A Description and Safety Overview of Irreversible Electroporation for Prostate Tissue Ablation in Intermediate-Risk Prostate Cancer Patients: Preliminary Results from the PRESERVE Trial.

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion. The primary endpoints included negative in-field biopsy and adverse event incidence, type, and severity through 12 months. At the time of analysis, the trial had completed accrual with preliminary follow-up available. Demographics, disease characteristics, procedural details, PSA responses, and adverse events (AEs) are presented. The median (IQR) age at screening was 67.0 (61.0-72.0) years and Gleason distribution 3 + 4 (80.2%) and 4 + 3 (19.8%). At 6 months, all patients with available data (n = 74) experienced a median (IQR) percent reduction in PSA of 67.6% (52.3-82.2%). Only ten subjects (8.3%) experienced a Grade 3 adverse event; five were procedure-related. No Grade ≥ 4 AEs were reported. This study supports prior findings that IRE prostate ablation with the NanoKnife System can be performed safely. Final results are required to fully assess oncological, functional, and safety outcomes.

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.

MicroSegNet: A deep learning approach for prostate segmentation on micro-ultrasound images.

Micro-ultrasound (micro-US) is a novel 29-MHz ultrasound technique that provides 3-4 times higher resolution than traditional ultrasound, potentially enabling low-cost, accurate diagnosis of prostate cancer. Accurate prostate segmentation is crucial for prostate volume measurement, cancer diagnosis, prostate biopsy, and treatment planning. However, prostate segmentation on micro-US is challenging due to artifacts and indistinct borders between the prostate, bladder, and urethra in the midline. This paper presents MicroSegNet, a multi-scale annotation-guided transformer UNet model designed specifically to tackle these challenges. During the training process, MicroSegNet focuses more on regions that are hard to segment (hard regions), characterized by discrepancies between expert and non-expert annotations. We achieve this by proposing an annotation-guided binary cross entropy (AG-BCE) loss that assigns a larger weight to prediction errors in hard regions and a lower weight to prediction errors in easy regions. The AG-BCE loss was seamlessly integrated into the training process through the utilization of multi-scale deep supervision, enabling MicroSegNet to capture global contextual dependencies and local information at various scales. We trained our model using micro-US images from 55 patients, followed by evaluation on 20 patients. Our MicroSegNet model achieved a Dice coefficient of 0.939 and a Hausdorff distance of 2.02 mm, outperforming several state-of-the-art segmentation methods, as well as three human annotators with different experience levels. Our code is publicly available at https://github.com/mirthAI/MicroSegNet and our dataset is publicly available at https://zenodo.org/records/10475293.

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.

Partial Gland Ablation of Prostate Cancer: Effects of Repeat Treatment.

OBJECTIVE: To evaluate the near-term clinical and pathological effects of repeat partial gland ablation (PGA) in men with intermediate-risk prostate cancer (PCa). MATERIALS AND METHODS: One hundred seventy men with focal lesions of PCa (all GG2 or GG3) underwent PGA with high-intensity focused ultrasound (HIFU) or cryotherapy (CRYO) in prospective trials. Residual PCa in or near the ablation zone was found in 37 men after a first PGA; 30 went on to receive a second PGA and were the subjects of study. At 3 timepoints, baseline and 6 months after first and second ablations, quality-of-life (QOL) questionnaires (IIEF, IPSS) and MRI-guided biopsies (MRGB) were performed. Biopsies were targeted and systematic at baseline and in follow-up, comprehensively about the ablation zone. RESULTS: All 30 patients completed QOL questionnaires and 26 had MRGB at the 3 timepoints. Mean QOL scores were not significantly different from the baseline after the first or second PGA. No operative complications were encountered; and "decisional regret" was reported in only 2/29 men after the repeat ablation. A decrease in semen volume was reported by 25% of patients. Repeat ablation was successful (absence of csPCa on MRGB) in 14/26 (53%) of men. PSA levels decreased and MRI lesions resolved after ablations, but neither was a reliable predictor of biopsy outcomes. CONCLUSION: When initial PGA fails, repeat PGA is a reasonable consideration, because in near-term follow-up, secondary procedures appear to be safe, causing only minimal detriment to urinary and sexual function, with csPCa becoming undetectable by MRGB in approximately half the patients.

