Optimizing Spatial Biopsy Sampling for the Detection of Prostate Cancer.

PURPOSE: The appropriate number of systematic biopsy cores to retrieve during magnetic resonance imaging (MRI)-targeted prostate biopsy is not well defined. We aimed to demonstrate a biopsy sampling approach that reduces required core count while maintaining diagnostic performance. MATERIALS AND METHODS: We collected data from a cohort of 971 men who underwent MRI-ultrasound fusion targeted biopsy for suspected prostate cancer. A regional targeted biopsy (RTB) was evaluated retrospectively; only cores within 2 cm of the margin of a radiologist-defined region of interest were considered part of the RTB. We compared detection rates for clinically significant prostate cancer (csPCa) and cancer upgrading rate on final whole mount pathology after prostatectomy between RTB, combined, MRI-targeted, and systematic biopsy. RESULTS: A total of 16,459 total cores from 971 men were included in the study data sets, of which 1,535 (9%) contained csPCa. The csPCa detection rates for systematic, MRI-targeted, combined, and RTB were 27.0% (262/971), 38.3% (372/971), 44.8% (435/971), and 44.0% (427/971), respectively. Combined biopsy detected significantly more csPCa than systematic and MRI-targeted biopsy (p <0.001 and p=0.004, respectively) but was similar to RTB (p=0.71), which used on average 3.8 (22%) fewer cores per patient. In 102 patients who underwent prostatectomy, there was no significant difference in upgrading rates between RTB and combined biopsy (p=0.84). CONCLUSIONS: A RTB approach can maintain state-of-the-art detection rates while requiring fewer retrieved cores. This result informs decision making about biopsy site selection and total retrieved core count.

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.

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.

SPARED Collaboration: Patient Selection for Partial Gland Ablation in Men with Localized Prostate Cancer.

PURPOSE: The SPARED CRN (Study of Prostate Ablation Related Energy Devices Coordinated Registry Network) is a private-public partnership between academic and community urologists, the FDA (U.S. Food and Drug Administration), the Medical Device Epidemiology Network and device manufacturers to examine the safety and effectiveness of technologies for partial gland ablation in men with localized prostate cancer. MATERIALS AND METHODS: We report on a recent workshop at the FDA with thought leaders to discuss a critical framework for partial gland ablation, focusing on patient selection, surgical planning, followup, study design and appropriate comparators in terms of adverse events and cancer control outcomes. We summarize salient points from experts in urology, oncology and epidemiology that were presented and discussed in an open forum. RESULTS: Given the challenges in achieving patient and physician equipoise to perform a randomized trial, as well as an inherent paradigm shift when comparing partial gland ablation (inability to assess prostate specific antigen recurrence) to whole gland treatments, the group focused on objective performance criteria and goals as a platform to guide the creation of single arm studies in the SPARED CRN. CONCLUSIONS: This summit lays the foundation for prospective, multi-center data collection and evaluation of novel medical devices and drug/device combinations for partial gland ablation.

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.

Focal Laser Ablation of Prostate Cancer: Feasibility of Magnetic Resonance Imaging-Ultrasound Fusion for Guidance.

PURPOSE: Focal laser ablation is a potential treatment in some men with prostate cancer. Currently focal laser ablation is performed by radiologists in a magnetic resonance imaging unit (in bore). We evaluated the safety and feasibility of performing focal laser ablation in a urology clinic (out of bore) using magnetic resonance imaging-ultrasound fusion for guidance. MATERIALS AND METHODS: A total of 11 men with intermediate risk prostate cancer were enrolled in this prospective, institutional review board approved pilot study. Magnetic resonance imaging-ultrasound fusion was used to guide laser fibers transrectally into regions of interest harboring intermediate risk prostate cancer. Thermal probes were inserted for real-time monitoring of intraprostatic temperatures during laser activation. Multiparametric magnetic resonance imaging (3 Tesla) was done immediately after treatment and at 6 months along with comprehensive fusion biopsy. RESULTS: Ten of 11 patients were successfully treated while under local anesthesia. Mean procedure time was 95 minutes (range 71 to 105). Posttreatment magnetic resonance imaging revealed a confined zone of nonperfusion in all 10 men. Mean zone volume was 4.3 cc (range 2.1 to 6.0). No CTCAE grade 3 or greater adverse events developed and no changes were observed in urinary or sexual function. At 6 months magnetic resonance imaging-ultrasound fusion biopsy of the treatment site showed no cancer in 3 patients, microfocal Gleason 3 + 3 in another 3 and persistent intermediate risk prostate cancer in 4. CONCLUSIONS: Focal laser ablation of prostate cancer appears safe and feasible with the patient under local anesthesia in a urology clinic using magnetic resonance imaging-ultrasound fusion for guidance and thermal probes for monitoring. Further development is necessary to refine out of bore focal laser ablation and additional studies are needed to determine appropriate treatment margins and oncologic efficacy.

