Urology Commons^™

Regulation Of Androgen Receptor Stability By The Β1pix/Stub1 Complex, Ahmed Chahdi, Carolina Jorgez, Abhishek Seth

Faculty, Staff and Students Publications

The Androgen Receptor (AR) is essential in the development and differentiation of testes and male genitalia. AR expression is tightly regulated at the translational and posttranslational levels. AR posttranscriptional regulation is a major determinant of AR availability since AR is a direct target of E3 ubiquitin ligase STUB1. Our work indicated that the Rac/Cdc42 guanosine triphosphatase guanine nucleotide exchange factor, β1Pix, enhanced AR levels after AR stimulation in HEK293 and HeLa cells. AR stimulation decreased AR ubiquitination which is accompanied by increased β1Pix binding to AR. Ectopic expression of β1Pix decreased AR ubiquitination in Tm4 and HEK293 cells. We demonstrated …

High Expression Of Trop2 Is Associated With Aggressive Localized Prostate Cancer And Is A Candidate Urinary Biomarker, Shiqin Liu, Sarah J Hawley, Christian A Kunder, En-Chi Hsu, Michelle Shen, Lennart Westphalen, Heidi Auman, Lisa F Newcomb, Daniel W Lin, Peter S Nelson, Ziding Feng, Maria S Tretiakova, Lawrence D True, Funda Vakar-Lopez, Peter R Carroll, Jeffry Simko, Martin E Gleave, Dean A Troyer, Jesse K Mckenney, James D Brooks, Michael A Liss, Tanya Stoyanova

Faculty, Staff and Student Publications

Distinguishing indolent from clinically significant localized prostate cancer is a major clinical challenge and influences clinical decision-making between treatment and active surveillance. The development of novel predictive biomarkers will help with risk stratification, and clinical decision-making, leading to a decrease in over or under-treatment of patients with prostate cancer. Here, we report that Trop2 is a prognostic tissue biomarker for clinically significant prostate cancer by utilizing the Canary Prostate Cancer Tissue Microarray (CPCTA) cohort composed of over 1100 patients from a multi-institutional study. We demonstrate that elevated Trop2 expression is correlated with worse clinical features including Gleason score, age, and …

Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance And Immune Evasion In Lethal Prostate Cancer, Sandra Santasusagna, Shijia Zhu, Vijayakumar Jawalagatti, Marc Carceles-Cordon, Adam Ertel, Saioa Garcia-Longarte, Won-Min Song, Naoto Fujiwara, Peiyao Li, Isabel Mendizabal, Daniel P. Petrylak, William Kevin Kelly, E. Premkumar Reddy, Liguo Wang, Matthew J. Schiewer, Amaia Lujambio, Jeffrey Karnes, Karen E. Knudsen, Carlos Cordon-Cardo, Haidong Dong, Haojie Huang, Arkaitz Carracedo, Yujin Hoshida, Veronica Rodriguez-Bravo, Josep Domingo-Domenech

Department of Medical Oncology Faculty Papers

Signaling rewiring allows tumors to survive therapy. Here we show that the decrease of the master regulator microphthalmia transcription factor (MITF) in lethal prostate cancer unleashes eukaryotic initiation factor 3B (eIF3B)-dependent translation reprogramming of key mRNAs conferring resistance to androgen deprivation therapy (ADT) and promoting immune evasion. Mechanistically, MITF represses through direct promoter binding eIF3B, which in turn regulates the translation of specific mRNAs. Genome-wide eIF3B enhanced cross-linking immunoprecipitation sequencing (eCLIP-seq) showed specialized binding to a UC-rich motif present in subsets of 5' untranslated regions. Indeed, translation of the androgen receptor and major histocompatibility complex I (MHC-I) through this motif …

