Why and Where do We Miss Significant Prostate Cancer with Multi-parametric Magnetic Resonance Imaging followed by Magnetic Resonance-guided and Transrectal Ultrasound-guided Biopsy in Biopsy-naïve Men?

BACKGROUND: Knowledge of significant prostate (sPCa) locations being missed with magnetic resonance (MR)- and transrectal ultrasound (TRUS)-guided biopsy (Bx) may help to improve these techniques. OBJECTIVE: To identify the location of sPCa lesions being missed with MR- and TRUS-Bx. DESIGN, SETTING, AND PARTICIPANTS: In a referral center, 223 consecutive Bx-naive men with elevated prostate specific antigen level and/or abnormal digital rectal examination were included. Histopathologically-proven cancer locations, Gleason score, and tumor length were determined. INTERVENTION: All patients underwent multi-parametric MRI and 12-core systematic TRUS-Bx. MR-Bx was performed in all patients with suspicion of PCa on multi-parametric MRI (n=142). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cancer locations were compared between MR- and TRUS-Bx. Proportions were expressed as percentages, and the corresponding 95% confidence intervals were calculated. RESULTS AND LIMITATIONS: In total, 191 lesions were found in 108 patients with sPCa. From these lesion 74% (141/191) were defined as sPCa on either MR- or TRUS-Bx. MR-Bx detected 74% (105/141) of these lesions and 61% (86/141) with TRUS-Bx. TRUS-Bx detected more lesions compared with MR-Bx (140 vs 109). However, these lesions were often low risk (39%). Significant lesions missed with MR-Bx most often had involvement of dorsolateral (58%) and apical (37%) segments and missed segments with TRUS-Bx were located anteriorly (79%), anterior midprostate (50%), and anterior apex (23%). CONCLUSIONS: Both techniques have difficulties in detecting apical lesions. MR-Bx most often missed cancer with involvement of the dorsolateral part (58%) and TRUS-Bx with involvement of the anterior part (79%). PATIENT SUMMARY: Both biopsy techniques miss cancer in specific locations within the prostate. Identification of these lesions may help to improve these techniques.

Location of Prostate Cancers Determined by Multiparametric and MRI-Guided Biopsy in Patients With Elevated Prostate-Specific Antigen Level and at Least One Negative Transrectal Ultrasound-Guided Biopsy.

OBJECTIVE: The purpose of this article is to identify histopathologically proven prostate cancer locations using MRI followed by MRI-guided biopsy in patients with elevated prostate-specific antigen (PSA) levels and at least one negative transrectal ultrasound (TRUS)-guided biopsy session. Our hypothesis is that in this patient group most cancers are located in the anterior portion of the prostate. This may have implications for the biopsy strategy regarding the location of sampling. MATERIALS AND METHODS: This retrospective study consisted of 872 consecutive men who had undergone MRI-guided prostate biopsy. Inclusion criteria were PSA level greater than or equal to 4 ng/mL, one or more negative TRUS-guided biopsy session, the presence of suspicious lesions on previous multiparametric MRI, and prostate cancer histopathologically proven by MRI-guided biopsy. Thereafter, the location of intermediate- or high-risk cancers and cancers with a maximum cancer core length of 6 mm or longer were determined. The proportion of cancer locations was compared using a chi-square test. One-way ANOVA analyses were performed to compare patient characteristics. RESULTS: Results were presented on both a patient and lesion basis because a single patient can have multiple lesions. In total, 176 of 872 patients met the inclusion criteria. Prostate cancer was detected in 202 of 277 (73%) suspicious lesions. In total, 76% of patients had cancer of the transition zone and anterior fibromuscular stroma. Peripheral zone cancers were found in 30% of the patients, and 6% had cancers in both zones. In 70% of cases (141/202; 95%, CI, 63-76%), lesions were located anteriorly; this included 75% (132/176; 95%, CI, 69-81%) of patients. Intermediate- or high-risk prostate cancer was found in 93% (128/138; 95%, CI, 88-96%) of patients. Of these patients, 73% (94/128; 95%, CI, 66-81%) had anterior involvement. Cancers with a maximum cancer core length of 6 mm or more were more likely to be located in the anterior part of the prostate than were cancers with a core length of less than 6 mm (66% vs 6%). Most cancers 58% (102/176; 95% CI, 51-65%) were found in the mid prostate. Anterior involvement of prostate cancer detected by MRI-guided biopsy was statistically significantly (p = 0.04) higher in patients with two or more negative TRUS-guided biopsy sessions (79%) than in those with one negative TRUS-guided biopsy session (55%). CONCLUSION: Anterior involvement was high (76%) in patients with an elevated PSA level and one or more negative TRUS-guided biopsy session, and the majority of these cancers (93%) were intermediate or high risk.