Focal Laser Ablation of Prostate Cancer: Phase I Clinical Trial.

PURPOSE: Focal laser ablation is an investigational technique to treat prostate cancer in a region confined manner via coagulative necrosis. This phase I trial primarily examines the safety of transrectal magnetic resonance imaging guided (in-bore) focal laser ablation in men with intermediate risk prostate cancer. An exploratory end point is cancer control after 6 months. MATERIALS AND METHODS: In an institutional review board approved trial we studied focal laser ablation in 8 men with intermediate risk prostate cancer diagnosed using magnetic resonance-ultrasound fusion. Focal laser ablation was performed by inserting a cylindrically diffusing, water cooled laser fiber into magnetic resonance visible regions of interest, followed by interstitial heating at 10 to 15 W for up to 3 minutes. Secondary safety monitors (thermal probes) were inserted to assess the accuracy of magnetic resonance thermometry. Comprehensive magnetic resonance-ultrasound fusion biopsy was performed after 6 months. Adverse events and health related quality of life questionnaires were recorded. RESULTS: Focal laser ablation was successfully performed in all 8 subjects. No grade 3 or greater adverse events occurred and no changes in International Prostate Symptom Score or International Index of Erectile Function 5 were observed. Ablation zones, as measured by posttreatment magnetic resonance imaging, had a median volume of 3 cc or 7.7% of prostate volume. Prostate specific antigen decreased in 7 men (p <0.01). At followup magnetic resonance-ultrasound fusion biopsy cancer was not detected in the ablation zone in 5 men but was present outside the treatment margin in 6 men. CONCLUSIONS: Focal laser ablation of the prostate is feasible and safe in men with intermediate risk prostate cancer without serious adverse events or changes in urinary or sexual function at 6 months. Comprehensive biopsy followup indicates that larger treatment margins than previously thought necessary may be required for complete tumor ablation.

Cryotherapy for partial gland ablation of prostate cancer: Oncologic and safety outcomes.

BACKGROUND: Partial gland ablation (PGA) is a new option for treatment of prostate cancer (PCa). Cryotherapy, an early method of PGA, has had favorable evaluations, but few studies have employed a strict protocol using biopsy endpoints in men with clinically significant prostate cancer (csPCa). METHODS: 143 men with unilateral csPCa were enrolled in a prospective, observational trial of outpatient PGA-cryotherapy. Treatment was a 2-cycle freeze of the affected prostate part. Participants were evaluated with MRI-guided biopsy (MRGB) at baseline and at 6 months and 18 months after treatment. Absence of csPCa upon MRGB was the primary endpoint; quality-of-life at baseline and at 6 months after treatment was assessed by EPIC-CP questionnaires in the domains of urinary and sexual function. RESULTS: Of the 143 participants, 136 (95%) completed MRGB at 6 months after treatment. In 103/136 (76%), the biopsy revealed no csPCa. Of the 103, 71 subsequently had an 18-month comprehensive biopsy; of the 71 with 18-month biopsies, 46 (65%) were found to have no csPCa. MRI lesions became undetectable in 96/130 (74%); declines in median serum PSA levels (6.9 to 2.5 ng/mL), PSA density (0.15 to 0.07), and prostate volume (42 to 34cc) were observed (all p < 0.01). Neither lesion disappearance on MRI nor PSA decline correlated with biopsy outcome. Urinary function was affected only slightly and sexual function moderately. CONCLUSION: In the near to intermediate term, partial gland ablation with cryotherapy was found to be a safe and moderately effective treatment of intermediate-risk prostate cancer. Eradication of cancer was better determined by MRI-guided biopsy than by MRI or PSA.

Targeted Prostate Biopsy: Umbra, Penumbra, and Value of Perilesional Sampling.