Targeting The Αvβ3/Ngr2 Pathway In Neuroendocrine Prostate Cancer, Anna Testa, Fabio Quaglia, Nicole M. Naranjo, Cecilia E. Verrillo, Christopher D. Shields, Stephen Lin, Maxwell W. Pickles, Drini F. Hamza, Tami Von Schalscha, David A. Cheresh, Benjamin E Leiby, Qin Liu, Jianyi Ding, William K. Kelly, D. Craig Hooper, Eva Corey, Edward F. Plow, Dario C. Altieri, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVβ3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically targets the human αVβ3 integrin, hinders the growth of neuroendocrine prostate cancer patient-derived xenografts in vivo. Our group has recently identified a novel αVβ3 integrin binding partner, NgR2, responsible for regulating the expression of neuroendocrine markers and for inducing neuroendocrine differentiation in prostate cancer cells. Through in …

Sigma1 Regulates Lipid Droplet-Mediated Redox Homeostasis Required For Prostate Cancer Proliferation, Halley Oyer, Alexandra Steck, Charles Longen, Sanjana Venkat, Konuralp Bayrak, Eleanor Munger, Dan Fu, Paola Castagnino, Christina Sanders, Nathalia Tancler, My Mai, Justin Myers, Matthew Schiewer, Nan Chen, Elahe Mostaghel, Felix Kim

Department of Urology Faculty Papers

UNLABELLED: Lipid droplets (LD) are dynamic organelles that serve as hubs of cellular metabolic processes. Emerging evidence shows that LDs also play a critical role in maintaining redox homeostasis and can mitigate lipid oxidative stress. In multiple cancers, including prostate cancer, LD accumulation is associated with cancer aggressiveness, therapy resistance, and poor clinical outcome. Prostate cancer arises as an androgen receptor (AR)-driven disease. Among its myriad roles, AR mediates the biosynthesis of LDs, induces autophagy, and modulates cellular oxidative stress in a tightly regulated cycle that promotes cell proliferation. The factors regulating the interplay of these metabolic processes downstream of …

Xaluritamig, A Steap1 × Cd3 Xmab 2+1 Immune Therapy For Metastatic Castration-Resistant Prostate Cancer: Results From Dose Exploration In A First-In-Human Study, William K. Kelly, Daniel C. Danila, Chia-Chi Lin, Jae-Lyun Lee, Nobuaki Matsubara, Patrick J. Ward, Andrew J. Armstrong, David Pook, Miso Kim, Tanya B. Dorff, Stefanie Fischer, Yung-Chang Lin, Lisa G. Horvath, Christopher Sumey, Zhao Yang, Gabor Jurida, Kristen M. Smith, Jamie N. Connarn, Hweixian L. Penny, Julia Stieglmaier, Leonard J. Appleman

Kimmel Cancer Center Faculty Papers

ABSTRACT : Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.001 to 2.0 mg weekly or every 2 weeks. MTD was identified as 1.5 mg i.v. weekly via a 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred primarily during …

Long-Term Risks Of Depression And Suicide Among Men With Prostate Cancer: A National Cohort Study, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Anna Bill-Axelson, Alexis C Edwards, Kristina Sundquist, Weiva Sieh

Faculty, Staff and Student Publications

BACKGROUND: A diagnosis of prostate cancer (PC) may cause psychosocial distress that worsens quality of life; however, long-term mental health outcomes are unclear.

OBJECTIVE: To determine the long-term risks of major depression and death by suicide in a large population-based cohort.

DESIGN, SETTING, AND PARTICIPANTS: This was a national cohort study of 180 189 men diagnosed with PC during 1998-2017 and 1 801 890 age-matched, population-based, control men in Sweden.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Major depression and death by suicide were ascertained from nationwide outpatient, inpatient, and death records up to 2018. Cox regression was used to compute hazard …

Implantable Penile Prosthesis For Erectile Dysfunction: Insurance Coverage In The United States, Mohit Khera, Joshua P Langston, Matthew E Pollard, Denise Asafu-Adjei, Natalie C Edwards, Krista D Nitschelm, Mital Patel, Samir K Bhattacharyya

Faculty, Staff and Students Publications

Introduction: A manufacturer's benefit verification database was evaluated to ascertain United States health plan insurance coverage for implantable penile prostheses for erectile dysfunction.

