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To analyze the effect on biochemical recurrence (BCR) of omitting PLND in subsequently upgraded/upstaged patients (pNx regret). Using nomograms, patients with low to intermediate-risk prostate cancer can be selected to omit a pelvic lymph node dissection (PLND) at the time of a radical prostatectomy (RP). However, some patients will experience upgraded pathology and/or stage.We searched a prospectively maintained single institution/multi-surgeon cohort of patients treated by RP and5-year follow-up. From 2006-2012, 1026 (521 pNx and 505 pN0/1) eligible patients with biopsy Gleason Score ≤3+4 and cT1c-cT2 undergoing RARP were included in the study.Gleason upgrading from ≤3+4 to3+4 and/or pT3-4 occurred in 17% of pNx and 32% of pN0/N1 (p0.001). BCR occurred in 5% of the pNx, and 7% of the PLND group. Five-year BCR free survival was higher in the pNx group (94.7% vs. 91%, P = .048). BCR occurred in 3% in the non-pNx regret and 18% in the pNx regret patients. However, with propensity score matching with pNx regret and pN0/N1 patients, 5-year BCR free survival rates were similar (81% vs 77%, P = .466).Low to favorable intermediate-risk patients who PLND was omitted and experienced upgrading or upstaging (pNx regret), have a higher predicted BCR. However, when matched to a similar cohort with pN0/N1, the BCR did not differ. Omission of a PLND does not appear to alter the rates of BCR compared to PLND inclusion.

Venous thromboembolic events (VTEs) are a major cause of morbidity following abdominopelvic oncologic surgery. Enoxaparin, a subcutaneous injectable low molecular weight heparin, is commonly used for extended-duration VTE prophylaxis (EP), but has been associated with noncompliance. Newer direct oral anticoagulants have not been prospectively studied in the urologic oncology post-discharge setting. We aimed to improve compliance with EP following abdominopelvic oncologic surgery and secondarily test the hypothesis that apixaban is noninferior to enoxaparin for EP.A single-center prospective quality improvement study measuring patient compliance and safety with EP was conducted between August 10, 2020 and September 21, 2021. Baseline data were continuously collected for 6 months, followed by a uniform departmental change from enoxaparin to apixaban. The duration of data collection was determinedA total of 161 patients were discharged with enoxaparin (baseline period) and 154 with apixaban (intervention period). Safety events occurred in 3.1% vs 0% of patients receiving enoxaparin and apixaban, respectively. The absolute risk difference of 3.1% (95% CI: 0.043%-5.8%) met the prespecified noninferiority threshold (p=0.028 for apixaban superiority). Compliance events occurred in 33.5% of enoxaparin patients and 14.3% of apixaban patients (p=0.0001).There were fewer compliance events using apixaban for EP than enoxaparin after urologic oncology surgery. Regarding safety, apixaban is noninferior to enoxaparin and may in fact have fewer associated major complications.

Therapeutic gene manipulation has been at the forefront of popular scientific discussion and basic and clinical research for decades. Basic and clinical research applications of CRISPR-Cas9-based technologies and ongoing clinical trials in this area have demonstrated the potential of genome editing to cure human disease. Evaluation of research and clinical trials in gene therapy reveals a concentration of activity in prostate cancer research and practice. Multiple aspects of prostate cancer care - including anatomical considerations that enable direct tumour injections and sampling, the availability of preclinical immune-competent models and the delineation of tumour-related antigens that might provide targets for an induced immune system - make gene therapy an appealing treatment option for this common malignancy. Vaccine-based therapies that induce an immune response and new technologies exploiting CRISPR-Cas9-assisted approaches, including chimeric antigen receptor (CAR) T cell therapies, are very promising and are currently under investigation both in the laboratory and in the clinic. Although laboratory and preclinical advances have, thus far, not led to oncologically relevant outcomes in the clinic, future studies offer great promise for gene therapy to become established in prostate cancer care.

TPS297 Background: Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor. In the phase 3 ARAMIS study (NCT02200614) in nonmetastatic castration-resistant prostate cancer (CRPC), DARO + ADT significantly improved metastasis-free survival and overall survival (OS) vs placebo + ADT, with a favorable tolerability and safety profile. In the phase 3 ARASENS study (NCT02799602) in metastatic hormone-sensitive prostate cancer (mHSPC), DARO + ADT + docetaxel significantly reduced the risk of death by 32.5% vs ADT + docetaxel (hazard ratio 0.68; 95% confidence interval 0.57–0.80; P

Both transperineal and transrectal ultrasound (TRUS)-guided systematic biopsy are accepted methods to diagnose prostate cancer (PCa). However, systematic sampling misses up to 47% of tumors 0.5 mL or larger and under-represents the tumor grade in 38% of cases [1,2]. These shortcomings result in underestimated risk and repeat prostate biopsies.

