Artificial Intelligence Improves the Ability of Physicians to Identify Prostate Cancer Extent.

PURPOSE: Defining prostate cancer contours is a complex task, undermining the efficacy of interventions such as focal therapy. A multireader multicase study compared physicians' performance using artificial intelligence (AI) vs standard-of-care methods for tumor delineation. MATERIALS AND METHODS: Cases were interpreted by 7 urologists and 3 radiologists from 5 institutions with 2 to 23 years of experience. Each reader evaluated 50 prostatectomy cases retrospectively eligible for focal therapy. Each case included a T2-weighted MRI, contours of the prostate and region(s) of interest suspicious for cancer, and a biopsy report. First, readers defined cancer contours cognitively, manually delineating tumor boundaries to encapsulate all clinically significant disease. Then, after ≥ 4 weeks, readers contoured the same cases using AI software. Using tumor boundaries on whole-mount histopathology slides as ground truth, AI-assisted, cognitively-defined, and hemigland cancer contours were evaluated. Primary outcome measures were the accuracy and negative margin rate of cancer contours. All statistical analyses were performed using generalized estimating equations. RESULTS: The balanced accuracy (mean of voxel-wise sensitivity and specificity) of AI-assisted cancer contours (84.7%) was superior to cognitively-defined (67.2%) and hemigland contours (75.9%; P < .0001). Cognitively-defined cancer contours systematically underestimated cancer extent, with a negative margin rate of 1.6% compared to 72.8% for AI-assisted cancer contours (P < .0001). CONCLUSIONS: AI-assisted cancer contours reduce underestimation of prostate cancer extent, significantly improving contouring accuracy and negative margin rate achieved by physicians. This technology can potentially improve outcomes, as accurate contouring informs patient management strategy and underpins the oncologic efficacy of treatment.

Prediction and Mapping of Intraprostatic Tumor Extent with Artificial Intelligence.

Background: Magnetic resonance imaging (MRI) underestimation of prostate cancer extent complicates the definition of focal treatment margins. Objective: To validate focal treatment margins produced by an artificial intelligence (AI) model. Design setting and participants: Testing was conducted retrospectively in an independent dataset of 50 consecutive patients who had radical prostatectomy for intermediate-risk cancer. An AI deep learning model incorporated multimodal imaging and biopsy data to produce three-dimensional cancer estimation maps and margins. AI margins were compared with conventional MRI regions of interest (ROIs), 10-mm margins around ROIs, and hemigland margins. The AI model also furnished predictions of negative surgical margin probability, which were assessed for accuracy. Outcome measurements and statistical analysis: Comparing AI with conventional margins, sensitivity was evaluated using Wilcoxon signed-rank tests and negative margin rates using chi-square tests. Predicted versus observed negative margin probability was assessed using linear regression. Clinically significant prostate cancer (International Society of Urological Pathology grade ≥2) delineated on whole-mount histopathology served as ground truth. Results and limitations: The mean sensitivity for cancer-bearing voxels was higher for AI margins (97%) than for conventional ROIs (37%, p < 0.001), 10-mm ROI margins (93%, p = 0.24), and hemigland margins (94%, p < 0.001). For index lesions, AI margins were more often negative (90%) than conventional ROIs (0%, p < 0.001), 10-mm ROI margins (82%, p = 0.24), and hemigland margins (66%, p = 0.004). Predicted and observed negative margin probabilities were strongly correlated (R2 = 0.98, median error = 4%). Limitations include a validation dataset derived from a single institution's prostatectomy population. Conclusions: The AI model was accurate and effective in an independent test set. This approach could improve and standardize treatment margin definition, potentially reducing cancer recurrence rates. Furthermore, an accurate assessment of negative margin probability could facilitate informed decision-making for patients and physicians. Patient summary: Artificial intelligence was used to predict the extent of tumors in surgically removed prostate specimens. It predicted tumor margins more accurately than conventional methods.

Domain generalization for prostate segmentation in transrectal ultrasound images: A multi-center study.

