Pre-radical Prostatectomy Research Articles

Correlation between pre-radical prostatectomy standardized SUVmax ratios detected on 68Ga-PSMA-I&T PET/CT and final histopathology outcomes: an in-depth analysis

ObjectiveTo evaluate the predictive potential of the maximum standardized uptake value(SUVmax) value of intraprostatic tumors derived from preoperative 68Ga-PSMA-I&T PET/CT (SUVT), and its ratios to SUVmax in the liver (SUVTLR) and parotid gland (SUVTPR) with respect to histopathological findings. Materials and methodsData from patients who underwent radical prostatectomy (RP) for prostate cancer (PC) at our clinic between 2017 and 2020 were assessed. Patients with a secondary malignancy, a history of transurethral prostate resection, prior treatment for PC, or who received salvage RP were excluded. Whole-body images obtained using the same device, as per the guidelines, were reviewed by two nuclear medicine specialists with more than a decade of experience to reach a consensus for each lesion. The relationships between age, PSA, Prostate Volume, clinical T stage, biopsy International Society of Urological Pathology grade (ISUP), D’amico risk group, intraprostatic tumor volume (HPTV) identified in the final histopathological specimen review, HP-ISUP grade, seminal vesicle invasion (SVI), extracapsular invasion (ECI), positive surgical margine (PSM), SUVT, SUVTLR, and SUVTPR were analyzed. ResultsThe mean age of the 64 included patients was 64.1 ± 5.3. A statistically significant correlation was found between SUVT, SUVTLR, SUVTPR values, and histopathologic stage parameters, such as biopsy ISUP, D'amico Risk Classification, HP-ISUP, HPTV (p < 0.05). PSMATV, SUVT, and SUVTLR were statistically significant predictors of extracapsular invasion, while PSA, PSMATV, and SUVTLR were significant predictors of SVI (p < 0.05). ConclusionThe standardized SUVT, SUVTLR, and SUVTPR values could be employed as noninvasive markers to assist in predicting postoperative histopathological findings, particularly ECI, SVI, and PSM.

Multi-Institutional Development and Validation of a Radiomic Model to Predict Prostate Cancer Recurrence Following Radical Prostatectomy

The use of multiparametric magnetic resonance imaging (mpMRI)-derived radiomics has the potential to offer noninvasive, imaging-based biomarkers for the identification of subvisual characteristics indicative of a poor oncologic outcome. The present study, therefore, seeks to develop, validate, and assess the performance of an MRI-derived radiomic model for the prediction of prostate cancer (PC) recurrence following radical prostatectomy (RP) with curative intent. mpMRI imaging was obtained from 251 patients who had undergone an RP for the treatment of localized prostate cancer across two institutions and three surgeons. All patients had a minimum of 2 years follow-up via prostate-specific antigen serum testing. Each prostate mpMRI was individually reviewed, and the prostate was delineated as a single slice (ROI) on axial T2 high-resolution image sets. A total of 924 radiomic features were extracted and tested for stability via intraclass correlation coefficient (ICC) following image normalization via histogram matching. Fourteen important and nonredundant features were found to be predictors of PC recurrence at a mean ± SD of 3.2 ± 2.2 years post-RP. Five-fold, ten-run cross-validation of the model containing these fourteen features yielded an area under the curve (AUC) of 0.89 ± 0.04 in the training set (n = 225). In comparison, the University of California San Fransisco Cancer of the Prostate Risk Assessment score (UCSF-CAPRA) and Memorial Sloan Kettering Cancer Center (MSKCC) Pre-Radical prostatectomy nomograms yielded AUC of 0.66 ± 0.05 and 0.67 ± 0.05, respectively (p &lt; 0.01). When the radiomic model was applied to the test set (n = 26), AUC was 0.78; sensitivity, specificity, positive predictive value, and negative predictive value were 60%, 86%, 52%, and 89%, respectively. Accuracy in predicting PC recurrence was 81%.

