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Prostate specific antigen (PSA) has transformed the diagnosis and treatment of prostate cancer by enabling early detection at global scale. Due to expression in both benign and malignant cells, PSA-based prostate cancer screening using single cut-points yields imperfect diagnostic performance and has led to the detection and over-treatment of low-grade prostate cancer. Additional challenges in the interpretation of PSA include substantial inter and intrapersonal variation, differences with age and prostate volume, and selection of standardized PSA value cutoffs for clinical application. In response, refinements to PSA including risk and age-based thresholds, age and genetic adjustments, PSA density, percentage free PSA, and PSA velocity have been proposed and extensively studied. In this review, we focus on the clinical role of PSA as a screening biomarker with a particular emphasis on its test characteristics, clinically actionable thresholds, and strategies to refine its clinical interpretation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objective: As most Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions on MRI harbor Gleason grade (GG) group ≥2 disease on biopsy, optimal management of patients with imaging-biopsy discordance remains unclear. To estimate grade misclassification, we evaluated the incidence of Gleason upgrading among patients with GG1 disease in the setting of a PI-RADS 5 lesion., Methods: We conducted a single-institution retrospective analysis to identify patients with GG1 prostate cancer on fusion biopsy with MRI demonstrating ≥1 PI-RADS 5 lesion. Primary study outcome was identification of ≥GG2 disease on subsequent active surveillance (AS) biopsy or radical prostatectomy (RP). We used multivariable models to examine factors associated with reclassification., Results: We identified 110 patients with GG1 disease on initial biopsy and ≥1 PI-RADS 5 lesion. There were 104 patients (94.6%) initially managed with AS and 6 (5.5%) received treatment. Sixty-one patients (58.7%) on AS underwent additional biopsies. Of these, 43 (70.5%) patients had tumor upgrading, with 32 (74.4%) upgraded on first surveillance biopsy. Forty-four (40%) patients ultimately received treatment, including prostatectomy in 15 (13.6%) and radiation in 25 (22.7%). Two patients (1.8%) developed metastases. In multivariable models, genomic classifier score was associated with upgrading. Limitations include a lack of multi-institutional data and long-term outcomes data., Conclusions: Most patients diagnosed with GG1 prostate cancer on MRI-Ultrasound fusion biopsy in the setting of a PI-RADS 5 lesion were found to have ≥GG2 disease on subsequent tissue sampling, suggesting substantial initial misclassification and reinforcing the need for confirmatory testing., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ML reports in-kind research collaboration with Verace Inc. CG has received research funding from NCCN Foundation (Astra-Zeneca) and Genentech, and funding from Johnson and Johnson through Yale University to help develop new approaches to sharing clinical trial data. TMS reports honoraria from Varian Medical Systems, GE Healthcare, Janssen, and WebMD; he has an equity interest in CorTechs Labs, Inc. and serves on its Scientific Advisory Board; he has received in-kind research support from GE Healthcare via a research agreement with the University of California San Diego. SL reports consulting with Astellas. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Radiation- (radio-)recurrent prostate cancer poses a significant challenge in clinical management due to its complexity and varied treatment responses. The recurrence of prostate cancer following radiotherapy necessitates a nuanced management strategy that considers disease stage and aggressiveness, patient health status, and prior treatment modalities. Androgen deprivation therapy (ADT), a cornerstone in the management of regional or distant relapse, often initiates the therapeutic cascade, effectively suppressing tumor growth by targeting androgen signaling. Second-line antiandrogen therapies such as abiraterone and enzalutamide, in conjunction with ADT, exhibit considerable clinical efficacy by delaying disease progression and ameliorating symptoms. However, in the absence of regional or distant disease, local relapse after radiation may be best managed with local salvage therapy. Salvage radical prostatectomy (SRP) may be considered in select cases of local recurrence, providing a potentially curative option. Salvage radiation therapy (RT), such as stereotactic body RT (SBRT), low-dose-rate (LDR), or high-dose-rate (HDR) brachytherapy (BT) is another viable option for localized recurrences. Other local treatments, such as cryotherapy, high-intensity focused ultrasound (HIFU) and irreversible electroporation (IRE) have been applied as salvage local therapy for radio-recurrent prostate cancer with promising results. Notwithstanding, exploring new avenues for improved outcomes and personalized treatment strategies as well as clinical trials investigating novel therapeutic agents and combination therapies remain imperative for these men. This comprehensive review aims to examine the current landscape of therapeutic approaches and emerging strategies for managing radio-recurrent prostate cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-245/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background and Objective: Comparative studies among biopsy strategies have not been conducted evaluating pathologic concordance at radical prostatectomy(RP), especially with novel micro-ultrasound (micro-US) image-guided biopsy., Methods: A retrospective study among patients with PCa who underwent RP following TRUS, MRI-TRUS fusion, microUS, or MRI-microUS fusion biopsy in a multi-site single institution. We compared GG-upgrade from biopsy to RP based on highest GG in any biopsy core and examined clinical/pathologic factors associated with pathologic upgrading using descriptive statistics, and multivariable logistic-regression analysis., Results: 429 patients between 1/2021 and 6/2023 including 10 (25.6%) who underwent systematic TRUS, 237 (55.2%) MRI-TRUS, 67 (15.6%) MRI-microUS and 15 (3.5%) micoUS-alone biopsy prior to RP. 78 (18.2%) were upgraded on final pathology (TRUS 31 (28.2%), MRI-TRUS 31 (13.1%), MRI-microUS 10 (14.9%), microUS: 6 (40%)) and 99 downgraded. 14 (3.5%) experienced a major upgrade (≥2 GG increase). On multivariable-analysis both MRI-TRUS (odds ratio, OR: 0.31,95% CI:0.17-0.56, P < 0.001) and MRI-microUS (OR: 0.43,95%CI: 0.19-0.98, P = 0.044) were associated with lower odds pathological-upgrade compared with TRUS biopsy alone. No significant differences in the odds of upgrade between TRUS and microUS alone (P > 0.05), or between MRI-microUS and MRI-TRUS(P = 0.696) on pairwise comparisons. MRI-microUS was associated with lower upgrade compared with microUS (OR: 0.26,95% CI:0.08-0.90, P = 0.034). No difference among the biopsy strategies in pathologic downgrading or overall GG concordance. Limitations include retrospective analysis, inter-clinician experience and lesion selection in varying biopsy techniques., Conclusion: Both MRI-microUS and MRI-TRUS fusion were associated with similarly improved GG concordance compared with TRUS biopsy. No significant differences between microUS-alone and TRUS or between MRI-microUS and MRI-TRUS fusion approaches, may suggest similar accuracy performance for disease sampling., What Does the Study Add: To our knowledge, this is the first study to investigate GG concordance based on type of biopsy, especially microUS related GG upgrading after RP. In a moderately sized cohort this is the first to investigate pathologic concordance in MRI-microUS fusion compared to MRI-TRUS fusion biopsy. Our study may help urologists in counseling patients after biopsy and choosing the ideal image guided biopsy technique, however randomized controlled trials are needed to validate our results., Patient Summary: We performed a study to see if the type of prostate biopsy, including use of MRI assistance as well as a new image-guided biopsy using a more advanced ultrasound, was better able to identify the aggressiveness of prostate cancer patients had. We found that the new biopsy type when fused with MRI and the existing MRI-guided biopsy type were similar in predicting the type of prostate cancer found at prostate surgery. These were both more accurate than the conventional ultrasound only biopsy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate if use of the Crowd-Sourced Assessment of Technical Skills (CSATS) platform and video peer review with constructive feedback is associated with improvement in technical skill and patient outcomes for robotic-assisted laparoscopic prostatectomy (RALP)., Methods: Five fellowship-trained urologists voluntarily submitted RALP cases for CSATS Global Evaluative Assessment of Robotic Skills (GEARS) scoring and expert narrative review between April 15, 2022-April 30, 2023. Surgeon-selected and randomly selected cases were reviewed. Surgeons underwent local peer review of videos with constructive feedback. Change in GEARS scores and frequency of postoperative outcomes over the 12-month periods before and during the study were analyzed in logistic regression models. Bias was assessed with sensitivity analysis comparing surgeon-selected to randomly selected cases., Results: GEARS scores for randomly selected vs surgeon-selected cases did not differ significantly. Overall GEARS score correlated positively with annual surgical RALP volume (r = 0.39, P = .003) and negatively with years in practice (r = -0.34, P = .01). After adjusting for confounders, there was no significant improvement in overall GEARS Score (0.01 ± 0.02/month, P = .48); but likelihood of sepsis (Odds Ratio 0.07, 95% CI 0.01-1.00, P = .05) and pelvic fluid collection (Odds Ratio 0.09, 95% CI 0.01-0.99, P = .049) were significantly decreased during the intervention period (n = 165) compared to the prior 12months (n = 144). No outcome increased in likelihood (P > .05)., Conclusion: Integration of CSATS and local video peer review is associated with significant improvement in patient outcomes after RALP, despite no significant change in surgeons' GEARS scores. This is the first study demonstrating improvement in patient RALP outcomes after implementation of such a paradigm in practicing surgeons., Competing Interests: Declaration of Competing Interest Isaac Y. Kim: ad hoc consultant to Intuitive Surgical. The other authors have no conflict of interest to declare., (Published by Elsevier Inc.)

Introduction: Although prostate MRI and tissue-based gene expression (genomic) tests improve staging and estimates of prostate cancer prognosis, their association with the intensity of treatment patients receive is not well understood., Methods: We performed a retrospective cohort study of Medicare beneficiaries diagnosed with clinically localized prostate cancer in 2013 through 2017 in the Surveillance, Epidemiology, and End Results database. The primary study outcome was the receipt of treatment intensification in the first 12 months after diagnosis (defined as the addition of androgen deprivation therapy among patients receiving radiation or pelvic lymphadenectomy among those undergoing radical prostatectomy). We assessed associations between the receipt of prostate MRI and genomic testing and treatment intensification, adjusting for clinical and sociodemographic factors and further stratifying the analyses by risk status., Results: We identified 37,064 patients with clinically localized prostate cancer, including 6398, 22,011, and 5976 with low, intermediate, and high D'Amico-risk disease, respectively. Among all treated patients, receipt of prostate MRI was associated with increased odds of treatment intensification (odds ratio 1.76, 95% CI 1.65-1.88, P < .001). In contrast, genomic testing was not significantly associated. Among treated patients with high-risk disease, genomic testing was associated with decreased odds of intensified treatment (odds ratio 0.59, 95% CI 0.35-1.00, P = .05)., Conclusions: Prostate MRI was associated with intensified treatment across risk strata, while genomic testing was associated with lower intensity of treatment among high-risk disease. Additional study is needed to determine whether use of imaging and risk stratification tools leads to improved long-term patient outcomes.