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.

The utility of prostate MRI within active surveillance: description of the evidence.

PURPOSE: We present an overview of the literature regarding the use of MRI in active surveillance of prostate cancer. METHODS: Both MEDLINE® and Cochrane Library were queried up to May 2020 for studies of men on active surveillance with MRI and later confirmatory biopsy. The terms studied were 'prostate cancer' as the anchor followed by two of the following: active surveillance, surveillance, active monitoring, MRI, NMR, magnetic resonance imaging,  MRI, and multiparametric MRI. Studies were excluded if pathologic reclassification (GG1 → ≥ GG2) and PI-RADS or equivalent was not reported. RESULTS: Within active surveillance, baseline MRI is effective for identifying clinically significant prostate cancer and thus associated with fewer reclassification events. A positive initial MRI (≥ PI-RADS 3) with GG1 identified at biopsy has a positive predictive value (PPV) of 35-40% for reclassification by 3 years. MRI possessed a stronger negative predictive value, with a negative MRI (≤ PI-RADS 2) yielding a negative predictive value of up to 85% at 3 years. Surveillance MRI, obtained after initial biopsy, yielded a PPV of 11-65% and NPV of 85-95% for reclassification. CONCLUSION: MRI is useful for initial risk stratification of prostate cancer in men on active surveillance, especially if MRI is negative when imaging is obtained during surveillance. While useful, MRI cannot replace biopsy and further research is necessary to fully integrate MRI into active surveillance.

Predicting Complete Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

Muscle-invasive bladder cancer is a life-threatening disease best managed with multimodal therapy. Neoadjuvant chemotherapy prior to cystectomy significantly improves survival with the greatest benefit noted in patients with a complete pathologic response noted at cystectomy. While radical cystectomy is currently an important part of the treatment plan, surgical morbidity remains high. Accurate prediction of complete responses to chemotherapy would enable avoiding the morbidity of radical cystectomy. Multiple clinical, pathologic, molecular, and radiographic predictors have been evaluated. Clinical and standard pathologic findings have not been found to be accurate predictors of complete response. To date, tumor genomic findings have been the most promising and have led to multiple clinical trials to evaluate if bladder preservation is possible in select patients. Radiomics has shown initial promise with larger validation series needed. These predictors can be further characterized as treatment specific and non-treatment specific. With the potential changing landscape of neoadjuvant therapy prior to radical cystectomy and the limitations of individual predictors of a complete response, a panel of several biomarkers may enhance patient selection for bladder preservation. The aim of this review is to summarize predictors of complete response to neoadjuvant chemotherapy.

Textured-Based Deep Learning in Prostate Cancer Classification with 3T Multiparametric MRI: Comparison with PI-RADS-Based Classification.

