Publications by authors named "Christian P Pavlovich"

117 Publications

Specific Detection of Prostate Cancer Cells in Urine by RNA in Situ Hybridization.

J Urol 2021 Feb 22:101097JU0000000000001691. Epub 2021 Feb 22.

The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland.

Purpose: Noninvasive tests that can accurately detect prostate cancer are urgently needed for prostate cancer diagnosis, surveillance, and prognosis. Exfoliated prostate cells captured in urine represent a promising resource for noninvasive detection of prostate cancer. We investigated performance of a novel cell-based urine test for detection of clinically significant prostate cancer.

Materials And Methods: We previously developed a multiplex RNA in situ hybridization (RISH) assay targeting NKX3-1, PRAC1 and PCA3 that enables identification and quantification of malignant and benign prostate cells released into urine. We investigated application of the assay for prostate cancer detection in a cohort of 98 patients suspected of harboring prostate cancer. Urine was collected following digital rectal exam and the sediment was isolated and evaluated by RISH. Samples were scored based on cellular expression of RISH targets. Cells of prostate origin were defined by positivity for NKX3-1 and/or PRAC1, and prostate cancer cells by positivity for PCA3.

Results: Prostate cells (NKX3-1/PRAC1+ cells) were detected in 69 samples, among which 20 were positive for PCA3 (i.e., positive for prostate cancer cells). Comparison of RISH results with biopsy outcome and clinical variables revealed that positivity for cancer by RISH significantly correlated with intermediate/high risk cancer (p=0.003), PSA density (p=0.022), significant disease (p <0.0001), and Gleason score (p=0.003). The test was 95% specific and 51% sensitive for detection of clinically significant prostate cancer.

Conclusions: Identification of exfoliated prostate cancer cells in urine by RISH provides a novel tool for highly specific and noninvasive detection of prostate cancer.
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http://dx.doi.org/10.1097/JU.0000000000001691DOI Listing
February 2021

Transperineal Prostate Biopsy Improves the Detection of Clinically Significant Prostate Cancer among Men on Active Surveillance.

J Urol 2020 Dec 1:101097JU0000000000001523. Epub 2020 Dec 1.

James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Purpose: Transperineal prostate biopsy offers improved sampling of the anterior prostate compared to the transrectal approach. The objective of this study was to determine if transperineal prostate biopsy is associated with an increased incidence of cancer upgrading among men on active surveillance for very low or low risk prostate cancer.

Materials And Methods: Our active surveillance registry was queried to identify patients who underwent a surveillance biopsy following the introduction of transperineal prostate biopsy at our institution. Patients were dichotomized by the type of biopsy performed. The baseline characteristics and rates of cancer upgrading were compared between groups.

Results: Between October 2017 and July 2020, 790 men with very low or low risk prostate cancer underwent a surveillance biopsy. In total, 59 of 279 men (21.2%) in the transperineal prostate biopsy group were upgraded to grade group ≥2 as compared to 75 of 511 (14.7%) in the transrectal biopsy group (p=0.01). Among patients who were upgraded to grade group ≥2, 26 of 59 (44%) had grade group ≥2 detected in the anterior/transition zone with transperineal prostate biopsy compared to 14 of 75 (18.7%) with transrectal biopsy (p=0.01). Additionally, 17 of 279 men (6.1%) who underwent transperineal prostate biopsy were upgraded to grade group ≥3 vs 17 of 511 (3.3%) who underwent transrectal biopsy (p=0.05). After adjusting for age, prostate specific antigen density, magnetic resonance imaging targeting and number of prior transrectal biopsies, transperineal prostate biopsy was significantly associated with upgrading to grade group ≥2 (OR 1.49, 95% CI 1.11-2.19, p=0.01).

Conclusions: Among men on active surveillance for very low or low risk prostate cancer, transperineal prostate biopsy is associated with an increased likelihood of upgrading to clinically significant prostate cancer. This is likely due to greater sampling of the anterior prostate.
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http://dx.doi.org/10.1097/JU.0000000000001523DOI Listing
December 2020

Molecular biomarkers in the context of focal therapy for prostate cancer: recommendations of a Delphi Consensus from the Focal Therapy Society.

Minerva Urol Nefrol 2021 01 13. Epub 2021 Jan 13.

Department of Urology, Institut Mutualiste Montsouris, Paris, France.

Background: Focal Therapy (FT) for Prostate Cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localised PCa.

Materials And Methods: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, i) the current/present role; ii) the potential/future role; iii) the recommended features for future studies. Consensus was defined using a 70% agreement threshold.

Results: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (n=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (n=3), a consensus on a partial agreement (n=1), and a consensus on uncertainty (n=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localised PCa. Research efforts in this field should be considered a priority.

Conclusions: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.
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http://dx.doi.org/10.23736/S0393-2249.20.04160-0DOI Listing
January 2021

Surgical ergonomics for urologists: a practical guide.

Nat Rev Urol 2021 Jan 11. Epub 2021 Jan 11.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Poor ergonomics in the operating room can have detrimental effects on a surgeon's physical, psychological and economic well-being. This problem is of particular importance to urologists who are trained in nearly all operative approaches (open, laparoscopic, robotic-assisted, microscopic and endoscopic surgery), each with their own ergonomic considerations. The vast majority of urologists have experienced work-related musculoskeletal pain or injury at some point in their career, which can result in leaves of absence, medical and/or surgical treatment, burnout, changes of specialty and even early retirement. Surgical ergonomics in urology has been understudied and underemphasized. In this Review, we characterize the burden of musculoskeletal injury in urologists and focus on various ergonomic considerations relevant to the urology surgeon. Although the strength of evidence remains limited in this space, we highlight several practical recommendations stratified by operative approach that can be incorporated into practice without interrupting workflow whilst minimizing injury to the surgeon. These recommendations might also serve as the foundation for ergonomics training curricula in residency and continuing medical education programmes. With improved awareness of ergonomic principles and the sequelae of injury related to urological surgery, urologists can be more mindful of their operating room environment and identify ways of reducing their own symptoms and risk of injury.
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http://dx.doi.org/10.1038/s41585-020-00414-4DOI Listing
January 2021

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer.

