A west African ancestry-associated SNP on 8q24 predicts a positive biopsy in African American men with suspected prostate cancer following PSA screening.

BACKGROUND: African American (AA) men have the highest incidence and mortality rates of prostate cancer (PCa) among all racial groups in the United States. While race is a social construct, for AA men, this overlaps with west African ancestry. Many of the PCa susceptibility variants exhibit distinct allele frequencies and risk estimates across different races and contribute substantially to the large disparities of PCa incidence among races. We previously reported that a single-nucleotide polymorphism (SNP) in 8q24, rs7824364, was strongly associated with west African ancestry and increased risks of PCa in both AA and Puerto Rican men. In this study, we determined whether this SNP can predict biopsy positivity and detection of clinically significant disease (Gleason score [GS] ≥ 7) in a cohort of AA men with suspected PCa. METHODS: SNP rs7824364 was genotyped in 199 AA men with elevated total prostate-specific antigen (PSA) (>2.5 ng/mL) or abnormal digital rectal exam (DRE) and the associations of different genotypes with biopsy positivity and clinically significant disease were analyzed. RESULTS: The variant allele carriers were significantly over-represented in the biopsy-positive group compared to the biopsy-negative group (44% vs. 25.7%, p = 0.011). In the multivariate logistic regression analyses, variant allele carriers were at a more than a twofold increased risk of a positive biopsy (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 1.06-4.32). Moreover, the variant allele was a predictor (OR = 2.26, 95% CI = 1.06-4.84) of a positive biopsy in the subgroup of patients with PSA < 10 ng/mL and normal DRE. The variant allele carriers were also more prevalent in cases with GS ≥ 7 compared to cases with GS < 7 and benign biopsy. CONCLUSIONS: This study demonstrated that the west African ancestry-specific SNP rs7824364 on 8q24 independently predicted a positive prostate biopsy in AA men who were candidates for prostate biopsy subsequent to PCa screening.

A Multi-Institutional Study of Magnetic Resonance/Ultrasound Fusion-Guided Nanoparticle-Directed Focal Therapy for Prostate Ablation.

PURPOSE: Focal therapy aims to provide a durable oncologic treatment option for men with prostate cancer (PCa), while preserving their quality of life. Most focal therapy modalities rely on the direct tissue effect, resulting in a possible nontargeted approach to ablation. Here, we report the results of the first human feasibility trial utilizing nanoparticle-directed focal photothermal ablation for PCa. MATERIALS AND METHODS: A prospective, open-label, single-arm, multicenter study of men with localized PCa in Gleason Grade Group 1 to 3 was conducted. Men received a single infusion of gold nanoparticles (AuroShells), followed by magnetic resonance (MR)/ultrasound (US) fusion-guided laser excitation of the target tissue to induce photothermal ablation. MRI was used to assess the effectiveness of prostate tissue ablation at 48 to 96 hours, 3 months, and 12 months post treatment. At 3 months, a targeted fusion biopsy of the lesion(s) was conducted. At 12 months, a targeted fusion biopsy and standard templated biopsy were performed. Treatment success was determined based on a negative MR/US fusion biopsy outcome within the treated area. RESULTS: Forty-six men were enrolled in the study, and 44 men with 45 lesions completed nanoparticle infusion and laser treatment. The mean PSA level at baseline was 9.5 ng/mL, which decreased to 5.9 ng/mL at 3 months and to 4.7 ng/mL at 12 months (P < .0001). The oncologic success rates at 3 and 12 months resulted in 29 (66%) and 32 (73%) of 44 patients, respectively, being successfully treated, confirmed with negative MR/US fusion biopsies within the ablation zone. Among Gleason Grade Group, maximum lesion diameter on MRI, prostate volume, and Prostate Imaging Reporting and Data System scoring, the maximum lesion diameter was significantly associated with the odds of treatment failure at 12 months (P = .046). CONCLUSIONS: Nanoparticle-directed focal laser ablation of neoplastic prostate tissue resulted in 73% of patients with successful treatment at 12 months post treatment, confirmed by negative MR/US fusion biopsy of the treated lesion and a systematic biopsy. CLINICAL TRIAL REGISTRATION NO.: 02680535.

Current Landscape of Surgical Assessment Models in Urology Residency Training.