PURPOSE: To report long term follow-up of the efficacy of subtotal prostate ablation using a “hockey-stick” template, including oncologic control and quality of life (QoL) impact. METHODS: We performed a prospective controlled trial to evaluate the efficacy of subtotal prostate ablation in selected men with baseline and confirmatory biopsy showing grade group (GG) 1–2 prostate cancer. “Hockey-stick” cryoablation that included the ipsilateral hemi-gland and contralateral anterior prostate was performed. Prostate biopsies and QOL queries were performed at 6, 18 and 36 months following regional ablation, and follow-up was updated to include subsequent clinic visits. RESULTS: Between August 2009 and January 2012, 72 men were screened for eligibility and 47 opted to undergo confirmatory biopsy. Of these, 23 were deemed eligible and treated with regional cryoablation. Median age was 64 years. Median follow-up was 74 months. A single patient had

Background High-risk (HR) prostate cancer (PCa) is a heterogeneous disease leading to difficulties in designing appropriate inclusion criteria for clinical trials. Objective To describe clinical predictors of organ-confined disease in HR or very-high-risk (VHR) PCa patients staged with multiparametric magnetic resonance imaging with endorectal coil (mp-MRI-ER). Design, setting, and participants We reviewed 366 HR/VHR PCa patients who had preoperative mp-MRI-ER, and underwent radical prostatectomy and extended pelvic lymph node dissection between 2006 and 2015. Intervention Radical prostatectomy with preoperative mp-MRI-ER. Outcome measurements and statistical analysis We used multivariable logistic regression modeling to assess for associations with ≤ pT2N0 stage and multivariable cox modeling to assess for associations with biochemical failure. Results and limitations Of 366 patients, 132 had ≤ pT2N0 disease. For the entire cohort, negative staging mp-MRI-ER (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.06–2.83, p = 0.03), lower prostate-specific antigen (PSA; OR 0.98, 95% CI 0.97–1.00, p = 0.02), and fewer cores of Gleason ≥8 cancer (OR 0.86, 95% CI 0.79–0.93, p = 0.0002) were associated with ≤pT2N0 disease. In HR patients only, negative mp-MRI-ER (OR 3.41, 95% CI 1.73–6.72, p = 0.0004) and fewer than four cores of Gleason ≥8 disease (OR 3.38, 95% CI 1.20–9.56, p = 0.02) were still associated with ≤pT2N0 disease. Lack of non–organ-confined disease on MRI was associated with superior biochemical recurrence-free survival (p = 0.02). Limitations of this study include lack of a central review or quality control of the MRI reporting. Conclusions In HR PCa, negative staging mp-MRI-ER, fewer positive cores of Gleason >8, and lower PSA were significant predictors of pathologic organ-confined disease. Improved prediction of organ-confined disease in HR patients may allow for their inclusion into studies evaluating treatments from which they would otherwise be excluded based solely on their HR status. Patient summary In patients with high-risk prostate cancer, prostate magnetic resonance imaging along with other clinical parameters may help determine which patients are likely to have disease confined to the prostate and thus be eligible for clinical trials that they otherwise might be excluded from based on their high-risk status alone.

Evidence suggests that visceral fat quantity may be associated with post-prostatectomy outcomes and risk of prostate cancer related death. We evaluated whether increased fat volume, normalized to prostate size, is associated with decreased risk of disease progression.Patients enrolled on a prospective active surveillance trial for at least 6 months who had magnetic resonance imaging within 2 years of enrollment were eligible. The surveillance protocol included a standardized followup regimen consisting of biennial prostate specific antigen and examination and yearly biopsy. Clinicopathological characteristics were collected at baseline. Three fat measurements were taken using prostate magnetic resonance imaging, including subcutaneous, linear periprostatic (pubic symphysis to prostate) and volumetrically defined periprostatic. Progression was defined as increase in Gleason grade group. Multivariable Cox proportional hazards models were used to evaluate fat volumes normalized by prostate size (stratified into tertiles).A total of 175 patients were included in the study. Average age was 62.5 years (SD 7.4) and average prostate specific antigen was 5.4 ng/dl (SD 3.9). Median followup was 42 months (IQR 18-60) and 50 patients (28.6%) had progression. Compared to the lowest tertile, the highest tertile of volumetric periprostatic fat measurement (HR 2.63, 95% CI 1.23-5.60, p=0.01) and linear periprostatic fat measurement (HR 2.30, 95% CI 1.01-5.22, p=0.05) were associated with worsened progression-free survival, while subcutaneous fat measurement (p=0.97) was not. Importantly, the model did not substantively change when accounting for patient body mass index and other factors.Increased periprostatic fat volume, normalized to prostate size, may be associated with shortened progression-free survival in men with prostate cancer on active surveillance.

Coffee intake may lower prostate cancer risk and progression, but postdiagnosis outcomes by caffeine metabolism genotype are not well characterized.To evaluate associations between coffee intake, caffeine metabolism genotype, and survival in a large, multicenter study of men with prostate cancer.Data from The PRACTICAL Consortium database for 5727 men with prostate cancer from seven US, Australian, and European studies were included. The cases included had data available for the CYP1A2 -163CA rs762551 single-nucleotide variant associated with caffeine metabolism, coffee intake, and6 mo of follow-up.Multivariable-adjusted Cox proportional hazards models across pooled patient-level data were used to compare the effect of coffee intake (categorized as low [reference], high, or none/very low) in relation to overall survival (OS) and prostate cancer-specific survival (PCSS), with stratified analyses conducted by clinical disease risk and genotype.High coffee intake appeared to be associated with longer PCSS (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.68-1.08; p = 0.18) and OS (HR 0.90, 95% CI 0.77-1.07; p = 0.24), although results were not statistically significant. In the group with clinically localized disease, high coffee intake was associated with longer PCSS (HR 0.66, 95% CI 0.44-0.98; p = 0.040), with comparable results for the group with advanced disease (HR 0.92, 95% CI 0.69-1.23; p = 0.6). High coffee intake was associated with longer PCSS among men with the CYP1A2 AA (HR 0.67, 95% CI 0.49-0.93; p = 0.017) but not the AC/CC genotype (p = 0.8); an interaction was detected (p = 0.042). No associations with OS were observed in subgroup analyses (p 0.05). Limitations include the nominal statistical significance and residual confounding.Coffee intake was associated with longer PCSS among men with a CYP1A2 -163AA (*1F/*1F) genotype, a finding that will require further replication.It is likely that coffee intake is associated with longer prostate cancer-specific survival in certain groups, but more research is needed to fully understand which men may benefit and why.