Methods: All-payer and employer-sponsored health plan benefit verification databases were queried to determine implantable penile prosthesis approval status. For the all-payer analysis, data by payer were available and presented for 2019-2021 to assess approval status varied by payer and over time. For the employer-sponsored health plan analysis, data by payer were available from 2018-2021.

Results: Benefit verification records for the all-payer database were available for 3,167 patients in 2019, 3,016 in 2020, and 2,837 in 2021. Insurance …

Urachal Xanthogranuloma: A Rare But Important Case Presenting As A Urachal Mass, Kunal Jain, Esha Jain, Richard Dilena, Rola Saleeb, Umesh Jain

Faculty, Staff and Student Publications

BACKGROUND: A urachal mass is a relatively rare presentation to the urologists' practice, often requiring radical surgical excision for a definitive diagnosis. Xanthogranulomatous inflammation of the urachus is an extremely rare entity with few cases reported worldwide, and to the best of our knowledge, no cases reported in the western world.

CASE PRESENTATION: In this case, a 55-year-old male patient presented with bothersome lower urinary tract symptoms and computed tomography findings demonstrating a urachal mass that was worrisome for urachal carcinoma. Following surgical intervention, histopathology revealed urachal xanthogranuloma. Post-operatively, the patient recovered well, and eventually, he had symptomatic and radiologic …

Should A Negative Microsurgical Testicular Sperm Extraction Be Repeated Routinely?, Raevti Bole, Scott D Lundy, Sarah Vij, Larry I Lipshultz, John P Lindsey, Juan R Torres-Anguiano, Michael L Eisenberg

Faculty, Staff and Students Publications

No abstract provided.

Evidence Of Novel Susceptibility Variants For Prostate Cancer And A Multiancestry Polygenic Risk Score Associated With Aggressive Disease In Men Of African Ancestry, Fei Chen, Ravi K Madduri, Alex A Rodriguez, Burcu F Darst, Alisha Chou, Xin Sheng, Anqi Wang, Jiayi Shen, Edward J Saunders, Suhn K Rhie, Jeannette T Bensen, Sue A Ingles, Rick A Kittles, Sara S Strom, Benjamin A Rybicki, Barbara Nemesure, William B Isaacs, Janet L Stanford, Wei Zheng, Maureen Sanderson, Esther M John, Jong Y Park, Jianfeng Xu, Ying Wang, Sonja I Berndt, Chad D Huff, Edward D Yeboah, Yao Tettey, Joseph Lachance, Wei Tang, Christopher T Rentsch, Kelly Cho, Benjamin H Mcmahon, Richard B Biritwum, Andrew A Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Thomas A Sellers, Kosj Yamoah, Adam B Murphy, Dana C Crawford, Alpa V Patel, William S Bush, Melinda C Aldrich, Olivier Cussenot, Gyorgy Petrovics, Jennifer Cullen, Christine M Neslund-Dudas, Mariana C Stern, Zsofia Kote-Jarai, Koveela Govindasami, Michael B Cook, Anand P Chokkalingam, Ann W Hsing, Phyllis J Goodman, Thomas J Hoffmann, Bettina F Drake, Jennifer J Hu, Jacob M Keaton, Jacklyn N Hellwege, Peter E Clark, Mohamed Jalloh, Serigne M Gueye, Lamine Niang, Olufemi Ogunbiyi, Michael O Idowu, Olufemi Popoola, Akindele O Adebiyi, Oseremen I Aisuodionoe-Shadrach, Hafees O Ajibola, Mustapha A Jamda, Olabode P Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa-Abrahams, James E Mensah, Halimatou Diop, Stephen K Van Den Eeden, Pascal Blanchet, Jay H Fowke, Graham Casey, Anselm J Hennis, Alexander Lubwama, Ian M Thompson, Robin Leach, Douglas F Easton, Michael H Preuss, Ruth J Loos, Susan M Gundell, Peggy Wan, James L Mohler, Elizabeth T Fontham, Gary J Smith, Jack A Taylor, Shiv Srivastava, Rosaline A Eeles, John D Carpten, Adam S Kibel, Luc Multigner, Marie-Élise Parent, Florence Menegaux, Geraldine Cancel-Tassin, Eric A Klein, Caroline Andrews, Timothy R Rebbeck, Laurent Brureau, Stefan Ambs, Todd L Edwards, Stephen Watya, Stephen J Chanock, John S Witte, William J Blot, J Michael Gaziano, Amy C Justice, David V Conti, Christopher A Haiman

Faculty, Staff and Student Publications

BACKGROUND: Genetic factors play an important role in prostate cancer (PCa) susceptibility.