J Urol 2021 Mar 6;205(3):769-779. Epub 2020 Oct 6.

University of Chicago.

Purpose: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal ultrasound under magnetic resonance imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT).

Materials And Methods: A total of 115 men with favorable to intermediate risk prostate cancer across 13 centers were treated with whole gland ablation sparing the urethra and apical sphincter. The co-primary 12-month endpoints were safety and efficacy.

Results: In all, 72 (63%) had grade group 2 and 77 (67%) had NCCN® intermediate risk disease. Median treatment delivery time was 51 minutes with 98% (IQR 95-99) thermal coverage of target volume and spatial ablation precision of ±1.4 mm on magnetic resonance imaging thermometry. Grade 3 adverse events occurred in 9 (8%) men. The primary endpoint (U.S. Food and Drug Administration mandated) of prostate specific antigen reduction ≥75% was achieved in 110 of 115 (96%) with median prostate specific antigen reduction of 95% and nadir of 0.34 ng/ml. Median prostate volume decreased from 37 to 3 cc. Among 68 men with pretreatment grade group 2 disease, 52 (79%) were free of grade group 2 disease on 12-month biopsy. Of 111 men with 12-month biopsy data, 72 (65%) had no evidence of cancer. Erections (International Index of Erectile Function question 2 score 2 or greater) were maintained/regained in 69 of 92 (75%). Multivariate predictors of persistent grade group 2 at 12 months included intraprostatic calcifications at screening, suboptimal magnetic resonance imaging thermal coverage of target volume and a PI-RADS™ 3 or greater lesion at 12-month magnetic resonance imaging (p <0.05).

Conclusions: The TACT study of magnetic resonance imaging-guided transurethral ultrasound whole gland ablation in men with localized prostate cancer demonstrated effective tissue ablation and prostate specific antigen reduction with low rates of toxicity and residual disease.
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http://dx.doi.org/10.1097/JU.0000000000001362DOI Listing
March 2021

Practice patterns related to prostate cancer grading: results of a 2019 Genitourinary Pathology Society clinician survey.

Urol Oncol 2020 Sep 15. Epub 2020 Sep 15.

Departments of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD; Departments of Urology and Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD.

Purpose: To survey urologic clinicians regarding interpretation of and practice patterns in relation to emerging aspects of prostate cancer grading, including quantification of high-grade disease, cribriform/intraductal carcinoma, and impact of magnetic resonance imaging-targeted needle biopsy.

Materials And Methods: The Genitourinary Pathology Society distributed a survey to urology and urologic oncology-focused societies and hospital departments. Eight hundred and thirty four responses were collected and analyzed using descriptive statistics.

Results: Eighty percent of survey participants use quantity of Gleason pattern 4 on needle biopsy for clinical decisions, less frequently with higher Grade Groups. Fifty percent interpret "tertiary" grade as a minor/<5% component. Seventy percent of respondents would prefer per core grading as well as a global/overall score per set of biopsies, but 70% would consider highest Gleason score in any single core as the grade for management. Seventy five percent utilize Grade Group terminology in patient discussions. For 45%, cribriform pattern would affect management, while for 70% the presence of intraductal carcinoma would preclude active surveillance.

Conclusion: This survey of practice patterns in relationship to prostate cancer grading highlights similarities and differences between contemporary pathology reporting and its clinical application. As utilization of Gleason pattern 4 quantification, minor tertiary pattern, cribriform/intraductal carcinoma, and the incorporation of magnetic resonance imaging-based strategies evolve, these findings may serve as a basis for more nuanced communication and guide research efforts involving pathologists and clinicians.
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http://dx.doi.org/10.1016/j.urolonc.2020.08.027DOI Listing
September 2020

A prospective comparative study of routine versus deferred pelvic drain placement after radical prostatectomy: impact on complications and opioid use.

World J Urol 2020 Sep 14. Epub 2020 Sep 14.

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Park 213, Baltimore, MD, 21287, USA.

Purpose: To evaluate the association of post-RP drain placement with post-operative complications and opioid use at a high-volume institution.

Methods: A prospective, comparative cohort study of patients undergoing robot-assisted or open RP was conducted. Patients for two surgeons did not routinely receive pelvic drains ("No Drain" arm), while the remainder routinely placed drains ("Drain" arm). Outcomes were evaluated at 30 days including Clavien-Dindo complications and opioid use. Intention-to-treat primary analysis and additional secondary analyses were performed using appropriate statistical tests and logistic regression.

Results: Of 498 total patients, 144 (28.9%) were in the No Drain arm (all robot-assisted) and 354 (71.1%) in the Drain arm. In the No Drain arm, 19 (13.2%) intraoperatively were chosen to receive drains. There was no difference in overall or major (Clavien ≥ 3) complications between groups (p = 0.2 and 0.4, respectively). Drain deferral did not predict complications on multivariable analysis adjusted for age, BMI, comorbidities, clinical risk, surgical approach, operating time, lymphadenectomy, and number of nodes removed [OR 0.61, 95% CI 0.34-1.11, p = 0.10]; nor did it predict symptomatic fluid collection, adjusting for lymphadenectomy and nodes removed [OR 1.14, 95% CI 0.43-3.60, p = 0.8]. Drain deferral did not decrease opioid use (p = 0.5). Per protocol analysis and restriction to robot-assisted cases demonstrated similar results.

Conclusion: There was no difference in adverse events, complications, symptomatic collections, or opioid use with deferral of routine drain placement after RP. Experienced surgeons may safely defer drain placement in the majority of robot-assisted RP cases.
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http://dx.doi.org/10.1007/s00345-020-03439-xDOI Listing
September 2020

A novel method for detection of exfoliated prostate cancer cells in urine by RNA in situ hybridization.

Prostate Cancer Prostatic Dis 2020 Aug 20. Epub 2020 Aug 20.