Summary Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for PC, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9 × 10−7 and GAB2, p = 2.0 × 10−6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 0.94–1.36); whereas decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04–1.50). These results suggest that germline genetics may help inform and individualize the decision of AS—or the intensity of monitoring on AS—versus treatment for the initial management of patients with low-risk PC., Genetic factors may distinguish who should receive active surveillance (AS) versus treatment following prostate cancer diagnosis. We undertook the first study to investigate this and report novel variants, genes, and risk scores associated with AS outcomes. These findings could help inform and individualize the decision of AS.

INTRODUCTION AND OBJECTIVE:Higher coffee intake has been associated with lower incidence of both localized and aggressive prostate cancers. Similarly, we have shown that coffee may also lower risk ...

Given that romantic partners play a pivotal role in patients’ survivorship period, integrating partners into survivorship care and broadening the focus of behavioral interventions from the individual (survivor) to the survivor-partner dyad may make healthy lifestyle behaviors more easily adopted and potentially maintained. Understanding the role of dyadic processes in Black survivors is particularly important because their lifestyle behaviors are poor and they have higher cancer-specific and all-cause mortality. To develop an effective dyadic lifestyle behavior intervention for Black survivors, micro-level investigations of interactions between Black survivors and their partners are necessary to pinpoint how survivors and partners facilitate or hinder each other’s lifestyle behaviors in their natural, everyday lives. Accordingly, the objective of the present study is to fill these gaps using ecological momentary assessment to eventually develop more effective lifestyle interventions for Black prostate cancer (PCa) survivors and partners. A total of 120 dyads (i.e., 240 individuals) who are Black adult survivors diagnosed with non-metastatic PCa and their romantic partners will be asked to complete four assessments per day for 14 consecutive days on a smartphone after an initial retrospective survey. Over the 14 days, participants will be asked to complete a brief survey regarding their lifestyle behaviors (physical activity, sedentariness and eating behaviors), contexts of lifestyle behaviors, stress, and coping. Physical activity and sedentary behavior will be assessed via accelerometer; eating behaviors will be assessed with the Automated Self-Administered 24-hour Dietary Assessment Tool. After completing the 14-day assessment, participants will be asked to complete a final retrospective survey. Results of the proposed study will inform the rigorous development of a theory-based dyadic lifestyle intervention in this vulnerable survivorship population with the ultimate goal to improve overall survival and reduce morbidities (for survivors) and reduce cancer incidence (for partners).

Objective This study aimed to identify factors associated with surgeon perception of robot‐assisted radical prostatectomy (RARP) difficulty. Patients and Methods This study surveyed surgeons performing RARP between 2017 and 2018 and asked them to rate operative conditions and difficulty as optimal, good, acceptable, or poor. These answers were stratified as optimal or suboptimal for this study. Associations between surgeon responses and variables hypothesized to affect surgical difficulty, including anatomic factors such as pelvic diameter and prostate volume:pelvic diameter ratio, were assessed. Results Between November 2017 and September 2018, a total of 100 patients were prospectively enrolled in the study of which 58 cases were rated as optimal and 42 were rated as suboptimal. Of the evaluated variables, only increasing clinical T stage (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.03–2.15, p = 0.03) and increasing body mass index (BMI) (OR 1.14, 95% CI 1.03–1.26, p = 0.01) were associated with increased difficulty; 90‐day complication rates were similar between the optimal and suboptimal cohorts (17.3% vs. 23.8%, respectively; p = 0.5). The number of patients with previous surgery, pelvic diameter, and prostate size:pelvic diameter ratio were not significantly different between cohorts (p > 0.05 for all). Operative time (ρ = 0.23, p = 0.02) and estimated blood loss (EBL) (ρ = 0.38, p = 0.0001) were correlated with suboptimal difficulty. Conclusion The factors associated with surgeon‐reported RARP difficulty were patient BMI and clinical T stage among surgeons with significant RARP experience. These data should be incorporated into surgical decision making and patient counseling prior to performing a RARP.

Purpose:Active surveillance is increasingly used as a management strategy for localized prostate cancer. Coffee intake has been associated with a lower prostate cancer incidence. We assessed whether coffee was associated with disease progression in men on active surveillance.Materials and Methods:A total of 411 patients with newly diagnosed Gleason score 6 or 7 prostate cancer were enrolled on a prospective active surveillance protocol for at least 6 months and completed a baseline dietary assessment. The active surveillance protocol included a biennial monitoring regimen with disease progression defined as an increase in the Gleason score. Cox proportional hazards models were used to evaluate associations of coffee intake with progression-free survival. We also evaluated patient genotype in the caffeine metabolism related single nucleotide polymorphism rs762551.Results:Median followup was 36 months (range 6 to 126) and the Gleason score progressed in 76 of the 411 patients (18.5%). Compared to 0 cups per...