Importance: The Prostate Imaging Reporting & Data System (PI-RADS) scoring guidelines were developed to address the substantial variation in interpretation and reporting of prostate cancer (PCa) multiparametric MRI (mpMRI) results, and subsequent updates have sought to further improve inter-reader reliability. Nonetheless, the variability of PI-RADS scoring in real-world settings may represent a continuing challenge to the widespread standardization of prostate mpMRI and limit its overall clinical benefit., Objective: To assess variability in mpMRI interpretation and reporting of PCa, we evaluated the discrepancies in PI-RADS scoring between community practices and a tertiary academic care center., Design, Setting, and Participants: We identified 262 mpMRI studies from nonacademic facilities, reinterpreted by radiologists at our institution between January 2016 and July 2022. Results of targeted MRI fusion biopsy were identified for 193 of these patients, totaling 302 lesions. PI-RADS scoring from both community and academic interpreters were recorded in addition to presence of clinically significant PCa (csPCa) on pathological analysis of targeted cores., Main Outcome and Measures: The primary outcome was inter-reader reliability via intraclass correlation (ICC) and the kappa statistic. We also assessed the diagnostic accuracy of PI-RADS scoring for detecting csPCa for both cohorts via receiver operator characteristics (ROC) analysis and compared these findings using paired-sample area difference under curve analysis., Results: Inter-reader agreement and reliability of PI-RADS scoring per lesion was generally poor (absolute agreement ICC = 0.393, 95% CI: 0.288-0.488; consistency ICC = 0.407, 95% CI: 0.308-0.497; kappa = 0.336, 95% CI: 0.267-0.406). Reliability results from studies obtained after the publication of PI-RADSv2.1 were similar to those of the overall analysis. No agreement was observed in the subgroup of lesions scored as PIRADS 3 by community interpreters. No statistically significant difference in diagnostic accuracy was observed between cohorts (ROC area under curve [AUC]: 0.759 vs. 0.785, respectively; P = 0.337). PI-RADS 3 was determined to be the optimal cutoff for detecting clinically significant disease in both cohorts., Conclusions and Relevance: Our results suggest that mpMRI diagnostic accuracy for detecting csPCa is not significantly different between academic and community practices. However, significantly poor reliability of mpMRI was observed between cohorts, suggesting the risk of introducing practice variation for community prostate cancer management. Variability, particularly for PI-RADS 3 lesions, can lead to inconsistent biopsy recommendations, which may result in missed csPCa or unnecessary biopsies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Although prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown improved sensitivity and specificity compared with conventional imaging for the detection of biochemical recurrent (BCR) prostate cancer, the long-term outcomes of a widespread shift in imaging are unknown., Objective: To estimate long-term outcomes of integrating PSMA-PET into the staging pathway for recurrent prostate cancer., Design, Setting, and Participants: This decision analytic modeling study simulated outcomes for patients with BCR following initial definitive local therapy. Inputs used were from the literature and a retrospective cohort study conducted at 2 institutions. The base case analysis assumed modest benefits of earlier detection and treatment, and scenario analyses considered prostate-specific antigen (PSA) level at imaging and different outcomes of earlier vs delayed treatment. The analysis was performed between April 1, 2023, and May 1, 2024., Exposures: (1) Immediate PSMA-PET imaging, (2) conventional imaging (computed tomography and bone scan [CTBS]) followed by PSMA-PET if CTBS findings were negative or equivocal, and (3) CTBS alone., Main Outcomes and Measures: The main outcomes were detection of metastases, deaths from prostate cancer, and life-years and quality-adjusted life-years (QALYs) gained., Results: The model estimated that per 1000 simulated patients with BCR (assumed median age, 66 years), PSMA-PET is expected to diagnose 611 (95% uncertainty interval [UI], 565-656) patients with metastasis compared with 630 (95% UI, 586-675) patients diagnosed using CTBS followed by PSMA-PET and 297 (95% UI, 202-410) patients diagnosed using CTBS alone. Moreover, the estimated number of prostate cancer deaths was 512 (95% UI, 472-552 deaths) with PSMA-PET, 520 (95% UI, 480-559 deaths) with CTBS followed by PSMA-PET, and 587 (95% UI, 538-632 deaths) with CTBS alone. Imaging with PSMA-PET yielded the highest number of QALYs, which were 824 (95% UI, 698-885) higher than CTBS. These results differed by PSA level at the time of testing, with the highest incremental life-years and QALYs and lowest number of deaths from prostate cancer among patients with PSA levels of at least 5.0 ng/mL. Finally, the estimates were sensitive to the expected benefit of initiating therapy for recurrent prostate cancer earlier in the disease course., Conclusions and Relevance: The results of this decision-analytic model suggest that upfront PSMA-PET imaging for the evaluation of BCR is expected to be associated with reduced cancer mortality and gains in life-years and QALYs compared with the conventional imaging strategy, assuming modest benefits of earlier detection and treatment.

Purpose of Review: Prostate fusion biopsy, an innovative imaging modality for diagnosing prostate cancer, presents certain challenges for patients including discomfort and emotional distress, leading to nonadherence to treatment and follow-ups. To inform clinicians and offer pain relief alternatives to patients, this review delves into the risk factors for increased pain and modern management options to alleviate pain during prostate biopsy., Recent Findings: Individual responses to pain vary, and the overall experience of pain during a prostate biopsy has been contributed to numerous factors such as patient age, prostate volume, previous biopsy experience, and more. As a result, several strategies aim to mitigate pain during in-office procedures. Notably, techniques including pharmacological analgesics, hand holding, heating pads, entertainment/virtual reality, and distraction have shown significant efficacy. Existing studies explore risk factors influencing pain intensity during prostate biopsy and effective pain management strategies. This review consolidates available information to guide clinicians in enhancing patient comfort and thus, encourage surveillance adherence., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objective: Although the prognostic significance of the Decipher prostate cancer genomic classifier (GC) has been established largely from analyses of archival tissue, less is known about the associations between the results of Decipher testing and oncologic outcomes among patients receiving contemporaneous testing and treatment in the real-world practice setting. Our objective was to assess the associations between the Decipher GC and risks of metastasis and biochemical recurrence (BCR) following prostate biopsy and radical prostatectomy (RP) among patients tested and treated in the real-world setting., Methods: A retrospective cohort study was conducted using a novel longitudinal linkage of transcriptomic data from the Decipher GC and real-world clinical data (RWD) aggregated from insurance claims, pharmacy records, and electronic health record data across payors and sites of care. Kaplan-Meier and Cox proportional hazards regressions were used to examine the associations between the GC and study outcomes, adjusting for clinical and pathologic factors., Key Findings and Limitations: Metastasis from prostate cancer and BCR after radical prostatectomy, Decipher GC continuous score, and risk categories were evaluated. We identified 58 935 participants who underwent Decipher testing, including 33 379 on a biopsy specimen and 25 556 on an RP specimen. The median age was 67 yr (interquartile range [IQR] 62-72) at biopsy testing and 65 yr (IQR 59-69) at RP. The median GC score was 0.43 (IQR 0.27-0.66) among biopsy-tested patients and 0.54 (0.32-0.79) among RP-tested patients. The GC was independently associated with the risk of metastasis among biopsy-tested (hazard ratio [HR] per 0.1 unit increase in GC 1.21 [95% confidence interval {CI} 1.16-1.27], p < 0.001) and RP-tested (HR 1.20 [95% CI 1.17-1.24], p < 0.001) patients after adjusting for baseline clinical and pathologic risk factors. In addition, the GC was associated with the risk of BCR among RP-tested patients (HR 1.12 [95% CI 1.10-1.14], p < 0.001) in models adjusted for age and Cancer of the Prostate Risk Assessment postsurgical score., Conclusions and Clinical Implications: This real-world study of a novel transcriptomic linkage conducted at a national scale supports the external prognostic validity of the Decipher GC among patients managed in contemporary practice., Patient Summary: This study looked at the use of the Decipher genomic classifier, a test used to help understand the aggressiveness of a patient's prostate cancer. Looking at the results of 58 935 participants who underwent testing, we found that the Decipher test helped estimate the risk of cancer recurrence and metastasis., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Importance: Although tissue-based gene expression testing has become widely used for prostate cancer risk stratification, its prognostic performance in the setting of clinical care is not well understood., Objective: To develop a linkage between a prostate genomic classifier (GC) and clinical data across payers and sites of care in the US., Design, Setting, and Participants: In this cohort study, clinical and transcriptomic data from clinical use of a prostate GC between 2016 and 2022 were linked with data aggregated from insurance claims, pharmacy records, and electronic health record (EHR) data. Participants were anonymously linked between datasets by deterministic methods through a deidentification engine using encrypted tokens. Algorithms were developed and refined for identifying prostate cancer diagnoses, treatment timing, and clinical outcomes using diagnosis codes, Common Procedural Terminology codes, pharmacy codes, Systematized Medical Nomenclature for Medicine clinical terms, and unstructured text in the EHR. Data analysis was performed from January 2023 to January 2024., Exposure: Diagnosis of prostate cancer., Main Outcomes and Measures: The primary outcomes were biochemical recurrence and development of prostate cancer metastases after diagnosis or radical prostatectomy (RP). The sensitivity of the linkage and identification algorithms for clinical and administrative data were calculated relative to clinical and pathological information obtained during the GC testing process as the reference standard., Results: A total of 92 976 of 95 578 (97.2%) participants who underwent prostate GC testing were successfully linked to administrative and clinical data, including 53 871 who underwent biopsy testing and 39 105 who underwent RP testing. The median (IQR) age at GC testing was 66.4 (61.0-71.0) years. The sensitivity of the EHR linkage data for prostate cancer diagnoses was 85.0% (95% CI, 84.7%-85.2%), including 80.8% (95% CI, 80.4%-81.1%) for biopsy-tested participants and 90.8% (95% CI, 90.5%-91.0%) for RP-tested participants. Year of treatment was concordant in 97.9% (95% CI, 97.7%-98.1%) of those undergoing GC testing at RP, and 86.0% (95% CI, 85.6%-86.4%) among participants undergoing biopsy testing. The sensitivity of the linkage was 48.6% (95% CI, 48.1%-49.1%) for identifying RP and 50.1% (95% CI, 49.7%-50.5%) for identifying prostate biopsy., Conclusions and Relevance: This study established a national-scale linkage of transcriptomic and longitudinal clinical data yielding high accuracy for identifying key clinical junctures, including diagnosis, treatment, and early cancer outcome. This resource can be leveraged to enhance understandings of disease biology, patterns of care, and treatment effectiveness.