BACKGROUND: Systematic prostate biopsies add to the cancer detection rate of targeted biopsies, but the explanation for that increased sensitivity is not yet clear. OBJECTIVE: To determine and quantify the utility of perilesional biopsies in the detection of clinically significant prostate cancer (csPCa). DESIGN, SETTING, AND PARTICIPANTS: Participants were 2048 men with magnetic resonance imaging (MRI) lesions (grades 3-5) who underwent targeted and systematic prostate biopsy via MRI/ultrasound fusion at University of California Los Angeles and Cornell between 2011 and 2019. The study is a retrospective examination of prospectively acquired data. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All biopsy cores (30191), locations of which had been stored digitally in the image-fusion device, were analyzed for tissue pathology and relationship with MRI lesions. A validated Matlab script was used to determine the distance between MRI lesions and cores containing csPCa (3552 cores from 927 men). Significance of distance measurements was determined by multilevel, multivariable logistic regression to account for within patient-biopsy correlation and control for patient characteristics. RESULTS AND LIMITATIONS: Overall, 90% (95% confidence interval [CI] = 89-91) of csPCa cores (3206/3552) were located within a radius of 10 mm from the nearest lesion: 65% (95% CI = 63-67) within the region of interest (ROI) and 26% (95% CI = 24-27) outside the ROI but within the 10-mm "penumbra." The width of the penumbra or concentric band, which enclosed 90% of csPCa, was primarily related to MRI grade of lesion: grade 5, 5 mm; grade 4, 12 mm; grade 3, 16 mm. In 18% (95% CI = 15-20) of patients (166/927), csPCa was diagnosed only by sampling outside the MRI lesion, the yield decreasing with increasing distance. Limitations of MRI interpretation and fusion biopsy performance could affect the utility of these data in individual patients. CONCLUSIONS: Perilesional biopsies, that is, samples taken from a band of 10-mm radius outside MRI lesions (the penumbra), contain most cores of csPCa that are not present within the lesion. These data may help increase the performance characteristics of targeted prostate biopsy. PATIENT SUMMARY: We studied the locations of cancer within the prostate in men undergoing magnetic resonance imaging (MRI)-guided biopsy. We found that not all cancers are located within the MRI lesion, but 90% (95% confidence interval = 89-91) of the cancers arewithin 1 cm of the lesions. Biopsies taken from both within and around MRI lesions provide greater sensitivity for cancer detection than samples taken from the lesion only.

Harnessing clinical annotations to improve deep learning performance in prostate segmentation.

PURPOSE: Developing large-scale datasets with research-quality annotations is challenging due to the high cost of refining clinically generated markup into high precision annotations. We evaluated the direct use of a large dataset with only clinically generated annotations in development of high-performance segmentation models for small research-quality challenge datasets. MATERIALS AND METHODS: We used a large retrospective dataset from our institution comprised of 1,620 clinically generated segmentations, and two challenge datasets (PROMISE12: 50 patients, ProstateX-2: 99 patients). We trained a 3D U-Net convolutional neural network (CNN) segmentation model using our entire dataset, and used that model as a template to train models on the challenge datasets. We also trained versions of the template model using ablated proportions of our dataset, and evaluated the relative benefit of those templates for the final models. Finally, we trained a version of the template model using an out-of-domain brain cancer dataset, and evaluated the relevant benefit of that template for the final models. We used five-fold cross-validation (CV) for all training and evaluation across our entire dataset. RESULTS: Our model achieves state-of-the-art performance on our large dataset (mean overall Dice 0.916, average Hausdorff distance 0.135 across CV folds). Using this model as a pre-trained template for refining on two external datasets significantly enhanced performance (30% and 49% enhancement in Dice scores respectively). Mean overall Dice and mean average Hausdorff distance were 0.912 and 0.15 for the ProstateX-2 dataset, and 0.852 and 0.581 for the PROMISE12 dataset. Using even small quantities of data to train the template enhanced performance, with significant improvements using 5% or more of the data. CONCLUSION: We trained a state-of-the-art model using unrefined clinical prostate annotations and found that its use as a template model significantly improved performance in other prostate segmentation tasks, even when trained with only 5% of the original dataset.

Federated learning improves site performance in multicenter deep learning without data sharing.