e17051 Background: Patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) are responsive to androgen deprivation therapy (ADT), but within 1–3 years most will develop metastatic castration-resistant prostate cancer (mCRPC). The CHAARTED trial showed a clear benefit of adding docetaxel (DTX) to ADT, prolonging median overall survival (OS) by 10.4 months (mo). ARASEC is a single-arm US study evaluating darolutamide + ADT in pts with mHSPC. Participants will be matched for comparison using patient-level data to the ADT alone arm of CHAARTED. The TIMES study evaluated a potential time bias in treatment patterns and clinical outcomes in pts with mHSPC before and after the OS analysis of CHAARTED was reported. Methods: This retrospective study used Flatiron Metastatic PC Core Registry data from January 1, 2013, to June 30, 2020, and the sample was divided into two cohorts: before and after June 30, 2016 (cohort 1: pre-CHAARTED; cohort 2: post-CHAARTED). Differences in OS and time to mCRPC were assessed using Cox proportional hazard models, controlling for baseline characteristics, including age, initial mHSPC treatment, Gleason score, and time from PC diagnosis to mHSPC. The test for equivalence used hazard ratio (HR) limits of 0.80 to 1.25 at a 2-sided 0.05 level. Results: Data from 9256 pts with mHSPC (4503 in cohort 1; 4753 in cohort 2) were analyzed; median age was 73 years for both cohorts. M1 status at initial diagnosis was 55% in cohort 1 and 60% in cohort 2. All other clinical characteristics and laboratory values were similar. Initial mHSPC treatment with DTX was 10.5% and 13.9%, whereas treatment with novel anti-hormonal agents (NAH) was 1.6% and 18.3% in cohorts 1 and 2, respectively. The percentage of pts who started with first-generation androgen receptor inhibitors decreased from 29.3% in cohort 1 to 19.6% in cohort 2, whereas the percentage of pts receiving ADT alone and/or supportive care remained stable (25.7% and 26.5%, respectively). In cohorts 1 and 2, treatment records during the mHSPC period could not be retrieved for 32.9% and 21.7% of pts, respectively. Median OS was 5.4 months longer for cohort 1 (43.7 mo) vs cohort 2 (38.3 mo). In multivariate analyses, cohort 2 had poorer survival, with an HR slightly outside the predefined limits for equivalence (HR 1.19; 95% CI 1.09, 1.29; P < 0.0001). The HR for time to mCRPC fell within the predefined limits (HR 1.16; 95% CI 1.09, 1.23). Conclusions: Changes in treatment patterns were observed following CHAARTED. Although DTX and NAH have demonstrated prolonged survival, their use increased only from 12% to 32%, comparing the cohorts before and after 2016, which is not in line with guideline recommendations. Clinical outcomes, despite the influence of multiple factors, have changed minimally during the past 5 years, suggesting that the risk of historical time bias associated with using the CHAARTED ADT alone arm as a comparator for ARASEC is low.

TPS5111 Background: Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor (ARI) that significantly improved metastasis-free survival by ̃2 years and reduced the risk of death by 31% vs placebo in patients with nonmetastatic castration-resistant prostate cancer (CRPC). Darolutamide has a favorable safety and tolerability profile, with only ≤2% difference vs placebo for most adverse events (AEs) of interest (falls, fractures, hypertension, mental impairment). Fatigue was the only AE with > 10% incidence in the darolutamide arm (13.2%; placebo, 8.3%). Darolutamide has shown lower blood–brain barrier penetration than other ARIs in preclinical models (supported by human neuroimaging studies), which may lead to a lower risk of central nervous system-related AEs and has a low potential for drug–drug interactions. For patients with metastatic hormone-sensitive prostate cancer (mHSPC), the combination of darolutamide and ADT is expected to offer a favorable benefit–risk profile. ARASEC will evaluate the efficacy and safety of darolutamide plus ADT in mHSPC in the US (NCT05059236) and complement the data in the ongoing ARANOTE study (NCT04736199). Methods: ARASEC is a US-based, phase 2, open-label, single-arm study with an external control arm. Eligible patients will have confirmed adenocarcinoma of the prostate, radiologic evidence of metastatic disease by conventional imaging, and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2. Patients with mHSPC will receive darolutamide 600 mg twice daily plus ADT (luteinizing hormone-releasing hormone agonist/antagonist or orchiectomy). The control arm for ARASEC will be derived from the 393 patients with mHSPC treated with ADT alone in the CHAARTED trial. Patients in the active arm will be matched 1:1 to patients in the control arm using important baseline characteristics such as age, ECOG PS, extent of disease defined as low or high volume according to CHAARTED, and presence of bone and visceral metastases. Study duration was defined as the time from the first patient’s first visit until either the event count threshold triggering the primary endpoint analysis has been met or all patients have been followed for ≥2 years after enrollment, whichever occurs later. The primary endpoint is progression-free survival (PFS), defined in CHAARTED as the time from enrollment to prostate-specific antigen (PSA) progression, clinical progression (including radiological or symptomatic progression or clinical deterioration), or death, whichever occurs first. Secondary endpoints are overall survival, radiographic PFS, time to CRPC, complete PSA response rate at 6 months, and safety. Patient recruitment is in progress. Clinical trial information: NCT05059236.

The adverse effects of overdiagnosis and overtreatment observed in men with clinically insignificant prostate cancers after the introduction of prostate-specific antigen-based screening are now being observed in those with thyroid cancer, owing to the introduction of new imaging technologies. Thus, the evolving paradigm of active surveillance in prostate and thyroid cancers might be valuable in informing the development of future active surveillance protocols. The lessons learned from active surveillance and their implications include the need to minimize the use of broad, population-based screening programmes that do not incorporate patient education and the need for individualized or shared decision-making, which can decrease the extent of overtreatment. Furthermore, from the experience in patients with prostate cancer, we have learned that consensus is required regarding the optimal selection of patients for active surveillance, using more-specific evidence-based methods for stratifying patients by risk. In this Review, we describe the epidemiology, pathology, and screening guidelines for the management of patients with prostate and thyroid cancers; the evidence of overdiagnosis and overtreatment; and provide overviews of existing international active surveillance protocols.