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: In the current study, we explore the feasibility of detecting exfoliated prostate cancer cells in urine using an RNA in situ hybridization (RISH) assay. We hypothesized that robust and specific labeling of prostate cancer cells could be achieved in post-digital rectal examination (DRE) urine samples using RISH.

Methods: We focused on method development, optimization, and analytical evaluation of RISH-based detection of prostate cancer in urine. We optimized a sample collection, processing, and target detection workflow for urine cytology specimens in conjunction with RNA target detection by RISH. We screened a panel of 11 prostate-specific RNA targets, and selected NKX3-1 and PRAC1 as markers for cells of prostate origin and PCA3 as a marker of prostate malignancy. Following analytical validation of a multiplexed NKX3-1/PRAC1/PCA3 assay, we evaluated whether prostate cancer cells can be detected in a pilot cohort of 19 post-DRE specimens obtained from men diagnosed with prostate cancer.

Results: Using cytology specimens prepared from spiked urine samples, we established the analytical validity of the RISH assay for detection and visualization of prostate cells in urine. Cells of prostate origin could be readily and specifically identified and separated into benign and malignant cell populations based on the multiplex test that consisted of markers specific for prostate cells (NKX3-1, PRAC1) and prostate cancer cells (PCA3). Upon evaluation of post-DRE urine from a pilot cohort of prostate cancer patients, we identified 11 samples in which prostate cells were present, 6 of which were also positive for prostate cancer cells.

Conclusions: Multiplex RISH enables the direct visualization and molecular characterization of individual exfoliated prostate cells in urine. This proof-of-principle study provides evidence supporting the application of RISH as a potential noninvasive tool for prostate cancer detection.
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http://dx.doi.org/10.1038/s41391-020-00272-6DOI Listing
August 2020

A Comparative Analysis of Surgical Scar Cosmesis Based on Operative Approach for Radical Prostatectomy.

J Endourol 2021 Feb 15;35(2):138-143. Epub 2020 Sep 15.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Recent developments in minimally invasive approaches to radical prostatectomy (RP) for localized prostate cancer have improved oncological outcomes, but may also affect surgical scar cosmesis, an important component of survivorship and patient quality of life. Our aim was to evaluate surgical scar appearance based on operative approach to RP using a validated tool for evaluating psychosocial impact of scar appearance. Men between the ages of 45 and 80 were surveyed on an online crowdsourcing platform. Well-healed surgical scars after open, multiport (MP) robotic (transperitoneal and extraperitoneal), and single-port (SP) robotic RP were digitally rendered on stock photos to control for patient appearance. Respondents evaluated images using the SCAR-Q© psychosocial impact domain. Additionally, different RP scars were ranked by appearance and assigned 10-point appearance scores. Two hundred thirty-four surveys were included for analysis (completion rate 84.2%). The median age was 54 (IQR: 49-61) and 35% (85/234) had previous abdominal surgery, of which 45% (38/85) was robotic or laparoscopic. SP scars had better psychosocial impact scores (median 100 out of 100 69 and 58) than MP and open, respectively (both  < 0.001). SP scars were consistently ranked higher by appearance (median rank 1, IQR: 1-1) than MP (2, IQR: 2-3) and open (3, IQR: 3-4) ( < 0.001). SP without assistant port had the highest appearance score (median 9, IQR: 7-9) among all scars ( < 0.001). SP scars scored highest on psychosocial impact and were consistently ranked highest in appearance. These findings may be informative for optimizing both cosmetic appearance and quality of life for patients undergoing RP.
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http://dx.doi.org/10.1089/end.2020.0649DOI Listing
February 2021

Complications after open and robot-assisted radical prostatectomy and association with postoperative opioid use: an analysis of data from the PREVENTER trial.

BJU Int 2021 Feb 17;127(2):190-197. Epub 2020 Aug 17.

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objective: To evaluate perioperative complications for open radical prostatectomy (ORP) and robot-assisted RP (RARP) for patients enrolled in the PREvention of VENous ThromboEmbolism Following Radical Prostatectomy (PREVENTER; ClinicalTrials.gov Identifier: NCT03006562) trial, to determine predictors and impact on opioid consumption.

Patients And Methods: A prospective cohort of 500 patients undergoing ORP and RARP was followed to determine rates of complications and opioid use. Complications were classified 30 days after RP using the Clavien-Dindo system. Patient characteristics and outcomes were compared using appropriate statistical tests. Logistic and linear regressions were performed to identify predictors of complications and evaluate the relationship between complications and postoperative opioid use.

Results: A total of 124 (24.8%) men underwent ORP and 376 (75.2%) RARP, with 418 (83.6%) receiving pelvic lymph node dissection (PLND). While 83 patients (16.6%) had complications, only 19 (3.8%) were major (Clavien-Dindo Grade ≥III), with no differences by surgical approach. PLND (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.25-8.71; P = 0.03) and Stage pT3b (OR 2.76, 95% CI 1.23-6.00;P = 0.01) were the only predictors of complications after controlling for potential confounders. Patients who had complications had greater inpatient (P = 0.02) and outpatient (P = 0.005) opioid use, which persisted after controlling for patient-reported pain, attending surgeon variation, surgical approach, and undergoing PLND (inpatient β:77.2, 95% CI 17.9-136.5,P = 0.03; and outpatient β:21.9, 95% CI 4.7-39.1,P = 0.01).

Conclusion: In an analysis of prospectively collected data, overall and major complications rates did not differ by surgical approach. Patients receiving PLND and with Stage pT3b disease had more complications. Complications were independently associated with higher inpatient and outpatient postoperative opioid use.
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http://dx.doi.org/10.1111/bju.15172DOI Listing
February 2021

Effect of Pharmacologic Prophylaxis on Venous Thromboembolism After Radical Prostatectomy: The PREVENTER Randomized Clinical Trial.

Eur Urol 2020 09 19;78(3):360-368. Epub 2020 May 19.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Direct high-quality evidence is lacking evaluating perioperative pharmacologic prophylaxis (PP) after radical prostatectomy (RP) to prevent venous thromboembolism (VTE) leading to significant practice variation.

