Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Male patients of age ≥18 suspected for prostate cancer who are scheduled for systematic and/or targeted biopsy after mpMRI examination.

No intervention study

Male patients of age ≥18 diagnosed with prostate cancer who are scheduled for radical prostatectomy

No intervention

Harrie Beerlage, Professor

Rationale: Current imaging techniques for the detection and grading of prostate cancer are imperfect, leading to unnecessary biopsies, suboptimal treatment decisions and missed clinically significant cancers. The hypothesis of this study is that computer assisted analysis of 3D multiparametric ultrasound (mpUS) images can accurately detect, grade and localize prostate cancer. 3D mpUS may then become a more cost-effective and more streamlined imaging strategy than the current standard: mpMRI.

Objective: The primary objective is to collect high-quality 3D mpUS and histology data, to train and improve the classifier algorithm with the goal of achieving an accurate ultrasound imaging tool for the detection of clinically significant prostate cancer.

Secondary objectives are related to the preliminary assessment of the performance of 3D mpUS with computer assisted analysis.

Study design: This is a prospective, multi-center study in men with a suspicion of prostate cancer who are scheduled for prostate biopsies, and men with confirmed prostate cancer who are scheduled to undergo a radical prostatectomy. Prior to prostate biopsies or the radical prostatectomy, 3D mpUS imaging will be performed. The ultrasound images will be analyzed and used for algorithm training using the biopsies and/or prostatecomy specimens as gold standard. Additional research coupes of pathology material (both biopsies and radical prostatectomy specimens) from study subjects will be anonymized and separately analyzed and stored in a central, independent institution. The outcome of the 3D mpUS analysis and the additional pathology evaluation are for research purposes only and will not interfere with standard patient care.

Study population: 1) Male patients of age ≥18 suspected for prostate cancer who are scheduled for systematic and/or targeted biopsy after mpMRI examination.

2) patients of age ≥18 with confirmed prostate cancer who are scheduled for radical prostatectomy.

Main study parameters/endpoints:

* Gleason/Grade group scoring based on histology. Using histology as the reference standard the accuracy of the algorithm will be optimized to be differentiating between benign tissue and various grades of malignancy.
* Localization and size of lesions at full-gland histology in the subset of patients undergoing radical prostatectomy. Correlation in tumour size and location will be optimized between 3D mpUS findings and histology of the full gland.

For the secondary objective, preliminary assessment of the performance of 3D mpUS, the following endpoints are evaluated

* Among all clinically significant detected cancers confirmed by histology, the proportion of these cancers that would have been detected by 3D mpUS will be calculated. The number of false positive findings by 3D mpUS both as an absolute count and expressed as a mean rate per patient.
* The concordance in the detection and grading of abnormalities between mpMRI and 3D mpUS by examining the frequency and type of disagreements and calculating the kappa statistic.

Biospecimens include:

- Histology slices form the prostatectomy specimen

Threedimensional Multiparametric Ultrasound for Prostate Cancer Detection

Improving the AI-based Image Analysis Algorithm for 3D Multiparametric Ultrasound for the Detection, Grading and Localization of Prostate Cancer

This is a diagnostic accuracy study with cross-sectional interest between 3D multiparametric ultrasound results and histological findings at biopsy or histological examination of the full grand as the reference standards.

Cancer detection rates, relative sensitivity / specificity

Angiogenesis Analytics

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

Principal investigator

All patients will undergo multiparametric ultrasound and multiparametric MRI. In case of suspicious multiparametric ultrasound and/or multiparametric MRI,they will undergo combined targeted biopsy and systematic biopsy. In case of nonsuspicious imaging findings, only systematic biopsy will be performed.

Multiparametric ultrasound (mpUS) The mpUS examinations are performed in the order of greyscale imaging, elastography and contrast-enhanced ultrasound (CEUS), with the patients in the left lateral decubitus position.Greyscale imaging and elastography are evaluated by one radiologist. After standard step-sectional greyscale imaging, transverse elastic images are obtained from the base to the apex by manual compression. The amplitude and frequency of compression are adjusted according to the visual compression indicator on the screen to minimize interoperator variability. CEUS is performed using a bolus of 2.4 mL contrast agents (SonoVue, Bracco) using Contrast mode.