Objective : To evaluate risks of peri-operative ureteral catheter placement in a consecutive patient-series. Methods : Patients who underwent peri-operative ureteral catheter placement at a single institution in 2018 were included. A retrospective review was conducted to evaluate patient and procedure related characteristics, including data on technique, perceived placement difficulty, operative details, and complications. Outcome Measurements and Statistical Analysis : Urologic complications within 30 days were evaluated using the Clavien-Dindo system. Statistical analysis for association was conducted using the X2 test or fisher's exact tests. Results : 413 patients were included. 50/413 (12.1%) cases had urologic complications within 30 days. 43 were Clavien-Dindo grade I-II. Six were grade III. 5/6 patients had oliguric, obstructive AKI. One had flank pain with hydronephrosis. Two patients each underwent placement of unilateral nephrostomy tube, bilateral double-J stent placement, and unilateral stent placement. One patient had a Grade V complication. They developed multi-system organ failure including renal failure with hydronephrosis.All patients who required re-intervention had bilateral peri-operative catheterization with use of a wire. Intraoperative difficulty with placement was associated with high-grade complication (p Conclusions : Rate of acute complication following ureteral catheter placement is 12%. 1.7% of patients develop post-operative ureteral obstruction requiring intervention within 30 days. Future studies are needed to determine patients most at risk for post-ureteral stent complication.

Background The Mediterranean diet (MD) may be beneficial for men with localized prostate cancer (PCa) on active surveillance (AS) because of its anti-inflammatory, antilipidemic, and chemopreventive properties. This study prospectively investigated adherence to the MD with Gleason score progression and explored associations by diabetes status, statin use, and other factors. Methods Men with newly diagnosed PCa on an AS protocol (n = 410) completed a baseline food frequency questionnaire, and the MD score was calculated across 9 energy-adjusted food groups. Cox proportional hazards models were fit to evaluate multivariable-adjusted associations of the MD score with progression-free survival; progression was defined as an increase in the Gleason grade group (GG) score over a biennial monitoring regimen. Results In this cohort, 15% of the men were diabetic, 44% of the men used statins, and 76 men progressed (median follow-up, 36 months). After adjustments for clinical factors, higher adherence to the MD was associated with a lower risk of GG progression among all men (hazard ratio [HR] per 1-unit increase in MD score, 0.88; 95% confidence interval [CI], 0.77-1.01), non-White men (HR per 1-unit increase in MD score, 0.64; 95% CI, 0.45-0.92; P for interaction = .07), and men without diabetes (HR per 1-unit increase in MD score, 0.82; 95% CI, 0.71-0.96; P for interaction = .03). When joint effects of the MD score and statin use were examined, a similar risk reduction was observed among men with high MD scores who did not use statins in comparison with men with low/moderate MD scores with no statin use. Conclusions The MD is associated with a lower risk of GG progression in men on AS, and this is consistent with prior reports about the MD and reduced cancer morbidity and mortality.

Although a number of lifestyle interventions have been developed for cancer survivors, the extent to which they are effective for African American men with cancer is unclear. Given that African American men have the highest prostate cancer burden and the lack of proven interventions, this study developed a culturally-tailored lifestyle intervention for African American men with prostate cancer and their partners that aimed to improve healthy lifestyle behaviors (physical activity and healthy eating) and quality of life. The aim of the present study is to provide a detailed overview of the model-based process of intervention adaptation. Based on the IM Adapt approach (Highfield et al., 2015) and Typology of Adaptation (Davidson et al., 2013), the present study adapted existing, evidence-based interventions to address African American prostate cancer survivors’ and their partners’ potential unmet needs including anxiety/uncertainty about cancer progression, communication between partners, cultural sensitivity, and concordance/discordance of motivation and behaviors between partners. The intervention adaptation was a comprehensive and fluid process. To the best knowledge of the author, this is the first couple-based lifestyle intervention specifically developed for African American men with prostate cancer. The present study will be highly informative to future investigators by providing flexible and detailed information regarding lifestyle intervention adaptation for racial/ethnic minority men with prostate cancer and their partners.

Objective To define the value of a digital rectal exam (DRE) in the prostate‐magnetic resonance imaging (MRI) era. Prostate MRI is increasingly used in men with elevated prostate‐specific antigen (PSA) prior to biopsy. Methods A retrospective study was performed in men with elevated PSA undergoing MRI followed by MRI fusion with systematic biopsy and men with elevated PSA/active surveillance with negative MRI followed by biopsy. Baseline clinicopathologic characteristics and DRE findings were collected. We examined performance of a positive DRE on sensitivity and specificity of diagnosing clinically significant prostate cancer (CSPC). Results A total of 339 patients had elevated PSA and positive MRI followed by MRI fusion guided with systematic biopsy. Pre‐biopsy DRE was documented in 286/339 patients, who were included in further analysis. About 81.6% positive, 78.7% questionable, and 55.8% negative DRE patients had CSPC. Positive DRE had 21.8% sensitivity and 91.3% specificity for CSPC. Positive or questionable DRE had 42.1% sensitivity and 81.5% specificity. Among 148 men with non‐CSPC (GG1)‐targeted biopsy, 28 had systematic biopsy with CSPC. About 5/28 had positive DRE and 8/28 had positive or questionable DRE. Twenty‐seven patients were included who had elevated PSA/on active surveillance with negative MRI and biopsy done within 2 years. About 77.8% had negative, 7.4% had questionable, and 14.8% men had positive DRE. About 7.4% had CSPC and all had a negative DRE. Conclusions Our study provides limited evidence for the value of a DRE. However, it does show occasional benefit in detecting GG2 or higher disease and given the lack of cost and side effects, should still be considered.