Objective: To study the impact of in-hospital PP on symptomatic VTE incidence and adverse events after RP at 30 d, with the secondary objective of evaluating overall VTE in a screening subcohort.

Design, Setting, And Participants: A prospective, phase 4, single-center, randomized trial of men with prostate cancer undergoing open or robotic-assisted laparoscopic RP was conducted (July 2017-November 2018).

Intervention: PP (subcutaneous heparin) plus routine care versus routine care alone. The screening subcohort was offered lower extremity duplex ultrasound at 30 d.

Outcomes Measurements And Statistical Analysis: The primary efficacy outcome was symptomatic VTE incidence (pulmonary embolism [PE] or deep venous thrombosis [DVT]). Primary safety outcomes included the incidence of symptomatic lymphocele, hematoma, or bleeding after surgery. Secondary outcomes were overall VTE, estimated blood loss, total surgical drain output, complications, and surveillance imaging bias. Fisher's exact test and modified Poisson regression were performed.

Results And Limitations: A total of 501 patients (75% robotic) were randomized and >99% (500/501) completed follow-up. At second interim analysis (N = 445), the symptomatic VTE rate was 2.3% (four PE + DVT and one DVT) for routine care versus 0.9% (one PE + DVT and one DVT) for PP (relative risk 0.40 [95% confidence interval 0.08-2.03], p = 0.3) meeting a futility threshold for early stopping. In the screening subcohort, the overall VTE rate was 3.3% versus 2.4% (p = 0.7). Results were similar at the final analysis (symptomatic VTE: 2.0% vs 0.8%, p = 0.3; overall VTE: 2.9% vs 2.8%, p = 1). No differences were observed in safety or secondary outcomes. All VTE events (seven symptomatic and three asymptomatic) occurred in patients undergoing pelvic lymph node dissection.

Conclusions: This study was not able to demonstrate a statistically significant reduction in symptomatic VTE associated with PP. There was no increase in the development of symptomatic lymphoceles, bleeding, or other adverse events. Given that the event rate was lower than powered for, further research is needed among high-risk patients (Caprini score ≥8) or patients receiving pelvic lymph node dissection.

Patient Summary: In this report, we randomized patients undergoing radical prostatectomy to perioperative pharmacologic prophylaxis or routine care alone. We found that pharmacologic prophylaxis did not reduce postoperative symptomatic venous thromboembolism significantly for men at routine risk. Importantly, pharmacologic prophylaxis did not increase adverse events, such as formation of lymphoceles or bleeding, and can safely be implemented when indicated for patients with risk factors undergoing radical prostatectomy.
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http://dx.doi.org/10.1016/j.eururo.2020.05.001DOI Listing
September 2020

Prostate Health Index and multiparametric magnetic resonance imaging to predict prostate cancer grade reclassification in active surveillance.

BJU Int 2020 09 2;126(3):373-378. Epub 2020 Jun 2.

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objective: To identify the value of combining the Prostate Health Index (PHI) and multiparametric magnetic resonance imaging (mpMRI), tools which have previously been shown to be independently predictive of prostate cancer (PCa) grade reclassification (GR; Gleason score >6), for the purpose of predicting GR at the next surveillance biopsy to reduce unnecessary prostate biopsies for men in PCa active surveillance (AS).

Patients And Methods: Between 2014 and 2019, we retrospectively identified 253 consecutive men in the Johns Hopkins AS programme who had mpMRI and PHI followed by a systematic ± targeted biopsy. PHI and PHI density (PHID) were evaluated across Prostate Imaging-Reporting and Data System version 2.0 (PI-RADSv2) scores and compared to those with and without GR. Next, the negative predictive value (NPV) and area under the receiver operating curve (AUC) were calculated to compare the diagnostic value of PI-RADSv2 score combined with PHI, PHID, or prostate-specific antigen density (PSAD) for GR using their respective first quartile as a cut-off.

Results: Of the 253 men, 38 men (15%) had GR. Men with GR had higher PHI values (40.7 vs 32.0, P = 0.001), PHID (0.83 vs 0.57, P = 0.007), and PSAD (0.12 vs 0.10, P = 0.037). A PI-RADSv2 ≤3 alone had a NPV of 91.6% for GR (AUC 0.67). Using a PHI cut-off of 25.6 in addition to PI-RADSv2 ≤3, the NPV and AUC were both increased to 98% and 0.70, respectively. Using a PSAD cut-off of 0.07 ng/mL/mL with PI-RADSv2 had an AUC of 0.69 and NPV of 95.4%. PHI and PI-RADSv2 together could have avoided 20% of biopsies at the cost of missing 2.6% of GRs.

Conclusions: The combination of PHI and mpMRI can aid in the prediction of GR in men on AS and may be useful for decreasing the burden of surveillance prostate biopsies.
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http://dx.doi.org/10.1111/bju.15101DOI Listing
September 2020

Cost-effectiveness Analysis of Tc-sestamibi SPECT/CT to Guide Management of Small Renal Masses.

Eur Urol Focus 2020 Feb 27. Epub 2020 Feb 27.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Background: Incidentally detected small renal masses (SRMs) may be one of several benign or malignant tumor histologies, and are heterogeneous in oncologic potential. Renal mass biopsy can be used to determine the histology of SRMs. However, this invasive approach has significant limitations. Technetium-99m sestamibi single photon emission computed tomography/computed tomography (Tc-sestamibi SPECT/CT) is a promising imaging tool that can aid in identifying benign renal oncocytomas and hybrid oncocytic/chromophobe tumors.

Objective: To evaluate the clinical and economic value of Tc-sestamibi SPECT/CT in guiding the management of SRMs.

Design, Setting, And Participants: We developed a decision analysis model to estimate the costs and health outcomes of competing management strategies for a healthy 65-yr-old patient with an asymptomatic SRM.

Intervention: Empiric surgery (reference); real-world clinical practice (RWCP) consisting of empiric surgery, thermal ablation, and active surveillance (alternative reference); renal mass biopsy (option 1); Tc-sestamibi SPECT/CT (option 2); and Tc-sestamibi SPECT/CT followed by biopsy to confirm benign SRMs (option 3).