OBJECTIVE: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.

DESIGN, SETTING, AND PARTICIPANTS: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness.

RESULTS AND LIMITATIONS: Nine …

Impact Of An Expanded Definition Of Family History On Outcomes Of Active Surveillance For Prostate Cancer, Adam C. Schneider, Thenappan Chandrasekar, Nicholas Bowler, Ryan Fogg, Joon Yau Leong, Andrew Gusev, Linda H. Rodgers, Shelley R. Mccormick, Douglas M. Dahl, Jason A. Efstathiou, Michael L. Blute, Anthony L. Zietman, Chin-Lee Wu, Matthew R. Smith, Eliezer M. Van Allen, Adam S. Feldman, Keyan Salari

Department of Urology Faculty Papers

PURPOSE: Despite family history being an established risk factor for prostate cancer, the role of a broader definition of family history inclusive of not just prostate cancer but other genetically related malignancies has not been investigated in the active surveillance population. Here, we evaluate the impact of an expanded definition of family history on active surveillance outcomes.

MATERIALS AND METHODS: Patients undergoing active surveillance for prostate cancer at Massachusetts General Hospital from 1997-2019 with detailed data available on family cancer history were identified. Primary outcome was biopsy progression-free survival, and secondary outcomes were treatment-free survival, adverse pathological features at prostatectomy, …

Patient With Genital Lymphedema, Pain, And Rash, Resa G Magill, Dylan Supak, Rachel Pham, Dustin Luse, Cooper R Benson

Faculty, Staff and Student Publications

No abstract provided.

Comprehensive Proteomics And Platform Validation Of Urinary Biomarkers For Bladder Cancer Diagnosis And Staging, Kamala Vanarsa, Jessica Castillo, Long Wang, Kyung Hyun Lee, Claudia Pedroza, Yair Lotan, Chandra Mohan

Faculty, Staff and Student Publications

BACKGROUND: Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease.

METHODS: An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity.

RESULTS: Systems biology analysis implicated molecular functions related to the …

Two Specialists, Two Recommendations: Discordance Between Urologists' & Radiation Oncologists' Prostate Cancer Treatment Recommendations, Rebecca K Delaney, Brittany L Sisco-Taylor, Xuechen Wang, Karen Scherr, Peter A Ubel, Benjamin Haaland, Valerie C Kahn, Daniel Hamstra, John T Wei, Farrah Madanay, J Kelly Davis, Taylor U Greeno, Angela Fagerlin

Center for Medical Ethics and Health Policy Staff Publications

Objective: To examine the treatment recommendation patterns among urologists and radiation oncologists, the level of concordance or discordance between physician recommendations, and the association between physician recommendations and the treatment that patients received.

Method: The study was a secondary analysis of data from a randomized clinical trial conducted November 2010 to April 2014 (NCT02053389). Eligible participants were patients from the trial who saw both specialists. The primary outcome was physician recommendations that were scored using an adapted version of the validated PhyReCS coding system. Secondary outcomes included concordance between physician recommendations and the treatment patients received.

Results: Participants …

Spontaneous Extraperitoneal Hematoma: An Unexpected Case Of Dysuria And Urinary Retention In A 77-Year-Old Male, Monica Diep, James Lee, James Espinosa, Joseph Pagano, Alan Lucerna

Rowan-Virtua Research Day

Urinary problems are common complaints in the Emergency Department and can present with any combination of lower urinary tract symptoms such as dysuria, hematuria, urgency, frequency, incontinence, or retention. We describe the case of a 77-year-old male who presented to the Emergency Department for five days of worsening dysuria. Two days prior, the patient was seen and evaluated for the same chief complaint, where he received intravenous antibiotics and was admitted to the hospital overnight for observation. The following day, the patient’s urinalysis and cultures were not consistent with a urinary tract infection (UTI) and was subsequently discharged without antibiotics. …