Prostate biopsy and image-guided treatment procedures are often performed under the guidance of ultrasound fused with magnetic resonance images (MRI). Accurate image fusion relies on accurate segmentation of the prostate on ultrasound images. Yet, the reduced signal-to-noise ratio and artifacts (e.g., speckle and shadowing) in ultrasound images limit the performance of automated prostate segmentation techniques and generalizing these methods to new image domains is inherently difficult. In this study, we address these challenges by introducing a novel 2.5D deep neural network for prostate segmentation on ultrasound images. Our approach addresses the limitations of transfer learning and finetuning methods (i.e., drop in performance on the original training data when the model weights are updated) by combining a supervised domain adaptation technique and a knowledge distillation loss. The knowledge distillation loss allows the preservation of previously learned knowledge and reduces the performance drop after model finetuning on new datasets. Furthermore, our approach relies on an attention module that considers model feature positioning information to improve the segmentation accuracy. We trained our model on 764 subjects from one institution and finetuned our model using only ten subjects from subsequent institutions. We analyzed the performance of our method on three large datasets encompassing 2067 subjects from three different institutions. Our method achieved an average Dice Similarity Coefficient (Dice) of 94.0±0.03 and Hausdorff Distance (HD95) of 2.28 mm in an independent set of subjects from the first institution. Moreover, our model generalized well in the studies from the other two institutions (Dice: 91.0±0.03; HD95: 3.7 mm and Dice: 82.0±0.03; HD95: 7.1 mm). We introduced an approach that successfully segmented the prostate on ultrasound images in a multi-center study, suggesting its clinical potential to facilitate the accurate fusion of ultrasound and MRI images to drive biopsy and image-guided treatments.

Interstitial Optical Monitoring of Focal Laser Ablation.

Focal laser ablation is a minimally invasive method of treating cancerous lesions in organs such as prostate, liver and brain. Oncologic control is achieved by inducing hyperthermia throughout the target while minimizing damage to surrounding tissue. Consequently, successful clinical outcomes are contingent upon achieving desired ablation volumes. Magnetic resonance thermometry is frequently used to monitor the formation of the induced thermal damage zone and inform the decision to terminate energy delivery. However, due to the associated cost and complexity there is growing interest in the development of alternative approaches. Here we investigate the utility of real-time interstitial interrogation of laser-tissue interaction as an inexpensive alternative monitoring modality that provides direct assessment of tissue coagulation without the need for organ specific calibration. The optical contrast mechanism was determined using a Monte Carlo model. Subsequently, four interstitial probe designs were manufactured and assessed in a tissue mimicking phantom under simultaneous magnetic resonance imaging. Finally, the optimal probe design was evaluated in ex vivo bovine muscle. It was found to be capable of providing sufficient feedback to achieve pre-defined ablation radii in the range 4-7 mm with a mean absolute error of 0.3 mm. This approach provides an inexpensive monitoring modality that may facilitate widespread adoption of focal laser ablation.

Methods of monitoring thermal ablation of soft tissue tumors - A comprehensive review.

Thermal ablation is a form of hyperthermia in which oncologic control can be achieved by briefly inducing elevated temperatures, typically in the range 50-80°C, within a target tissue. Ablation modalities include high intensity focused ultrasound, radiofrequency ablation, microwave ablation, and laser interstitial thermal therapy which are all capable of generating confined zones of tissue destruction, resulting in fewer complications than conventional cancer therapies. Oncologic control is contingent upon achieving predefined coagulation zones; therefore, intraoperative assessment of treatment progress is highly desirable. Consequently, there is a growing interest in the development of ablation monitoring modalities. The first section of this review presents the mechanism of action and common applications of the primary ablation modalities. The following section outlines the state-of-the-art in thermal dosimetry which includes interstitial thermal probes and radiologic imaging. Both the physical mechanism of measurement and clinical or pre-clinical performance are discussed for each ablation modality. Thermal dosimetry must be coupled with a thermal damage model as outlined in Section 4. These models estimate cell death based on temperature-time history and are inherently tissue specific. In the absence of a reliable thermal model, the utility of thermal monitoring is greatly reduced. The final section of this review paper covers technologies that have been developed to directly assess tissue conditions. These approaches include visualization of non-perfused tissue with contrast-enhanced imaging, assessment of tissue mechanical properties using ultrasound and magnetic resonance elastography, and finally interrogation of tissue optical properties with interstitial probes. In summary, monitoring thermal ablation is critical for consistent clinical success and many promising technologies are under development but an optimal solution has yet to achieve widespread adoption.

Focal Laser Ablation of Prostate Cancer: An Office Procedure.