Automated real-time needle-guide tracking for fast 3-T MR-guided transrectal prostate biopsy: a feasibility study.

PURPOSE: To assess the feasibility of automatic needle-guide tracking by using a real-time phase-only cross correlation ( POCC phase-only cross correlation ) algorithm-based sequence for transrectal 3-T in-bore magnetic resonance (MR)-guided prostate biopsies. MATERIALS AND METHODS: This study was approved by the ethics review board, and written informed consent was obtained from all patients. Eleven patients with a prostate-specific antigen level of at least 4 ng/mL (4 µg/L) and at least one transrectal ultrasonography-guided biopsy session with negative findings were enrolled. Regions suspicious for cancer were identified on 3-T multiparametric MR images. During a subsequent MR-guided biopsy, the regions suspicious for cancer were reidentified and targeted by using the POCC phase-only cross correlation -based tracking sequence. Besides testing a general technical feasibility of the biopsy procedure by using the POCC phase-only cross correlation -based tracking sequence, the procedure times were measured, and a pathologic analysis of the biopsy cores was performed. RESULTS: Thirty-eight core samples were obtained from 25 regions suspicious for cancer. It was technically feasible to perform the POCC phase-only cross correlation -based biopsies in all regions suspicious for cancer in each patient, with adequate biopsy samples obtained with each biopsy attempt. The median size of the region suspicious for cancer was 8 mm (range, 4-13 mm). In each region suspicious for cancer (median number per patient, two; range, 1-4), a median of one core sample per region was obtained (range, 1-3). The median time for guidance per target was 1.5 minutes (range, 0.7-5 minutes). Nineteen of 38 core biopsy samples contained cancer. CONCLUSION: This study shows that it is feasible to perform transrectal 3-T MR-guided biopsies by using a POCC phase-only cross correlation algorithm-based real-time tracking sequence.

On the importance of modelling organ geometry and boundary conditions for predicting three-dimensional prostate deformation.

The use of an ultrasound probe or a needle guide during biopsy deforms both the rectal wall and the prostate, resulting in lesion motion. An accurate patient-specific finite element (FE)-based biomechanical model can be used to predict prostate deformations. In this study, an FE model of a prostate phantom is developed using magnetic resonance images, while soft-tissue elasticity is estimated in vivo using an ultrasound-based acoustic radiation force impulse imaging technique. This study confirms that three-dimensional FE-predicted prostate deformation is predominantly dependent on accurate modelling of prostate geometry and boundary conditions. Upon application of various compressive displacements, our results show that a linear elastic FE model can accurately predict prostate deformations. The maximum global error between FE-predicted simulations and experimental results is 0.76 mm. Moreover, the effect of including the urethra, puboprostatic ligament and urinary bladder on prostate deformations is investigated by a sensitivity study.

Differentiation of prostatitis and prostate cancer by using diffusion-weighted MR imaging and MR-guided biopsy at 3 T.

PURPOSE: To determine if prostatitis and prostate cancer (PCa) can be distinguished by using apparent diffusion coefficients (ADCs) on magnetic resonance (MR) images, with specimens obtained at MR-guided biopsy as the standard of reference. MATERIALS AND METHODS: The need for institutional review board approval and informed consent was waived. MR-guided biopsies were performed in 130 consecutive patients with cancer-suspicious regions (CSRs) on multiparametric MR images obtained at 3 T. In this retrospective study, 88 patients met the inclusion criteria. During the biopsy procedure, an axial diffusion-weighted sequence was performed and ADC maps were generated (repetition time msec/echo time msec, 2000/67; section thickness, 4 mm; in-plane resolution, 1.8 × 1.8 mm; and b values of 0, 100, 500, and 800 sec/mm(2)). Subsequently, a confirmation image with the needle left in situ was acquired and projected on the ADC map. The corresponding ADCs at the biopsy location were compared with the histopathologic outcomes of the biopsy specimens. Linear mixed-model regression analyses were used to test for ADC differences between the histopathologic groups. RESULTS: The study included 116 biopsy specimens. Median ADCs of normal prostate tissue, prostatitis, low-grade PCa (Gleason grade components 2 or 3), and high-grade PCa (Gleason grade components 4 or 5) were 1.22 × 10(-3) mm(2)/sec (standard deviation, ± 0.21), 1.08 × 10(-3) mm(2)/sec (± 0.18), 0.88 × 10(-3) mm(2)/sec (± 0.15), and 0.88 × 10(-3) mm(2)/sec (± 0.13), respectively. Although the median ADCs of biopsy specimens with prostatitis were significantly higher compared with low- and high-grade PCa (P < .001), there is a considerable overlap between the tissue types. CONCLUSION: Diffusion-weighted imaging is a noninvasive technique that shows differences between prostatitis and PCa in both the peripheral zone and central gland, although its usability in clinical practice is limited as a result of significant overlap in ADCs.