Introduction: Although the clinical benefits of pelvic lymph node dissection (PLND) at the time of radical prostatectomy for prostate cancer remain uncertain, major guidelines recommend PLND based on risk profile. Thus, the objective of this study was to examine the association between PLND and survival among patients undergoing RP stratified by Gleason grade group (GG) with the aim of allowing patients and physicians to make more informed care decisions about the potential risks and benefits of PLND., Materials and Methods: From the SEER-17 database, we examined overall (OS) and prostate cancer-specific (PCSS) survival of prostate cancer patients who underwent RP from 2010 to 2015 stratified by GG. We applied propensity score matching to balance pre-operative characteristics including race, age, PSA, household income, and housing status (urban/rural) between patients who did and did not undergo PLND for each GG. Statistical analyses included log-rank test and Kaplan-Meier curves., Results: We extracted a matched cohort from 80,287 patients with GG1-5 who underwent RP. The median PSA value was 6.0 ng/mL, and the median age was 62-years-old. 49,453 patients underwent PLND (61.60%), while 30,834 (38.40%) did not. There was no difference in OS and PCSS between patients who received PLND and those who did not for all Gleason GG (OS-GG1: P  = 0.20, GG2: P  = 0.34, GG3: P  > 0.05, GG4: P  = 0.55, GG5: P  = 0.47; PCSS-GG1: P  = 0.11, GG2: P  = 0.96, GG3: P  = 0.81, GG4: P  = 0.22, GG5: P  = 0.14)., Conclusions: In this observational study, PLND at the time of RP was not associated with improved OS or PCSS among patients with cGS of 3 + 3, 3 + 4, 4 + 3, 4 + 4, 4 + 5, and 5 + 4. These findings suggest that until definitive clinical trials are completed, prostate cancer patients who have elected RP should be appropriately counseled on the potential risks and lack of proven survival benefit of PLND., Competing Interests: No significant conflict of interest., (© 2024 The Asian Pacific Prostate Society. Published by Elsevier B.V.)

Objective: Cytologic evaluation of the upper urinary tract (UUT) can be challenging due to instrumentation artefacts. This study retrospectively reviewed UUT specimens using The Paris System for Reporting Urinary Cytopathology, second edition (TPS 2.0), compared it with the original reporting system (ORS) and correlated it with histopathologic follow-up., Methods: An institutional database was reviewed for the UUT biopsy/resection histopathologic specimens, and we included 52 UUT cytology specimens pertinent to these cases in the study. These specimens were blindly reviewed and reclassified using TPS 2.0. The correlation between TPS 2.0, ORS and histopathologic follow-up was assessed., Results: The UUT cytology specimens corresponded to 21 (40.4%) high-grade urothelial carcinoma (HGUC), 27 (51.9%) low-grade urothelial carcinoma (LGUC) and 4 (7.7%) benign cases on follow-up. For HGGC cases, the associated TPS categories included unsatisfactory (n = 1, 4.8%), negative for HGUC (NHGUC; n = 3, 14.3%), atypical urothelial cells (AUC; n = 6, 28.6%), suspicious for HGUC (SHGUC; n = 3, 14.3%) and HGUC (n = 8, 38.1%), while ORS categorised the specimens as unsatisfactory (n = 1, 4.8%), negative for malignant cells (NFMC; n = 3, 14.3%), AUC (n = 5, 23.8%), low-grade urothelial carcinoma (LGUC; n = 0, 0%), SHGUC (n = 5, 23.8%) and HGUC (n = 7, 33.3%). The risks of high-grade malignancy among cytologic categories were similar between ORS and TPS (p > 0.05). The majority of LGUC were classified as AUC similarly by ORS and TPS (55.6% vs. 59.3%)., Conclusions: Our study demonstrated comparable performance between TPS 2.0 and ORS for UUT cytology specimens. Cytological diagnosis of UUT specimens remains challenging, especially for LGUC., (© 2023 John Wiley & Sons Ltd.)

Objective: To compute a dense prostate cancer risk map for the individual patient post-biopsy from magnetic resonance imaging (MRI) and to provide a more reliable evaluation of its fitness in prostate regions that were not identified as suspicious for cancer by a human-reader in pre- and intra-biopsy imaging analysis., Methods: Low-level pre-biopsy MRI biomarkers from targeted and non-targeted biopsy locations were extracted and statistically tested for representativeness against biomarkers from non-biopsied prostate regions. A probabilistic machine learning classifier was optimized to map biomarkers to their core-level pathology, followed by extrapolation of pathology scores to non-biopsied prostate regions. Goodness-of-fit was assessed at targeted and non-targeted biopsy locations for the post-biopsy individual patient., Results: Our experiments showed high predictability of imaging biomarkers in differentiating histopathology scores in thousands of non-targeted core-biopsy locations (ROC-AUCs: 0.85-0.88), but also high variability between patients (Median ROC-AUC [IQR]: 0.81-0.89 [0.29-0.40])., Conclusion: The sparseness of prostate biopsy data makes the validation of a whole gland risk mapping a non-trivial task. Previous studies i) focused on targeted-biopsy locations although biopsy-specimens drawn from systematically scattered locations across the prostate constitute a more representative sample to non-biopsied regions, and ii) estimated prediction-power across predicted instances (e.g., biopsy specimens) with no patient distinction, which may lead to unreliable estimation of model fitness to the individual patient due to variation between patients in instance count, imaging characteristics, and pathologies., Significance: This study proposes a personalized whole-gland prostate cancer risk mapping post-biopsy to allow clinicians to better stage and personalize focal therapy treatment plans.

Aim: Prostate biopsy can be prone to complications and thus should be avoided when unnecessary. Although the combination of magnetic resonance imaging (MRI), the prostate health index (PHI), and PHI density (PHID) has been shown to improve detection of clinically significant prostate cancer (csPCa), there is limited information available assessing its clinical utility. We sought to determine whether using PHID could enhance the detection of PCa on MRI ultrasound fusion-targeted biopsy (MRF-TB) compared to other biomarker cutoffs., Methods: Between June 2015 and December 2020, 302 men obtained PHI testing before MRF-TB at a single institution. We used descriptive statistics, multivariable logistic regression, and receiver operating characteristic curves to determine the predictive accuracy of PHID and PHI to detect ≥ Gleason grade group (GGG) 2 PCa and identify cutoff values., Results: Any cancer grade was identified in 75.5% of patients and ≥ GGG2 PCa was identified in 45% of patients. The median PHID was 1.05 [interquartile range (IQR) 0.59-1.64]. A PHID cutoff of 0.91 had a higher discriminatory ability to predict ≥ GGG2 PCa compared to PHI > 27, PHI > 36, and prostate specific-antigen (PSA) density > 0.15 (AUC: 0.707 vs. 0.549 vs. 0.620 vs. 0.601), particularly in men with Prostate Imaging Reporting and Data System (PI-RADS) 1-2 lesions on MRI (AUC: 0.817 vs. 0.563 vs. 0.621 vs. 0.678). At this cutoff, 35.0% of all the original biopsies could be safely avoided (PHID < 0.91 and no ≥ GGG2 PCa) and csPCa would be missed in 9.67% of patients who would have been biopsied. In patients with PI-RADS 1-2 lesions using a PHID cutoff of 0.91, 56.8% of biopsies could be safely avoided while missing 0 csPCa., Conclusions: These findings suggest that a PHID cutoff of 0.91 improves the selection of patients with elevated prostate-specific antigen who are referred for prostate biopsy, and potentially in patients with PI-RADS 1-2 lesions., Competing Interests: The authors declare that they have no conflicts of interest., (© The Author(s) 2024.)

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

Background: Most Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions do not contain clinically significant prostate cancer (CSPCa; grade group ≥2). This study was aimed at identifying clinical and magnetic resonance imaging (MRI)-derived risk fac- tors that predict CSPCa in men with PI-RADS 3 lesions., Methods: This study analyzed the detection of CSPCa in men who underwent MRI-targeted biopsy for PI-RADS 3 lesions. Multivariable logistic regression models with goodness-of-fit testing were used to identify variables associated with CSPCa. Receiver operating curves and decision curve analyses were used to estimate the clinical utility of a predictive model., Results: Of the 1784 men reviewed, 1537 were included in the training cohort, and 247 were included in the validation cohort. The 309 men with CSPCa (17.3%) were older, had a higher prostate-specific antigen (PSA) density, and had a greater likelihood of an anteriorly located lesion than men without CSPCa (p < .01). Multivariable analysis revealed that PSA density (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.05-1.85; p < .01), age (OR, 1.05; 95% CI, 1.02-1.07; p < .01), and a biopsy-naive status (OR, 1.83; 95% CI, 1.38-2.44) were independently associated with CSPCa. A prior negative biopsy was negatively associated (OR, 0.35; 95% CI, 0.24-0.50; p < .01). The application of the model to the validation cohort resulted in an area under the curve of 0.78. A predicted risk threshold of 12% could have prevented 25% of biopsies while detecting almost 95% of CSPCas with a sensitivity of 94% and a specificity of 34%., Conclusions: For PI-RADS 3 lesions, an elevated PSA density, older age, and a biopsy-naive status were associated with CSPCa, whereas a prior negative biopsy was negatively associated. A predictive model could prevent PI-RADS 3 biopsies while missing few CSPCas., Lay Summary: Among men with an equivocal lesion (Prostate Imaging-Reporting and Data System 3) on multiparametric magnetic resonance imaging (mpMRI), those who are older, those who have a higher prostate-specific antigen density, and those who have never had a biopsy before are at higher risk for having clinically significant prostate cancer (CSPCa) on subsequent biopsy. However, men with at least one negative biopsy have a lower risk of CSPCa. A new predictive model can greatly reduce the need to biopsy equivocal lesions noted on mpMRI while missing only a few cases of CSPCa., (© 2022 American Cancer Society.)