Diagnostic performance of a novel radiomic model for predicting post-treatment prostate cancer recurrence: A comparison to CAPRA and MSKCC nomograms.

76 Background: mpMRI-derived radiomic features have been shown to capture sub-visual patterns for quantitative characterization of tumor phenotype. We seek to compare the diagnostic performance of a mpMRI-based radiomic model to currently available nomograms for prediction of post-radical prostatectomy (RP) biochemical recurrence (BCR). Methods: mpMRI was obtained from 76 patients who had underwent RP for treatment of localized PCa. All patients had ≥2 years follow-up and those with neo-adjuvant or adjuvant treatment were excluded. Radiomic analysis and cross-validation of mpMRI features yielded features significantly correlated with BCR, defined as two consecutive serum PSA≥0.2ng/ml. These features were aggregated to construct a radiomic model, which was compared to the risk scores generated by inputting patients’ clinicodemographic features into the USCF Cancer of the Prostate Risk Assessment (UCSF-CAPRA) score and Memorial Sloan Kettering Cancer Center (MSKCC) Pre-Radical Prostatectomy nomogram. The performance of each model was compared utilizing receiver-operator curve (ROC) analysis and area under the curve (AUC) was reported. Results: In feature extraction and ranking, six radiomic features were determined to be important and non-redundant in predicting PCa recurrence (least material condition, gray-level non-uniformity, shape-elongation, shape-sphericity, first-order skewness). These features were aggregated into the radiomic model and repeated five-fold cross validation yielded a model with AUC of 0.95±0.06, 33% sensitivity, and 100% specificity. UCSF-CAPRA and MSKCC nomograms yielded AUC of 0.72±0.07 and 0.82±0.07, respectively. Conclusions: The mpMRI-derived radiomic model performed well when compared to the UCSF-CAPRA score and MSKCC Pre-Radical Prostatectomy nomogram. Future projects will incorporate patient demographics and disease characteristics available at the time of initial PCa diagnosis to improve the radiomic model accuracy.

MP09-04 DIAGNOSTIC PERFORMANCE OF A NOVEL RADIOMIC MODEL FOR PREDICTING POST-TREATMENT PROSTATE CANCER RECURRENCE: A COMPARISON TO CAPRA AND MSKCC NOMOGRAMS

You have accessJournal of UrologyCME1 Apr 2023MP09-04 DIAGNOSTIC PERFORMANCE OF A NOVEL RADIOMIC MODEL FOR PREDICTING POST-TREATMENT PROSTATE CANCER RECURRENCE: A COMPARISON TO CAPRA AND MSKCC NOMOGRAMS Linda Huynh, Olivia Taylor, Shuo Wang, Thomas Ahlering, and Michael Baine Linda HuynhLinda Huynh More articles by this author , Olivia TaylorOlivia Taylor More articles by this author , Shuo WangShuo Wang More articles by this author , Thomas AhleringThomas Ahlering More articles by this author , and Michael BaineMichael Baine More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003224.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: mpMRI-derived radiomic features have been shown to capture sub-visual patterns for quantitative characterization of tumor phenotype. We seek to compare the diagnostic performance of a mpMRI-based radiomic model to currently available nomograms for prediction of post-radical prostatectomy (RP) biochemical recurrence (BCR). METHODS: mpMRI was obtained from 76 patients who had underwent RP for treatment of localized PCa. All patients had ≥2 years follow-up and those with neo-adjuvant or adjuvant treatment were excluded. Radiomic analysis and cross-validation of mpMRI features yielded features significantly correlated with BCR, defined as two consecutive serum PSA ≥0.2ng/ml. These features were aggregated to construct a radiomic model, which was compared to the risk scores generated by inputting patients’ clinicodemographic features into the USCF Cancer of the Prostate Risk Assessment (UCSF-CAPRA) score and Memorial Sloan Kettering Cancer Center (MSKCC) Pre-Radical Prostatectomy nomogram. The performance of each model was compared utilizing receiver-operator curve (ROC) analysis and area under the curve (AUC) was reported. RESULTS: Table 1 illustrates the clinicopathologic characteristics. In feature extraction and ranking, six radiomic features were determined to be important and non-redundant in predicting PCa recurrence (Figure 1). These features were aggregated into the radiomic model and repeated five-fold cross validation yielded a model with AUC of 0.95±0.06, 33% sensitivity, and 100% specificity. UCSF-CAPRA and MSKCC nomograms yielded AUC of 0.72±0.07 and 0.82±0.07, respectively. CONCLUSIONS: The mpMRI-derived radiomic model performed well when compared to the UCSF-CAPRA score and MSKCC Pre-Radical Prostatectomy nomogram. Future projects will incorporate patient demographics and disease characteristics available at the time of initial PCa diagnosis to improve the radiomic model accuracy. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e105 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Linda Huynh More articles by this author Olivia Taylor More articles by this author Shuo Wang More articles by this author Thomas Ahlering More articles by this author Michael Baine More articles by this author Expand All Advertisement PDF downloadLoading ...