INTRODUCTION AND OBJECTIVE:Organ preserving therapies are of particular interest in the treatment of localized prostate cancer (PC) with a goal of decreasing morbidity associated with radical treat...

To report biopsy-related and oncologic outcomes in a large prospective active surveillance cohort that was initiated in the premagnetic resonance imaging era and to additionally identify clinical factors associated with disease reclassification in order to inform future studies designed to improve enrollment and follow-up on active surveillance.Patients were prospectively enrolled at a single institution from 2006 to 2014 and followed until 2016. Men with Gleason 6 or 7 disease were eligible, and those with6 months follow-up were included in the analysis. Patients were risk stratified based on clinical/pathologic criteria, including based on a combination of baseline and confirmatory biopsy tumor characteristics. Reclassification-free survival, based on tumor volume increase or Gleason score increase, was analyzed using multivariable Cox proportional hazards models.Of 825 enrolled patients, 682 met inclusion criteria. Median follow-up was 40 months (range 6.6-126.8). Disease was reclassified in 249 (36.5%), and 157 (23.0%) underwent treatment. A single positive core with a negative confirmatory biopsy was significantly associated with time to reclassification (median not met vs 43 months, log rank test P.001). Composite tumor length, defined as the combined tumor length between baseline and confirmatory biopsies, was associated with shorter Gleason upgrade-free survival (hazard ratio 1.24, 95% confidence interval 1.11-1.40, P.001) in multivariable analysis.Baseline stratification using clinical factors including tumor length may refine risk stratification and offer the foundation on which new systems that incorporate modalities such as magnetic resonance imaging may be based.

Symptomatic urinary tract infection is a complication of office based cystourethroscopy. Studies are mixed regarding the efficacy of antibiotic prophylaxis to prevent urinary tract infections. Our aim was to develop and evaluate an evidence-based protocol that reduces unnecessary antibiotic use while avoiding an increase in urinary tract infections.We created a clinic antibiogram based on all urology office visits performed during a 2-year period. Bacterial resistance rates, institutional risk related data and clinical guidelines were applied to create a protocol for antibiotic administration before cystourethroscopy. We then analyzed 1,245 consecutive patients without a renal transplant who underwent outpatient cystourethroscopy, including 610 after protocol initiation. Urinary tract infection rates and antibiotic use were analyzed for an association with the protocol change using the Fisher exact test.Cultures had an overall 20% rate of resistance to fluoroquinolones, representing 40% of the cultures that grew Escherichia coli. Before the protocol change 602 of 635 patients (94.8%) received a preprocedural antibiotic compared to 426 of 610 (69.9%) after protocol initiation (p0.01). A total of 19 patients (3.0%) had a symptomatic urinary tract infection prior to the protocol change while 16 (2.6%) had a urinary tract infection after the change (p = 0.69). Regarding resistance, fluoroquinolone resistant organisms grew in the cultures of 12 of 19 patients (63.2%) with a urinary tract infection before the protocol change compared to 5 of 16 (31.3%) with a urinary tract infection after the change. Recent antibiotic administration, hospitalization and chronic catheterization were associated with urinary tract infection in the entire cohort (all p ≤0.01).A local antibiogram with infection related risk data effectively risk stratifies patients before cystourethroscopy, decreasing the use of antibiotics without increasing the rate of symptomatic urinary tract infection.

Purpose: We sought to determine whether bladder neck size is associated with incontinence scores after robot-assisted laparoscopic radical prostatectomy.Materials and Methods: Consecutive eligible patients undergoing robot-assisted laparoscopic radical prostatectomy between July 19 and December 28, 2016 were enrolled in a prospective, longitudinal, observational cohort study. The primary outcome was patient reported urinary incontinence on the EPIC (Expanded Prostate Cancer Index Composite) scale 6 and 12 weeks postoperatively. The relationship between the EPIC score of urinary incontinence and bladder neck size was evaluated by multiple regression. Predicted EPIC scores for incontinence were displayed graphically after using restricted cubic splines to model bladder neck size.Results: A total of 107 patients were enrolled. The response rate was 98% and 87% at 6 and 12 weeks, respectively. Bladder neck size was not significantly associated with incontinence scores at 6 and 12 weeks. Comparing the 90th per...