Purpose: There is ongoing clinical need to improve estimates of disease outcome in prostate cancer. Machine learning (ML) approaches to pathologic diagnosis and prognosis are a promising and increasingly used strategy. In this study, we use an ML algorithm for prediction of adverse outcomes at radical prostatectomy (RP) using whole-slide images (WSIs) of prostate biopsies with Grade Group (GG) 2 or 3 disease., Methods: We performed a retrospective review of prostate biopsies collected at our institution which had corresponding RP, GG 2 or 3 disease one or more cores, and no biopsies with higher than GG 3 disease. A hematoxylin and eosin-stained core needle biopsy from each site with GG 2 or 3 disease was scanned and used as the sole input for the algorithm. The ML pipeline had three phases: image preprocessing, feature extraction, and adverse outcome prediction. First, patches were extracted from each biopsy scan. Subsequently, the pre-trained Visual Geometry Group-16 convolutional neural network was used for feature extraction. A representative feature vector was then used as input to an Extreme Gradient Boosting classifier for predicting the binary adverse outcome. We subsequently assessed patient clinical risk using CAPRA score for comparison with the ML pipeline results., Results: The data set included 361 WSIs from 107 patients (56 with adverse pathology at RP). The area under the receiver operating characteristic curves for the ML classification were 0.72 (95% CI, 0.62 to 0.81), 0.65 (95% CI, 0.53 to 0.79) and 0.89 (95% CI, 0.79 to 1.00) for the entire cohort, and GG 2 and GG 3 patients, respectively, similar to the performance of the CAPRA clinical risk assessment., Conclusion: We provide evidence for the potential of ML algorithms to use WSIs of needle core prostate biopsies to estimate clinically relevant prostate cancer outcomes., Competing Interests: Preston C. SprenkleHonoraria: Telix PharmaceuticalsConsulting or Advisory Role: Boston Scientific, Intuitive Surgical, Profound MedicalResearch Funding: Profound Medical Peter A. HumphreyConsulting or Advisory Role: Johnson & Johnson/JanssenNo other potential conflicts of interest were reported.

Background: The utility of Multiparametric magnetic resonance imaging (mpMRI) guided prostate biopsy among patients with prostate cancer (CaP) managed with active surveillance (AS) with low-suspicion lesions remains unsettled., Methods: We performed a retrospective analysis of 415 men with low-risk CaP managed with active surveillance. We selected men with mpMRI visible index lesions scored as 2 or 3 according to Prostate Imaging Reporting and Data System (PI-RADS) version 2. The primary outcome was detection of clinically significant prostate cancer (csCaP) was defined as Gleason grade group ≥ 2. We assessed the diagnostic accuracy of biopsy approaches using area under the receiver operator characteristic (ROC) curve and evaluated factors associated with csCaP in these patients using multivariate logistic regression., Results: CsCaP was identified in 22 of 125 patients (17.6%) with PI-RADS 2 or 3 index lesions during surveillance prostate biopsies. These included 10 (45.5%) diagnosed by systematic biopsy alone, 9 (40.9%) by targeted alone, and 3 (13.6%) by both approaches. On multivariable analysis, the only significant variable predicting the detection of csCaP in men with low-risk imaging mpMRI characteristics was higher PSAD (OR per 0.1 unit=2.26, 95% CI 1.25-4.06, P = 0.007. A PSAD cutoff of 0.1, 0.12 and 0.15 resulted in a negative predictive value (NPV) of 90.9%, 87.1% and 86.2%, respectively. When stratified by PI-RADS score, a PSAD cutoff of 0.1, 0.12 and 0.15 resulted in NPV of 96.2%, 90.6% and 89.7% and 86.2%, 84.2% and 83.3% for detection of csCaP in PI-RADS 2 and 3 lesions, respectively. In patients with PIRDAS 2 lesions, using a PSAD of 0.1 would potentially allow 51% of patients to avoid biopsy with only a 3.8% chance of missing csCaP., Conclusion: In men with clinical low-risk prostate cancer on active surveillance with PI-RADS 2 and 3 lesions, there is an almost 18% risk of upgrade to csCaP. Integration of PSAD may be a useful adjunctive tool in identifying patients at highest risk for upgrade despite favorable imaging findings. In men with PIRADS 2 lesions with PSAD ≤0.12 biopsy can be avoided. For men with PIRADS 2 lesions with PSAD ≤0.15 informed decision making regarding the AS intensity should include that these patients have a low risk (>10%) of developing csCaP. In men with PIRADS 3 lesions with PSAD >0.1, shared decision making should include discussion of a >10% miss rate of csCaP., (Published by Elsevier Inc.)

Introduction: We sought to understand patient- and institution-level factors associated with use of locoregional therapy for newly diagnosed metastatic prostate cancer in the era before the availability of evidence supporting its efficacy., Methods: We queried the National Cancer Database to identify patients diagnosed with metastatic prostate adenocarcinoma (stage M1) between 2004 and 2017. We assessed patient factors associated with definitive local therapy with radiotherapy or radical prostatectomy using multilevel logistic regression accounting for clustering within institutions. We further characterized trends in facility-level use and examined institutional factors associated with utilization., Results: We identified 35,933 patients with M1 prostate cancer at 1,188 facilities. A total of 4,146 patients (11.5%) received local therapy for M1 disease (radiation therapy in 3,378 and radical prostatectomy in 768). Use of local treatment was concentrated among a smaller number of facilities: 50% of all local therapy was delivered at 161 facilities (14% of total). At the patient level, uninsured status (OR 0.62, 95% CI 0.49-0.79, p <0.01) and high comorbidity (Charlson-Deyo score, OR 0.39, 95% CI 0.26-0.6, p <0.01) were associated with lower odds of local therapy. High-utilizing facilities (top quartile) were more commonly community centers (OR 1.76, 95% CI 10.7-2.95, p <0.01) and differed by geographic region (South Atlantic vs West South Central region: OR 0.48, 95% CI 0.25-0.88, p=0.02)., Conclusions: In the period before locoregional therapy was supported by clinical practice guidelines, locoregional therapy use varied significantly at the facility level and was driven by a smaller number of high-utilizing facilities. These findings can contextualize expected increase in the use of local therapy for metastatic prostate cancer.

Background: Although the Decipher genomic classifier has been validated as a prognostic tool for several prostate cancer endpoints, little is known about its role in assessing the risk of biopsy reclassification for patients on active surveillance, a key event that often triggers treatment., Objective: To evaluate the association between Decipher genomic classifier scores and biopsy Gleason upgrading among patients on active surveillance., Design Setting and Participants: This was a retrospective cohort study among patients with low- and favorable intermediate-risk prostate cancer on active surveillance who underwent biopsy-based Decipher testing as part of their clinical care., Outcome Measurements and Statistical Analysis: We evaluated the association between the Decipher score and any increase in biopsy Gleason grade group (GG) using univariable and multivariable logistic regression. We compared the area under the receiver operating characteristic curve (AUC) for models comprising baseline clinical variables with or without the Decipher score., Results and Limitations: We identified 133 patients for inclusion with a median age of 67.7 yr and median prostate-specific of 5.6 ng/ml. At enrollment, 75.9% had GG1 and 24.1% had GG2 disease. Forty-three patients experienced biopsy upgrading. On multivariable logistic regression, the Decipher score was significantly associated with biopsy upgrading (odds ratio 1.37 per 0.10 unit increase, 95% confidence interval [CI] 1.05-1.79; p = 0.02). The Decipher score was associated with upgrading among patients with biopsy GG 1 disease, but not GG2 disease. The discriminative ability of a clinical model (AUC 0.63, 95% CI 0.51-0.74) was improved by integration of the Decipher score (AUC 0.69, 95% CI 0.58-0.80)., Conclusions: The Decipher genomic classifier score was associated with short-term biopsy Gleason upgrading among patients on active surveillance., Patient Summary: The results from this study indicate that among patients with prostate cancer undergoing active surveillance, those with higher Decipher scores were more likely to have higher-grade disease found over time. These findings indicate that the Decipher test might be useful for guiding the intensity of monitoring during active surveillance, such as more frequent biopsy for patients with higher scores., (© 2022 The Author(s).)

Purposeof Review: The use of genomic testing for prostate cancer continues to grow; however, utilization remains institutionally dependent. Herein, we review current tissue-based markers and comment on current use with active surveillance and prostate MRI., Recent Findings: While data continues to emerge, several studies have shown a role for genomic testing for treatment selection. Novel testing options include ConfirmMDx, ProMark, Prolaris, and Decipher, which have shown utility in select patients. The current body of literature on this specific topic remains very limited; prospective trials with long-term follow-up are needed to improve our understanding on how these genomic tests fit when combined with our current clinical tools. As the literature matures, it is likely that newer risk calculators that combine our classic clinical variables with genomic and imaging data will be developed to bring about standard protocols for prostate cancer decision-making., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Magnetic resonance is a key imaging tool for the detection of prostate cancer; however, better tools focusing on cancer specificity are required to distinguish benign from cancerous regions. We found higher expression of claudin-3 (CLDN-3) and -4 (CLDN-4) in higher grade than lower-grade human prostate cancer biopsies (n = 174), leading to the design of functionalized nanoparticles (NPs) with a non-toxic truncated version of the natural ligand Clostridium perfringens enterotoxin (C-CPE) that has a strong binding affinity to Cldn-3 and Cldn-4 receptors. We developed a first-of-its-type, C-CPE-NP-based MRI detection tool in a prostate tumor-bearing mouse model. NPs with an average diameter of 152.9 ± 15.7 nm (RS1) had a 2-fold enhancement of tumor specificity compared to larger (421.2 ± 33.8 nm) NPs (RS4). There was a 1.8-fold (P < 0.01) and 1.6-fold (P < 0.01) upregulation of the tumor-to-liver signal intensities of C-RS1 and C-RS4 (functionalized NPs) compared to controls, respectively. Also, tumor specificity was 3.1-fold higher (P < 0.001) when comparing C-RS1 to C-RS4. This detection tool improved tumor localization of contrast-enhanced MRI, supporting potential clinical applicability., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Context.—: Multiparametric magnetic resonance imaging (mpMRI) of prostate with targeted biopsy has enhanced detection of high-grade prostatic adenocarcinoma (HG PCa). However, utility of amount of HG PCa (Gleason pattern 4/5) in mpMRI-targeted biopsies versus standard 12-core biopsies in predicting adverse outcomes on radical prostatectomy (RP) is unknown., Objective.—: To examine the utility of amount of HG PCa in mpMRI-targeted biopsies versus standard 12-core biopsies in predicting adverse RP outcomes., Design.—: We performed a retrospective review of prostate biopsies that had corresponding RP, 1 or more mpMRI-targeted biopsy, and Grade Group 2 disease or higher. For the 169 cases identified, total millimeters of carcinoma and HG PCa and longest length HG PCa in a single core were recorded for 12-core biopsies and each set of mpMRI-targeted biopsies. For RP specimens, Gleason grade, extraprostatic extension, seminal vesicle involvement, and lymph node metastasis were recorded. The main outcome studied was prostate-confined disease at RP. A logistic regression model was used to test which pre-RP variables related to this outcome., Results.—: Univariate analysis showed significant associations with adverse RP outcomes in 5 of 8 quantifiable variables; longest millimeter HG PCa in a single 12-core biopsy, highest Grade Group in any core, and total millimeter HG in mpMRI-targeted biopsies showed no statistical association (P = .54, P = .13, and P = .55, respectively). In multivariate analysis, total millimeter carcinoma in all cores, highest Grade Group in any core, and longest millimeter HG PCa in a single mpMRI-targeted core provided additional predictive value (P < .001, P = .004, and P = .03, respectively)., Conclusions.—: Quantitation of HG PCa in mpMRI-targeted biopsies provides additional value over 12-core biopsies alone in predicting nonorgan confined prostate cancer at RP. Linear millimeters of HG PCa in mpMRI-targeted biopsies is a significant parameter associated with higher pathologic stage and could be of value in risk models.