Three-Tesla magnetic resonance-guided prostate biopsy in men with increased prostate-specific antigen and repeated, negative, random, systematic, transrectal ultrasound biopsies: detection of clinically significant prostate cancers.

BACKGROUND: Patients with elevated prostate-specific antigen (PSA) and one or more previous negative transrectal ultrasound (TRUS) biopsy sessions are subject to diagnostic uncertainty due to TRUS-biopsy undersampling. Magnetic resonance (MR)-guided biopsy (MRGB) has shown high prostate cancer (PCa)-detection rates in studies with limited patient numbers. OBJECTIVE: Determine the detection rate of (clinically significant) PCa for MRGB of cancer-suspicious regions (CSRs) on 3-T multiparametric MR imaging (MP-MRI) in patients with elevated PSA and one or more negative TRUS-biopsy sessions. DESIGN, SETTING, AND PARTICIPANTS: Of 844 patients who underwent 3-T MP-MRI in our referral centre between March 2008 and February 2011, 438 consecutive patients with a PSA >4.0 ng/ml and one negative TRUS-biopsy session or more were included. MRGB was performed in 265 patients. Exclusion criteria were existent PCa, endorectal coil use, and MP-MRI for indications other than cancer detection. INTERVENTION: Patients underwent MRGB of MP-MRI CSRs. MEASUREMENTS: (Clinically significant) MRGB cancer-detection rates were determined. Clinically significant cancer was defined by accepted (i.a. Epstein and d'Amico) criteria based on PSA, Gleason score, stage, and tumour volume. Follow-up PSA and histopathology were collected. Sensitivity analysis was performed for patients with MP-MRI CSRs without MRGB. RESULTS AND LIMITATIONS: In a total of 117 patients, cancer was detected with MRGB (n=108) or after negative MRGB (n=9). PCa was detected in 108 of 438 patients (25%) and in 41% (108 of 265) of MRGB patients. The majority of detected cancers (87%) were clinically significant. Clinically significant cancers were detected in seven of nine (78%) negative MRGB patients in whom PCa was detected during follow-up. Sensitivity analysis resulted in increased cancer detection (47-56%). Complications occurred in 0.2% of patients (5 of 265). CONCLUSIONS: In patients with elevated PSA and one or more negative TRUS-biopsy sessions, MRGB of MP-MRI CSRs had a PCa-detection rate of 41%. The majority of detected cancers were clinically significant (87%).

Evaluation of a robotic technique for transrectal MRI-guided prostate biopsies.

OBJECTIVES: To evaluate the accuracy and speed of a novel robotic technique as an aid to perform magnetic resonance image (MRI)-guided prostate biopsies on patients with cancer suspicious regions. METHODS: A pneumatic controlled MR-compatible manipulator with 5 degrees of freedom was developed in-house to guide biopsies under real-time imaging. From 13 consecutive biopsy procedures, the targeting error, biopsy error and target displacement were calculated to evaluate the accuracy. The time was recorded to evaluate manipulation and procedure time. RESULTS: The robotic and manual techniques demonstrated comparable results regarding mean targeting error (5.7 vs 5.8 mm, respectively) and mean target displacement (6.6 vs 6.0 mm, respectively). The mean biopsy error was larger (6.5 vs 4.4 mm) when using the robotic technique, although not significant. Mean procedure and manipulation time were 76 min and 6 min, respectively using the robotic technique and 61 and 8 min with the manual technique. CONCLUSIONS: Although comparable results regarding accuracy and speed were found, the extended technical effort of the robotic technique make the manual technique - currently - more suitable to perform MRI-guided biopsies. Furthermore, this study provided a better insight in displacement of the target during in vivo biopsy procedures.