The current standardized scheme for interpreting MRI requires a high level of expertise and exhibits a significant degree of inter-reader and intra-reader variability. An automated prostate cancer (PCa) classification can improve the ability of MRI to assess the spectrum of PCa. The purpose of the study was to evaluate the performance of a texture-based deep learning model (Textured-DL) for differentiating between clinically significant PCa (csPCa) and non-csPCa and to compare the Textured-DL with Prostate Imaging Reporting and Data System (PI-RADS)-based classification (PI-RADS-CLA), where a threshold of PI-RADS ≥ 4, representing highly suspicious lesions for csPCa, was applied. The study cohort included 402 patients (60% (n = 239) of patients for training, 10% (n = 42) for validation, and 30% (n = 121) for testing) with 3T multiparametric MRI matched with whole-mount histopathology after radical prostatectomy. For a given suspicious prostate lesion, the volumetric patches of T2-Weighted MRI and apparent diffusion coefficient images were cropped and used as the input to Textured-DL, consisting of a 3D gray-level co-occurrence matrix extractor and a CNN. PI-RADS-CLA by an expert reader served as a baseline to compare classification performance with Textured-DL in differentiating csPCa from non-csPCa. Sensitivity and specificity comparisons were performed using Mcnemar's test. Bootstrapping with 1000 samples was performed to estimate the 95% confidence interval (CI) for AUC. CIs of sensitivity and specificity were calculated by the Wald method. The Textured-DL model achieved an AUC of 0.85 (CI [0.79, 0.91]), which was significantly higher than the PI-RADS-CLA (AUC of 0.73 (CI [0.65, 0.80]); p < 0.05) for PCa classification, and the specificity was significantly different between Textured-DL and PI-RADS-CLA (0.70 (CI [0.59, 0.82]) vs. 0.47 (CI [0.35, 0.59]); p < 0.05). In sub-analyses, Textured-DL demonstrated significantly higher specificities in the peripheral zone (PZ) and solitary tumor lesions compared to the PI-RADS-CLA (0.78 (CI [0.66, 0.90]) vs. 0.42 (CI [0.28, 0.57]); 0.75 (CI [0.54, 0.96]) vs. 0.38 [0.14, 0.61]; all p values < 0.05). Moreover, Textured-DL demonstrated a high negative predictive value of 92% while maintaining a high positive predictive value of 58% among the lesions with a PI-RADS score of 3. In conclusion, the Textured-DL model was superior to the PI-RADS-CLA in the classification of PCa. In addition, Textured-DL demonstrated superior performance in the specificities for the peripheral zone and solitary tumors compared with PI-RADS-based risk assessment.

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.

Comparison of clinician and patient users of a mobile phone application to assess penile curvature in Peyronie's disease.

Assessment of Peyronie's disease with penile injection is invasive and uncomfortable. We developed a smartphone application (UWPEN) to assess penile angulation in the home environment. The purpose of this study was to compare clinician and patient measurements and assess the patient experience with UWPEN in a clinical setting. We prospectively enrolled patients with Peyronie's disease undergoing intracavernosal injection of alprostadil. Penile angulation and narrowing were then assessed by patients and clinicians using UWPEN and compared to values obtained via a goniometer and a ruler (gold standard). Measurements were compared using the Pearson correlation test. Upon completion of measurements, patients were surveyed regarding the ease of use, confidence with use, and measurement preferences. Twenty patients were enrolled in the study; two patients were excluded for poor penile turgidity after a maximum dosage of intracavernosal alprostadil. Correlation between UWPEN and gold standard measurements by patients and clinicians was R = 0.55 (p = 0.01) and R = 0.87 (p < 0.01) for dorsal measurements, R = 0.62 (p = 0.01) and R = 0.77 (p < 0.01) for lateral measurements, and R = 0.73 (p < 0.01) and R = 0.64 (p < 0.01) for girth measurements, respectively. Prior evaluation of correlation suggests a strong correlation at R = 0.8, and good correlation at R = 0.5. Overall, patients preferred using UWPEN to traditional measurements, and 75% reported UWPEN as their first preference for measurements. UWPEN enables patients to assess their disease severity with good correlation to gold standard measurements. Patients prefer mobile platforms for disease monitoring, and development of technology for disease monitoring should be a priority within the Peyronie's disease research community.

Nonmuscle Invasive Bladder Cancer Influences Physical Health Related Quality of Life and Urinary Incontinence.