Importance: In April 2017, the US Preventive Services Task Force (USPSTF) published a draft guideline that reversed its 2012 guidance advising against prostate-specific antigen (PSA)-based screening for prostate cancer in all men (grade D), instead endorsing individual decision-making for men aged 55 to 69 years (grade C)., Objective: To evaluate changes in rates of PSA testing after revisions in the USPSTF guideline on prostate cancer screening., Design, Setting, and Participants: This retrospective cohort study used deidentified claims data from Blue Cross Blue Shield beneficiaries aged 40 to 89 years from January 1, 2013, through December 31, 2019., Exposures: Publication of the USPSTF's draft (April 2017) and final (May 2018) recommendation on prostate cancer screening., Main Outcomes and Measures: Age-adjusted rates of PSA testing in bimonthly periods were calculated, and PSA testing rates from calendar years before (January 1 to December 31, 2016) and after (January 1 to December 31, 2019) the guideline change were compared. Interrupted time series analyses were used to evaluate the association of the draft (April 2017) and published (May 2018) USPSTF guideline with rates of PSA testing. Changes in rates of PSA testing were further evaluated among beneficiaries within the age categories reflected in the guideline: 40 to 54 years, 55 to 69 years, and 70 to 89 years., Results: The median number of eligible beneficiaries for each bimonthly period was 8 087 565 (range, 6 407 602-8 747 308), and the median age of all included eligible beneficiaries was 53 years (IQR, 47-59 years). Between 2016 and 2019, the mean (SD) rate of PSA testing increased from 32.5 (1.1) to 36.5 (1.1) tests per 100 person-years, a relative increase of 12.5% (95% CI, 1.1%-24.4%). During the same period, mean (SD) rates of PSA testing increased from 20.6 (0.8) to 22.7 (0.9) tests per 100 person-years among men aged 40 to 54 years (relative increase, 10.1%; 95% CI, -2.8% to 23.7%), from 49.8 (1.9) to 55.8 (1.8) tests per 100 person-years among men aged 55 to 69 years (relative increase, 12.1%; 95% CI, -0.2% to 25.2%), and from 38.0 (1.4) to 44.2 (1.4) tests per 100 person-years among men aged 70 to 89 years (relative increase, 16.2%; 95% CI, 4.2%-29.0%). Interrupted time series analysis revealed a significantly increasing trend of PSA testing after April 2017 among all beneficiaries (0.30 tests per 100 person-years for each bimonthly period; P < .001)., Conclusions and Relevance: This large national cohort study found that rates of PSA testing increased after the USPSTF's draft statement in 2017, reversing trends seen after earlier guidance against PSA testing for all patients. Increased testing was also observed among older men, who may be less likely to benefit from prostate cancer screening.

Importance: The clinical decisions that arise from prostate magnetic resonance imaging (MRI) and genomic testing in patients with prostate cancer are not well understood., Objective: To evaluate the association between regional uptake of prostate MRI and genomic testing and observation vs treatment for prostate cancer., Design, Setting, and Participants: This retrospective cohort study of commercial insurance claims for prostate MRI and genomic testing included 65 530 patients 40 to 89 years of age newly diagnosed with prostate cancer from July 1, 2012, through June 30, 2019., Exposures: Patient- and regional-level use of prostate MRI and genomic testing., Main Outcomes and Measures: Observation vs definitive treatment for prostate cancer. Patient-level analyses examined the association between receipt of testing or residing in a hospital referral region (HRR) that adopted testing and observation. In regional-level analyses, the dependent variable was the change in the proportion of patients observed for prostate cancer at the HRR level between 2 periods: July 1, 2012, to June 30, 2014, and July 1, 2017, to June 20, 2019. The independent study variables included HRR-level changes in the proportion of men undergoing prostate MRI and genomic testing between these periods, and the models were adjusted for contextual factors associated with prostate cancer care and socioeconomic status., Results: This study identified 65 530 patients, including 27 679 in the early period (mean [SD] age, 58.0 [5.9] years) and 37 851 in the late period (mean [SD] age, 59.0 [5.7] years). Use of prostate MRI increased significantly from 7.2% (95% CI, 6.9%-7.5%) to 16.7% (95% CI, 16.3%-17.1%) from the early to late period. Use of genomic testing increased significantly from 1.3% (95% CI, 1.1%-1.4%) to 12.7% (95% CI, 12.3%-13.0%) from the early to late period. Compared with the lowest, the highest HRR quartiles of prostate MRI and genomic testing uptake were associated with an adjusted 4.1% (SE, 1.1%; P < .001) and 2.5% (SE, 1.1%; P = .03) absolute increase in the proportion of patients receiving observation, respectively., Conclusions and Relevance: In this cohort study, uptake of prostate MRI and genomic testing was associated with increased use of initial observation vs treatment for prostate cancer. Marked geographic variation supports the need for further patient-level research to optimize the dissemination and outcome of testing.

Purpose: Although the Prostate Imaging-Reporting and Data System™ version 2 (PI-RADS™ v2) is a reliable diagnostic tool for significant prostate cancer, less is known about the prognostic significance of the structured reporting scheme for estimating oncologic outcomes after treatment. We aimed to synthesize the available evidence regarding the association of PI-RADS v2 score and risk of biochemical recurrence (BCR) among patients undergoing primary definitive treatment for prostate cancer., Materials and Methods: We systematically queried the PubMed® and Web of Science™ databases to identify studies addressing the association between the PI-RADS v2 and treatment outcomes. We included studies through November 2020 that assessed the independent prognostic significance of PI-RADS v2. After assessing risk of bias and quality, we conducted a formal meta-analysis to estimate the pooled effects of prostate magnetic resonance imaging (MRI) classification on the risk of BCR., Results: We identified 9 and 7 eligible studies including 2,274 and 1,215 patients for the systematic review and meta-analysis, respectively. Eight were conducted in the context of radical prostatectomy and 1 post-radiation. Among patients treated with radical prostatectomy, higher PI-RADS v2 scores were significantly associated with risk of BCR (pooled HR 3.06, 95% CI 2.16-4.33; p <0.01). There was no significant heterogeneity among studies. For all studies, PI-RADS v2 score remained significantly associated with BCR (pooled HR 3.19, 95% CI 2.28-4.45; p <0.01)., Conclusions: Prostate MRI findings assessed with the PI-RADS v2 classification were independently associated with risk of BCR after definitive local therapy, primarily based on data from radical prostatectomy. These findings support the prognostic significance of MRI, in addition to its role in prostate cancer diagnosis.

Objectives: To determine whether PSA density (PSAD), can sub-stratify risk of biopsy upgrade among men on active surveillance (AS) with normal baseline MRI., Methods: We identified a cohort of patients with low and favorable intermediate-risk prostate cancer on AS at two large academic centers from February 2013 - December 2017. Analysis was restricted to patients with GG1 cancer on initial biopsy and a negative baseline or surveillance mpMRI, defined by the absence of PI-RADS 2 or greater lesions. We assessed ability of PSA, prostate volume and PSAD to predict upgrading on confirmatory biopsy., Results: We identified 98 patients on AS with negative baseline or surveillance mpMRI. Median PSA at diagnosis was 5.8 ng/mL and median PSAD was 0.08 ng/mL/mL. Fourteen men (14.3%) experienced Gleason upgrade at confirmatory biopsy. Patients who were upgraded had higher PSA (7.9 vs 5.4 ng/mL, P = .04), PSAD (0.20 vs 0.07 ng/mL/mL, P < .001), and lower prostate volumes (42.5 vs 65.8 mL, P = .01). On multivariate analysis, PSAD was associated with pathologic upgrade (OR 2.23 per 0.1-increase, P = .007). A PSAD cutoff at 0.08 generated a NPV of 98% for detection of pathologic upgrade., Conclusion: PSAD reliably discriminated the risk of Gleason upgrade at confirmatory biopsy among men with low-grade prostate cancer with negative MRI. PSAD could be clinically implemented to reduce the intensity of surveillance for a subset of patients., (Published by Elsevier Inc.)