Predictive Value of Cribriform and Intraductal Carcinoma for the Nomogram-based Selection of Prostate Cancer Patients for Pelvic Lymph Node Dissection

ObjectiveTo assess the predictive value of biopsy-identified cribriform carcinoma and/or intraductal carcinoma (CR/IDC) within the Briganti and MSKCC nomograms predicting lymph node metastasis (LNM) in patients with primary prostate cancer (PCa). MethodsWe retrospectively included 393 PCa patients who underwent radical prostatectomy with extended pelvic lymph node dissection at 3 tertiary referral centers. We externally validated 2 prediction tools: the Briganti 2012 nomogram and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Both nomograms were augmented with CR/IDC. The original model was compared with the CR/IDC-updated model using the likelihood ratio test. The performance of the prediction tools was assessed using calibration, discrimination, and clinical utility. ResultsOverall, 109 (28%) men were diagnosed with LNM. Calibration plots of the Briganti and MSKCC nomograms demonstrated an underestimation of the LNM risk across clinically relevant thresholds (≤15%). The addition of CR/IDC to the Briganti nomogram increased the fit of the data (χ2(1) = 4.30, P = .04), but did not improve the area under the curve (AUC) (0.69, 95% CI 0.63-0.75 vs 0.69, 95% CI 0.64-0.75). Incorporation of CR/IDC in the MSKCC nomogram resulted in an increased fit on the data (χ2(1) = 10.04, P <.01), but did not increase the AUC (0.66, 95% CI 0.60-0.72 vs 0.68, 95% CI 0.62-0.74). The addition of CR/IDC to the Briganti and MSKCC nomograms did not improve the clinical risk prediction. ConclusionIncorporation of CR/IDC into the 2 clinically most used pre-radical prostatectomy nomograms does not improve LNM prediction in a multinational, contemporary PCa cohort.

Metabolomics of prostate cancer: Knock-in versus knock-out prostate

Several metabolomics-derived biomarkers of prostate cancer (PC) have been reported with pre-radical prostatectomy (RP) (knock-in PC) conditions; however, uncontested PC biomarkers panel appraisal and investigation of correlative evidence of these measures is lacking through post-RP (knock-out PC). We sought to explore patients’ filtered serum-based metabolomics derived signature measures in knock-in PC (n = 90) using nuclear magnetic resonance spectroscopy and multiple rigorous statistical analyses, and to develop the correlative evidence of these measures through knock-out PC (n = 90) follow-up on the 15th and 30th days. The glutamate, citrate and glycine were observed as hallmarks of PC. Observed trends revealed; augmented glutamate level in knock-in PC following a sudden drop and subsequently upside of glutamate at 15th and 30th days of knock-out PC, reduction of citrate in knock-in PC subsequently gradual increase of citrate in knock-out PC, and glycine lessening in knock-in PC following augmentation on 30th day of knock-out PC. This study-based evidence clears the doubts regarding the discovery of metabolomics-derived PC biomarkers.