PURPOSE: Assessing trainees' surgical proficiency is an important aspect of urological surgical training. The current standard is the Urology Milestone Project, initially implemented in 2013. This evaluation is limited in that it contains only 3 questions on surgical competency per surgical modality with assessments occurring semi-annually without real-time operative feedback. However, since the Urology Milestones Project's inception a plethora of competency-based surgical assessment tools have been described. We aim to perform a comprehensive review of the literature of these available tools and analyze their strengths and weaknesses as a way of providing a repository of available assessment strategies for further development of a more comprehensive and standardized assessment tool. MATERIALS AND METHODS: A review of the primary literature was performed using key words such as "surgical assessment tools urology," "surgical assessment tools prostate," "bladder surgical assessment tools," "renal surgical assessment tools urology," and "surgical assessment tools urology task specific." Technical and nontechnical skill assessments were included. One reviewer identified and analyzed studies that published assessment tools for use in surgical and urological training. RESULTS: A total of 1,497 articles published between 1997-2022 were identified. Of these, 34 met the inclusion criteria. Eighteen (52.9%) were specialty nonspecific and 16 (47.1%) were specific for urological training. Of the 18 tools developed for general surgical principles, 12 (66.7%) had some form of validity, 9 (50.0%) were significantly reliable, and 2 (11.1%) were externally validated. Of the 16 tools developed specifically for use in urology training, 13 (81.3%) had some form of validity, 7 (43.8%) were significantly reliable, and none were externally validated. Of these 16 tools, 12 (75.0%) were procedure-specific and 4 (25.0%) were developed for general use in endourological procedures. CONCLUSIONS: Surgical training is evolving toward a competency-based model, as evidenced by the increase in assessment tools created within the past 10 years. These instruments not only provide objective feedback to trainees, but also monitor progression. However, they are heterogeneous in construct and utilization. There remains a need for the adoption of a standardized, valid, and reliable tool, ie, both procedure-specific and generalizable across multiple procedures for use in urology training.

Gold nanoshell-localized photothermal ablation of prostate tumors in a clinical pilot device study.

Biocompatible gold nanoparticles designed to absorb light at wavelengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance-ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function.

Informed decision making before prostate-specific antigen screening: Initial results using the American Cancer Society (ACS) Decision Aid (DA) among medically underserved men.

BACKGROUND: The American Cancer Society (ACS) recommends men have the opportunity to make an informed decision about screening for prostate cancer (PCa). The ACS developed a unique decision aid (ACS-DA) for this purpose. However, to date, studies evaluating the efficacy of the ACS-DA are lacking. The authors evaluated the ACS-DA among a cohort of medically underserved men (MUM). METHODS: A multiethnic cohort of MUM (n = 285) was prospectively included between June 2010 and December 2014. The ACS-DA was presented in a group format. Levels of knowledge on PCa were evaluated before and after the presentation. Participants' decisional conflict and thoughts about the presentation also were evaluated. Logistic regression analyses were performed to determine factors associated with having an adequate level of knowledge. RESULTS: Before receiving the ACS-DA, 33.1% of participants had adequate knowledge on PCa, and this increased to 77% after the DA (P < .0001). On multivariate analysis, higher education level (odds ratio, 11.19; P = .001) and history of another cancer (odds ratio, 7.45; P = .03) were associated with having adequate knowledge after receiving the DA. Levels of decisional conflict were low and were correlated with levels of knowledge after receiving the DA. The majority of men also rated the presentation as favorable and would recommend the ACS-DA to others. CONCLUSIONS: Use of the ACS-DA was feasible among MUM and led to increased PCa knowledge. This also correlated with low levels of decisional conflict. The ACS-DA presented to groups of men may serve as a feasible tool for informed decision making in a MUM population. Cancer 2017;123:583-591. © 2016 American Cancer Society.

Local treatments for metastases of renal cell carcinoma: a systematic review.

Local treatment of metastases such as metastasectomy or radiotherapy remains controversial in the treatment of metastatic renal cell carcinoma. To investigate the benefits and harms of various local treatments, we did a systematic review of all types of comparative studies on local treatment of metastases from renal cell carcinoma in any organ. Interventions included metastasectomy, radiotherapy modalities, and no local treatment. The results suggest that patients treated with complete metastasectomy have better survival and symptom control (including pain relief in bone metastases) than those treated with either incomplete or no metastasectomy. Nevertheless, the available evidence was marred by high risks of bias and confounding across all studies. Although the findings presented here should be interpreted with caution, they and the identified gaps in knowledge should provide guidance for clinicians and researchers, and directions for further research.