Multiparametric MRI (mpMRI) Prostate mpMRI images were acquired using a 3-T scanner with an external phased-array coil.

Prostate imaging

All patients will undergo standard 12-core systematic biopsy (SB) within 1 week following the imaging protocol in conjunction with targeted biopsy (TB) for suspicious lesions on mpUS and/or mpMRI. First, 12-core SB is performed, followed by cognitive mpUS-TB with 2-3 cores for each suspicious lesion. The suspicious lesions on mpUS include hypoechoic lesion(s) on greyscale imaging, reproducible stiff lesion(s) on elastography, and hypoperfused area(s) with ill-defined boundaries or increased focal/asymmetric contrast enhancement on CEUS. Thereafter, MRI/US fusion TB is performed sampling 2-3 cores for each lesion with a Prostate Imaging Reporting and Data System (PI-RADS) version 2 score of 3 or above.Each biopsy sample is placed in the micro-cassette and labelled to identify the biopsy technique and location.

Prostate biopsy

Yunkai Zhu

Guangyu Chen

Wenbin Guan

The goal of this cohort study is to investigate multiparametric ultrasound versus multiparametric MRI for clinically significant prostate cancer detection in patients scheduled for initial biopsy. The main questions it aims to answer are:

* whether the clinically significant prostate cancer detection rate of multiparametric ultrasound is comparable to multiparametric MRI
* the any cancer detection of multiparametric ultrasound versus multiparametric MRI

Participants will undergo multiparametric ultrasound and multiparametric MRI before prostate biopsy. In case of suspicious findings on ultrasound or MRI, they will undergo combined systematic biopsy and targeted biopsy. In case of nonsuspicious imaging finding, they will undergo systematic biopsy alone.

In recent years, the multi-parametric MRI targeted biopsy showed inspiring results for improving clinically significant prostate cancer (PCa) detection rate \[1\]. Two techniques have been developed for MRI targeted prostate biopsy: in-bore MRI guided biopsy and MRI/ultrasound fusion biopsy. However, these biopsy techniques require specific equipment and software. Moreover, MRI has contradictions and cannot be performed in all patients. Therefore, an imaging targeted biopsy adjunct to MRI targeted biopsy is needed.

Besides MRI, multi-parametric ultrasound can also visualize PCa lesions by providing information about the blood supply, perfusion and stiffness of the prostate gland for PCa detection. Our hypothesis is as follows, (1) clinically significant PCa detection rate by multi-parametric ultrasound targeted biopsy is comparable with multi-parametric MRI targeted biopsy; (2) clinically significant PCa detection rate by either multi-parametric ultrasound targeted biopsy or multi-parametric ultrasound targeted biopsy is higher than standard systematic biopsy. Our secondary outcome also includes the any cancer detection rate and clinically insignificant prostate cancer detection rate.

Multi-parametric Ultrasound Versus Multi-parametric MRI for Prostate Cancer Detection

A Prospective Cohort Study Comparing Multi-parametric Ultrasound Versus Multi-parametric MRI for Clinically Significant Prostate Cancer Detection

individual participant data are only available from the investigator on reasonable request

The primary definition was Grade Group(GG) ≥ 2. The secondary definition included PROMIS definition 1 (GG ≥ 3 and/or maximal cancer core length ≥ 6 mm) and PROMIS definition 2 (GG ≥ 2 and/or maximal cancer core length ≥ 4 mm). The measurement that will be based on biopsy histopathology.

Any cancer at biopsy histopathology. The measurement that will be based on biopsy histopathology.

Clinically insignificant prostate cancer at biopsy histopathology. The measurement that will be based on biopsy histopathology.

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

The procedure of 3D multiparametric ultrasound consists of 3 components: (1) intravenous administration of ultrasound contrast; (2) rectal multi-parametric ultrasound imaging; (3) PCaVision: artificial intelligence algorithm analyzing the images.