Predictive value of MRI in the localization, staging, volume estimation, assessment of aggressiveness, and guidance of radiotherapy and biopsies in prostate cancer.

Multiparametric magnetic resonance imaging (MRI) has the potential of being the ideal prostate cancer (PCa) assessment tool. Information gathered with multiparametric MRI can serve therapy choice, guidance of interventions, and treatments. The purpose of this review is to discuss the potential role of multiparametric MRI in focal therapy with respect to patient selection and directing (robot-guided) biopsies and intensity-modulated radiation therapy (IMRT). Multiparametric MRI is a versatile and promising technique. It appears to be the best available imaging technique at the moment in localizing, staging (primary as well as recurrent disease, and local as well as distant disease), determining aggressiveness, and volume of PCa. However, larger study populations in multicenter settings have to confirm these promising results. However, before such studies can be performed more research is needed in order to achieve standardized imaging protocols.

Feasibility of a pneumatically actuated MR-compatible robot for transrectal prostate biopsy guidance.

PURPOSE: To assess the feasibility of using a remote-controlled, pneumatically actuated magnetic resonance (MR)-compatible robotic device to aid transrectal biopsy of the prostate performed with real-time 3-T MR imaging guidance. MATERIALS AND METHODS: This prospective study was approved by the ethics review board, and written informed consent was obtained from all patients. Twelve consecutive men who were clinically suspected of having prostate cancer and had a history of at least one transrectal ultrasonography (US)-guided prostate biopsy with negative results underwent diagnostic multiparametric MR imaging of the prostate. Two radiologists in consensus identified cancer-suspicious regions (CSRs) in 10 patients. These regions were subsequently targeted with the robot for MR imaging-guided prostate biopsy. To direct the needle guide toward the CSRs, the MR-compatible robotic device was remote controlled at the MR console by means of a controller and a graphical user interface for real-time MR imaging guidance of the needle guide. The ability to reach the CSRs with the robot for biopsy was analyzed. RESULTS: A total of 17 CSRs were detected in 10 patients at the diagnostic MR examinations. These regions were targeted for MR imaging-guided robot-assisted prostate biopsy. Thirteen (76%) of the 17 CSRs could be reached with the robot for biopsy. Biopsy of the remaining four CSRs was performed without use of the robot. CONCLUSION: It is feasible to perform transrectal prostate biopsy with real-time 3-T MR imaging guidance with the aid of a remote-controlled, pneumatically actuated MR-compatible robotic device.

The accuracy and safety aspects of a novel robotic needle guide manipulator to perform transrectal prostate biopsies.

PURPOSE: To introduce a new in-house developed pneumatically controlled magnetic field compatible manipulator as an aid to perform magnetic resonance (MR)-guided biopsies of the prostate. METHODS: A pneumatic controlled manipulator with five degrees of freedom constructed of plastic to achieve magnetic field compatibility was developed to guide biopsies. A risk analysis, mechanical tests, and RF safety tests with respect to needle tip heating were performed to assure future patient safety and to meet standard safety requirements for the use in a medical environment. The accuracy of needle positioning with the needle guide manipulator to sample a predefined target was measured in agar phantoms on a 3 T whole body MR system. The in-plane error was used to evaluate the accuracy, which is defined as the orthogonal distance between target and biopsy needle. The time for each step in the biopsy procedure was recorded to evaluate the procedure time. The influence of the insertion angle with respect to the static field of the MR scanner on the needle artifact was investigated. RESULTS: The risk analyses met patient safety requirements. No RF induced local heating around the needle tip was observed. The average in-plane error in 19 measurements was 3.0 mm (range 0-5.6 mm). The average time needed for manipulation to place the needle guide in the desired position was 5 min (range 3-8 min). Total procedure time was 30 min. The needle artifact size increases with the insertion angle with respect to the static field of the MR scanner. CONCLUSIONS: The new MR compatible manipulator can be used safely for patient care. It showed a high accuracy and short total procedure time, demonstrating great potential to improve the transrectal prostate biopsy procedure.