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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. [ABSTRACT FROM AUTHOR]

Abstract: Background: Indications for partial nephrectomy (PN) in the treatment of renal cell carcinoma are evolving, particularly for larger, more complex tumors. Objective: Compare single-institution outcomes for minimally invasive partial nephrectomy (MIPN) and open partial nephrectomy (OPN) for tumors >4–7cm. Design, setting, and participants: A total of 2290 patients underwent PN from 2002 to 2010 at Memorial Sloan-Kettering Cancer Center; 280 had >4–7cm renal cortical tumors. Of these 280 patients, 230 had pT1b, 48 had pT3a, and 2 had angiomyolipomas; 226 underwent OPN and 54 underwent MIPN (16 robot-assisted and 37 laparoscopic procedures). Perioperative management was uniform on the clinical pathway. Perioperative data, clinicopathologic variables, complications within 30 d, and oncologic outcomes were reviewed. Measurements: Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Complications were reported from prospectively collected data based on a modified Clavien system. The Fisher exact and Mann-Whitney U tests were used for descriptive statistical analysis. Kaplan-Meier methods were used to estimate survival. Results and limitations: Median follow-up for OPN and MIPN was 29 and 13 mo, respectively. There were no statistically significant differences in age, gender, preoperative American Society of Anesthesiologists score, laterality, histologic subtype, tumor size, tumor stage, or margin status between procedures. Univariate analysis revealed significantly greater values in the OPN group for preoperative eGFR, renal artery clamp time, estimated blood loss, use of renal hypothermia, and length of stay. Differences in overall survival and recurrence-free survival were not statistically significant; however, short median follow-up times limit comparison. There was no significant difference in the number of complications grade ≥3 (p =0.1) or urine leaks requiring intervention (p =0.7). Limitations include the retrospective nature of the study and the possibility of selection bias. Conclusions: OPN and MIPN procedures performed in patients with tumors >4–7cm offer acceptable and comparable results in terms of operative, functional, and convalescence measures, regardless of approach. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Magnetic resonance imaging has shown to be a reliable imaging method for detecting clinically significant prostate cancer and directly targeting lesions during biopsy. As newer treatment methods emerge, the role of MRI in minimally-invasive (focal) treatment of prostate cancer is also increasing. Here, we review the real-time MRI-guided prostate interventions for prostate cancer diagnosis and treatment, focusing on the technical aspects of each modality. Prostate cancer (PCa) is the second most common cause of cancer death in males. Targeting MRI-visible lesions has led to an overall increase in the detection of clinically significant PCa compared to the prior practice of random ultrasound-guided biopsy of the prostate. Additionally, advances in MRI-guided minimally invasive focal treatments are providing new options for patients with PCa. This review summarizes the currently utilized real-time MRI-guided interventions for PCa diagnosis and treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Most Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions on prostate MRI are found to harbor Gleason grade group ≥2 prostate cancer on initial biopsy. As a result, the optimal management of patients found to have Gleason grade group 1 (GG1) prostate cancer despite PI-RADS 5 lesions on prostate MRI remains unclear. To estimate risks of grade misclassification, we evaluated the occurrence of Gleason upgrade on subsequent active surveillance (AS) prostate biopsy or radical prostatectomy among patients diagnosed with GG1 prostate cancer with PI-RADS 5 lesions on MRI. We conducted a retrospective analysis at a single institution to identify patients diagnosed with GG1 prostate cancer whose MRI nearest to diagnosis demonstrated ≥1 lesion classified as PI-RADS 5. The primary study outcome was the presence of Gleason reclassification to GG≥2 prostate cancer on subsequent prostate biopsy or radical prostatectomy. The secondary outcomes included rates of grade reclassification on prostate biopsy, or conversion to active treatment among patients managed with initial active surveillance. We used multivariable logistic regression to identify factors associated with Gleason reclassification on subsequent biopsy or radical prostatectomy. Among 3,042 patients undergoing prostate biopsy between 01/2013-12/2022, we identified 110 with GG1 prostate cancer and PI-RADS 5 lesions on;MRI who received a total of 216 biopsies. The median age was 69 years and median PSA at diagnosis was 6.4 ng/mL. There were 104 patients (94.6%) who elected initial AS and six (5.5%) were treated. Sixty-one patients managed with AS underwent ≥1 additional biopsy. Among this group, 43 (70.5%) experienced Gleason upgrade including 32 (74.4%) on second, 9 (20.9%) on third, and one (2.3%) each on fourth and fifth biopsy. A total of 44 (40%) patients received definitive treatment including prostatectomy in 15 (13.6%) and radiation in 25 (22.73%). Two patients (1.8%) developed metastatic disease, of whom one patient later demonstrated higher grade disease on biopsy, and one died of disease. In multivariable logistic regression, no clinical or pathological factors were significantly associated with odds of Gleason upgrade. The majority of patients diagnosed with GG1 prostate cancer in the setting of a PI-RADS 5 lesion will be found to have GG2 or higher disease in the short term during active surveillance or during treatment, suggesting substantial initial misclassification. These findings reinforce the need for confirmatory testing in these patients due to risks of disease under-sampling. [ABSTRACT FROM AUTHOR]