3D multi-parametric ultrasound targeted biopsy pathway using PcaVision

MRI sequences will include at least T1-weighted, T2-weighted, Diffusion-weighted imaging (DWI) and calculation of apparent diffusion coefficient (ADC) maps. Scoring of suspicion will be performed using the European Society of Urogenital Radiology (ESUR) PI-RADS standardized scoring system. All lesions will be marked and delineated for MRI-TRUS fusion 3D multiparametric ultrasound (mpUS).

MRI targeted biopsy pathway

Daniel van den Kroonenberg, MD

Auke Jager, MD

The primary objective is to demonstrate non-inferiority of the detection rate of clinically significant prostate cancer (csPCa) in targeted biopsies based on PCaVision imaging (PCaVision pathway) in comparison with the detection rate of clinically significant cancer in targeted biopsies based on MRI (MRI pathway).

All patients will undergo imaging using MRI and PCaVision during which suspicious lesions will be identified based on each imaging technique independently with readers being blinded for the results of the other imaging technique. Thereafter, a MRI targeted 3-core biopsy per lesion (maximum of 2 lesions) and/ or a PCaVision targeted 3-core biopsy (maximum of 2 lesions) will be performed by a one physician if suspicious lesions have been identified based on imaging. If lesions have been identified with both PCaVision and MRI in the same patient, the order of the targeted biopsies will be randomized. If the same lesion has been identified on both MRI and PCaVision, both a MRI-targeted and a PCaVision targeted biopsy will be separately performed. Histological examination of the targeted biopsies will be performed to determine presence of clinically significant prostate cancer.

Prostate Cancer Detection Rate of Targeted Biopsies With PCaVision

Clinical Validation of Transrectal Multiparametric Ultrasound Imaging Strategy (PCaVision) for the Detection of Clinically Significant Prostate Cancer: a Head-to-head Comparison With the MRI-based Strategy

csPCa defined as GG ≥ 2 in any of the biopsy cores taken from a lesion

Defined as the number of men in whom no lesions for target biopsies have been identified by PCaVision while no CsPCa is detected in either MRI targeted biopsies or systematic biopsies.

(i) ISUP ≥ 3 in any of the biopsy cores taken from a lesion; (ii) ISUP ≥ 2 with cribriform growth and/or intraductal carcinoma (CR/IDC) in any of the biopsy cores taken from a lesion; (iii) ISUP = 1

Prof.dr. H.P. Beerlage

All consenting patients will undergo mpUS imaging prior to surgery with the ultrasound contrast agent Sonovue for the CEUS specific mode.

The ultrasound contrast agent used for the CEUS specific ultrasound mode

SonoVue

H. Wijkstra, Prof dr ir

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

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.

Multiparametric Ultrasound Imaging in Prostate Cancer

Multiparametric Ultrasound (mpUS) as Imaging Modality for the Detection and Localization of Prostate Cancer

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

Parameters of mpUS (echogenicity, contrast-agent perfusion, contrast-agent dispersion, contrast-agent velocity, tissuedensity) will be assessed

Comparison of predictive accuracy in terms of sensitivity and specificity of mpMRI imaging and mpUS imaging

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Threedimensional Multiparametric Ultrasound for Prostate Cancer Detection	NCT04605276	Prostate Cancer	No intervention	18 Years -	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Multi-parametric Ultrasound Versus Multi-parametric MRI for Prostate Cancer Detection	NCT06183905	PROSTATE CANCER Prostate Biopsy	Prostate imagin... Prostate biopsy	-	Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Prostate Cancer Detection Rate of Targeted Biopsies With PCaVision	NCT06281769	Prostate Cancer	3D multi-parame... MRI targeted bi...	18 Years -	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Multiparametric Ultrasound Imaging in Prostate Cancer	NCT03101176	Prostate Cancer Prostatic Neopl...	SonoVue	18 Years -	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Spots Global Cancer Trial Database for multiparametric ultrasound