Introduction Symptomatic urinary tract infection is a known complication of cystoscopy with ureteral stent removal. However, little is known about the incidence and risk factors for urinary tract infection after cystoscopy in renal transplant recipients, who likely represent a high risk cohort. In this study we determined the infection rate after cystoscopy with stent removal in this population and identified opportunities for care improvement. Methods We performed a retrospective cohort study of office cystoscopies with stent removal in renal transplant recipients performed at a single institution from April 2012 through May 2014. Strict criteria were used to determine the presence of symptomatic urinary tract infection within 1 month of the procedure. Fisher’s exact tests were completed to examine associations between patient characteristics and post-transplant outcomes with urinary tract infection. Results A total of 324 patients were included in the study. Mean age was 50.0 years (SD 13.1) and 187 patients (57.7%) were male. In this group 165 patients (52.5%) received an oral fluoroquinolone antibiotic before the procedure. Nine patients had symptomatic urinary tract infections (2.8%), of which 3 infections (33.3%) were due to quinolone-resistant organisms. Female sex but no other patient or postoperative characteristic was associated with symptomatic urinary tract infection (p=0.04), including the use of peri-procedural antibiotics. Conclusions The incidence of symptomatic urinary tract infection after cystoscopy with ureteral stent removal in renal transplant recipients is less than 3%, comparable to the risk of urinary tract infection after cystoscopy in the general population. Female sex is associated with symptomatic urinary tract infection. Further investigation is needed to identify the groups at greatest risk for urinary tract infection and other complications.

Plasma and tumor caveolin-1 (Cav-1) are linked with disease progression in prostate cancer. Here we report that metabolomic profiling of longitudinal plasmas from a prospective cohort of 491 active surveillance (AS) participants indicates prominent elevations in plasma sphingolipids in AS progressors that, together with plasma Cav-1, yield a prognostic signature for disease progression. Mechanistic studies of the underlying tumor supportive onco-metabolism reveal coordinated activities through which Cav-1 enables rewiring of cancer cell lipid metabolism towards a program of 1) exogenous sphingolipid scavenging independent of cholesterol, 2) increased cancer cell catabolism of sphingomyelins to ceramide derivatives and 3) altered ceramide metabolism that results in increased glycosphingolipid synthesis and efflux of Cav-1-sphingolipid particles containing mitochondrial proteins and lipids. We also demonstrate, using a prostate cancer syngeneic RM-9 mouse model and established cell lines, that this Cav-1-sphingolipid program evidences a metabolic vulnerability that is targetable to induce lethal mitophagy as an anti-tumor therapy., The mechanisms associated with Caveolin-1 (Cav-1) mediated metabolic changes in prostate cancer are unclear. Here, the authors show that Cav-1 promotes rewiring of cancer cell lipid metabolism towards a program of exogenous lipid scavenging and vesicle biogenesis that intersects with mitochondrial dynamics in prostate tumors.

Determining prostate cancer (PCa) aggressiveness and reclassification are critical events during the treatment of localized disease and for patients undergoing active surveillance (AS). Since T cells play major roles in cancer surveillance and elimination, we aimed to identify genetic biomarkers related to T cell cancer immune response which are predictive of aggressiveness and reclassification risks in localized PCa. The genotypes of 3,586 single nucleotide polymorphisms (SNPs) from T cell cancer immune response pathways were analyzed in 1762 patients with localized disease and 393 who elected AS. The aggressiveness of PCa was defined according to pathological Gleason score (GS) and D’Amico criteria. PCa reclassification was defined according to changes in GS or tumor characteristics during subsequent surveillance biopsies. Functional characterization and analysis of immune phenotypes were also performed. In the localized PCa cohort, seven SNPs were significantly associated with the risk of aggressive disease. In the AS cohort, another eight SNPs were identified as predictors for aggressiveness and reclassification. Rs1687016 of PSMB8 was the most significant predictor of reclassification. Cumulative analysis showed that a genetic score based on the identified SNPs could significantly predict risk of D’Amico high risk disease (P-trend = 2.4E-09), GS4 + 3 disease (P-trend = 1.3E-04), biochemical recurrence (P-trend = 0.01) and reclassification (P-trend = 0.01). In addition, the rs34309 variant was associated with functional somatic mutations in the PI3K/PTEN/AKT/MTOR pathway and tumor lymphocyte infiltration. Our study provides plausible evidence that genetic variations in T cell cancer immune response can influence risks of aggressiveness and reclassification in localized PCa, which may lead to additional biological insight into these outcomes. Abbreviations: PCa, prostate cancer; AS, active surveillance; GS, Gleason score; PSA, prostate specific antigen; TCGA, The Cancer Genome Atlas; SNP, single nucleotide polymorphisms; UFG, unfavorable genotype.

Introduction Symptomatic urinary tract infection is a complication of office based cystoscopy. AUA guidelines recommend prophylactic antibiotics for patients with an increased risk of urinary tract infection. However, study results are mixed regarding the efficacy of prophylaxis for urinary tract infection prevention. We evaluate predictors of infection to identify groups at increased risk for urinary tract infection after cystoscopy. Methods We identified all office cystoscopies performed at a single institution from April 2012 through May 2014. Patients with a positive urine culture within 30 days of the procedure were reviewed for symptomatic urinary tract infection. Those with a urinary tract infection were matched to 4 controls. Patient characteristics were extracted and examined for association with urinary tract infection. A multivariable logistic regression model was fit to identify associations between composite clinical variables and urinary tract infection. Results During the study period 5,488 patients underwent cystoscopy, of whom 29 (0.53%) had a urinary tract infection. Cultures showed quinolone resistant organisms in 13 of 29 (45%) urinary tract infections. The use of an external catheter or intermittent catheterization (p=0.04), hospitalization within 4 weeks (p=0.04) and the use of antibiotics within 6 months of cystoscopy (p=0.01) were associated with urinary tract infection. Recent antibiotic exposure, recent nongenitourinary infection or recent hospitalization was associated with urinary tract infection on multivariable analysis (OR 5.26, 95% CI 1.87–14.8, p Conclusions Recent antibiotic exposure, infection or hospitalization is associated with an increased risk of urinary tract infection after cystoscopy. Most symptomatic urinary tract infections are due to quinolone resistant organisms in this population. The optimal prophylactic regimen should be tailored to regional antibiotic susceptibility patterns and individual patient risk factors.