* 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Are social factors associated with the diagnosis of lethal prostate cancer (CaP) in younger patients? • Uninsured younger patients more commonly presented with advanced or metastatic CaP. • These findings support greater attention to social factors including the role of health insurance in early detection of prostate cancer. A subset of patients are diagnosed with lethal prostate cancer (CaP) early in life before prostate-specific antigen (PSA) screening is typically initiated. To identify opportunities for improved detection, we evaluated patient sociodemographic factors associated with advanced vs. localized (CaP) diagnosis across the age spectrum. We conducted a retrospective cohort study using the National Cancer Database, identifying patients diagnosed with CaP from 2004 to 2020. We compared characteristics of patients diagnosed at the advanced (cN1 or M1) versus localized (cT1-4N0M0) stage. Using multivariable logistic regression, we evaluated the associations among patient clinical and sociodemographic factors and advanced diagnosis, stratifying patients by age as ≤55 (before screening is recommended for most patients), 56 to 65, 66 to 75, and ≥76 years. We identified 977,722 patients who met the inclusion criteria. The mean age at diagnosis was 65.3 years and 50,663 (5.1%) had advanced disease. Overall, uninsured (OR = 3.20, 95% CI 3.03–3.78) and Medicaid-insured (OR 2.58, 95% CI 2.48–2.69) vs. privately insured status was associated with higher odds of diagnosis with advanced disease and this effect was more pronounced for younger patients. Among patients ≤55 years, uninsured (OR 4.14, 95% CI 3.69–4.65) and Medicaid-insured (OR 3.39, 95% CI 3.10–3.72) vs. privately insured patients were associated with higher odds of advanced cancer at diagnosis. Similarly, residence in the lowest vs. highest income quartile was associated with increased odds of advanced CaP in patients ≤55 years (OR 1.15, 95% CI 1.02–1.30). Black vs. White race was associated with increased odds of advanced CaP at diagnosis later in life (OR 1.17, 95% CI 1.09–1.25); however, race was not significantly associated with advanced stage CaP in those ≤55 years (P = 0.635). Sociodemographic disparities in diagnosis at advanced stages of CaP were more pronounced in younger patients, particularly with respect to insurance status. These findings may support greater attention to differential use of early CaP screening based on patient health insurance. [ABSTRACT FROM AUTHOR]