SC46 - Oncotype DX genomic prostate score and final tumor pathology: A new instrument in pre-radical prostatectomy counseling

SC46 - Oncotype DX genomic prostate score and final tumor pathology: A new instrument in pre-radical prostatectomy counseling

Questioning the Status Quo: Should Gleason Grade Group 1 Prostate Cancer be Considered a “Negative Core” in Pre-Radical Prostatectomy Risk Nomograms? An International Multicenter Analysis

To assess the impact of excluding Gleason Grade Group 1 (GG1) prostate cancer (CaP) cores from current pre-radical prostatectomy (RP) nomograms. Multi-institutional retrospective chart review was performed on all RP patients with prostate biopsy between 2008 and 2018. Patients were individually assessed using the Memorial Sloan Kettering Cancer Center (MSKCC) and Briganti nomograms using the following iterations: (1) Original [ORIG] - all available core data and (2) Selective [SEL] - GG1 cores considered negative. Nomogram outcomes - lymph node invasion (LNI), extracapsular extension (ECE), organ-confined disease (OCD), seminal vesicle invasion (SVI), were compared across iterations and stratified based on biopsy GG. Clinically significant impact on management (CSIM) was defined as change in LNI risk above or below 2% or 5% (Δ2/Δ5). Nomogram outcomes were validated with RP pathology. 7718 men met inclusion criteria. In men with GG2 who also had GG1 cores, SEL better predicted LNI (MSKCC - ORIG 4.97% vs SEL 3.50%; Briganti - ORIG 4.81% vs SEL 2.49%, RP outcome 2.46%), OCD (MSKCC - ORIG 40.91% vs SEL 48.44%, RP outcome: 68.46%) and ECE (MSKCC - ORIG 57.87% vs SEL 50.38%, RP outcome: 30.41%), but not SVI (MSKCC - ORIG 5.42% vs SEL 3.34%, RP outcome: 5.62%). This was also consistent in patients with GG3-5 disease. The greatest CSIM was on GG1-2 CaP; Δ2 and Δ5 in GG1 patients was 26.3%-31.0% and 1.5%-5.2%, respectively, and Δ2 and Δ5 in GG2 patients was 3.4%-22.2% and 12.3%-13.6%, respectively. Excluding GG1 CaP cores from pre-RP nomograms better predicts final RP pathologic outcomes. More importantly, this may better reflect extent of true cancer burden.

MP30-13 INCORPORATING MPMRI BIOPSY DATA INTO ESTABLISHED PRE-RP NOMOGRAMS: POTENTIAL IMPACT OF AN INCREASINGLY COMMON CLINICAL SCENARIO

INTRODUCTION AND OBJECTIVES:Current pre-radical prostatectomy (RP) nomograms predicting lymph node involvement (LNI) are based on systematic 12-core prostate biopsies (PBx). With the introduction o...

Questioning the status quo: Should Gleason 3+3=6 PCa be considered a “negative core” for pre-RP risk nomograms?

