 with cribriform growth and/or intraductal carcinoma (CR/IDC)
• ISUP = 1

3. Comparing the number of participants for whom PCaVision or MRI produced insufficient image quality.

4. Calculating csPCa detection rates across specific subgroups:

• Men treated with 5-alpha reductase inhibitors (5-ARI) for ≥3 months
• Men with a history of prostate surgery for lower urinary tract symptoms (LUTS)
• Biopsy-naïve and prior-negative patients excluding those under 5-ARI treatment or with prostate surgery history
• AS patients excluding those under 5-ARI treatment or with prostate surgery history Study Design This is a prospective, diagnostic accuracy study using a fully paired design. Study Population The study will include men aged 18 years or older who are scheduled for prostate MRI due to either a suspicious digital rectal examination (DRE) and/or elevated PSA, or as part of routine active surveillance follow-up.

Intervention

All participants will undergo both:

• 3D multiparametric ultrasound (mpUS) imaging using PCaVision
• Multiparametric MRI Suspicious lesions will be identified independently on each modality. If lesions are detected, targeted biopsies will be performed based on the findings.

Biopsy procedure:

• If one lesion is detected: 3 targeted biopsies
• If two lesions: 3 biopsies per lesion (6 total)
• If three or more lesions: 2 selected lesions will be biopsied (3 biopsies per lesion)

Selection criteria:

• For MRI: PI-RADS score and lesion size
• For PCaVision: predicted csPCa probability and lesion size A maximum of 6 biopsies per imaging technique will be performed (maximum 12 study-driven biopsies per participant). This does not include systematic biopsies, which may be conducted according to the standard of care at the participating center. All biopsies will be conducted during a single visit.

Main Study Endpoint The primary endpoint is the detection of clinically significant prostate cancer (GG ≥ 2) based on histopathological examination of targeted biopsies. The study aims to demonstrate that detection using the PCaVision pathway is not inferior to detection using the MRI pathway within a predefined non-inferiority margin of 5 percentage points for both patient cohorts.

Burden, Risks, and Benefits In most participating centers, current clinical care involves MRI-targeted and possibly systematic biopsies. These care practices will remain unchanged in the study. Systematic biopsies are not part of the formal head-to-head comparison between MRI and PCaVision.

Potential benefits to participants include detection of additional cancers that MRI may miss. Broader study results may help expand access to effective diagnostic imaging, especially in settings with limited MRI availability.

Additional targeted biopsies may be required based on PCaVision findings, which carry minor risks such as infection or bleeding. The use of ultrasound contrast agent may pose minimal and rare risks, typically transient and mild. Overall, the burden and risk associated with participation are considered low.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

PCaVision Imaging + PCaVision-Targeted Biopsy

Participants undergo 3D multiparametric ultrasound (mpUS) imaging using PCaVision, a software-assisted diagnostic tool that combines B-mode, Shear Wave Elastography, and Contrast-Enhanced Ultrasound (CEUS).

Suspicious lesions identified by PCaVision will be targeted for biopsy (up to 2 lesions, 3 cores each).

• Transrectal 3D mpUS using PCaVision software (v1.1)
• Injection of ultrasound contrast agent (SonoVue)
• Targeted biopsy based on PCaVision lesion detection (up to 6 cores total)

Group Type: EXPERIMENTAL

transrectal ultrasound of prostate (TRUS) with AI software algorithm

Intervention Type: DIAGNOSTIC_TEST

Transrectal ultrasound of prostate (TRUS) with AI software algorithm for detection of lesions suspected for prostate cancer

MRI Imaging + MRI-Targeted Biopsy

Participants undergo multiparametric MRI (mpMRI) of the prostate using 1.5T or 3T MRI systems.

Suspicious lesions identified by MRI will be targeted for biopsy (up to 2 lesions, 3 cores each).