Background High diet quality may support a metabolic and anti-inflammatory state less conducive to tumour progression. We prospectively investigated diet quality in relation to Gleason grade progression among localised prostate cancer patients on active surveillance, a clinical management strategy of disease monitoring and delayed intervention. Methods Men with newly diagnosed Gleason score 6 or 7 prostate cancer enroled on a biennial monitoring regimen. Patients completed a food frequency questionnaire (FFQ) at baseline (n = 411) and first 6-month follow-up (n = 263). Cox proportional hazards models were fitted to evaluate multivariable-adjusted associations of diet quality [defined via the Healthy Eating Index (HEI)-2015] with Gleason grade progression. Results After a median follow-up of 36 months, 76 men progressed. Following adjustment for clinicopathologic factors, we observed a suggestive inverse association between baseline diet quality and Gleason grade progression [hazard ratio (HR) and 95% confidence interval (CI) for the highest vs. the lowest HEI-2015 tertile: 0.59 (0.32–1.08); Ptrend = 0.06]. We observed no associations with diet quality at 6-month follow-up, nor change in diet quality from baseline. Conclusions In localised prostate cancer patients on surveillance, higher diet quality or conformance with United States dietary guidelines at enrolment may lower risk of Gleason grade progression, though additional confirmatory research is needed.

Purpose Risk stratification underlies system-wide efforts to promote the delivery of appropriate prostate cancer care. Although the elements of risk stratum are available in the electronic medical record, manual data collection is resource intensive. Therefore, we investigated the feasibility and accuracy of an automated data extraction method using natural language processing (NLP) to determine prostate cancer risk stratum. Methods Manually collected clinical stage, biopsy Gleason score, and preoperative prostate-specific antigen (PSA) values from our prospective prostatectomy database were used to categorize patients as low, intermediate, or high risk by D’Amico risk classification. NLP algorithms were developed to automate the extraction of the same data points from the electronic medical record, and risk strata were recalculated. The ability of NLP to identify elements sufficient to calculate risk (recall) was calculated, and the accuracy of NLP was compared with that of manually collected data using the weighted Cohen’s κ statistic. Results Of the 2,352 patients with available data who underwent prostatectomy from 2010 to 2014, NLP identified sufficient elements to calculate risk for 1,833 (recall, 78%). NLP had a 91% raw agreement with manual risk stratification (κ = 0.92; 95% CI, 0.90 to 0.93). The κ statistics for PSA, Gleason score, and clinical stage extraction by NLP were 0.86, 0.91, and 0.89, respectively; 91.9% of extracted PSA values were within ± 1.0 ng/mL of the manually collected PSA levels. Conclusion NLP can achieve more than 90% accuracy on D’Amico risk stratification of localized prostate cancer, with adequate recall. This figure is comparable to other NLP tasks and illustrates the known tradeoff between recall and accuracy. Automating the collection of risk characteristics could be used to power real-time decision support tools and scale up quality measurement in cancer care.

The scenario discussed in this chapter involves the management of castration-resistant prostate cancer (CRPC) in the setting of prior prostatectomy with lymphadenectomy with likely disease recurrence in a pelvic lymph node. Treating this patient is both nuanced and complicated given the rapidly evolving management of advanced prostate cancer and paucity of data guiding salvage lymphadenectomy in the setting of CRPC. Options for treatment include multiple modalities, including systemic therapies (such as chemo- or hormonal therapy) that have proven efficacy in the metastatic CPRC setting, and localized treatment such as radiation or surgery. This chapter aims to outline the issues and reasoning behind various treatment options for patients with CRPC and local disease recurrence and specifically updates evidence related to salvage lymphadenectomy in this setting.

BACKGROUND: To evaluate the impact of salvage therapy (ST) on overall survival (OS) in recurrent primary urethral cancer (PUC). PATIENTS: A series of 139 patients (96 men, 43 women; median age = 66, interquartile range: 57–77) were diagnosed with PUC at 10 referral centers between 1993 and 2012. The modality of ST of recurrence (salvage surgery vs. radiotherapy) was recorded. Kaplan-Meier analysis with log-rank was used to estimate the impact of ST on OS (median follow-up = 21, interquartile range: 5–48). RESULTS: The 3-year OS for patients free of any recurrence (I), with solitary or concomitant urethral recurrence (II), and nonurethral recurrence (III) was 86.5%, 74.5%, and 48.2%, respectively (P = 0.002 for I vs. III and II vs. III; P = 0.55 for I vs. II). In the 80 patients with recurrences, the modality of primary treatment of recurrence was salvage surgery in 30 (37.5%), salvage radiotherapy (RT) in 8 (10.0%), and salvage surgery plus RT in 5 (6.3%) whereas 37 patients did not receive ST for recurrence (46.3%). In patients with recurrences, those who underwent salvage surgery or RT-based ST had similar 3-year OS (84.9%, 71.6%) compared to patients without recurrence (86.7%, P = 0.65), and exhibited superior 3-year OS compared to patients who did not undergo ST (38.0%, P < 0.001 compared to surgery, P = 0.045 to RT-based ST, P = 0.29 for surgery vs. RT-based ST). CONCLUSIONS: In this study, patients who underwent ST for recurrent PUC demonstrated improved OS compared to those who did not receive ST and exhibited similar survival to those who never developed recurrence after primary treatment.