31 Background: Current pre-radical prostatectomy (RP) nomograms predicting RP pathology do not differentiate between Gleason 6 prostate cancer (Gl6 PCa) and clinically significant Gleason 7-10 PCa. As such, use of these nomograms can be problematic. We assess the impact of excluding Gl6 PCa on nomogram and RP outcomes. Methods: Utilizing a prospectively maintained database, all men who underwent prostate biopsy (PBx) prior to RP were identified. Each patient was assessed using the MSKCC Kattan and Briganti nomogram using the following iterations: 1) “Original” [ORIG] (all available core data) and 2) "Selective” [SEL] (only cores Gleason score ≥7). Nomogram outcomes (risk of LNI, ECE, SVI, and OCD), were compared across iterations and stratified based on pre-RP risk classification (3+3 [low], 3+4, 4+3, 8-10 [high]). Clinically significant impact on management [CSIM] was defined as a change in risk of LNI above or below 2% (Δ2) or 5% (Δ5), based on current guidelines recommendations for PLND. Nomogram outcomes were validated using RP pathology. Results: 1118 men met inclusion criteria. Using the Kattan nomogram, when compared to actual RP pathology, the SEL iteration was a better predictor of LNI, ECE and OCD than the ORIG iteration, but not SVI. Using the Briganti nomogram, the SEL iteration was a better predictor of LNI. As for CSIM, the greatest impact was on men with Gl7 PCa. In the 359 Gl 3+4 patients, Δ2 was 3.9-28.13% and Δ5 was 12.81-17.27%. In the 184 Gl 4+3 patients, Δ2 was 0% and Δ5 was 7.61-11.41%. In all cases, the change favored decreased need for PLND. Conclusions: As Gleason 3+3=6 PCa is increasingly being considered an insignificant prostate cancer, its inclusion in established pre-RP nomograms becomes problematic. We find that excluding Gl6 PCa cores from these nomograms can reduce the need to complete a PLND at the time of RP, and more importantly, may better reflect the true extent of cancer. [Table: see text]

Incorporating mpMRI Biopsy data into established pre-RP nomograms: Potential impact of an increasingly common clinical scenario.

32 Background: Current pre-radical prostatectomy (RP) nomograms predicting lymph node involvement (LNI) are based on systematic 12-core prostate biopsies (PBx). With the introduction of mpMRI, cognitive or fusion biopsies have become prevalent, often in the absence of systematic cores. We examine the practical application of MR biopsy data using established pre-RP nomograms and the potential implications on RP intra-operative decision making. Methods: Utilizing a prospectively maintained single institution database, all patients who underwent MRI-based PBx prior to RP were identified. Each patient was assessed using the MSKCC Kattan nomogram and the Briganti nomogram using the following iterations: 1) Targeted [T] (targeted cores alone), 2) Targeted &amp; Systematic [TS] and 3) Targeted Augmented [TA]. The TA iteration utilized targeted core data alone and assumed negative remaining systematic cores for a total 12 core. Nomogram outcomes, specifically risk of LNI, was compared across iterations. Clinically significant impact was defined as a change in risk above or below 2% (Δ2) or 5% (Δ5), based on current guidelines recommendations for lymph node dissection. Results: 69 men met inclusion criteria (6 targeted, 63 systematic + targeted PBx). In the 6 men with targeted only biopsies, using the Kattan and Briganti nomograms, Δ2 occurred in 1 patient (16.7%) and Δ5 in 1-2 patients (16.7-33.3%); in all, TA iteration LNI was lower than the T iteration. In the 58 patients with positive targeted biopsy cores, Δ2 and Δ5 were 8.62-32.76% and 25.86-37.93%, respectively. In the subset of 52 patients with both targeted and systematic biopsies, using their TS nomogram as an internal validation, the TA iteration was a better approximation of their TS outcomes than their T iteration in 48% (Kattan) and 67% (Briganti) of patients. Conclusions: mpMRI-based PBx results, and in particular those from targeted biopsy cores alone, yield significantly different results using established pre-RP nomograms. Therefore, future nomograms must better incorporate MRI biopsy data and provide guidelines on how to account for targeted cores. In the interim, augmenting targeted biopsy data may bridge the gap.

A Phase 1 Pilot Study of Preoperative Radiation Therapy for Prostate Cancer: Long-Term Toxicity and Oncologic Outcomes