Rating the quality of evidence and the strength of recommendations using GRADE.

OBJECTIVES: Urologists can benefit from a standardized system for guideline development and presentation. This article introduces the GRADE system and explains how it may be useful for Urologic physicians, in their practice and in their healthcare systems. METHODS: The GRADE system is reviewed. Specific aspects of how GRADE rates the quality of the evidence and the strength of recommendations are explored. RESULTS: GRADE can provide explicit and structured guidance, which separates the quality of evidence from the strength of recommendations. This information can be used by consumers of guidelines, including patients, physicians, and policy makers. CONCLUSIONS: Urologists can benefit from a more transparent and rigorous framework when formulating recommendations. GRADE is an emergent proposal with broader implications for healthcare policy as well.

Patient Perceptions of Telephonic Visits during the COVID-19 Pandemic-Is Video Connectivity Imperative?

INTRODUCTION: We characterize patient perceptions of telemedicine (video-enabled) and telephonic (audio-only) visits conducted during the COVID-19 pandemic. METHODS: A single-center cohort of 76 patients who underwent remote ambulatory visits from March 2020 to July 2020 was evaluated. Patients responded to a questionnaire assessing perception of timeliness, efficiency, overall satisfaction and willingness to have a remote appointment after the pandemic. Responses were compared for telephonic (audio-only) vs telemedicine (video) visits. RESULTS: High satisfaction scores were reported for both telephonic and telemedicine appointments, with a mean score of 6.61 out of 7 (SD 1.0) for overall satisfaction. Telephonic visits demonstrated higher scores regarding timeliness and efficiency of the visit (6.58 vs 5.92, p=0.017) and willingness to have a remote encounter with a urology resident (6.58 vs 5.61, p=0.001) or advanced practice provider (6.21 vs 5.51, p=0.015). No difference in perception of confidentiality or overall satisfaction was observed between both groups. In all, 91% of participants desired the option of a virtual visit with their provider after the pandemic. CONCLUSIONS: Patients undergoing remote urology appointments during the COVID-19 pandemic report high satisfaction rates, though telephonic encounters were more favorable for patients in regard to timeliness and efficiency. Importantly, most patients desired the option of telephonic and telemedicine calls after the pandemic. Further analysis on safety, efficacy, provider perceptions, outcomes and economic impact is needed to assess the feasibility of continuing regular telephonic and telemedicine visits after the COVID-19 pandemic is over.

Assessment of the methodological quality of systematic reviews published in the urological literature from 1998 to 2008.

PURPOSE: Well done systematic reviews provide the highest quality evidence for clinical questions of therapeutic effectiveness. We assessed the methodological quality of systematic reviews in the urological literature. MATERIALS AND METHODS: We systematically investigated all systematic reviews published in 4 major urological journals from 1998 to 2008. Studies were identified using a predefined search strategy in PubMed and confirmed by a hand search of journal tables of contents. A validated 11-point instrument to assess the methodological quality of systematic reviews was applied by 2 independent reviewers after a pilot testing phase. Disagreements were discussed and resolved by consensus. RESULTS: The systematic literature search identified 217 individual systematic reviews, of which 57 ultimately met study eligibility criteria. Ten (17.5%), 20 (35.1%) and 27 (47.4%) systematic reviews were published in 1998 to 2001, 2002 to 2005 and 2006 to 2008, respectively. Using the measurement tool to assess systematic reviews the mean +/- SD score was 4.8 +/- 2.0 points. Fewer than half of all systematic reviews performed a systematic literature search that included at least 2 databases (49.1%) or unpublished studies (31.6%), or provided a list of included and excluded studies (45.6%). Of the systematic reviews 63.2% assessed and documented the methodological quality of included studies. Systematic reviews with The Cochrane Collaboration authorship affiliation had a higher mean score than those with no such reported affiliation (6.5 +/- 1.2 vs 4.4 +/- 1.9 points, p <0.001). CONCLUSIONS: Results suggest that an increasing number of systematic reviews are published in the urological literature. However, many systematic reviews fail to meet established methodological standards, raising concerns about validity. Increased efforts are indicated to promote quality standards for performing systematic reviews among the authors and readership of the urological literature.