The Impact Of Racial Disparities And Outcomes On Urinary Anastomotic Leak In Radical Prostatectomy, Young Son, Benjamin A. Fink, Lance Earnshaw, Brian Thomas, Fred Okoye, Ryan Moriarty, Kathryn Goettle, Thomas Mueller

Rowan-Virtua Research Day

Prostate cancer is the leading malignancy and third most common cause of cancer death among men. In the United States, racial disparities exist in prostate cancer incidence and mortality rates. According to the National Cancer Institute, African American (AA) men have a significantly increased incidence of prostate cancer compared to Caucasians or Asians. Urinary leak at the urethrovesical anastomosis has been cited as a complication of radical prostatectomy (RP), with incidence rates as high as 23%. Urinary anastomotic leak is associated with increased rates of ileus, prolonged hospitalization rates, and longer time to achieve continence. The etiology of risk factors …

Breakthroughs In Hormonal Male Contraception, Alexander Patton, Seth Vann

Physician Assistant Capstones, 2020-current

Objective: Assess the efficacy of a nestorone plus testosterone gel at suppressing progestin levels and spermatogenesis.

Design: Systematic literature review.

Methods: Searches were done in PubMed and Dartmouth library using the terms nestorone, randomized control trial, human, and male. Limits used while searching included published in the last 10 years, randomized control trials, and English.

Results: Using the search criteria the following three studies were found that met the inclusion/exclusion criteria of this study: Ilani et al, Zitzmann et al, and Anawalt et al. All three studies were found on PubMed and reference the Ilani et al study.

Conclusion: Nestorone …

Downregulation Of Cenpf Remodels Prostate Cancer Cells And Alters Cellular Metabolism., Muhammad Shahid, Minhyung Kim, Min Young Lee, Austin Yeon, Sungyong You, Hyung L Kim, Jayoung Kim

Articles, Abstracts, and Reports

Metabolic alterations in prostate cancer (PC) are associated with progression and aggressiveness. However, the underlying mechanisms behind PC metabolic functions are unknown. The authors' group recently reported on the important role of centromere protein F (CENPF), a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis, in PC MRI visibility. This study focuses on discerning the role of CENPF in metabolic perturbation in human PC3 cells. A series of bioinformatics analyses shows that CENPF is one gene that is strongly associated with aggressive PC and that its expression is positively correlated with metastasis. By identifying and reconstructing the …

Altered Detrusor Contractility And Voiding Patterns In Mice Lacking The Mechanosensitive Trek-1 Channel., Ricardo H. Pineda, Joseph Hypolite, Sanghee Lee, Alonso Carrasco, Nao Iguchi, Randall B. Meacham, Anna P. Malykhina

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Previously published results from our laboratory identified a mechano-gated two-pore domain potassium channel, TREK-1, as a main mechanosensor in the smooth muscle of the human urinary bladder. One of the limitations of in vitro experiments on isolated human detrusor included inability to evaluate in vivo effects of TREK-1 on voiding function, as the channel is also expressed in the nervous system, and may modulate micturition via neural pathways. Therefore, in the present study, we aimed to assess the role of TREK-1 channel in bladder function and voiding patterns in vivo by using TREK-1 knockout (KO) mice.

METHODS: Adult C57BL/6 …

A Clinician's Guide To Next Generation Imaging In Patients With Advanced Prostate Cancer (Radar Iii)., E. David Crawford, Phillip J. Koo, Neal Shore, Susan F. Slovin, Raoul S. Concepcion, Stephen J. Freedland, Leonard G. Gomella, Lawrence Karsh, Thomas E. Keane, Paul Maroni, David Penson, Daniel P. Petrylak, Ashley Ross, Vlad Mouraviev, Robert E. Reiter, Chaitanya Divgi, Evan Y. Yu

Department of Urology Faculty Papers

PURPOSE: The advanced prostate cancer therapeutic landscape has changed dramatically in the last several years, resulting in improved overall survival of patients with castration naïve and castration resistant disease. The evolution and development of novel next generation imaging techniques will affect diagnostic and therapeutic decision making. Clinicians must navigate when and which next generation imaging techniques to use and how to adjust treatment strategies based on the results, often in the absence of correlative therapeutic data. Therefore, guidance is needed based on best available information and current clinical experience.