In this article, we describe and illustrate an outpatient procedure for focal laser ablation (FLA) of prostate cancer (PCa). The procedure is conceptually similar to a fusion biopsy and is performed under local anesthesia in a clinic setting; treatment time is usually less than one hour. Laser insertion is guided by ultrasound; lesion targeting is via magnetic resonance imaging-ultrasound (MRI/US) fusion, as in targeted prostate biopsy. Real-time ablation monitoring is achieved utilizing a thermal probe adjacent to the laser fiber. The video demonstrates procedure planning, patient preparation, various steps during the procedure, and treatment monitoring. Safety, feasibility, and efficacy of this approach have been established during a previous trial. Outpatient FLA under local anesthesia is an option for management of intermediate risk prostate cancer.

Serial Molecular Profiling of Low-grade Prostate Cancer to Assess Tumor Upgrading: A Longitudinal Cohort Study.

BACKGROUND: The potential for low-grade (grade group 1 [GG1]) prostate cancer (PCa) to progress to high-grade disease remains unclear. OBJECTIVE: To interrogate the molecular and biological features of low-grade PCa serially over time. DESIGN, SETTING, AND PARTICIPANTS: Nested longitudinal cohort study in an academic active surveillance (AS) program. Men were on AS for GG1 PCa from 2012 to 2017. INTERVENTION: Electronic tracking and resampling of PCa using magnetic resonance imaging/ultrasound fusion biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: ERG immunohistochemistry (IHC) and targeted DNA/RNA next-generation sequencing were performed on initial and repeat biopsies. Tumor clonality was assessed. Molecular data were compared between men who upgraded and those who did not upgrade to GG ≥ 2 cancer. RESULTS AND LIMITATIONS: Sixty-six men with median age 64 yr (interquartile range [IQR], 59-69) and prostate-specific antigen 4.9 ng/mL (IQR, 3.3-6.4) underwent repeat sampling of a tracked tumor focus (median interval, 11 mo; IQR, 6-13). IHC-based ERG fusion status was concordant at initial and repeat biopsies in 63 men (95% vs expected 50%, p < 0.001), and RNAseq-based fusion and isoform expression were concordant in nine of 13 (69%) ERG+ patients, supporting focal resampling. Among 15 men who upgraded with complete data at both time points, integrated DNA/RNAseq analysis provided evidence of shared clonality in at least five cases. Such cases could reflect initial undersampling, but also support the possibility of clonal temporal progression of low-grade cancer. Our assessment was limited by sample size and use of targeted sequencing. CONCLUSIONS: Repeat molecular assessment of low-grade tumors suggests that clonal progression could be one mechanism of upgrading. These data underscore the importance of serial tumor assessment in men pursuing AS of low-grade PCa. PATIENT SUMMARY: We performed targeted rebiopsy and molecular testing of low-grade tumors on active surveillance. Our findings highlight the importance of periodic biopsy as a component of monitoring for cancer upgrading during surveillance.

Monitoring Focal Laser Ablation with Interstitial Fluence Probes: Monte Carlo Simulation and Phantom Validation.

Focal laser ablation offers a minimally invasive method of treating solid organ tumors via hyperthermia. Real-time monitoring of the induced tissue damage is critical for clinical success, and is typically accomplished using thermal measurements and Arrhenius models. In this manuscript, the utility of interstitial fluence probes in assessing coagulation directly in real-time was assessed through a Monte Carlo simulation and an experimental study in tissue mimicking prostate phantoms. In the simulation results, fluence increases greater than 100% were observed inside the coagulation zone, as coagulation effectively acts as a 'light trap'. Moreover, the passing of the coagulation boundary at any given point was shown to correspond with an inflection in fluence with a mean absolute difference of 0.1mm and 0.4mm observed for the simulation and phantom respectively. These results suggest that interstitial fluence probes may be capable of providing real-time feedback during focal laser ablation.

Multicenter analysis of clinical and MRI characteristics associated with detecting clinically significant prostate cancer in PI-RADS (v2.0) category 3 lesions.

