International Prostate Cancer Update 2020

An Introduction to the Urinary Microbiome: Part 3 – Manipulating the Microbiome for Urologic Health

In the third lecture of a three-part foundational series for Grand Rounds in Urology’s Next Generation Microbiome and Urologic Infections Learning Center, J. Curtis Nickel, MD, FRCSC, Professor of Urology at Queen’s University in Ontario, Canada, discusses possible ways to manipulate the microbiome to promote urologic health. He explains that, at present, there are four basic ways to positively influence the microbiome: eating a good diet, exercising, avoiding environmental pollution, and avoiding unnecessary antibiotics. Dr. Nickel also discusses various potential treatments currently being explored that involve manipulating the microbiome for managing disease, such as: gastrointestinal recolonization with Oxalobacter formigenes to treat urinary stone disease; targeting particular microbiota for cancer management; using Lactobacillus probiotics, fecal transplants, urine transplants, and a whole-cell inactivated bacteria vaccine to protect against urinary tract infections; and phage therapy. Dr. Nickel concludes that urologists do not have to always kill off bacteria, including seemingly pathogenic bacteria, but rather they need to understand how the bacteria changes in various disease states.

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An Introduction to the Urinary Microbiome: Part 2 – Impact on Urinary Disease

In the second lecture of a three-part foundational series for Grand Rounds in Urology’s Next Generation Microbiome and Urologic Infections Learning Center, J. Curtis Nickel, MD, FRCSC, Professor of Urology at Queen’s University in Ontario, Canada, discusses how changes to the urinary microbiome, which he previously described as helping maintain urinary health, can contribute to the development of urinary disease. Dr. Nickel summarizes the findings of several studies that evaluate the impact of the microbiome on urologic chronic pelvic pain, observing that dysbiosis appears to be more important than any particular bacterium in the development of chronic prostatitis/chronic pelvic pain syndrome, female bladder pain, and female lower urinary tract symptoms (LUTS), although researchers have identified some candidate organisms. Dr. Nickel notes that the development of struvite stones and calcium oxalate stones are also associated with dysbiosis. He concludes by discussing the role of bacteria in urinary cancers, explaining that distinct microbiome patterns appear to be related to certain responses to bladder cancer, and that prostate cancer is often associated with prostate inflammation caused by bacterial infection, although the role of the microbiome in prostate cancer development has yet to be determined.

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An Introduction to the Urinary Microbiome: Part 1 – A Primer

In the first lecture in a three-part foundational series for Grand Rounds in Urology’s Next Generation Microbiome and Urologic Infections Learning Center, J. Curtis Nickel, MD, FRCSC, discusses the urology community’s evolving understanding of the urinary microbiome’s role in promoting urinary health. He observes that while doctors have recognized the importance of the gut microbiome for some time, most urologists held the traditional belief that the urinary tract was sterile until the past decade. However, with next-generation sequencing, researchers have rapidly discovered that the urinary tract is a “veritable microbial jungle” that is home to more than 4,000 species. Now that researchers are aware of its existence, Dr. Nickel emphasizes that it is necessary to study the normal urinary microbiome in order to better understand the changes that might result in dysbiosis and disease, discussing the results of past small studies as well as the potential of his team’s recently-initiated, 600-subject ongoing normal microbiome study.

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Accuracy of ExactVu™ Micro-Ultrasound for Diagnosis of Prostate Cancer

Priya N. Werahera, PhD, Research Assistant Professor in the Departments of Pathology and Bioengineering at the University of Colorado Anschutz Medical Campus, shares results from a study that compared ExactVu™ Micro-Ultrasound’s accuracy with that of mapping biopsy’s. He specifies that although more studies are needed to confirm these positive findings, this study has shown that the PRIMUS scoring system (similar to PIRADS) is consistent, and that there is potential clinical utility thanks to ExactVu’s™ ability to deliver real-time diagnoses and be used with or without MRI.

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Improving Specificity of PSA Screening with Serum and Urine Markers – Who Doesn’t Need a Prostate Biopsy?

Daniel W. Lin, MD, Chief of Urologic Oncology at the University of Washington, discusses improving the specificity of PSA screening using serum and urine markers to determine which patients do not need a prostate biopsy. He lists the ideal biomarker characteristics, including sensitivity and specificity, correlation with disease outcome, reproducibility, low cost, quick and easy assay, and high negative predictive value. He then discusses some of the major studies done on pre-diagnosis biomarkers for prostate cancer, highlighting how PHI score, 4Kscore, and PCA3, among other markers, all significantly reduce the biopsy rate compared with older diagnostics like percent free PSA. Dr. Lin concludes by noting how urologists can further reduce unnecessary biopsies through smart screening strategies, including biennial rather than annual PSA screenings and considering not biopsying men with low early PSA scores.