MATERIALS AND METHODS: The RADAR (Radiographic Assessments for Detection of Advanced …

Profiling Prostate Cancer Therapeutic Resistance, Cameron A. Wade, Natasha Kyprianou

Urology Faculty Publications

The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival and invasion via resistance to anoikis. In particular, the process of epithelial-mesenchymal-transition (EMT), directed by transforming growth factor-β (TGF-β), confers stem cell properties and acquisition of a migratory and invasive phenotype via resistance to anoikis. Our …

First Report Of Nrg Oncology/Radiation Therapy Oncology Group 0622: A Phase 2 Trial Of Samarium-153 Followed By Salvage Prostatic Fossa Irradiation In High-Risk Clinically Nonmetastatic Prostate Cancer After Radical Prostatectomy., Richard K. Valicenti, Stephanie L. Pugh, Edouard J. Trabulsi, Oliver Sartor, Eric C. Ko, Michael R. Girvigian, Seth A. Rosenthal, Mark E. Shaves, Jean Hoffman-Censits, John Schallenkamp, Howard M. Sandler

Department of Urology Faculty Papers

PURPOSE: To investigate the utility of ¹⁵³Sm lexidronam (Quadramet) in the setting of men with prostate cancer status post radical prostatectomy who develop biochemical failure with no clinical evidence of osseous metastases.

PATIENTS AND METHODS: Trial NRG Oncology RTOG 0622 is a single-arm phase 2 trial that enrolled men with pT2-T4, N0-1, M0 prostate cancer status post radical prostatectomy, who meet at least 1 of these biochemical failure criteria: (1) prostate-specific antigen (PSA) > 1.0 ng/mL; (2) PSA > 0.2 ng/mL if Gleason score 9 to 10; or (3) PSA > 0.2 ng/mL if N1. Patients received ¹⁵³Sm (2.0 mCi/kg intravenously …

Mechanisms Of Therapeutic Resistance In Prostate Cancer, Mary Nakazawa, Channing Paller, Natasha Kyprianou

Urology Faculty Publications

Prostate cancer is the second leading cause of cancer deaths in the USA. The challenge in managing castration-resistant prostate cancer (CRPC) stems not from the lack of therapeutic options but from the limited duration of clinical and survival benefit offered by treatments in this setting due to primary and acquired resistance. The remarkable molecular heterogeneity and tumor adaptability in advanced prostate cancer necessitate optimization of such treatment strategies. While the future of CRPC management will involve newer targeted therapies in deliberately biomarker-selected patients, interventions using current approaches may exhibit improved clinical benefit if employed in the context of optimal sequencing …

An Approach Using Psa Levels Of 1.5 Ng/Ml As The Cutoff For Prostate Cancer Screening In Primary Care., E. David Crawford, Matt T. Rosenberg, Alan W. Partin, Matthew R. Cooperberg, Michael Maccini, Stacy Loeb, Curtis A. Pettaway, Neal D. Shore, Paul Arangua, John Hoenemeyer, Mike Leveridge, Michael Leapman, Peter Pinto, Ian M. Thompson, Peter Carroll, James Eastham, Leonard G. Gomella, Eric A. Klein

Department of Urology Faculty Papers

No abstract provided.

Characterization Of 1577 Primary Prostate Cancers Reveals Novel Biological And Clinicopathologic Insights Into Molecular Subtypes., Scott A. Tomlins, Mohammed Alshalalfa, Elai Davicioni, Nicholas Erho, Kasra Yousefi, Shuang Zhao, Zaid Haddad, Robert B. Den, Adam P. Dicker, Bruce J. Trock, Angelo M. Demarzo, Ashley E. Ross, Edward M. Schaeffer, Eric A. Klein, Cristina Magi-Galluzzi, R. Jeffrey Karnes, Robert B. Jenkins, Felix Y. Feng

Department of Radiation Oncology Faculty Papers

BACKGROUND: Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease stratification, complementing available prognostic tests.