Outcome Measurements And Statistical Analysis: We assessed lifetime health utilities, measured in quality-adjusted life years (QALYs), and direct medical costs from a health payer perspective. We calculated the incremental cost-effectiveness ratio (ICER) for options 1-3 versus the reference and alternative reference arms, with a willingness-to-pay threshold of $50 000/QALY. Univariate, multivariate, and probabilistic sensitivity analyses were performed.

Results And Limitations: Option 3 had a very low risk of untreated malignant tumors (0.2%, vs 2.1% for option 1, 4.2% for option 2, and 0% for empiric surgery) and the highest probability of leaving benign tumors untreated (84.4%, vs 53.9% for option 1, 51.7% for option 2, and 0% for empiric surgery). Option 3 dominated empiric surgery and options 1 and 2 (ie, lower costs and higher QALYs). Compared with RWCP, options 1-3 were all cost effective; option 3 had the lowest ICER of $18 821/QALY. These findings were robust to alternative input values. Study limitations included data uncertainties and a limited number of centers from which Tc-sestamibi SPECT/CT performance data were collected.

Conclusions: Tc-sestamibi SPECT/CT followed by confirmatory biopsy helps avoid surgery for benign SRMs, minimizes untreated malignant SRMs, and is cost effective compared with existing strategies.

Patient Summary: Our research suggests that by using a noninvasive imaging test, known as technetium-99m sestamibi single photon emission computed tomography/computed tomography, to diagnose small renal masses, urologists may avoid unnecessary surgery for benign tumors and minimize the risk of leaving a malignant tumor untreated. Moreover, the use of this strategy to diagnose small renal masses is cost effective for the health care system.
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http://dx.doi.org/10.1016/j.euf.2020.02.010DOI Listing
February 2020

Integrated RNA and metabolite profiling of urine liquid biopsies for prostate cancer biomarker discovery.

Sci Rep 2020 02 28;10(1):3716. Epub 2020 Feb 28.

Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, 600 6th Avenue South, St. Petersburg, FL, 33701, USA.

Sensitive and specific diagnostic and prognostic biomarkers for prostate cancer (PCa) are urgently needed. Urine samples are a non-invasive means to obtain abundant and readily accessible "liquid biopsies". Herein we used urine liquid biopsies to identify and characterize a novel group of urine-enriched RNAs and metabolites in patients with PCa and normal individuals with or without benign prostatic disease. Differentially expressed RNAs were identified in urine samples by deep sequencing and metabolites in urine were measured by mass spectrometry. mRNA and metabolite profiles were distinct in patients with benign and malignant disease. Integrated analysis of urinary gene expression and metabolite signatures unveiled an aberrant glutamate metabolism and tricarboxylic acid (TCA) cycle node in prostate cancer-derived cells. Functional validation supported a role for glutamate metabolism and glutamate oxaloacetate transaminase 1 (GOT1)-dependent redox balance in PCa, which could be exploited for novel biomarkers and therapies. In this study, we discovered cancer-specific changes in urinary RNAs and metabolites, paving the way for the development of sensitive and specific urinary PCa diagnostic biomarkers either alone or in combination. Our methodology was based on single void urine samples (i.e., without prostatic massage). The integrated analysis of metabolomic and transcriptomic data from these liquid biopsies revealed a glutamate metabolism and tricarboxylic acid cycle node that was specific to prostate-derived cancer cells and cancer-specific metabolic changes in urine.
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http://dx.doi.org/10.1038/s41598-020-60616-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048821PMC
February 2020

Downgrading of grade group 2 intermediate-risk prostate cancer from biopsy to radical prostatectomy: Comparison of outcomes and predictors to identify potential candidates for active surveillance.

Cancer 2020 04 7;126(8):1632-1639. Epub 2020 Feb 7.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Background: A proportion of men with grade group (GG) 2 intermediate risk (IR) prostate cancer are downgraded to GG1 or harbor favorable pathology (FP, defined as GG1 or GG2 with <5% Gleason pattern 4) at radical prostatectomy (RP). Prediction of downgrading or FP may help identify potential active surveillance candidates within this group that have outcomes similar to biopsy low-risk (LR) disease.

Methods: We performed a comparative cohort study of biopsy LR and IR men who underwent RP at The Johns Hopkins Hospital and Bayview Medical Center between 2005 and 2018. We evaluated pathological outcomes at RP and recurrence-free survival (RFS). Multivariable logistic regression and Cox proportional hazards regression were applied and individual predicted probabilities were calculated.

Results: Among 2943 biopsy GG2 IR patients, 223 (7.6%) were downgraded to GG1, while 525 (17.8%) had FP; 730 of 1325 biopsy LR patients (55.1%) were upgraded (GG >1). Concordance statistics for final predictive regression models were 0.76 for downgrading and 0.70 for upgrading. Biopsy GG2 IR patients downgrading to GG1 or harboring FP had similar RFS to biopsy LR patients. A cutoff of >10% predicted probability of downgrading (24.7% of patients; hazard ratio [HR], 1.55; 95% CI, 0.89-2.68) or >20% predicted probability of FP (37.0% of patients; HR, 1.35; 95% CI, 0.81-2.24) led to similar RFS to biopsy LR patients.

Conclusion: GG2 IR patients who experience downgrading or harbor FP had similar oncologic outcomes as LR patients. The developed models may serve as tools to inform patients about the risks of pathological downgrading/upgrading and help identify a segment of GG2 IR patients who would consider pursuing active surveillance based on predicted probability cutoffs.
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http://dx.doi.org/10.1002/cncr.32709DOI Listing
April 2020

Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma.

Cell 2019 10;179(4):964-983.e31

Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA. Electronic address:

To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology.
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http://dx.doi.org/10.1016/j.cell.2019.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331093PMC
October 2019

Effect of a prospective opioid reduction intervention on opioid prescribing and use after radical prostatectomy: results of the Opioid Reduction Intervention for Open, Laparoscopic, and Endoscopic Surgery (ORIOLES) Initiative.