Neoadjuvant radiation therapy (RT) improves disease control in various cancers and has become an established oncologic treatment strategy. During 2001 to 2004, we conducted a phase 1 pilot study assessing the role of short-course preoperative RT (PreORT) for men with unfavorable intermediate- and high-risk localized prostate cancer. Herein, we present long-term follow-up toxicity and oncologic outcomes. Eligible patients had histologically proven prostate cancer, cT1-T2N0M0 disease, prostate-specific antigen >15 to 35ng/mL regardless of Gleason score, or prostate-specific antigen 10 to 15ng/mL with Gleason score ≥7. Patients received 25Gy in 5 consecutive daily fractions (5Gy per fraction) to the prostate only, followed by radical prostatectomy within 14days after RT completion. Primary outcomes were intraoperative morbidity and late genitourinary (GU) and gastrointestinal toxicities. In total, 15 patients were enrolled; 14 patients completed PreORT followed by radical prostatectomy, which also included bilateral lymph node dissections in 13 cases. Median follow-up was 12.2years (range, 6.7-16.3). Late GU toxicity was common, with 2 patients (13.3%) experiencing G2 toxicity and 6 patients (40%) G3 toxicity. There were no patients with G4 to G5 late GU toxicity. Late gastrointestinal toxicity was infrequent, with only 1 patient (6.7%) experiencing transient G2 proctitis. At last follow-up, 8 (53.3%) and 6 (40%) patients experienced biochemical and metastatic disease recurrence, respectively. The use of PreORT in men with high-risk prostate cancer is associated with unexpected high rates of late GU toxicity. Future studies examining the role of RT preradical prostatectomy must cautiously select RT technique and dose schedule. Importantly, long-term follow-up data are essential to fully determine the therapeutic index of PreORT in the management of localized disease.

Brief behavioural intervention, delivered as standard care, to support physical activity engagement in men with prostate cancer: a pilot study protocol

IntroductionPhysical activity is beneficial to men with prostate cancer, but there remain barriers to fulfilling the potential of National Health Service trusts to support men with prostate cancer to be...

A hypothesis for the mechanism of urine incontinence in patients after radical prostatectomy due to urinary bladder hypertrophy.

Prostate cancer is one of the most common neoplasms in elderly males in Europe and is rapidly becoming a major health burden throughout the world. Radical prostatectomy is a first-line treatment in the case of organ-confined prostate cancer and in selected cases of locally advanced disease. Recent studies have suggested that the urinary bladder wall thickness (BWT) is an important predictor of an overactive bladder (OAB). This article focuses on a hypothesis for the mechanism of urine incontinence in patients after radical prostatectomy due to urinary bladder hypertrophy. To verify the possible influence of changes in the urinary bladder structure on urine incontinence development, we designed an experiment in which patients with prostate cancer were qualified for radical prostatectomy. Our hypothesis that urinary bladder hypertrophy influences urine incontinence development in patients after radical prostatectomy may provide an insight toward the prevention and control of urine incontinence after surgery by oral pharmacotherapy or intravesical onabotulinumtoxinA injections in pre-radical prostatectomy mode.

Added Value of Multiparametric Magnetic Resonance Imaging to Clinical Nomograms for Predicting Adverse Pathology in Prostate Cancer

We examined the additional value of preoperative prostate multiparametric magnetic resonance imaging and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy when performed in combination with clinical nomograms to predict adverse pathology at radical prostatectomy. We identified all patients who underwent 3 Tesla multiparametric magnetic resonance imaging prior to fusion biopsy and radical prostatectomy. The Partin and the MSKCC (Memorial Sloan Kettering Cancer Center) preradical prostatectomy nomograms were applied to estimate the probability of organ confined disease, extraprostatic extension, seminal vesicle invasion and lymph node involvement using transrectal ultrasound guided systematic biopsy and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy Gleason scores. With radical prostatectomy pathology as the gold standard we developed multivariable logistic regression models based on these nomograms before and after adding multiparametric magnetic resonance imaging to assess any additional predictive ability. A total of 532 patients were included in study. When multiparametric magnetic resonance imaging findings were added to the systematic biopsy based MSKCC nomogram, the AUC increased by 0.10 for organ confined disease (p<0.001), 0.10 for extraprostatic extension (p = 0.003), 0.09 for seminal vesicle invasion (p = 0.011) and 0.06 for lymph node involvement (p = 0.120). Using Gleason scores derived from targeted biopsy compared to systematic biopsy provided an additional predictive value of organ confined disease (Δ AUC 0.07, p = 0.003) and extraprostatic extension (Δ AUC 0.07, p = 0.048) at radical prostatectomy with the MSKCC nomogram. Similar results were obtained using the Partin nomogram. Magnetic resonance imaging alone or in addition to standard clinical nomograms provides significant additional predictive ability of adverse pathology at the time of radical prostatectomy. This information can be greatly beneficial to urologists for preoperative planning and for counseling patients regarding the risks of future therapy.

