Combined T2 and diffusion-weighted MR Imaging with template prostate biopsies in men suspected with prostate cancer but negative transrectal ultrasound-guided biopsies

PURPOSE: Transperineal template prostate (TPB) biopsy has been shown to improve prostate cancer detection in men with rising PSA and previous negative TRUS biopsies. Diagnostic performance of this approach especially MR imaging and using reliable reference standard remains scantly reported. MATERIALS AND METHODS: A total of 200 patients, who were previously TRUS biopsy negative, were recruited in this study. All the participants had at least 28-core TPB under general anesthetic within 8 weeks of previous negative TRUS biopsies. In 15 men undergoing laparoscopic radical prostatectomy, prostate specimens were sectioned using custom-made molds and analyzed by experienced pathologist as a feasibility study. RESULTS: In total, 120 of 200 patients (60 %) had positive TPB biopsy results. All of these men had at least one negative biopsy from transrectal route. T2 diffusion-weighted MR imaging showed no lesion in almost one-third of these men (61/200; 30.5 %). Out of these, 33 (33/61; 54 %) showed malignancy on TPB including high-grade tumors (>Gleason 7). Out of 15 patients underwent surgery with a total of 52 lesions (mean 3.5) on radical prostatectomy histology analyses, TPB detected 36 (70 %) lesions only. Some of these lesions were Gleason 7 and more mostly located in the posterior basal area of prostate. CONCLUSIONS: Transperineal template biopsy technique is associated with significantly high prostate cancer detection rate in men with previous negative TRUS biopsies, however compared to radical prostatectomy histology map, a significant number of lesions can still be missed in the posterior and basal area of prostate

Image-based registration methods for quantification and compensation of prostate motion during trans-rectal ultrasound (TRUS)-guided biopsy

Prostate biopsy is the clinical standard for cancer diagnosis and is typically performed under two-dimensional (2D) transrectal ultrasound (TRUS) for needle guidance. Unfortunately, most early stage prostate cancers are not visible on ultrasound and the procedure suffers from high false negative rates due to the lack of visible targets. Fusion of pre-biopsy MRI to 3D TRUS for targeted biopsy could improve cancer detection rates and volume of tumor sampled. In MRI-TRUS fusion biopsy systems, patient or prostate motion during the procedure causes misalignments in the MR targets mapped to the live 2D TRUS images, limiting the targeting accuracy of the biopsy system. In order to sample smallest clinically significant tumours of 0.5 cm3with 95% confidence, the root mean square (RMS) error of the biopsy system needs to be The target misalignments due to intermittent prostate motion during the procedure can be compensated by registering the live 2D TRUS images acquired during the biopsy procedure to the pre-acquired baseline 3D TRUS image. The registration must be performed both accurately and quickly in order to be useful during the clinical procedure. We developed an intensity-based 2D-3D rigid registration algorithm and validated it by calculating the target registration error (TRE) using manually identified fiducials within the prostate. We discuss two different approaches that can be used to improve the robustness of this registration to meet the clinical requirements. Firstly, we evaluated the impact of intra-procedural 3D TRUS imaging on motion compensation accuracy since the limited anatomical context available in live 2D TRUS images could limit the robustness of the 2D-3D registration. The results indicated that TRE improved when intra-procedural 3D TRUS images were used in registration, with larger improvements in the base and apex regions as compared with the mid-gland region. Secondly, we developed and evaluated a registration algorithm whose optimization is based on learned prostate motion characteristics. Compared to our initial approach, the updated optimization improved the robustness during 2D-3D registration by reducing the number of registrations with a TRE \u3e 5 mm from 9.2% to 1.2% with an overall RMS TRE of 2.3 mm. The methods developed in this work were intended to improve the needle targeting accuracy of 3D TRUS-guided biopsy systems. The successful integration of the techniques into current 3D TRUS-guided systems could improve the overall cancer detection rate during the biopsy and help to achieve earlier diagnosis and fewer repeat biopsy procedures in prostate cancer diagnosis

Toward optimization of target planning for magnetic resonance image-targeted, 3D transrectal ultrasound-guided fusion prostate biopsy