BJU Int 2020 03 15;125(3):426-432. Epub 2019 Nov 15.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objectives: To evaluate the effect of a prospective opioid reduction intervention after radical prostatectomy (RP; based on a surgery-specific guideline and education) on post-discharge opioid prescribing, use, disposal, and need for additional opioid medication.

Patients And Methods: A prospective, non-randomised, pre-post interventional trial of patients undergoing RP for prostate cancer (August 2017-November 2018) was conducted as part of the Opioid Reduction Intervention for Open, Laparoscopic, and Endoscopic Surgery (ORIOLES) Initiative. An evidence-based intervention including: a discharge sheet, nursing education, and standardised prescribing guideline, was applied with the primary outcome of total oral morphine equivalents (OMEQ) used after RP. Secondary outcomes included opioid prescribing, opioid disposal, need for additional opioid medication, and presence of incisional/post-surgical abdominal pain at 30 days after RP.

Results: A total of 214 (Pre-Intervention arm) and 229 (Post-Intervention arm) adult patients were enrolled (100% follow-up). The intervention reduced post-discharge opioid prescribing (from 224.3 to 120.3 mg; -46.4%, P = 0.01), reduced opioid use (from 52.1 to 38.3 mg; -26.5%, P < 0.01), and increased opioid disposal (+13.5%, P < 0.01). Greater prescribing of opioids at discharge, higher body mass index, and use of opioid medication prior to surgery, were independently associated with greater post-discharge opioid use, while history of a chronic pain diagnosis was not statistically significant. In the Post-Intervention cohort, 2.2% of patients needed additional medication for post-surgical pain (0.9% obtained a prescription) and 1.3% initiated long-term use.

Conclusions: A prospective, evidence-based intervention reduced post-discharge opioid prescribing and use, while increasing disposal after RP. Risk factors for increased opioid use were identified. The results support expanding the use of evidence-based opioid reduction interventions to other surgical specialties.
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http://dx.doi.org/10.1111/bju.14932DOI Listing
March 2020

Is Pelvic Lymph Node Dissection Necessary During Cytoreductive Radical Prostatectomy?

Eur Urol Oncol 2019 09 9;2(5):549-550. Epub 2019 Aug 9.

Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

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http://dx.doi.org/10.1016/j.euo.2019.07.007DOI Listing
September 2019

Surgical removal of renal tumors with low metastatic potential based on clinical radiographic size: A systematic review of the literature.

Urol Oncol 2019 08 13;37(8):519-524. Epub 2019 Jun 13.

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD.

Introduction: Many patients with small renal masses (SRM) undergo surgical resection of benign and potentially indolent renal masses. We review the available literature to quantify the proportion of renal tumors that are low-risk based on clinical radiographic size, and quantify the number of low-risk masses surgically removed in the United States.

Methods: We systematically reviewed the literature for studies including pathologic findings after excision of renal masses. Inclusion criteria required studies capture both benign and malignant histology at surgical pathology, tumor grade, and stratification by radiographic tumor size. We queried our institutional database using the same parameters. Meta-analysis results were applied to SEER incidence and management data for renal masses. Very-low-risk tumors were defined as benign or grade 1 cT1a, and low-risk tumors as benign, grade 1, or grade 2 cT1a.

Results: A total of 733 titles were reviewed at title screening with 6 full text articles and our institutional database included for meta-analysis. Pooled estimates of benign, very-low-risk, and low-risk tumors were stratified by tumor size: ≤2 cm (25.5%, 40.1%, and 89.3%), 2 to 3 cm (21.2%, 34.1%, and 84.5%), 3 to 4 cm (16.1%, 26.6%, and 77.1%), 4 to 6 cm (11.9%, 23.8%, and 66.4%), and >6 cm (7.2%, 12.6%, and 50.3%). An estimated 3,300 benign, 5,400 very-low-risk, and 13,600 low-risk SRMs were resected in 2014 in the United States.

Conclusion: A substantial portion of patients with SRM are undergoing surgical excision despite harboring tumors of low metastatic potential. The rate of high-grade histology increased with increasing clinical radiographic size, which can be used in counseling and decision-making regarding placement on active surveillance. The number of low-risk SRM removed annually in the United States increased from 8,500 in 2000 to 13,600 in 2014 with stabilization in recent years.
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http://dx.doi.org/10.1016/j.urolonc.2019.05.013DOI Listing
August 2019

Re: Active Surveillance Magnetic Resonance Imaging Study (ASIST): Results of a Randomized Multicenter Prospective Trial.

Eur Urol 2019 05 28;75(5):876. Epub 2019 Feb 28.

James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2019.02.024DOI Listing
May 2019

Approaches to urinary detection of prostate cancer.

Prostate Cancer Prostatic Dis 2019 09 17;22(3):362-381. Epub 2019 Jan 17.

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Prostate cancer is the most common cancer in American men that ranges from low risk states amenable to active surveillance to high-risk states that can be lethal especially if untreated. There is a critical need to develop relatively non-invasive and clinically useful methods for screening, detection, prognosis, disease monitoring, and prediction of treatment efficacy. In this review, we focus on important advances as well as future efforts needed to drive clinical innovation in this area of urine biomarker research for prostate cancer detection and prognostication.

Methods: We provide a review of current literature on urinary biomarkers for prostate cancer. We evaluate the strengths and limitations of a variety of approaches that vary in sampling strategies and targets measured; discuss reported urine tests for prostate cancer with respect to their technical, analytical, and clinical parameters; and provide our perspectives on critical considerations in approaches to developing a urine-based test for prostate cancer.

Results: There has been an extensive history of exploring urine as a source of biomarkers for prostate cancer that has resulted in a variety of urine tests that are in current clinical use. Importantly, at least three tests have demonstrated high sensitivity (~90%) and negative predictive value (~95%) for clinically significant tumors; however, there has not been widespread adoption of these tests.