OBJECTIVE: To determine the analytical validity and clinicopatholgic associations of microarray-based molecular subtyping.

DESIGN, SETTING, AND PARTICIPANTS: We analyzed Affymetrix GeneChip expression profiles for 1577 patients from eight radical prostatectomy cohorts, including 1351 cases assessed using the Decipher prognostic assay (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with Clinical Laboratory Improvements Amendment certification. A microarray-based (m-) random forest ERG classification model …

Long-Term Oncological Outcomes Of A Phase Ii Trial Of Neoadjuvant Chemohormonal Therapy Followed By Radical Prostatectomy For Patients With Clinically Localised, High-Risk Prostate Cancer., Jonathan L. Silberstein, Stephen A. Poon, Daniel D. Sjoberg, Alexandra C. Maschino, Andrew J. Vickers, Aaron Bernie, Badrinath R. Konety, William Kevin Kelly, James A. Eastham

Department of Urology Faculty Papers

OBJECTIVE: To determine long-term oncological outcomes of radical prostatectomy (RP) after neoadjuvant chemohormonal therapy (CHT) for clinically localised, high-risk prostate cancer.

PATIENTS AND METHODS: In this phase II multicentre trial of patients with high-risk prostate cancer (PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only.

RESULTS: In all, 34 patients were enrolled and followed for a median of 13.1 years. …

The Significance Of Functional Renal Obstruction In Predicting Pathologic Stage Of Upper Tract Urothelial Carcinoma., Michael J. Amirian, Kushan Radadia, Hadley Narins, Kelly A. Healy, Scott G. Hubosky, Demetrius H. Bagley, Edouard J. Trabulsi, Costas D. Lallas

Department of Urology Faculty Papers

BACKGROUND AND PURPOSE: Assessing the severity of upper tract urothelial carcinoma (UTUC) has been difficult because of inadequate biopsy specimens. Additional predictive parameters of disease stage would be useful when deciding a treatment plan; it has been suggested that preoperative hydronephrosis can be a surrogate. We examined the relationship between preoperative ipsilateral renal obstruction identified by imaging with final pathologic stage after nephroureterectomy (NU) for UTUC. We then analyzed those patients with ipsilateral renal obstruction and examined if tumor location is associated with an advanced pathologic stage.

METHODS: Patients who underwent NU for UTUC between the years 2001 to 2013 …

Safety Of Hexaminolevulinate For Blue Light Cystoscopy In Bladder Cancer. A Combined Analysis Of The Trials Used For Registration And Postmarketing Data., J Alfred Witjes, Leonard G. Gomella, Arnulf Stenzl, Sam S. Chang, Dirk Zaak, H Barton Grossman

Department of Urology Faculty Papers

OBJECTIVE: To detail and put into perspective, safety of hexaminolevulinate blue light cystoscopy (HAL-BLC), including repeated use, based on combined data of controlled trials used for registration of HAL and postmarketing experience.

METHODS: Safety data of 2 randomized comparative studies (group 1) and 4 within patient control studies (group 2) were combined. Postmarketing data from >200,000 patients were analyzed.

RESULTS: In group 1, 533 patients were examined with HAL-BLC and 499 with white light (WL) cystoscopy. In group 2, 791 patients were examined with both WL and HAL-BLC. Between 73% and 93% of these patients had concomitant diseases. Between 41% …

Prostate Cancer: Alcohol, Cancer And 5Α-Reductase Inhibitors-Is There A Link?, Leonard G Gomella

Department of Urology Faculty Papers

Two major trials have been performed to determine the effect of 5α-reductase inhibitors on subsequent diagnoses of prostate cancer. Both trials showed that high alcohol intake significantly increased prostate cancer risk among men allocated to the treatment arms. The recommendation that patients eliminate alcohol when taking 5α-reductase inhibitors seems appropriate.