Androgen Receptor Splice Variant, AR-V7, as a Biomarker of Resistance to Androgen Axis-Targeted Therapies in Advanced Prostate Cancer.

Many therapeutic options are now available for men with metastatic castration-resistant prostate cancer (mCRPC), including next-generation androgen receptor axis-targeted therapies (AATTs), immunotherapy, chemotherapy, and radioisotope therapies. No clear consensus has been reached for the optimal sequencing of treatments for patients with mCRPC, and few well-validated molecular markers exist to guide the treatment decisions for individual patients. The androgen receptor splice variant 7 (AR-V7), a splice variant of the androgen receptor mRNA resulting in the truncation of the ligand-binding domain, has emerged as a biomarker for resistance to AATT. AR-V7 expression in circulating tumor cells has been associated with poor outcomes in patients treated with second- and third-line AATTs. Clinically validated assays are now commercially available for the AR-V7 biomarker. In the present review of the current literature, we have summarized the biology of resistance to AATT, with a focus on the AR-V7; and the clinical studies that have validated AR-V7 expression as a strong independent predictor of a lack of clinical benefit from AATTs. Existing evidence has indicated that patients with AR-V7-positive mCRPC will have better outcomes if treated with taxane chemotherapy regimens rather than additional AATTs.

Cultural Adaptation of Evidence-Based Lifestyle Interventions for African American Men With Prostate Cancer: A Dyadic Approach.

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.

Creation of a Novel Digital Rectal Examination Evaluation Instrument to Teach and Assess Prostate Examination Proficiency.

OBJECTIVE: To create a validated tool to measure digital rectal examination proficiency and aid with teaching of the examination. DESIGN: The Digital Rectal Examination Clinical Tool was created using a modified Delphi method with 5 urologists and 5 radiation oncologists. The instrument was then validated in a population of preclinical medical students examining male urological teaching associates, and clinical trainees (third- and fourth-year medical students and urology resident physicians) examining prospectively enrolled subjects. Trainees completed paired examinations with an attending urologist, and responses were scored with reference to the attending responses. SETTING: The instrument was validated at the University of Virginia in the urology clinic, endoscopic operating room, and main operating room settings. PARTICIPANTS: We tested the instrument on consenting subjects consisting of male urologic teaching associates (n = 12), clinic patients (n = 4), and operating room patients (n = 64). The participants were undergraduate (n = 302) and graduate (n = 9) medical trainees. RESULTS: In preclerkship trainees, improved scores in subjects without abnormal compared to those with abnormal findings demonstrated validity. In clinical trainees, scores on the Digital Rectal Examination Clinical Tool increased by 2% for each additional year of training, demonstrating construct validity. CONCLUSIONS: We used an expert panel to create a novel instrument for measuring digital rectal examination proficiency and validated it with preclinical and clinical trainee cohorts at our institution.

Bortezomib inhibits docetaxel-induced apoptosis via a p21-dependent mechanism in human prostate cancer cells.

Bortezomib (PS-341, Velcade) is a peptide boronate inhibitor of the 20S proteasome that is currently being combined with taxanes in several clinical trials in patients with prostate cancer. Here, we report that bortezomib inhibited docetaxel-induced M-phase arrest and apoptosis in androgen-dependent LNCaP-Pro5 cells. Direct analysis of kinase activity in immune complex kinase assays revealed that docetaxel activated cyclin-dependent kinase (CDK) 1 (CDC2) and that bortezomib blocked this activation. The effects of bortezomib were associated with accumulation of p21 and mimicked by chemical CDK inhibitors or by transfecting cells with a small interfering RNA construct specific for CDK1. Transient transfection with p21 also inhibited docetaxel-induced apoptosis; conversely, p21 silencing reversed the antagonistic effects of bortezomib on docetaxel-induced apoptosis. Together, our data show that bortezomib interferes with docetaxel-induced apoptosis via a p21-dependent mechanism that is associated with CDK1 inhibition. These observations may have important implications for the ongoing bortezomib-docetaxel combination trials as well as trials using bortezomib and other cell cycle-sensitive agents.