Prostate Magnetic Resonance Imaging Provides Limited Incremental Value Over the Memorial Sloan Kettering Cancer Center Preradical Prostatectomy Nomogram

To examine the incremental value of prostate magnetic resonance imaging (MRI) when used in combination with the currently available preoperative risk stratification tool, the Memorial Sloan Kettering Cancer Center (MSKCC) preradical prostatectomy nomogram. We reviewed our institutional database of prostate MRI performed before radical prostatectomy between December 2014 and March 2016 (n = 236). We generated a logistic regression model based on observed final pathology results and the MSKCC nomogram predictions for organ-confined disease, extracapsular extension (ECE), seminal vesicle invasion, and lymph node involvement (LNI) ("MSKCC only"). We then generated a combined regression model incorporating both the MSKCC nomogram prediction with the degree of prostate MRI suspicion ("MSKCC + MRI"). Receiver operating characteristic curves were generated, and the area under the curves (AUCs) were compared. When independently examining the MSKCC nomogram predicted risk and the degree of prostate MRI suspicion, MRI was a predictor for ECE (odds ratio 2.8, P <.01) and LNI (odds ratio 5.6, P = .01). When examining the "MSKCC + MRI" and "MSKCC only" models, the incremental benefit in risk discrimination from the combined model ("MSKCC + MRI") was not significant for organ-confined disease, ECE, seminal vesicle invasion, or LNI (ΔAUC +0.03, P = .10; ΔAUC +0.03, P = .08; ΔAUC 0.63, P = .63; ΔAUC +0.04, P = .42; respectively). A combined model with prostate MRI and the MSKCC nomogram provides no additional risk discrimination over the MSKCC nomogram-based model alone. Evaluation of prostate MRI as a predictive tool should be performed in combination with, not independent of, these clinical risk stratification models.

Impact of bladder dysfunction in the management of post radical prostatectomy stress urinary incontinence-a review.

Bladder dysfunction is a relatively common urodynamic finding post radical prostatectomy (RP). It can be the sole cause of post prostatectomy incontinence (PPI) or may be found in association with stress urinary incontinence (SUI). The aim of this review is to provide a comprehensive review of the diagnosis and different treatments of post RP bladder dysfunction. A comprehensive literature review using medical search engines was performed. The search included a combination of the following terms, PPI, detrusor overactivity (DO), detrusor underactivity (DU), impaired compliance, anticholinergic, onabotulinumtoxinA (Botox®) and sacral neuromodulation (SNM). Definitions, general overview and management options were extracted from the relevant medical literature. DO, DU and impaired compliance are common and may occur alone or in combination with SUI. In some patients the conditions exist pre RP, in others they arise due to denervation and surgical changes. DO can be treated with anticholinergics, Botox® and SNM. DO may need to be treated before SUI surgery. DU may be a contraindication to male sling surgery as some patients may go into urinary retention. Severely impaired bladder compliance may be a contraindication to SUI surgery as the upper tracts may be at risk. Each individual dysfunction may affect the outcome of PPI treatments and clinicians should be alert to managing bladder dysfunction in PPI patients.

Urine Exosomes for Non-Invasive Assessment of Gene Expression and Mutations of Prostate Cancer.