Background: To develop an international, multi-site nomogram for side-specific prediction of extraprostatic extension (EPE) of prostate cancer based on clinical, biopsy, and magnetic resonance imaging- (MRI) derived data., Methods: Ten institutions from the USA and Europe contributed clinical and side-specific biopsy and MRI variables of consecutive patients who underwent prostatectomy. A logistic regression model was used to develop a nomogram for predicting side-specific EPE on prostatectomy specimens. The performance of the statistical model was evaluated by bootstrap resampling and cross validation and compared with the performance of benchmark models that do not incorporate MRI findings., Results: Data from 840 patients were analyzed; pathologic EPE was found in 320/840 (31.8%). The nomogram model included patient age, prostate-specific antigen density, side-specific biopsy data (i.e., Gleason grade group, percent positive cores, tumor extent), and side-specific MRI features (i.e., presence of a PI-RADSv2 4 or 5 lesion, level of suspicion for EPE, length of capsular contact). The area under the receiver operating characteristic curve of the new, MRI-inclusive model (0.828, 95% confidence limits: 0.805, 0.852) was significantly higher than that of any of the benchmark models ( p < 0.001 for all)., Conclusions: In an international, multi-site study, we developed an MRI-inclusive nomogram for the side-specific prediction of EPE of prostate cancer that demonstrated significantly greater accuracy than clinical benchmark models.

Context.—: Pathologist interobserver discordance is significant in grading of prostate cancer, limiting reliability. Diagnostic reproducibility may be improved with digital images, but adoption faces workflow, cost, and quality challenges. A novel digital method using an alternative tissue processing approach and novel laser microscopy system potentially addresses these issues., Objective.—: To evaluate the capability of this new method for primary diagnostic interpretation in clinical prostate biopsy specimens., Design.—: Forty patients with a high likelihood of prostate cancer based on magnetic resonance imaging consented to investigational core biopsy. A subset of samples was used for direct comparison of physical slide preparation effects and time-tracking determination with multiphoton microscopy. Twenty samples were processed for diagnostic comparison between multilevel digital slides and subsequently produced physical slides. A reference diagnosis based on all data was established using grade groups. Level of diagnostic match and requests for immunohistochemistry were compared between physical and digital diagnoses. Immunohistochemical staining and length measurements were secondary outcomes., Results.—: Interpretations based on direct multiphoton imaging yielded diagnoses that were at least as accurate as standard histology; cancer diagnosis correlation was 89% (51 of 57) by physical slides and 95% (53 of 56) by multiphoton microscopy. Grade-level concordance was 73% (44 of 60) by either method. Immunohistochemistry for routine prostate cancer-associated markers on these alternatively processed tissues was unaffected. Alternatively processed tissues resulted in longer measured core and cancer lengths, suggestive of improved orientation and visualization., Conclusions.—: Findings support high potential for complete interpretation of prostate core biopsies using solely multiphoton microscopy of intact specimens, with potential diagnostic benefits as well as reduced processing time and reduced processing complexity., (© 2021 College of American Pathologists.)

Purpose: To evaluate practice patterns of planned post-operative radiation therapy (RT) among men with positive surgical margins (PSM) at radical prostatectomy., Methods: We identified 43,806 men within the National Cancer Database with pathologic node-negative prostate cancer diagnosed in 2010 through 2014 with PSM. The primary endpoint was receipt of planned (RT) within a patient's initial course of treatment. We examined post-RP androgen deprivation therapy (ADT) with RT as a secondary endpoint. We evaluated patterns of post-operative management and characteristics associated with planned post-prostatectomy RT., Results: Within 12 months of RP, 87.0% received no planned RT, 8.5% RT alone, 1.3% ADT alone, and 3.1% RT with ADT. In a multivariable logistic regression model, planned RT use was associated with clinical and pathologic characteristics as estimated by surgical Cancer of the Prostate Risk Assessment (CAPRA-S) category (intermediate versus low, OR = 2.87, 95% CI 2.19-3.75, P < 0.001; high versus low, OR = 10.23, 95% CI 7.79-13.43, P < 0.001), treatment at community versus academic centers (OR = 1.24, 95% CI 1.15-1.34, P < 0.001), shorter distance to a treatment facility (OR = 0.97 for each 10-mile, 95% CI 0.96-0.98, P < 0.001), and uninsured status (OR = 1.39, 95% CI 1.10-1.77, P = 0.005). The odds of receiving planned RT were lower in 2014 versus 2010 (OR = 0.76, 95% CI 0.68-0.85, P < 0.001). There was no significant change in the use of ADT with RT. High versus low CAPRA-S category was associated with the use of ADT in addition to RT (OR = 5.13, 95% CI 1.57-16.80, P = 0.007)., Conclusion: The use of planned post-prostatectomy RT remained stable among patients with PSM and appears driven primarily by the presence of other adverse pathologic features.

The utility of serial Decipher biopsy scores in a true active surveillance population is still unknown. In a man on active surveillance for low-risk prostate cancer, a doubling of the Decipher biopsy score within genomic low-risk category from first to the second biopsy related to biopsy reclassification to Gleason grade group 4 on the third biopsy. However, the final pathology at radical prostatectomy showed Gleason grade group 2 with an organ-confined disease. This case suggests that the genomic risk category of Decipher biopsy scores during active surveillance may be more informative than either the interval genomic score change or the biopsy Gleason grade group., Competing Interests: Preston Sprenkle serves as a consultant for Boston Scientific and GenomeDx Biosciences., (Copyright © 2021 Kamyar Ghabili et al.)

Despite widespread adoption of active surveillance (AS) for low-risk prostate cancer, less is known about how or when monitoring should be deintensified. We performed a narrative review of the available evidence and guidelines addressing transitions from active to passive monitoring, including watchful waiting. Increasing age and comorbidity limit quality-adjusted life years gained from curative intervention, although no universal thresholds exist to denote a transition from active monitoring. Despite observational studies indicating that AS intensity decreases over time, the risk of distant progression also increases with age, suggesting an opportunity to improve decision support that incorporates multiple factors when navigating these decisions. PATIENT SUMMARY: We reviewed the available evidence surrounding transitioning from active monitoring to observation. Clinical practice guidelines and research studies support decreasing intensity based on an appreciation of age, other medical problems, and patient preferences., (Copyright © 2020 European Association of Urology. All rights reserved.)

Background: Outcomes of serial multiparametric magnetic resonance imaging (mpMRI) and subsequent biopsy in monitoring prostate cancer (PCa) in men on active surveillance (AS) have not been defined clearly., Objective: To determine whether changes in serial mpMRI can predict pathological upgrade among men with grade group (GG) 1 PCa managed with AS., Design, Setting, and Participants: Retrospective analysis of men with GG1 on AS with at least two consecutive mpMRI examinations during 2012-2018 who underwent mpMRI/ultrasound fusion or systematic biopsies., Outcome Measurements and Statistical Analysis: Progression on serial mpMRI was evaluated as a predictor of pathological upgrading to GG≥2 on a follow-up biopsy using clinical, pathological, and imaging factors in binary logistic regression. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were determined., Results and Limitations: Of 122 patients, 29 men (23.8%) experienced pathological upgrade on the follow-up biopsy. Progression on mpMRI was not associated with pathological upgrade. The sensitivity, specificity, PPV, and NPV of mpMRI progression for predicting pathological upgrade were 41.3%, 54.8%, 22.2%, and 75%, respectively. Age (odds ratio [OR] 1.17, p=0.006), Prostate Imaging Reporting and Data System (PI-RADS) score on initial mpMRI (4-5 vs ≤3, OR 7.48, p=0.01), number of positive systematic cores (OR 1.84, p=0.03), number of positive targeted cores (OR 0.44, p=0.04), and maximum percent of targeted core tumor involvement (OR 1.04, p=0.01) were significantly associated with pathological upgrade., Conclusions: We did not observe an association between mpMRI progression and pathological upgrade; however, a PI-RADS score of 4-5 on initial mpMRI was predictive of subsequent pathological progression. The continued use of systematic and fusion biopsies appears necessary due to risks of reclassification over time., Patient Summary: Progression on serial multiparametric magnetic resonance imaging during active surveillance (AS) is not associated with progression on the follow-up biopsy. Both systematic and fusion biopsies are necessary to sufficiently capture progression during AS., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Management options for localized prostate cancer include definitive radiation therapy (RT) or radical prostatectomy, with a subset of surgical patients requiring adjuvant or salvage RT after prostatectomy. The use of a peri-rectal hydrogel spacer in patients receiving definitive RT has been shown to reduce rectal doses and toxicity. However, in the postprostatectomy setting, a hydrogel spacer cannot be routinely placed. Therefore, we sought to compare rectal dosimetry between definitive RT with a hydrogel spacer versus postoperative RT., Methods and Materials: We identified patients with prostate cancer who underwent conventionally fractionated RT. Rectal dosimetry was evaluated between 2 groups: definitive RT with a hydrogel spacer (79.2 Gy, group 1) and postoperative RT (70.2 Gy, group 2). Rectal dosimetry values were tabulated and compared using Mann-Whitney U test. We implemented a Bonferroni correction to account for multiple comparisons (threshold P < .005). Linear regression analysis evaluated predictors of candidate rectal dose-volume parameters., Results: We identified 51 patients treated during years 2017 to 2018; 16 (31%) and 35 (69%) patients were included in groups 1 and 2, respectively. The rectal volume receiving ≥65 Gy (V65) was significantly lower in group 1 (median, 2.1%; interquartile range, 0.9%-3.1%) than in group 2 (10.7%, 6.6%-14.5%) ( P < .001). Use of a hydrogel spacer in the definitive setting was independently associated with lower V65 ( P < .001). Similar results were found for V60, V55, V50, and V45 ( P < .005 for all)., Conclusions: Rectal dosimetry is more favorable for definitive RT (79.2 Gy) with a hydrogel spacer compared with postoperative RT (70.2 or 66.6 Gy). This may inform shared decision-making regarding primary management of prostate cancer, especially among patients at high risk of needing postoperative RT after prostatectomy., (© 2020 The Author(s).)