Conclusions: Conceptual and methodological advances in the field will help to drive the development of novel urinary tests that in turn may lead to a shift in the clinical paradigm for prostate cancer diagnosis and management.
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http://dx.doi.org/10.1038/s41391-019-0127-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640078PMC
September 2019

Clinical, Pathological and Oncologic Findings of Radical Prostatectomy with Extraprostatic Extension Diagnosed on Preoperative Prostate Biopsy.

J Urol 2019 05;201(5):937-942

Brady Urological Institute, The Johns Hopkins University School of Medicine , Baltimore , Maryland.

Purpose: Prostatic adenocarcinoma with extraprostatic extension detected on prostate needle biopsy is an uncommon finding. We describe clinical and pathological findings in a large cohort of patients with prostatic adenocarcinoma who were treated with radical prostatectomy and in whom extraprostatic extension was identified on prostate needle biopsy.

Materials And Methods: Using our institutional pathology database we identified 83 patients with prostatic adenocarcinoma and with extraprostatic extension on prostate needle biopsy between 2000 to 2018 who underwent radical prostatectomy and had clinical followup information. Clinical and pathological outcomes were examined.

Results: Of the 83 patients 54 (65%) presented with clinical stage T2 or greater disease. On biopsy 50 of the 83 patients (60%) had Grade Group 4-5 and 66 (81%) had perineural invasion. Extraprostatic extension was confirmed in the radical prostatectomy specimen in 81 of 83 cases (98%). At radical prostatectomy 49 of 83 patients (59%) had positive surgical margins, 37 (45%) had seminal vesicle invasion and 30 (37%) had lymph node involvement. Median followup after radical prostatectomy was 2 years. Overall 34 of 76 men (45%) received postoperative radiation a median of 1 year after radical prostatectomy and 8 (11%) received chemotherapy a median of 2 years after radical prostatectomy. The 3-year biochemical recurrence-free survival rate was 48.4% (95% CI 0.345-0.610) and the 3-year metastasis-free survival rate was 75.2% (95% CI 0.603-0.851).

Conclusions: Patients in whom extraprostatic extension is detected on prostate needle biopsy almost always have extraprostatic disease and markedly adverse pathology findings at radical prostatectomy. Many of them experience biochemical recurrence and most will require multimodal therapy. These data can be useful to counsel such patients in regard to the treatment approach and the expected outcomes after surgery.
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http://dx.doi.org/10.1016/j.juro.2018.10.023DOI Listing
May 2019

A Randomized, Double-blind, Phase II Trial of PSA-TRICOM (PROSTVAC) in Patients with Localized Prostate Cancer: The Immunotherapy to Prevent Progression on Active Surveillance Study.

Eur Urol Focus 2018 09 7;4(5):636-638. Epub 2018 Sep 7.

University of Arizona Cancer Center, Tucson, AZ, USA.

The Immunotherapy to Prevent Progression on Active Surveillance Study is the first trial of immunotherapy for localized prostate cancer. We randomized active surveillance patients to PSA-TRICOM (PROSTVAC) or placebo for 5mo. Final results will be available in 2019.
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http://dx.doi.org/10.1016/j.euf.2018.08.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524340PMC
September 2018

Older Age Predicts Biopsy and Radical Prostatectomy Grade Reclassification to Aggressive Prostate Cancer in Men on Active Surveillance.

J Urol 2019 01;201(1):98-104

Purpose: Age at prostate cancer diagnosis has been positively associated with prostate cancer specific mortality and in men on active surveillance with a higher risk of biopsy grade reclassification to Gleason score 3 + 4 or greater (Grade Group 2 or greater). However, to our knowledge the association between age and biopsy grade reclassification to an aggressive phenotype (Gleason score 4 + 3 or greater [Grade Group 3 or greater]) has not been explored.

Materials And Methods: From 1995 to 2016 we followed 1,625 men 41 to 81 years old with NCCN® (National Comprehensive Cancer Network®) very low (68%) or low (32%) risk prostate cancer on active surveillance. We determined the rate of biopsy grade reclassification to Grade Group 3 or greater. Competing risk analysis was applied to evaluate the association between age at enrollment and the risk of biopsy grade reclassification. Additionally, in men who underwent radical prostatectomy after biopsy grade reclassification we assessed the rate of radical prostatectomy grade reclassification (ie radical prostatectomy Grade Group greater than biopsy Grade Group).

Results: The 5-year incidence of biopsy grade reclassification to Grade Group 3 or greater was 4%, 7% and 14% in men younger than 60, 60 to 69 and 70 years old or older, respectively (p <0.001). On univariate analysis older age was associated with biopsy grade reclassification to Grade Group 3 or greater (per 10-year increase HR 2.43, p <0.001). On multivariable analysis adjusting for year of diagnosis, race, prostate specific antigen density and cancer volume at diagnosis older age remained associated with biopsy grade reclassification to Grade Group 3 or greater (per 10-year increase HR 2.19, p <0.001). In men who underwent radical prostatectomy after biopsy grade reclassification those who were older had a higher rate of radical prostatectomy grade reclassification (p <0.05).

Conclusions: In men on active surveillance older age at diagnosis was positively associated with biopsy grade reclassification to Grade Group 3 or greater and radical prostatectomy grade reclassification. These observations imply that for many older men, active surveillance as opposed to watchful waiting remains a more appropriate management strategy.
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http://dx.doi.org/10.1016/j.juro.2018.08.023DOI Listing
January 2019

Easy, reproducible extraperitoneal pelvic access for robot - assisted radical prostatectomy.

Int Braz J Urol 2019 Jan-Feb;45(1):189

Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.