OBJECTIVES: We sought to identify clinical and magnetic resonance imaging (MRI) characteristics in men with the Prostate Imaging - Reporting and Data System (PI-RADS) category 3 index lesions that predict clinically significant prostate cancer (CaP) on MRI targeted biopsy. MATERIALS AND METHODS: Multicenter study of prospectively collected data for biopsy-naive men (n = 247) who underwent MRI-targeted and systematic biopsies for PI-RADS 3 index lesions. The primary endpoint was diagnosis of clinically significant CaP (Grade Group ≥2). Multivariable logistic regression models assessed for factors associated with clinically significant CaP. The probability distributions of clinically significant CaP based on different levels of predictors of multivariable models were plotted in a heatmap. RESULTS: Men with clinically significant CaP had smaller prostate volume (39.20 vs. 55.10 ml, P < 0.001) and lower apparent diffusion coefficient (ADC) values (973 vs. 1068 µm2/s, P = 0.013), but higher prostate-specific antigen (PSA) density (0.21 vs. 0.13 ng/ml2, P = 0.027). On multivariable analyses, lower prostate volume (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.92-0.97), lower ADC value (OR: 0.99, 95% CI: 0.99-1.00), and Prostate-specific antigen density >0.15 ng/ml2 (OR: 3.51, 95% CI 1.61-7.68) were independently associated with significant CaP. CONCLUSION: Higher PSA density, lower prostate volume and ADC values are associated with clinically significant CaP in biopsy-naïve men with PI-RADS 3 lesions. We present regression-derived probabilities of detecting clinically significant CaP based on various clinical and imaging values that can be used in decision-making. Our findings demonstrate an opportunity for MRI refinement or biomarker discovery to improve risk stratification for PI-RADS 3 lesions.

Prostate Multiparametric Magnetic Resonance Imaging Features Following Partial Gland Cryoablation.

OBJECTIVE: To assess the qualitative and quantitative changes on prostate multiparametric magnetic resonance imaging (mpMRI) following partial gland ablation (PGA) with cryotherapy and correlate with histopathology. METHODS: We used 3D Slicer to generate prostate models and segment ipsilateral (treated) and contralateral peripheral and transition zones in 10 men who underwent MRI/transrectal ultrasound fusion-guided PGA during 2017-2018. Pre- and post-PGA volumes of prostate segments were compared. Post-PGA mpMRI were categorized according to PI-RADS v2 and treatment response on mpMRI was assessed in a manner similar to the radiology evaluation framework following liver lesion ablation. RESULTS: Median volume of ipsilateral peripheral and transition zones decreased from 10.9 mL and 13.0 mL to 7.2 mL and 10.8 mL (P = .005), respectively. Median volume of contralateral peripheral and transition zones also decreased from 12.1 mL and 12.5 mL to 9.9 mL to 10.4 mL (P = .005), respectively. Five men had clinically significant disease (Grade group ≥2) on post-PGA biopsy (3 within treatment field and 2 outside). Of the men with clinically significant prostate cancer, mpMRI revealed PI-RADS 3 lesions in 2. However, the treatment response framework did not detect residual disease. CONCLUSION: PGA results in asymmetrical and significant reductions in prostate volume. Our results highlight the need for a separate assessment framework to enable standardization of the interpretation and reporting of post-PGA surveillance mpMRI. Moreover, our findings have significant implications for MRI-targeted surveillance biopsy following PGA with cryotherapy.

Prostate Cancer Detection Rate of Freehand versus 3-Dimensional Template Mapping Biopsy Using a Magnetic Resonance Imaging-Ultrasound Fusion Device in Biopsy Naïve Men.

PURPOSE: Targeted prostate biopsy devices include a 3-dimensional digital template grid to guide systematic biopsy locations. Following a template could better ensure uniform and well distributed sampling of the prostate compared to the traditional freehand biopsy approach, possibly decreasing the chance of false-negative biopsy. Thus, we determined cancer detection rates obtained by conventional freehand systematic sampling vs template mapping sampling using a magnetic resonance imaging-ultrasound fusion device. MATERIALS AND METHODS: Men who underwent first line conventional or image guided prostate biopsy were identified retrospectively in an institutional review board approved protocol. Excluded from study were men with prior biopsy or treatment or fewer than 10 cores taken. Targeted cores obtained by image guided biopsy were censored from analysis to simulate systematic template biopsy. The resulting cancer detection rate was compared to that of conventional biopsy. RESULTS: We identified 1,582 patients between 2006 and 2014 who met the criteria for analysis, including 1,052 who underwent conventional biopsy and 530 who underwent template biopsy with a magnetic resonance imaging-ultrasound fusion device. Patient age, prostate specific antigen and the number of systematic cores were the same in the 2 groups. Template biopsy detected any prostate cancer in 257 of 530 men (48.5%) and clinically significant cancer in 196 (37.0%) while conventional biopsy detected any cancer in 432 of 1,052 (41.0%) (p=0.005) and clinically significant cancer in 308 (29.2%) (p=0.002). CONCLUSIONS: Template mapping systematic biopsy detected more prostate cancer than conventional sampling in biopsy naïve men. It is a promising cost-effective alternative to magnetic resonance imaging-ultrasound fusion biopsy as an upfront screening tool.