Objective: To improve the tolerability of transrectal ultrasound guided prostate biopsy through use of diaphragmatic breathing., Methods: Forty-seven patients, aged 52-79 years, who were scheduled for a transrectal ultrasound guided prostate biopsy with or without MRI guidance, were recruited at a single Veterans Affairs medical center for the diagnosis or evaluation of prostate cancer. Patients either met with a health psychologist for a 1-time, diaphragmatic breathing intervention immediately prior to their biopsy, or received usual care. All biopsies were performed using local anesthetic without sedation or anxiolytic therapy. The primary outcome was the difference in self-reported procedural situational anxiety as measured with the State Trait Anxiety Inventory, assessed both pre- and post-transrectal ultrasound guided prostate biopsy. We also examined secondary outcomes including physiological parameters (heart rate and blood pressure)., Results: There were no significant differences in preprocedural anxiety or physiological parameters between patients who received the intervention and those who received usual care. Patients who received the intervention had a significantly larger decrease in situational anxiety from pre- to postprocedure (M = 14.15, SD = 6.64) compared with those who received usual care (M = 3.45, SD = 9.97); t (38) = -4.0, P <.000; d = 1.26. Patients who received the intervention had a significantly larger decrease in heart rate (bpm) from pre- to postprocedure (M = 10.63, SD = 12.21) compared with those who received usual care (M = 0.07, SD = 9.25); t (31) = 2.75 P = 0.010; d = 0.97., Conclusion: A guided diaphragmatic breathing intervention reduced procedural anxiety during prostate biopsy and improved patient experience., (Published by Elsevier Inc.)

Objective: To investigate whether presence of multifocality on multi-parametric magnetic resonance imaging would increase the likelihood of detecting clinically-significant prostate cancer in a PI-RADS 4 lesion., Methods: We identified patients with at least 1 PI-RADS 4 lesion who underwent multi-parametric magnetic resonance imaging-ultrasound fusion prostate biopsy. Patients were grouped into 1 of 4 cohorts-cohort 1 (a PI-RADS 4 index lesion and an additional PI-RADS 2 or 3 lesion), cohort 2 (single lesion with PI-RADS 4), cohort 3 (2 or more PI-RADS 4 lesions), or cohort 4 (a PI-RADS 4 lesion and an index lesion with PI-RADS 5). We compared the rate of grade group (GG) ≥ 2 pathology on targeted biopsy of PI-RADS 4 lesions between cohorts and evaluated clinical and radiological factors associated with cancer detection., Results: The overall rate of GG ≥ 2 pathology in the PI-RADS 4 lesions was 35.2%. The rate of GG ≥ 2 pathology in the cohorts 1, 2, 3, and 4 was 21.7%, 36.3%, 49.1%, and 42.7%, respectively (P< .001). On multivariable analysis, age (OR1.06, P < .001), clinical stage T2 (OR1.59, P= .03), prostate-specific antigen density (OR1.43, P < .001), peripheral zone lesion (OR1.62, P = .04), and study cohort (cohort 2 vs 1, OR1.93, P = .006; and cohort 3 vs 1, OR3.28, P < .001) were significantly associated with the risk of GG ≥ 2 in the PI-RADS 4 lesion., Conclusion: On targeted biopsy of the PI-RADS 4 lesions, the proportion of GG ≥ 2 pathology is approximately 35%. Rate of GG ≥ 2 detection in PI-RADS 4 lesions might differ based on their location, multifocality, and PI-RADS classifications of other lesions identified., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The optimal method of magnetic resonance imaging (MRI)-ultrasound (US) fusion biopsy to adequately sample regions of interest (ROIs) remains unknown. We sought to determine the number and location of cores needed to adequately detect clinically significant prostate cancer (PCa). We identified patients undergoing MRI-US fusion prostate biopsy at our institution for known history or clinical suspicion of PCa. Multiparametric MRI studies were reviewed using Likert and Prostate Imaging Reporting and Data System (PI-RADS) v2 schema. Multiple targeted cores were taken from each ROI followed by 12-core systematic biopsy. In a distinct cohort of patients, lesions were targeted using a predetermined five-core template. We estimated cancers detected through sampling of five or fewer cores, assessed by core number and core location. We identified 744 patients with 581 lesions with PCa. Seventy-seven percent (279/361) of Gleason (G) ≥3+4 tumors and 72% (137/189) of G >3+4 tumors were detected on two-core sampling. Relative to all targeted cores, a two-core approach missed 16% of clinically significant cancers at first biopsy, 27% in prior negative, and 32% in active surveillance patients. Detection of G ≥3+4 cancers did not differ by core location. Sampling of two cores of ROIs misses nearly one-quarter of clinically significant PCa detected on additional sampling. PATIENT SUMMARY: We aimed to understand how the number of cores obtained from a suspicious area during prostate magnetic resonance imaging-ultrasound fusion biopsy affects cancer detection. We found that sampling of five cores missed substantially fewer cancers compared to two cores., (Published by Elsevier B.V.)

The ability of medical image analysis deep learning algorithms to generalize across multiple sites is critical for clinical adoption of these methods. Medical imging data, especially MRI, can have highly variable intensity characteristics across different individuals, scanners, and sites. However, it is not practical to train algorithms with data from all imaging equipment sources at all possible sites. Intensity normalization methods offer a potential solution for working with multi-site data. We evaluate five different image normalization methods on training a deep neural network to segment the prostate gland in MRI. Using 600 MRI prostate gland segmentations from two different sites, our results show that both intra-site and inter-site evaluation is critical for assessing the robustness of trained models and that training with single-site data produces models that fail to fully generalize across testing data from sites not included in the training.

Objective: To assess the association between Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) score, the Decipher score, and histologic grade of carcinoma in biopsy tissue among low- to intermediate-risk prostate cancer patients., Methods: MRI-ultrasound targeted biopsy of regions of interest and concurrent 12-core systematic biopsy was performed on men with Gleason grade group (GG) 1 and 2. We compared Decipher score with PI-RADS scores and biopsy Gleason GG. Subgroup analyses were performed to evaluate patients who underwent radical prostatectomy (RP), and men with Decipher testing from a targeted biopsy core., Results: One hundred two patients with GG1 and GG2 had biopsy Decipher testing. There was no significant difference in the median Decipher scores among the 3 multiparametric magnetic resonance imaging categories. Patients with GG2 vs GG1 in the setting of PI-RADS 4-5 had higher genomic scores (P = .01), but no significant difference was noted in patients with PI-RADS ≤3. The rate of genomic higher-risk disease on a targeted biopsy from PI-RADS5 was higher in GG2 (75%) vs GG1 (11.1%; P = .01). On multivariable logistic regression analysis, the Decipher score ≥0.45, (odds ratio (OR) 2.71; P = .02), and age (OR 1.11; P = .004) remained significant factors associated with Gleason GG2 on biopsy., Conclusion: High-risk genomic classification can be seen across all combinations of PI-RADS categories and Gleason GG1 and GG2, confirming a potential utility for Decipher testing in men with low- to favorable intermediate-risk prostate cancer. The Decipher biopsy genomic test related to Gleason GG independent of PI-RADSv2 score. Confirmatory genomic testing for patients undergoing active surveillance appears more valuable than PI-RADSv2 score., (Copyright © 2018 Elsevier Inc. All rights reserved.)

If prostate-specific antigen (PSA) trends help identify elevated prostate cancer (PCa) risk, they might provide early warning of progressing cancer for further evaluation and justify annual testing. Our objective was to determine whether PSA trends predict PCa likelihood. A biopsy cohort of 361,657 men was obtained from a Veterans Affairs database (1999-2012). PSA trends were estimated for the 310,458 men with at least 2 PSA tests prior to biopsy. Cancer tumors may grow exponentially with cells doubling periodically. We hypothesized that PSA from prostate cancer grows exponentially above a no cancer baseline. We estimated PSA trends on that basis along with five descriptive variables: last PSA before biopsy, growth rate in PSA from cancer above a baseline, PSA variability around the trend, number of PSA tests, and time span of tests. PSA variability is a new variable that measures percentage deviations of PSA tests from estimated trends with 0% variability for a smoothly increasing trend. Logistic regression models were used to estimate relationships between the probability of PCa at biopsy and the trend variables and age. All five PSA trend variables and age were significant predictors of prostate cancer at biopsy ( p < 0.0001). An overall logistic regression model achieved an AUC of 0.67 for men with at least 4 tests over at least 3 years, which was a substantial improvement over a single PSA (AUC 0.58). High probability of PCa was associated with low PSA variability (smooth trends), high PSA, high growth rate, many tests over a long time-span and older age. For example, at 4.0 PSA the probability of cancer is 32% for 1 PSA test and increases to 68% for 8 tests over 7 years with smooth, fast growth (0% variability and 50% exponential growth). Our results show that smooth, fast exponential growth in PSA above a baseline predicts an increased probability of PCa. The probability increases as smooth (low variability) trends are observed for more tests over a longer time span, which makes annual testing worth considering. Worrisome PSA trends might be used to trigger further evaluation and continued monitoring of the trends-even at low PSA levels.

Objective: The objective of this study is to determine the frequency of clinically significant cancer (CSC) in Prostate Imaging Reporting and Data System (PI-RADS) category 3 (equivocal) lesions prospectively identified on multiparametric prostate MRI and to identify risk factors (RFs) for CSC that may aid in decision making., Materials and Methods: Between January 2015 and July 2016, a total of 977 consecutively seen men underwent multiparametric prostate MRI, and 342 underwent MRI-ultrasound (US) fusion targeted biopsy. A total of 474 lesions were retrospectively reviewed, and 111 were scored as PI-RADS category 3 and were visualized using a 3-T MRI scanner. Multiparametric prostate MR images were prospectively interpreted by body subspecialty radiologists trained to use PI-RADS version 2. CSC was defined as a Gleason score of at least 7 on targeted biopsy. A multivariate logistic regression model was constructed to identify the RFs associated with CSC., Results: Of the 111 PI-RADS category 3 lesions, 81 (73.0%) were benign, 11 (9.9%) were clinically insignificant (Gleason score, 6), and 19 (17.1%) were clinically significant. On multivariate analysis, three RFs were identified as significant predictors of CSC: older patient age (odds ratio [OR], 1.13; p = 0.002), smaller prostate volume (OR, 0.94; p = 0.008), and abnormal digital rectal examination (DRE) findings (OR, 3.92; p = 0.03). For PI-RADS category 3 lesions associated with zero, one, two, or three RFs, the risk of CSC was 4%, 16%, 62%, and 100%, respectively. PI-RADS category 3 lesions for which two or more RFs were noted (e.g., age ≥ 70 years, gland size ≤ 36 mL, or abnormal DRE findings) had a CSC detection rate of 67% with a sensitivity of 53%, a specificity of 95%, a positive predictive value of 67%, and a negative predictive value of 91%., Conclusion: Incorporating clinical parameters into risk stratification algorithms may improve the ability to detect clinically significant disease among PI-RADS category 3 lesions and may aid in the decision to perform biopsy.