• Prostate mpMRI with or without contrast
• Image analysis following PI-RADS criteria
• Targeted biopsy based on MRI lesion detection (up to 6 cores total)

Group Type: ACTIVE_COMPARATOR

MRI prostate

Intervention Type: DIAGNOSTIC_TEST

MRI for detection of lesions suspected for prostate cancer

Interventions

transrectal ultrasound of prostate (TRUS) with AI software algorithm

Transrectal ultrasound of prostate (TRUS) with AI software algorithm for detection of lesions suspected for prostate cancer

Intervention Type: DIAGNOSTIC_TEST

MRI prostate

MRI for detection of lesions suspected for prostate cancer

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

1. male

2. 18 years of age or older

3. scheduled for evaluation by prostate MRI due to:

• suspicious digital rectal examination (DRE) and/or
• Elevated serum PSA levels, or as part of active surveillance (AS) follow-up

4. Have provided written informed consent

Exclusion Criteria

1. Active urinary tract infection or prostatitis

2. A history of cardiac right-to-left shunt

3. Allergy to sulphur hexafluoride or any other ingredient in the ultrasound contrast agent SonoVue

4. Current treatment with dobutamine

5. Severe pulmonary hypertension (pulmonary artery pressure > 90 mmHg), uncontrolled systemic hypertension, or respiratory distress syndrome

6. Any other contraindication to MRI or 3D mpUS imaging

7. Inability to understand the language of the patient information (i.e., language barrier)

8. Previous treatment with focal therapy for prostate cancer (e.g., HIFU, cryotherapy, laser ablation, etc.)

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Angiogenesis Analytics

INDUSTRY

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: lead

Responsible Party

Harrie P. Beerlage

Prof. Dr. H.P. Beerlage

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

dr. Oddens, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC

Locations

Institut Paoli- Calmettes

Marseille, , France

L'Institut Mutualiste Montsouris

Paris, , France

University Klinikum Bonn

Bonn, , Germany

Martini-Klinik am UKE

Hamburg, , Germany

Urologische Klinik München- Planegg

Planegg, , Germany

Università degli Studi di Foggia

Foggia, , Italy

University of Padua

Padua, , Italy

Amsterdam UMC

Amsterdam, , Netherlands

Oslo University hospital Ullevål

Oslo, , Norway

Fundació Puigvert

Barcelona, , Spain

Countries

France; Germany; Italy; Netherlands; Norway; Spain

References

Jager A, Vilanova JC, Michi M, Wijkstra H, Oddens JR. The challenge of prostate biopsy guidance in the era of mpMRI detected lesion: ultrasound-guided versus in-bore biopsy. Br J Radiol. 2022 Mar 1;95(1131):20210363. doi: 10.1259/bjr.20210363. Epub 2021 Jul 29.

Reference Type: BACKGROUND

PMID: 34324383 (View on PubMed)

van Moorselaar RJ, Voest EE. Angiogenesis in prostate cancer: its role in disease progression and possible therapeutic approaches. Mol Cell Endocrinol. 2002 Nov 29;197(1-2):239-50. doi: 10.1016/s0303-7207(02)00262-9.

Reference Type: BACKGROUND

PMID: 12431818 (View on PubMed)

van den Kroonenberg DL, Jager A, Garrido-Utrilla A, Reitsma JB, Postema AW, Beerlage HP, Oddens JR. Clinical Validation of Multiparametric Ultrasound for Detecting Clinically Significant Prostate Cancer Using Computer-Aided Diagnosis: A Direct Comparison with the Magnetic Resonance Imaging Pathway. Eur Urol Open Sci. 2024 Jul 1;66:60-66. doi: 10.1016/j.euros.2024.06.012. eCollection 2024 Aug.

Reference Type: BACKGROUND

PMID: 39050912 (View on PubMed)

Jager A, Zwart MJ, Postema AW, van den Kroonenberg DL, Zwart W, Beerlage HP, Oddens JR, Mischi M. Development and validation of a framework for registration of whole-mount radical prostatectomy histopathology with three-dimensional transrectal ultrasound. BMC Urol. 2025 Apr 3;25(1):73. doi: 10.1186/s12894-025-01736-4.

Reference Type: BACKGROUND

PMID: 40175990 (View on PubMed)

Other Identifiers

NL87353.000.24

Identifier Type: -

Identifier Source: org_study_id