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. 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. Considerable variability exists in the methodology of targeted fusion prostate biopsy. In this institutional study, we found a two-core biopsy substantially misses high-grade cancers within a lesion while core location is not significant. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: While multiparametric MRI (mpMRI) has high sensitivity for detection of clinically significant prostate cancer (CSC), false positives and negatives remain common. Calculators that combine mpMRI with clinical variables can improve cancer risk assessment, while providing more accurate predictions for individual patients. We sought to create and externally validate nomograms incorporating Prostate Imaging Reporting and Data System (PIRADS) scores and clinical data to predict the presence of CSC in men of all biopsy backgrounds.Methods: Data from 2125 men undergoing mpMRI and MR fusion biopsy from 2014 to 2018 at Stanford, Yale, and UAB were prospectively collected. Clinical data included age, race, PSA, biopsy status, PIRADS scores, and prostate volume. A nomogram predicting detection of CSC on targeted or systematic biopsy was created.Results: Biopsy history, Prostate Specific Antigen (PSA) density, PIRADS score of 4 or 5, Caucasian race, and age were significant independent predictors. Our nomogram-the Stanford Prostate Cancer Calculator (SPCC)-combined these factors in a logistic regression to provide stronger predictive accuracy than PSA density or PIRADS alone. Validation of the SPCC using data from Yale and UAB yielded robust AUC values.Conclusions: The SPCC combines pre-biopsy mpMRI with clinical data to more accurately predict the probability of CSC in men of all biopsy backgrounds. The SPCC demonstrates strong external generalizability with successful validation in two separate institutions. The calculator is available as a free web-based tool that can direct real-time clinical decision-making. [ABSTRACT FROM AUTHOR]

OBJECTIVE To examine the relationship between the presence of high-grade prostatic intraepithelial neoplasia (HGPIN) in retropubic radical prostatectomy (RP) specimens and cancer-specific outcomes, including pathological variables and biochemical disease-free survival (bDFS), as HGPIN shares many histopathological characteristics with prostate carcinoma and has been considered a precursor lesion to prostate cancer. PATIENTS AND METHODS The Columbia University Urologic Oncology Database was reviewed; 3460 patients were identified who underwent RP between 1988–2006, and 2133 with or without HGPIN and >12 months of follow-up were included in the analysis. Analysis of variance methods were used to evaluate the relationship between HGPIN and pathological stage, Gleason sum, perineural invasion, multifocality, extraprostatic extension, margin and nodal status. Kaplan-Meier analysis with the log-rank test and a multivariate Cox proportional hazard model fitted for preoperative prostate-specific antigen (PSA) level, Gleason sum and pathological stage were used to assess differences in bDFS. RESULTS In all, 1885 (88.4%) patients had HGPIN in the RRP specimen and 248 (11.6%) had no HGPIN. There was no significant difference in the distribution of PSA level ( P = 0.27), pathological stage ( P = 0.18) or Gleason sum ( P = 0.84) between patients with and with no HGPIN. The HGPIN-positive group had higher rates of perineural invasion (69.9 vs 57.5%; P = 0.003) and multifocality (63.0 vs 38.4%; P < 0.001). Patients with no HGPIN had a better bDFS, at 87.3% vs 81.0% at a median follow-up of 50 months, and 73.6% vs 67.0% at 9 years ( P = 0.045). The risk of biochemical failure was 1.9 times greater in the HGPIN-positive group than the negative group ( P = 0.006) when controlling for PSA level, pathological stage and Gleason sum. CONCLUSIONS In addition to traditional pathological prognostic variables, the absence of HGPIN in RRP specimens, although found in a minority of patients, denotes a significantly lower rate of tumour multifocality, perineural invasion and ultimately biochemical recurrence. [ABSTRACT FROM AUTHOR]

Removal of toxic substances from the blood depends on patent connections between the kidney, ureters and bladder that are established when the ureter is transposed from its original insertion site in the male genital tract to the bladder. This transposition is thought to occur as the trigone forms from the common nephric duct and incorporates into the bladder. Here we re-examine this model in the context of normal and abnormal development. We show that the common nephric duct does not differentiate into the trigone but instead undergoes apoptosis, a crucial step for ureter transposition controlled by vitamin A–induced signals from the primitive bladder. Ureter abnormalities occur in 1–2% of the human population and can cause obstruction and end-stage renal disease. These studies provide an explanation for ureter defects underlying some forms of obstruction in humans and redefine the current model of ureter maturation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]