PurposeThe analysis of exosome/microvesicle (extracellular vesicles (EVs)) and the RNA packaged within them (exoRNA) has the potential to provide a non-invasive platform to detect and monitor disease related gene expression potentially in lieu of more invasive procedures such as biopsy. However, few studies have tested the diagnostic potential of EV analysis in humans.Experimental DesignThe ability of EV analysis to accurately reflect prostate tissue mRNA expression was examined by comparing urinary EV TMPRSS2:ERG exoRNA from pre-radical prostatectomy (RP) patients versus corresponding RP tissue in 21 patients. To examine the differential expression of TMPRSS2:ERG across patient groups a random urine sample was taken without prostate massage from a cohort of 207 men including prostate biopsy negative (Bx Neg, n = 39), prostate biopsy positive (Bx Pos, n = 47), post-radical prostatectomy (post-RP, n = 37), un-biopsied healthy age-matched men (No Bx, n = 44), and young male controls (Cont, n = 40). The use of EVs was also examined as a potential platform to non-invasively differentiate Bx Pos versus Bx Neg patients via the detection of known prostate cancer genes TMPRSS2:ERG, BIRC5, ERG, PCA3 and TMPRSS2.ResultsIn this technical pilot study urinary EVs had a sensitivity: 81% (13/16), specificity: 80% (4/5) and an overall accuracy: 81% (17/21) for non-invasive detection of TMPRSS2:ERG versus RP tissue. The rate of TMPRSS2:ERG exoRNA detection was found to increase with age and the expression level correlated with Bx Pos status. Receiver operator characteristic analyses demonstrated that various cancer-related genes could differentiate Bx Pos from Bx Neg patients using exoRNA isolated from urinary EVs: BIRC5 (AUC 0.674 (CI:0.560–0.788), ERG (AUC 0.785 (CI:0.680–0.890), PCA3 (AUC 0.681 (CI:0.567–0.795), TMPRSS2:ERG (AUC 0.744 (CI:0.600–0.888), and TMPRSS2 (AUC 0.637 (CI:0.519–0.754).ConclusionThis pilot study suggests that urinary EVs have the potential to be used as a platform to non-invasively differentiate patients with prostate cancer with very good accuracy. Larger studies are needed to confirm the potential for clinical utility.

A non-invasive urine exosome gene expression assay (ExoIntelliScore Prostate) to predict pathologic stage and grade in the prostatectomy specimen.

46 Background: Non-invasive screening tools that add predictive value for identifying high-grade, Gleason score (GS) ≥7 should impact on the current diagnostic and subsequent treatment decision process. We have developed standardized processes to isolate exosomal-RNA from first-catch, non-DRE, urine specimens and have validated a three gene signature (ExoIntelliScore Prostate) that reliably differentiates GS7+ from GS6 and benign at the time of an initial biopsy. In addition to the biopsy outcomes, we sought to understand the performance of the assay in predicting objective pathology in the prostatectomy specimen. Methods: Pre-radical prostatectomy first-catch non-DRE urine specimens were collected from 5 urology practices (academic/community practices) without preservative, stored at 2-8C (up to 2 weeks) and shipped on ice to a central laboratory (Exosome Diagnostics, St. Paul, MN). Exosomes were isolated and RNA extraction performed. RT-qPCR RNA copy numbers of ERG and PCA3 were normalized to SPDEF. Spearman and Pearson correlation along with AUC was used to evaluate performance. Results: Pre-RP urine samples from 430 patients were collected: 16% GS6, 45% GS7 (3+4), 39% (&gt;/=GS4+3) and 85% PSA &lt;10 ng/mL. 359 patients had complete clinical and ExoIntelliScore Prostate assay results with comparable demographics. Importantly, the Exo106 significantly correlated with prostatectomy GS (p=0.025; Spearman’s rank-order). In addition, Exo106 significantly correlated with both tumor volume and pathologic stage (p=0.002, Pearson). Conclusions: A previously validated non-invasive urine exosome gene signature (ExoIntelliScore Prostate) accurately reflects what is present within the prostatectomy specimen with respect to grade, stage and tumor volume. Such information could be incorporated into the treatment decision process, including active surveillance.

Editorial Comment on: Pharmacological Approaches to Reducing the Risk of Prostate Cancer

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