Robot - assisted radical prostatectomy is commonly performed transperitoneally (tRARP), although the extraperitoneal (eRARP) approach is a safe and effective alternative that may be preferred in certain situations. We developed a novel method of direct access into the space of Retzius with a visual obturator port (VisiportTM) for laparoscopic or robotic prostatectomy. We present an instructional video of extraperitoneal pelvic access for eRARP with both internal and external camera views. The patient is first placed in lithotomy and 15° Trendelenburg position. The camera is inserted infraumbilically and angled caudally. The pre-peritoneal space is accessed through the anterior rectus fascia using a VisiportTM (Covidien, $ 60 www.esutures.com), and the working space is developed with a kidney - shaped balloon OMSPDBS2TM (Covidien, $ 49 www.esutures.com). After the space is insufflated, subsequent trocars are angled in extraperitoneally under direct vision. The average time from incision to final port placement after a learning curve of about 50 cases is 8 minutes (IQR 7-10). We have performed over 1.000 cases using this technique and eRARP has become our procedure of choice. Our last 500 + cases were performed robotically. Approximately 10% of the time peritoneotomies were noted, but rarely did these require conversion to tRARP. There have been no bowel or other abdominal organ injuries, major vascular or other complications in any of these cases.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2018.0175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442130PMC
June 2019

Challenges and opportunities in the proteomic characterization of clear cell renal cell carcinoma (ccRCC): A critical step towards the personalized care of renal cancers.

Semin Cancer Biol 2019 04 25;55:8-15. Epub 2018 Jul 25.

Department of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, United States.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, comprising approximately 75% of all kidney tumors. Recent the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) studies have significantly advanced the molecular characterization of RCC and facilitated the development of targeted therapies. Such advances have improved the median survival of patients with advanced disease from less than 10 months prior to 2004 to 30 months by 2011. However, approximately 30% of localized ccRCC patients will nevertheless develop recurrence or metastasis after surgical resection of their tumor. Therefore, it is critical to further analyze potential tumor-associated proteins and their profiles during disease progression. Over the past decade, tremendous effort has been focused on the study of molecular pathways, including genomics, transcriptomics, and proteomics in order to identify potential molecular biomarkers, as well as to facilitate early detection, monitor tumor progression and uncover potentially therapeutic targets. In this review, we focus on recent advances in the proteomic analysis of ccRCC, current strategies and challenges, and perspectives in the field. This insight will highlight the discovery of tumor-associated proteins, and their potential clinical impact on personalized precision-based care in ccRCC.
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http://dx.doi.org/10.1016/j.semcancer.2018.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624650PMC
April 2019

Editorial Comment.

J Urol 2018 08 27;200(2):281. Epub 2018 Apr 27.

James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1016/j.juro.2018.02.3113DOI Listing
August 2018

Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017.

J Clin Oncol 2018 02 13;36(4):414-424. Epub 2017 Dec 13.

Veda N. Giri, Karen E. Knudsen, William K. Kelly, Robert B. Den, Adam P. Dicker, Jean Hoffman-Censits, Mark D. Hurwitz, Colette Hyatt, Grace Lu-Yao, Mark J. Mann, James R. Mark, Peter A. McCue, Ronald E. Myers, Stephen C. Peiper, Edouard J. Trabulsi, and Leonard G. Gomella, Jefferson Sidney Kimmel Cancer Center; Justin E. Bekelman, University of Pennsylvania Perelman School of Medicine; S. Bruce Malkowicz, University of Pennsylvania; Elias Obeid and Robert Uzzo, Fox Chase Cancer Center; Gordon F. Schwartz, Foundation for Breast and Prostate Health, Philadelphia; Mark S. Shahin, Hanjani Institute for Gynecologic Oncology, Abington Hospital-Jefferson Health, Abington, PA; Wassim Abida, Philip Kantoff, and Mark E. Robson, Memorial Sloan Kettering Cancer Center; Mitchell C. Benson, Columbia University, New York, NY; Gerald L. Andriole, Washington University School of Medicine, St Louis, MO; Chris H. Bangma, Erasmus Medical Center, Rotterdam, the Netherlands; Amie Blanco, and Matthew Cooperberg, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco; Christopher J. Kane, University of California San Diego, San Diego; Howard Sandler, Cedars-Sinai Medical Center, Los Angeles; Howard R. Soule, Prostate Cancer Foundation, Santa Monica, CA; Arthur Burnett, William B. Isaacs, Christian P. Pavlovich, and Patrick C. Walsh, Johns Hopkins Medical Institutions, Baltimore; Peter A. Pinto and Carol J. Weil, National Cancer Institute, Bethesda, MD; William J. Catalona and Edward Schaeffer, Northwestern University Feinberg School of Medicine; Scott Eggener, Sarah M. Nielsen, and Donald J. Vander Griend, University of Chicago, Chicago, IL; Kathleen A. Cooney, University of Utah School of Medicine, Salt Lake City, UT; David E. Crawford, University of Colorado, Aurora; Lawrence I. Karsh, The Urology Center of Colorado, Denver; Wendy Poage, Prostate Conditions Education Council, Elizabeth, CO; Neil Fleshner, University of Toronto Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Matthew L. Freedman, Kevin R. Loughlin, and Timothy R. Rebbeck, Dana Farber Cancer Institute, and Harvard TH Chan School of Public Health, Boston, MA; Freddie C. Hamdy, University of Oxford, Oxford, England; R. Jeffrey Karnes, Mayo Clinic, Rochester, MN; Eric A. Klein, Cleveland Clinic, Cleveland; Robert Pilarski, The Ohio State University, Columbus, OH; Daniel W. Lin, University of Washington, Seattle, WA; Martin M. Miner, Brown University, Providence, RI; Todd Morgan and Scott A. Tomlins, University of Michigan, Ann Arbor; Matt T. Rosenberg, Mid-Michigan Health Center, Jackson, MI; Judd W. Moul, Duke University, Duke Cancer Institute, Durham, NC; David F. Penson, Vanderbilt University Medical Center, Nashville, TN; Daniel Petrylak and Brian Shuch, Yale University, New Haven, CT; Curtis A. Pettaway, The University of Texas MD Anderson Cancer Center, Houston; Ganesh V. Raj, University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Oliver Sartor, Tulane University Medical School, New Orleans, LA; Neal D. Shore, Atlantic Urology Clinics/Carolina Urologic Research Center, Myrtle Beach, SC; and Richard Wender, American Cancer Society, Atlanta, GA.

Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease.
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http://dx.doi.org/10.1200/JCO.2017.74.1173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075860PMC
February 2018