The current clinical standard for diagnosis of prostate cancer (PCa) is 2D transrectal ultrasound (TRUS)-guided biopsy. However, this procedure has a false negative rate of 21-47% and therefore many patients return for repeat biopsies. A potential solution for improving upon this problem is “fusion” biopsy, where magnetic resonance imaging (MRI) is used for PCa detection and localization prior to biopsy. In this procedure, tumours are delineated on pre-procedural MRI and registered to the 3D TRUS needle guidance modality. However, fusion biopsy continues to yield false negative results and there remains a gap in knowledge regarding biopsy needle target selection. Within-tumour needle targets are currently chosen ad hoc by the operating clinician without accounting for guidance system and registration errors. The objective of this thesis was to investigate how the choice of target selection strategy and number of biopsy attempts made per lesion may affect PCa diagnosis in the presence of needle delivery error. A fusion prostate biopsy simulation software platform was developed, which allowed for the investigation of how needle delivery error affects PCa diagnosis and cancer burden estimation. Initial work was conducted using 3D lesions contoured on MRI by collaborating radiologists. The results indicated that more than one core must be taken from the majority of lesions to achieve a sampling probability 95% for a biopsy system with needle delivery error ≥ 3.5 mm. Furthermore, it was observed that the optimal targeting scheme depends on the relative levels of systematic and random needle delivery errors inherent to the specific fusion biopsy system. Lastly, PCa tumours contoured on digital histology images by genitourinary pathologists were used to conduct biopsy simulations. The results demonstrated that needle delivery error has a substantial impact on the biopsy core involvement observed, and that targeting of high-grade lesions may result in higher core involvement variability compared with lesions of all grades. This work represents a first step toward improving the manner in which lesions are targeted using fusion biopsy. Successful integration of these findings into current fusion biopsy system operation could lead to earlier PCa diagnosis with the need for fewer repeat biopsy procedures

Multi Parametric Magnetic Resonance Imaging in the early detection and risk stratification of prostate cancer: The PROMIS trial

Although prostate cancer is the most common cancer in men, it remains a difficult and controversial disease in terms of its diagnostic, risk stratification and treatment pathway. This is mainly due to the shortcomings of the standard diagnostic test, trans rectal ultrasound guided biopsy (TRUSBx), that is triggered following an elevated serum prostate specific antigen (PSA) test and the lack of agreement on disease thresholds that correlate to patient risk, if left untreated (and thus undetected). These factors often complicate the selection of the appropriate management that best fits the individual patient. In this doctoral thesis I propose, examine and validate a different approach that aims to shift the current diagnostic paradigm to that of incorporating an imaging test, multi-parametric magnetic resonance imaging (MP-MRI), prior to TRUS biopsy. First, I will discuss the nature of prostate cancer and highlight the shortcomings of the current diagnostic pathway and their implications. Second, I will analyze the shortcomings in early MP-MRI research that might have hindered its acceptance and adoption into the pathway and review the advances in research that occurred since I started my research. Third, I will discuss the rationale and methodological design considerations behind the PROstate Mri Imaging Study (PROMIS). PROMIS was a multicentre diagnostic paired validating confirmatory cohort study conducted to provide level 1b evidence on diagnostic accuracy of MP-MRI. It was designed to avoid the pitfalls identified in the current literature. I will discuss and analyze the design, conduct and results of the trial and its implications. Finally, I will discuss the wider implications of my work on the clinical practice of prostate cancer management and the future research opportunities made possible by the PROMIS data and its findings

Prostate cancer detection and characterisation using innovative medical imaging

Prostate cancer is the second most common cancer affecting men worldwide. All prostate cancer however, is not equal: some forms of the disease are inert and do not require intervention; other, more aggressive forms benefit from early detection and treatment. Thus, accurate risk stratification is paramount. Inadequacies in the current diagnostic pathway for prostate cancer lead to incorrect risk assignment. Ways of enhancing the diagnostic pathway and improving risk stratification using novel bio-markers are being actively researched worldwide. This thesis focuses on work carried out at University College London (UCL)/University College London Hospitals (UCLH), investigating imaging as a biomarker in prostate cancer. The development of an enhanced form of ultrasound imaging - Prostate HistoScanning (PHS), and the use of multi-parametric magnetic resonance imaging (mpMRI) for prostate cancer detection and risk stratification are investigated. The main body of work: Prostate Imaging Compared to Transperineal Ultrasound guided biopsy for significant prostate cancer Risk Evaluation; the acronym for this is the PICTURE Study, was designed and carried out at UCLH between 2012 and 2014. This research aimed to establish if imaging has a role in improving prostate cancer detection and, if by utilizing imaging in the form of either multi-parametric MRI (mpMRI) or prostate HistoScanning (PHS), men with a negative test may be spared further prostate biopsy. Additionally, for men with a lesion detected on imaging, could a targeted sampling strategy afford accurate disease detection and risk stratification. Despite initial promising results, prostate HistoScanning was found to have no role in prostate cancer detection. Multiparametric MRI however, demonstrated high performance characteristics for the detection of disease. It shows potential as a useful tool for men in whom diagnostic uncertainty remains following primary biopsy; it is asserted that it should therefore be used to help risk stratify these men. Moreover, mpMRI targeted biopsy provides accurate risk stratification; and is an approach that should be adopted