OBJECTIVE: To evaluate the effects of nonmuscle invasive bladder cancer (NMIBC) on health-related quality of life (HRQOL) and urinary function within patients diagnosed with NMIBC as compared to the general population. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare Health Outcome Survey (SEER-MHOS) database (1998-2013), 325 patients diagnosed with NMIBC with baseline and postdiagnosis MHOS surveys were propensity-matched 1:5 to noncancer controls (NCC). Multivariate linear regression analysis compared NMIBC patients with matched NCC in terms of physical component summary (PCS), mental component summary (MCS), and health domain scales. Changes in urinary function were assessed using χ2 testing. RESULTS: Patients diagnosed with NMIBC experienced significant decline in PCS vs NCC (-3.0, 95% confidence interval [CI -4.1, -2.0] vs -1.5, 95%CI [-2.0, -1.0], P = .01), while the observed decline in MCS was not significantly different (P = .09) between groups. On sub-analysis, the significant decline in PCS was confined to patients with high-risk NMIBC (P = .01). NMIBC patients had significantly greater decline in role physical (P = .04), general health (P = .04) and role emotional (P <0.01) health domain scales. NMIBC patients were more likely to report worsened urinary leakage, require physician intervention, and receive new treatment for urinary leakage (P values all <.01). CONCLUSION: NMIBC diagnosis was associated with significant decreases in physical HRQOL and urinary function compared with NCC. Further study focused on NMIBC patients, and the inherent HRQOL factors to this diagnosis is needed to assess where improvements can be made in treating this patient population.

Anaphylactoid Reactions After Instillation of Contrast Material Into the Urinary Tract: A Survey of Contemporary Practice Patterns and Review of the Literature.

OBJECTIVE: To assess drug reactions (ADRs) encountered by practicing urologists for contrast instilled into the urinary collecting system, and to describe current practice patterns regarding contrast administration into the urinary tract for patients with known contrast allergies. METHODS: Endourological Society members were e-mailed a web-based survey about their prior experience with contrast-related ADRs and practices for contrast administration into the urinary tract among patients with known intravenous contrast allergies. Chi-squared analysis was used to compare management patterns between patients with established allergies and those without. RESULTS: An estimated 2300-2500 e-mails were reached, resulting in an estimated response rate of 6.3%-8%. Over 75% of respondents were fellowship trained. Average time in practice was 16 years, and respondents performed a mean of 6.7 urologic contrast studies per week. Among respondents, 32.6%, 14.7%, and 4.0% had treated at least 1 patient with a mild, moderate, or severe reaction, respectively. Contrast-related ADRs were most commonly associated with retrograde pyelogram (50%). For patients with known contrast allergies, 5.4% pursue additional work-up before administering contrast in the urinary tract. Pretreatment with antihistamine or steroids is used by 24.8% and 23.4%, respectively. When performing retrograde pyelograms for such patients, urologists are more likely to use dilute contrast (P = .003), but otherwise do not significantly alter technique. CONCLUSION: Contrast ADRs are encountered not infrequently among practicing urologists. There is notable practice variation in the management of patients with known contrast allergies, though the overall perceived risk of contrast use in these patients is low, provided good technique is used.

Comparing radiation exposure between ablative therapies for small renal masses.

PURPOSE: The purpose of this study was to evaluate the amount of radiation exposure patients with small renal masses undergoing percutaneous cyroablation (PCA) or percutaneous radiofrequency ablation (PRFA) received during treatment and follow up. MATERIALS AND METHODS: A retrospective review was conducted on all patients with small renal masses <4 cm treated with PCA or PRFA over a 7-year period in a single academic center. Preoperative, operative, and post-operative variables were collected and compared. Radiation exposure received during treatment and 1 year of follow up were also determined for each modality. Statistical analysis was conducted using SPSS V.17 (SPSS, Chicago, IL). The groups were compared using the Mann-Whitney U and Pearson Chi-Square tests. Statistical significance was considered at p<0.05. RESULTS: There was no significant difference in pretreatment parameters or oncologic outcomes. The average PCA treatment radiation exposure was 39.7 mSv (15.5-133.4 mSv) compared with 22.2 mSv (8.1-67.7 mSv) for PRFA (p=0.001). During the initial year after treatment, the estimated mean treatment and follow-up radiation exposure for PCA was 134.5 mSv, compared with 117 mSv for RFA when routine computerized tomography imaging was employed. CONCLUSION: To our knowledge, this is the first published study that quantifies radiation exposure in PCA and PRFA treatment for small renal masses. These relatively high radiation exposures should be included in the informed consent for these procedures. In addition, caution should be employed when applying these technologies in young patients who are most susceptible to long-term radiation damage.