Using spatial tracking with magnetic resonance imaging/ultrasound-guided biopsy to identify unilateral prostate cancer.

OBJECTIVES: To create reliable predictive metrics of unilateral disease using spatial tracking from a fusion device, thereby improving patient selection for hemi-gland ablation of prostate cancer. PATIENTS AND METHODS: We identified patients who received magnetic resonance imaging (MRI)/ultrasound-guided biopsy and radical prostatectomy at a single institution between 2011 and 2018. In addition to standard clinical features, we extracted quantitative features related to biopsy core and MRI target locations predictive of tumour unilaterality. Classification and Regression Tree (CART) analysis was used to create a decision tree (DT) for identifying cancer laterality. We evaluated concordance of model-determined laterality with final surgical pathology. RESULTS: A total of 173 patients were identified with biopsy coordinates and surgical pathology available. Based on CART analysis, in addition to biopsy- and MRI-confirmed disease unilaterality, patients should be further screened for cancer detected within 7 mm of midline in a 40 mL prostate, which equates to the central third of any-sized prostate by radius. The area under the curve for this DT was 0.82. Standard diagnostics and the DT correctly identified disease laterality in 73% and 80% of patients, respectively (P = 0.13). Of the patients identified as unilateral by standard diagnostics, 47% had undetected contralateral disease or were otherwise incorrectly identified. This error rate was reduced to 17% (P = 0.01) with the DT. CONCLUSION: Using spatial tracking from fusion devices, a DT was more reliable for identifying laterality of prostate cancer compared to standard diagnostics. Patients with cancer detected within the central third of the prostate by radius are poor hemi-gland ablation candidates due to the risk of midline extension of tumour.

Comparison of Targeted vs Systematic Prostate Biopsy in Men Who Are Biopsy Naive: The Prospective Assessment of Image Registration in the Diagnosis of Prostate Cancer (PAIREDCAP) Study.

Importance: Magnetic resonance imaging (MRI) guidance improves the accuracy of prostate biopsy for the detection of clinically significant prostate cancer, but the optimal use of such guidance is not yet clear. Objective: To determine the cancer detection rate (CDR) of targeting MRI-visible lesions vs systematic prostate sampling in the diagnosis of clinically significant prostate cancer in men who were biopsy naive. Design, Setting, and Participants: This paired cohort trial, known as the Prospective Assessment of Image Registration in the Diagnosis of Prostate Cancer (PAIREDCAP) study, was conducted in an academic medical center from January 2015 to April 2018. Men undergoing first-time prostate biopsy were enrolled. Paired-cohort participants were a consecutive series of men with MRI-visible lesions (defined by a Prostate Imaging Reporting & Data System version 2 score ≥ 3), who each underwent 3 biopsy methods at the same sitting: first, a systematic biopsy; second, an MRI-lesion biopsy targeted by cognitive fusion; and third, an MRI-lesion targeted by software fusion. Another consecutive series of men without MRI-visible lesions underwent systematic biopsies to help determine the false-negative rate of MRI during the trial period. Main Outcomes and Measures: The primary end point was the detection rate of clinically significant prostate cancer (Gleason grade group ≥2) overall and by each biopsy method separately. The secondary end points were the effects of the Prostate Imaging Reporting & Data System version 2 grade, prostate-specific antigen density, and prostate volume on the primary end point. Tertiary end points were the false-negative rate of MRI and concordance of biopsy-method results by location of detected cancers within the prostate. Results: A total of 300 men participated; 248 had MRI-visible lesions (mean [SD] age, 65.5 [7.7] years; 197 were white [79.4%]), and 52 were control participants (mean [SD] age, 63.6 [5.9] years; 39 were white [75%]). The overall CDR was 70% in the paired cohort group, achieved by combining systematic and targeted biopsy results. The CDR by systematic sampling was 15% in the group without MRI-visible lesions. In the paired-cohort group, CDRs varied from 47% (116 of 248 men) when using cognitive fusion biopsy alone, to approximately 60% when using systematic biopsy (149 of 248 men) or either fusion method alone (154 of 248 men), to 70% (174 of 248 men) when combining systematic and targeted biopsy. Discordance of tumor locations suggests that the different biopsy methods detect different tumors. Thus, combining targeting and systematic sampling provide greatest sensitivity for detection of clinically significant prostate cancer. For all biopsy methods, the Prostate Imaging Reporting & Data System version 2 grade and prostate-specific antigen density were directly associated with CDRs, and prostate volume was inversely associated. Conclusions and Relevance: An MRI-visible lesion in men undergoing first-time prostate biopsy identifies those with a heightened risk of clinically significant prostate cancer. Combining targeted and systematic biopsy offers the best chances of detecting the cancer.