Purpose: To evaluate the positive predictive value (PPV) of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) assessment method in patients with a single suspicious finding on prostate multiparametric magnetic resonance imaging (mpMRI)., Patients and Methods: A total of 176 patients underwent MRI/ultrasound fusion-targeted prostate biopsy after the detection of a single suspicious finding on mpMRI. The PPV for cancer detection was determined based on PI-RADS v2 assessment score and location., Results: Fusion biopsy detected prostate cancer in 60.2% of patients. Of these patients, 69.8% had Gleason score (GS) ≥7 prostate cancer. Targeted biopsy detected 90.5% of all GS≥7 prostate cancer. The PPV for GS≥7 detection of PI-RADS v2 category 5 (P5) and category 4 (P4) lesions was 70.2% and 37.7%, respectively. This increased to 88% and 38.5% for P5 and P4 lesions in the peripheral zone (PZ), respectively. Targeted biopsy did not miss GS≥7 disease compared with systematic biopsy in P5 lesions in the PZ and transition zone., Conclusion: The PPV of PI-RADS v2 for prostate cancer in patients with a single lesion on mpMRI is dependent on PI-RADS assessment category and location. The highest PPV was for a P5 lesion in the PZ., (Published by Elsevier Inc.)

Accurate and robust non-rigid registration of pre-procedure magnetic resonance (MR) imaging to intra-procedure trans-rectal ultrasound (TRUS) is critical for image-guided biopsies of prostate cancer. Prostate cancer is one of the most prevalent forms of cancer and the second leading cause of cancer-related death in men in the United States. TRUS-guided biopsy is the current clinical standard for prostate cancer diagnosis and assessment. State-of-the-art, clinical MR-TRUS image fusion relies upon semi-automated segmentations of the prostate in both the MR and the TRUS images to perform non-rigid surface-based registration of the gland. Segmentation of the prostate in TRUS imaging is itself a challenging task and prone to high variability. These segmentation errors can lead to poor registration and subsequently poor localization of biopsy targets, which may result in false-negative cancer detection. In this paper, we present a non-rigid surface registration approach to MR-TRUS fusion based on a statistical deformation model (SDM) of intra-procedural deformations derived from clinical training data. Synthetic validation experiments quantifying registration volume of interest overlaps of the PI-RADS parcellation standard and tests using clinical landmark data demonstrate that our use of an SDM for registration, with median target registration error of 2.98 mm, is significantly more accurate than the current clinical method. Furthermore, we show that the low-dimensional SDM registration results are robust to segmentation errors that are not uncommon in clinical TRUS data., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To determine the negative predictive value of multiparametric magnetic resonance imaging (mpMRI), we evaluated the frequency of prostate cancer detection by 12-core template mapping biopsy in men whose mpMRI showed no suspicious regions., Methods: Six hundred seventy patients underwent mpMRI followed by transrectal ultrasound (TRUS)-guided systematic prostate biopsy from December 2012 to June 2016. Of this cohort, 100 patients had a negative mpMRI. mpMRI imaging sequences included T2-weighted and diffusion-weighted imaging, and dynamic contrast enhancement sequences., Results: The mean age, prostate-specific antigen, and prostate volume of the 100 men included were 64.3 years, 7.2 ng/mL, and 71 mL, respectively. Overall cancer detection was 27% (27 of 100). Prostate cancer was detected in 26.3% (10 of 38) of patients who were biopsy-naïve, 12.1% (4 of 33) of patients who had a prior negative biopsy, and in 44.8% (13 of 29) of patients previously on active surveillance; Gleason grade ≥7 was detected in 3% of patients overall (3 of 100). The negative predictive value of a negative mpMRI was 73% for all prostate cancer and 97% for Gleason ≥7 prostate cancer., Conclusion: There is an approximately 3% chance of detecting clinically significant prostate cancer with systematic TRUS-guided biopsy in patients with no suspicious findings on mpMRI. This information should help guide recommendations to patients about undergoing systematic TRUS-guided biopsy when mpMRI is negative., (Published by Elsevier Inc.)

Purpose of Review: Active surveillance has been increasingly utilized as a strategy for the management of favorable-risk, localized prostate cancer. In this review, we describe contemporary management strategies of active surveillance, with a focus on traditional stratification schemes, new prognostic tools, and patient outcomes., Recent Findings: Patient selection, follow-up strategy, and indication for delayed intervention for active surveillance remain centered around PSA, digital rectal exam, and biopsy findings. Novel tools which include imaging, biomarkers, and genetic assays have been investigated as potential prognostic adjuncts; however, their role in active surveillance remains institutionally dependent. Although 30-50% of patients on active surveillance ultimately undergo delayed treatment, the vast majority will remain free of metastasis with a low risk of dying from prostate cancer. The optimal method for patient selection into active surveillance is unknown; however, cancer-specific mortality rates remain excellent. New prognostication tools are promising, and long-term prospective, randomized data regarding their use in active surveillance will be beneficial.

A single early prostate-specific antigen (PSA) level has been correlated with a higher likelihood of prostate cancer diagnosis and death in younger men. PSA testing in older men has been considered of limited utility. We evaluated prostate cancer death in relation to age and PSA level immediately prior to prostate cancer diagnosis. Using the Veterans Affairs database, we identified 230,081 men aged 50-89 years diagnosed with prostate cancer and at least one prior PSA test between 1999 and 2009. Prostate cancer-specific death over time was calculated for patients stratified by age group (e.g., 50-59 years, through 80-89 years) and PSA range at diagnosis (10 ranges) using Kaplan-Meier methods. Risk of 10-year prostate cancer mortality across age and PSA was compared using log-rank tests with a Bonferroni adjustment for multiple testing. 10.5% of men diagnosed with prostate cancer died of cancer during the 10-year study period (mean follow-up = 3.7 years). Higher PSA values prior to diagnosis predict a higher risk of death in all age groups (p < 0.0001). Within the same PSA range, older age groups are at increased risk for death from prostate cancer (p < 0.0001). For PSA of 7-10 ng/mL, cancer-specific death, 10 years after diagnosis, increased from 7% for age 50-59 years to 51% for age 80-89 years. Men older than 70 years are more likely to die of prostate cancer at any PSA level than younger men, suggesting prostate cancer remains a significant problem among older men (even those aged 80+) and deserves additional study.

Objectives: To test a novel porcine two-kidney model for evaluating the effect of controlled acute kidney injury (AKI) related to induced unilateral ischaemia on both renal units (RUs) To use neutrophil gelatinase-associated lipocalin (NGAL) and physiological serum and urinary markers to assess AKI and renal function., Methods: Twelve female Yorkshire pigs had bilateral cutaneous ureterostomies placed laparoscopically with identical duration of pneumoperitoneum for all cases. An experimental group (n = 9) underwent induced unilateral renal ischaemia with left hilar clamping of timed duration (15, 30, 60 min) and a control group (n = 3) had no induced renal ischaemia. Urine was collected and analysed from each RU to assess creatinine and NGAL concentration preoperatively and at multiple postoperative time points. Serum was collected and analysed daily for creatinine and NGAL levels. Statistical comparisons were made using the rank-sum and sign-rank tests., Results: Three pigs were excluded because of intra-operative and postoperative complications. In the RUs that experienced renal ischaemia (n = 7),the median urine volume was lower (P = 0.04) at 6, 12, 24 and 48 h and the median NGAL concentration was higher (P = 0.04) at 12 and 48 h compared with the RUs of control pigs that experienced no renal ischaemia (n = 2). When comparing the ischaemic (left) RU of the pigs in the experimental group with their contralateral non-ischaemic (right) RU, ischaemic RUs had a lower median cumulative urine volume at 6, 12, 24 and 48 h (P = 0.05) and a higher median NGAL concentration at 12, 24 and 48 h (P < 0.05). At 48 h, no significant increase was found in serum NGAL in pigs in the experimental group compared with controls (P = 0.2). Creatinine clearance (CC) was lower in ischaemic RUs compared with non-ischaemic RUs 1 day after surgery (P = 0.04) with decreasing CC as the duration of ischaemia increased., Conclusions: We have developed a promising novel small-scale pilot surgical model that allowed the evaluation of bilateral RU function separately during and after unilateral renal ischaemia. The induction of unilateral renal ischaemia corresponds with physiological changes in both the ischaemic and contralateral RU. AKI as measured by increases in NGAL and decreased renal function as measured by decreases in CC, are specific to the RU exposed to ischaemia., (© 2013 BJU International.)

Purpose: We evaluated urine NGAL as a marker of acute kidney injury in patients undergoing partial nephrectomy. We sought to identify the preoperative clinical features and surgical factors during partial nephrectomy that are associated with renal injury, as measured by increased urine NGAL vs controls., Materials and Methods: Using patients treated with radical nephrectomy or thoracic surgery as controls, we prospectively collected and analyzed urine and serum samples from patients treated with partial or radical nephrectomy, or thoracic surgery between April 2010 and April 2012. Urine was collected preoperatively and at multiple time points postoperatively. Differences in urine NGAL levels were analyzed among the 3 surgical groups using a generalized estimating equation model. The partial nephrectomy group was subdivided based on a preoperative estimated glomerular filtration rate of less than 60, or 60 ml/minute/1.73 m(2) or greater., Results: Of 162 patients included in final analysis more than 65% had cardiovascular disease. The median estimated glomerular filtration rate was greater than 60 ml/minute/1.73 m(2) in the radical and partial nephrectomy, and thoracic surgery groups (61, 78 and 84.5 ml/minute/1.73 m(2), respectively). Preoperatively, a 10 unit increase in the estimated glomerular filtration rate was associated with a 4 unit decrease in urine NGAL in the partial nephrectomy group. Postoperatively, urine NGAL in the partial nephrectomy group was not higher than in controls and did not correlate with ischemia time. Patients with partial nephrectomy with a preoperative estimated glomerular filtration rate of less than 60 ml/minute/1.73 m(2) had higher urine NGAL postoperatively than those with a higher preoperative estimated rate., Conclusions: Urine NGAL does not appear to be a useful marker for detecting renal injury in healthy patients treated with partial nephrectomy. However, patients with poorer preoperative renal function have higher baseline urine levels and appear more susceptible to acute kidney injury, as detected by urine levels and Acute Kidney Injury Network criteria, than those with a normal estimated glomerular filtration rate., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)