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Clinical Implications of Genetics in Prostate Cancer

A. Karim Kader, MD, PhD, Professor in the Department of Urology and Director of Urologic Oncology at the University of California, San Diego, discusses the use of genetic and genomic prostate cancer markers as a risk assessment tool in men from screening to post-treatment workup. He describes several case studies in-depth, notes what markers were used for each individual case, and details the patient-specific outcomes associated with each case.

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Physician Burnout: Facts, Fiction, and Fixes

Peter M. Knapp, MD, FACS, a urologist with Urology of Indiana, LLC in Carmel, Indiana, discusses how doctors burnout at nearly 2x the rate of the general population and urologists are ranked second amongst all doctors. The AUA found that 40% of urologists reported burnout in their annual census and that this directly correlated to the number of hours worked and number of patients seen – the higher the number the higher the chance of burnout. Urologists who do not have a specialization also seem to have a higher likelihood of burnout. Dr. Knapp suggests three fixes to address this issue: finding free-time, finding a sub-specialization, and utilizing team-based care.

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Immunotherapy Trials

Daniel P. Petrylak, MD, Director of Genitourinary Oncology, Professor of Medicine and Urology, Co-Leader of Cancer Signaling Networks, and Co-Director of the Signal Transduction Program at Yale University Cancer Center, discusses the various trials currently evaluating immunotherapies for castration-resistant prostate cancer (CRPC) and metastatic castration-resistant prostate cancer (mCRPC). To this point, Dr. Petrylak explains, there have not been many obvious survival benefits from immunotherapy in prostate cancer, except in patients with specific tumor mutations; therefore, sipuleucel-T and pembrolizumab are currently the only FDA-approved immunotherapeutic agents for CRPC. Fortunately, numerous trials are underway that study more effective ways to use immunotherapies for prostate cancer, including trials to improve sipuleucel-T, trials researching vaccine-based immunotherapy regimens, and numerous combination therapy trials. Dr. Petrylak also discusses alternative approaches to immune treatment, including CAR-T cell and BiTE studies in CRPC.

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Theranostics & Radiopharmaceutical Trials

Daniel P. Petrylak, MD, Director of Genitourinary Oncology, Professor of Medicine and Urology, Co-Leader of Cancer Signaling Networks, and Co-Director of the Signal Transduction Program at Yale University Cancer Center, reviews several studies in which radium-223 is used both alone and in combination with other treatments for prostate cancer. Since radium-223 is an alpha particle, it requires fewer hits to damage DNA, offering an advantage over beta particles. Dr. Petrylak further explains the benefits of theranostics which deliver isotopes directly to the tumor site. He concludes that radium-223 is effective in treating metastatic castration-resistant prostate cancer (mCRPC), but cautions that until potential toxicity levels are better understood, combining radium-223 with either abiraterone or prednisone is not advised.

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GRU Challenging Case: Androgen Deprivation Therapy

Neal D. Shore, MD, FACS, Medical Director for the Carolina Urologic Research Center, discusses the physiological and economic factors impacting the ADT selection process. He particularly emphasizes the impact of the current volume-based and economically incentivized model of treatment and how this can restrict urologists. He also discusses the physiological impacts of drug-drug interactions, alternate modes of administration, and the complex prospect of an oral alternative.

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A Better Abiraterone: The Backdoor Pathway for Intracrine Androgen Metabolism

James L. Mohler, MD, Associate Director and Senior Vice President for Translational Research and Professor of Oncology at Roswell Park Comprehensive Cancer Center in Buffalo, New York, discusses the cause of and potential solutions to androgen receptor expression in castration-recurrent prostate cancer. He explains that prostate cancer tissue in a patient with castration-recurrent disease actually has greater levels of testosterone than benign prostate tissue and that castration-resistant prostate cancer relies on a backdoor pathway of manufacturing testosterone by which dihydrotestosterone (DHT) is made from androstanediol. Abiraterone is intended to inhibit CYP17A1 and therefore prevent the manufacture of DHT, but Dr. Mohler suggests that abiraterone inhibits CYP17A1 that is too far from DHT synthesis to achieve long term response by inhibition. He then discusses current research about a promising drug that targets the catalytic domain shared by the five 3α-oxidoreductases associated with DHT production.

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Molecular Imaging For Staging and Advanced Disease – Axumin and PSMA

Robert E. Reiter, MD, Bing Professor of Urology and Molecular Biology, Director of the Prostate Cancer Program, and Director of Urologic Research at the David Geffen School of Medicine at the University of California, Los Angeles, discusses the benefits of PSMA imaging in the context of biochemical recurrence. He reviews data from an Australian and an American study which both depict a positive correlation between PSA levels and PSMA prostate cancer detection rates, as well as high sensitivities for detection of recurrence based on pathologic confirmation. He then discusses the results of a study which compared PSMA with Axumin and found PSMA to be more than twice as effective in all areas but the prostate bed, which is most likely due to PSMA being excreted through the bladder. He argues that PSMA imaging can produce between a 29% and 76% change in prostate cancer management and allows for greater precision in treatment, resulting in fewer occurrences of unnecessary radiation therapy and long term systemic therapy.

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