Do contemporary imaging and biopsy techniques reliably identify unilateral prostate cancer? Implications for hemiablation patient selection.

BACKGROUND: Hemiablation is a less morbid treatment alternative for appropriately selected patients with unilateral prostate cancer (PCa). However, to the authors' knowledge, traditional diagnostic techniques inadequately identify appropriate candidates. In the current study, the authors quantified the accuracy for identifying hemiablation candidates using contemporary diagnostic techniques, including multiparametric magnetic resonance imaging (mpMRI) and MRI-fusion with complete systematic template biopsy. METHODS: A retrospective analysis of patients undergoing MRI and MRI-fusion prostate biopsy, including full systematic template biopsy, prior to radical prostatectomy in a single tertiary academic institution between June 2010 and February 2018 was performed. Hemiablation candidates had unilateral intermediate-risk PCa (Gleason score [GS] of 3+4 or 4+3, clinical T classification ≤T2, and prostate-specific antigen level <20 ng/dL) on MRI-fusion biopsy and 2) no contralateral highly or very highly suspicious Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) MRI lesions. Hemiablation candidates were inappropriately selected if pathologists identified contralateral GS ≥3+4 or high-risk ipsilateral PCa on prostatectomy. The authors tested a range of hemiablation inclusion criteria and performed multivariable analysis of preoperative predictors of undetected contralateral disease. RESULTS: Of 665 patients, 92 met primary hemiablation criteria. Of these 92 patients, 44 (48%) were incorrectly identified due to ipsilateral GS ≥3+4 tumors crossing the midline (21 patients), undetected distinct contralateral GS ≥3+4 tumors (20 patients), and/or ipsilateral high-risk PCa (3 patients) on prostatectomy. The rate of undetected contralateral disease ranged from 41% to 48% depending on inclusion criteria. On multivariable analysis, men with anterior index tumors were found to be 2.4 times more likely to harbor undetected contralateral GS ≥3+4 PCa compared with men with posterior lesions (P < .05). CONCLUSIONS: Clinicians and patients must weigh the risk of inadequate oncologic treatment against the functional benefits of hemiablation. Further investigation into methods for improving patient selection for hemiablation is necessary.

Registration Accuracy of Patient-Specific, Three-Dimensional-Printed Prostate Molds for Correlating Pathology With Magnetic Resonance Imaging.

OBJECTIVE: This investigation was performed to evaluate the registration accuracy between magnetic resonance imaging (MRI) and pathology using three-dimensional (3-D) printed molds. METHODS: Tissue-mimicking prostate phantoms were manufactured with embedded fiducials. The fiducials were used to measure and compare target registration error (TRE) between phantoms that were sliced by hand versus phantoms that were sliced within 3-D-printed molds. Subsequently, ten radical prostatectomy specimens were placed inside molds, scanned with MRI, and then sliced. The ex vivo scan was used to assess the true location of whole mount (WM) slides relative to in vivo MRI. The TRE between WM and in vivo MRI was measured using anatomic landmarks. RESULTS: Manually sliced phantoms had a 4.1-mm mean TRE, whereas mold-sliced phantoms had a 1.9-mm mean TRE. Similarly, mold-assisted slicing reduced mean angular misalignment around the left-right (LR) anatomic axis from 10.7° to 4.5°. However, ex vivo MRI revealed that excised prostates were misaligned within molds, including a mean 14° rotation about the LR axis. The mean in-plane TRE was 3.3 mm using molds alone and 2.2 mm after registration was corrected with ex vivo MRI. CONCLUSION: Patient-specific molds improved accuracy relative to manual slicing techniques in a phantom model. However, the registration accuracy of surgically resected specimens was limited by their imperfect fit within molds. This limitation can be overcome with the addition of ex vivo imaging. SIGNIFICANCE: The accuracy of 3-D-printed molds was characterized, quantifying their utility for facilitating MRI-pathology registration.

