Multiparametric Ultrasound Imaging in Prostate Cancer

Not Applicable

• Conditions: Prostatic Neoplasms; Prostate Cancer
• Interventions: Drug: SonoVue

• Registration Number: NCT03101176
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary

Rationale: The current limitations in prostate cancer diagnostics, due to lack of accuracy of the available techniques, lead to over- and undertreatment for a significant fraction of patients with prostate cancer. Multiparametric ultrasound (mpUS), a new imaging modality combining different ultrasound parameters, heralds the potential for an accurate imaging-based diagnostic approach accessible to the community at large but formal validation of mpUS against final pathology results are still lacking.

Objective: To validate mpUS as imaging modality for detection and localization of prostate cancer by direct correlation with histopathology of radical prostatectomy specimens

Detailed Description

Systematic transrectal ultrasound (TRUS)-guided biopsies in men with a clinical suspicion of prostate cancer, based on digital rectal examination (DRE) and/or prostate-specific antigen (PSA) has been the diagnostic strategy for years. However, this method has known limited sensitivity and risks, as many men without cancer undergo unnecessary biopsies, clinically insignificant cancers are often detected while significant cancers are missed or under-graded and the biopsy procedure itself carries discomfort and morbidity. Prostate imaging capable of identifying clinically significant disease for targeted biopsy with high accuracy and efficiency is thus of importance. mpMRI (multiparametric magnetic resonance imaging) and mpMRI-targeted biopsies are being increasingly used, and they have improved the ability to detect clinically significant cancers, while reducing the diagnosis of insignificant cancers compared to TRUS-guided biopsies. Nevertheless, mpMRI has been limited by inter-reader variability, high level of expertise requirements and heterogeneity in definitions while mpMRI-targeted biopsies alone still misses clinical significant cancers revealed by TRUS-guided biopsies.

There is an ongoing search for new cost-effective, manageable imaging technologies for adequate prostate cancer diagnosis. Various ultrasound modalities are in development striving to increase cancer detection among which contrast-enhanced ultrasound (CEUS) and elastography. Preliminary results of a multiparametric ultrasound (mpUS) approach, combining these different ultrasound modalities, seem promising. The number and quality of studies available, however, is relatively low, emphasizing the need for further work to define the role of mpUS.

This is an investigator-initiated, prospective in-vivo validation study in humans to validate mpUS as imaging modality for detection and localization of prostate cancer by direct correlation with histopathology. Biopsy-proven prostate cancer patients scheduled for radical prostatectomy will be approached and consented to enter this study. Information about the study will be provided both verbally and in written form.

Participants will undergo a mpUS imaging prior to their surgery. For the contrast enhanced mode of the mpUS an additional infusion of an ultrasound contrast agent through an intravenous cannula will be used during transrectal ultrasound scanning for the purpose of the study.

The mpUS imaging data will be evaluated qualitatively and semi-quantitatively using parametric maps by prostate ultrasound experts blinded for radical prostatectomy histopathology. Histopathology will be evaluated qualitatively by an uro-pathologist blinded for mpUS imaging results. Hence, imaging data will be correlated with histopathology in a blinded fashion using a 3D registration system and 3D reconstruction model. Predictive accuracy of mpUS imaging for detection and localization of prostate cancer on histopathology will be analyzed.

At a later stage, a mpUS classifier, most optimally combining the most relevant ultrasound parameters of each modality in one single resulting mpUS parameter will be developed. Furthermore, the additional clinical value of mpUS imaging in prostate cancer diagnostics will be determined by comparing mpUS results with that of available mpMRI data. mpMRI imaging data will be evaluated by an uro-radiologist using the PI-RADS (Prostate Imaging Reporting and Data System) criteria blinded for radical prostatectomy results.

Study Timeline

• Study First Submitted: 2017-03-23
• Study First Submitted QC: 2017-03-29
• Study First Posted: 2017-04-05
• Study Start: 2017-09-07
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-16
• Last Update Posted: 2019-01-17
• Primary Completion: 2022-09-01
• Study Completion: 2022-09-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 200

Inclusion Criteria

• age ≥ 18 years
• biopsy proven prostate carcinoma
• planned treatment by (robot laparoscopic) radical prostatectomy
• signed informed consent

Exclusion Criteria

• Chemotherapy, radiotherapy or focal therapy of the prostate for prostate cancer
• Hormonal therapy for prostate cancer within last six months
• History of any clinically evidence of cardiac right-to-left shunts
• Receives treatment that includes dobutamine
• Severe pulmonary hypertension (pulmonary artery pressure >90 mmHg) or uncontrolled systemic hypertension or respiratory distress syndrome
• Has any medical condition or other circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study
• Is incapable of understanding the language in which the information for the patient is given

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental: Single Arm	SonoVue	All consenting patients will undergo mpUS imaging prior to surgery with the ultrasound contrast agent Sonovue for the CEUS specific mode.

Primary Outcome Measures

Name	Time	Method
Validation of mpUS	5 years	Predictive accuracy in terms of sensitivity and specificity of mpUS imaging in the detection and localization of prostate cancer by qualitatively and semi-quantitatively correlation of mpUS imaging to corresponding radical prostatectomy histopathology

Secondary Outcome Measures

Name	Time	Method
Differences in mpUS parameters between benign and malignant (low-grade and high-grade) prostate tissue	5 years	Parameters of mpUS (echogenicity, contrast-agent perfusion, contrast-agent dispersion, contrast-agent velocity, tissuedensity) will be assessed
mpUS and mpMRI comparison	5 years	Comparison of predictive accuracy in terms of sensitivity and specificity of mpMRI imaging and mpUS imaging

Trial Locations

Locations (1)

AMC University Hospital; 🇳🇱 Amsterdam, Netherlands