OBJECTIVE: To demonstrate enabling multi-institutional training without centralizing or sharing the underlying physical data via federated learning (FL). MATERIALS AND METHODS: Deep learning models were trained at each participating institution using local clinical data, and an additional model was trained using FL across all of the institutions. RESULTS: We found that the FL model exhibited superior performance and generalizability to the models trained at single institutions, with an overall performance level that was significantly better than that of any of the institutional models alone when evaluated on held-out test sets from each institution and an outside challenge dataset. DISCUSSION: The power of FL was successfully demonstrated across 3 academic institutions while avoiding the privacy risk associated with the transfer and pooling of patient data. CONCLUSION: Federated learning is an effective methodology that merits further study to enable accelerated development of models across institutions, enabling greater generalizability in clinical use.

An Electronic Form for Reporting Results of Targeted Prostate Biopsy: Urology Integrated Diagnostic Report (Uro-IDR).

OBJECTIVE: To detail the development of an electronic report that graphically conveys all relevant information from targeted prostate biopsy. METHODS: The Urology Integrated Diagnostic Report (Uro-IDR) is based on a published framework (RadPath) which enables the compilation of diagnostic data from urology, radiology, and pathology. Each component of the Uro-IDR is generated by the contributing clinician, is assembled in one document, and provides correlation of the 3 inputs at a glance. Upon completion, the Uro-IDR is automatically linked to the electronic medical record as an interactive file and can also be downloaded for offline sharing as a PDF. RESULTS: At our institution, 1638 individual Uro-IDRs were generated between June 2016 and April 2019. There were 5715 views of these documents via the EMR. The average turnaround time for the creation of an individual report decreased from nearly 8 days at the time of its launch to 2 days after 6 months of use. The average time for report generation was 22 seconds for the pathologist and 69 seconds for the radiologist. An instructive video is linked to this article. CONCLUSION: The Uro-IDR has proven to be a feasible, efficient, clinically useful form to concisely transmit key information about targeted prostate biopsy to both clinicians and patients.

Use of MRI-ultrasound Fusion to Achieve Targeted Prostate Biopsy.

Here, we present a protocol to perform targeted prostate biopsy using a magnetic resonance imaging-ultrasound (MRI/US) fusion system. Prostate cancer has traditionally been diagnosed via transrectal ultrasound (TRUS) biopsy. Though considered the gold standard, TRUS is unable to visualize most prostate cancer lesions and therefore requires sampling of the entire prostate. This biopsy method often undergrades prostate cancer and fails to detect up to 35% of cancers on initial biopsy. Prostate MRI has been shown to have excellent sensitivity in the detection of cancerous lesions, and advancements in MRI technology during the last decade have led to the development of targeted biopsy. In targeted biopsy, a software platform overlays MRI data onto live TRUS images to create a fused MRI/US three-dimensional model of the prostate. Regions suspicious for malignancy on MRI are contoured by a radiologist, uploaded into the fusion system, and then displayed within the live MRI/US fused model. The urologist is then able to directly biopsy these targets. When compared to conventional TRUS biopsy, MRI/US fusion technology has been demonstrated to improve the detection of clinically significant cancer while reducing insignificant cancer detection. This technology, therefore, has the potential to diagnose prostate cancer primarily in men who would benefit from treatment.

Focal Laser Ablation of Prostate Cancer.

Herein, we describe a case of a 63-year-old male who underwent magnetic resonance imaging (MRI)-guided biopsy of a suspicious lesion in the prostate followed by focal laser ablation. Radical prostatectomy was performed 15 months following focal laser ablation for persistent cancer adjacent to the treatment zone. We provide images from the initial MRI, postablation MRI, and the whole-mount radical prostatectomy specimen. The present case demonstrates the confined, localized effect of focal laser ablation, and also illustrates the advantage of expanded treatment margins.

Robotic ultrasound systems in medicine.

Robots ultrasound (RUS) can be defined as the combination of ultrasound imaging with a robotic system in medical interventions. With their potential for high precision, dexterity, and repeatability, robots are often uniquely suited for ultrasound integration. Although the field is relatively young, it has already generated a multitude of robotic systems for application in dozens of medical procedures. This paper reviews the robotic ultrasound systems that have been developed over the past two decades and describes their potential impact on modern medicine. The RUS projects reviewed include extracorporeal devices, needle guidance systems, and intraoperative systems.