A system using patient-specific 3D-printed molds to spatially align in vivo MRI with ex vivo MRI and whole-mount histopathology for prostate cancer research.

BACKGROUND: Patient-specific 3D-printed molds and ex vivo MRI of the resected prostate have been two important strategies to align MRI with whole-mount histopathology (WMHP) for prostate cancer (PCa) research, but the combination of these two strategies has not been systematically evaluated. PURPOSE: To develop and evaluate a system that combines patient-specific 3D-printed molds with ex vivo MRI (ExV) to spatially align in vivo MRI (InV), ExV, and WMHP in PCa patients. STUDY TYPE: Prospective cohort study. POPULATION: Seventeen PCa patients who underwent 3T MRI and robotic-assisted laparoscopic radical prostatectomy (RALP). FIELD STRENGTH/SEQUENCES: T2 -weighted turbo spin-echo sequences at 3T. ASSESSMENT: Immediately after RALP, the fresh whole prostate specimens were imaged in patient-specific 3D-printed molds by 3T MRI and then sectioned to create WMHP slides. The time required for ExV was measured to assess impact on workflow. InV, ExV, and WMHP images were registered. Spatial alignment was evaluated using: slide offset (mm) between ExV slice locations and WMHP slides; overlap of the 3D prostate contour on InV versus ExV using Dice's coefficient (0 to 1); and 2D target registration error (TRE, mm) between corresponding landmarks on InV, ExV, and WMHP. Data are reported as mean ± standard deviation (SD). STATISTICAL TESTING: Differences in 2D TRE before versus after registration were compared using the Wilcoxon signed-rank test (P < 0.05 considered significant). RESULTS: ExV (duration 115 ± 15 min) was successfully incorporated into the workflow for all cases. Absolute slide offset was 1.58 ± 1.57 mm. Dice's coefficient was 0.865 ± 0.035. 2D TRE was significantly reduced after registration (P < 0.01) with mean (±SD of per patient means) of 1.9 ± 0.6 mm for InV versus ExV, 1.4 ± 0.5 mm for WMHP versus ExV, and 2.0 ± 0.5 mm for WMHP versus InV. DATA CONCLUSION: The proposed system combines patient-specific 3D-printed molds with ExV to achieve spatial alignment between InV, ExV, and WMHP with mean 2D TRE of 1-2 mm. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:270-279.

Focal Therapy Eligibility Determined by Magnetic Resonance Imaging/Ultrasound Fusion Biopsy.

PURPOSE: We assessed focal therapy eligibility in men who underwent multiparametric magnetic resonance imaging and targeted biopsy with correlation to whole mount histology after radical prostatectomy. MATERIALS AND METHODS: Subjects were selected from among the 454 men in whom targeted biopsy proven prostate cancer was derived from regions of interest on multiparametric magnetic resonance imaging from 2010 to 2016. Focal therapy eligibility was limited to a maximum Gleason score of 4 + 3 in regions of interest with or without other foci of low risk prostate cancer (Gleason score 3 + 3 and less than 4 mm). Men who did not meet NCCN® intermediate risk criteria were classified as ineligible for focal therapy. Of the 454 men 64 underwent radical prostatectomy and biopsy findings were compared to final pathology findings. RESULTS: Of the 454 men with a biopsy proven region of interest 175 (38.5%) were eligible for focal therapy. Fusion biopsy, which combined targeted and template biopsy, had 80.0% sensitivity (12 of 15 cases), 73.5% specificity (36 of 49) and 75.0% accuracy (48 of 64) for focal therapy eligibility. Targeted cores alone yielded 73.3% sensitivity (11 of 15 cases), 47.9% specificity (23 of 48) and 54.7% accuracy (35 of 64). Gleason score and extension across the midline differed in 4 and 9, respectively, of the 13 cases that showed discordant biopsy and whole mount histology. CONCLUSIONS: Using intermediate risk eligibility criteria more than a third of men with a targeted biopsy proven lesion identified on multiparametric magnetic resonance imaging would have been eligible for focal therapy. Eligibility determined by fusion biopsy was concordant with whole mount histology in 75% of cases. Improved selection criteria are needed to reliably determine focal therapy eligibility.

Value of Tracking Biopsy in Men Undergoing Active Surveillance of Prostate Cancer.

PURPOSE: We compared the upgrading rate obtained by resampling precise spots of prostate cancer (tracking biopsy) vs conventional systematic resampling during followup of men on active surveillance. MATERIALS AND METHODS: From 2009 to 2017 in 352 men prostate cancer was Gleason 3 + 3 in 268 and Gleason 3 + 4 in 84 at initial magnetic resonance imaging-ultrasound fusion biopsy. These men subsequently underwent a second fusion biopsy. At the first biopsy session all men underwent 12-core systematic biopsies and, when magnetic resonance imaging visible lesions were present, targeted biopsies. All cancerous sites were recorded electronically. During active surveillance at a second fusion biopsy session 6 to 18 months later tracking and systematic nontracking samples were obtained. The primary outcome measure was an increase in Gleason score (upgrading) at followup sampling, which was stratified by biopsy method. RESULTS: Overall 91 of the 352 men (25.9%) experienced upgrading at the second biopsy during a median 11-month interval. The upgrade rate in the Gleason 3 + 3 and 3 + 4 groups was 26.9% and 22.6%, respectively. The mean number of cores taken at second biopsy was 12.2 ± 3.3 in men with upgrading and 12.4 ± 4.1 in those who remained stable (p not significant). Men with grade 0 to 4 magnetic resonance imaging targets were all upgraded at approximately the same rate of 20% to 30% (p not significant). However, 58.8% of the men with grade 5 magnetic resonance imaging targets were upgraded. Of the 91 upgrades 48 (53%) were detected only by tracking. CONCLUSIONS: The tracking function of magnetic resonance imaging-ultrasound fusion biopsy warrants further study. When specific sites are resampled in men undergoing active surveillance of prostate cancer, upgrading is detected more often than by nontracking biopsy.

Risk Stratification Among Men With Prostate Imaging Reporting and Data System version 2 Category 3 Transition Zone Lesions: Is Biopsy Always Necessary?

OBJECTIVE: The objective of our study was to determine the clinical and MRI characteristics of clinically significant prostate cancer (PCA) (Gleason score ≥ 3 + 4) in men with Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) category 3 transition zone (TZ) lesions. MATERIALS AND METHODS: From 2014 to 2016, 865 men underwent prostate MRI and MRI/ultrasound (US) fusion biopsy (FB). A subset of 90 FB-naïve men with 96 PI-RADSv2 category 3 TZ lesions was identified. Patients were imaged at 3 T using a body coil. Images were assigned a PI-RADSv2 category by an experienced radiologist. Using clinical data and imaging features, we performed univariate and multivariate analyses to identify predictors of clinically significant PCA. RESULTS: The mean patient age was 66 years, and the mean prostate-specific antigen density (PSAD) was 0.13 ng/mL2. PCA was detected in 34 of 96 (35%) lesions, 14 of which (15%) harbored clinically significant PCA. In univariate analysis, DWI score, prostate volume, and PSAD were significant predictors (p < 0.05) of clinically significant PCA with a suggested significance for apparent diffusion coefficient (ADC) and prostate-specific antigen value (p < 0.10). On multivariate analysis, PSAD and lesion ADC were the most important covariates. The combination of both PSAD of 0.15 ng/mL2 or greater and an ADC value of less than 1000 mm2/s yielded an AUC of 0.91 for clinically significant PCA (p < 0.001). If FB had been restricted to these criteria, only 10 of 90 men would have undergone biopsy, resulting in diagnosis of clinically significant PCA in 60% with eight men (9%) misdiagnosed (false-negative). CONCLUSION: The yield of FB in men with PI-RADSv2 category 3 TZ lesions for clinically significant PCA is 15% but significantly improves to 60% (AUC > 0.9) among men with PSAD of 0.15 ng/mL2 or greater and lesion ADC value of less than 1000 mm2/s.