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AUA Investigator 2020: April Issue

Feature Articles

Congratulations 2020 Urology Care Foundation Awardees of Distinction!

The Urology Care Foundation acknowledges outstanding contributions to urology research with its annual Awards of Distinction. These awards honor contributions to pediatric urology and prostate cancer research, and recognize the accomplishments of previous Urology Care Foundation awardees and mentors. Congratulations to the 2020 Urology Care Foundation Awardees of Distinction!

John W. Duckett, Jr., MD Pediatric Urology Research Excellence Award

Thomas F. Kolon, MD, Associate Chief of the Division of Urology at the Children's Hospital of Philadelphia and Professor of Urology at the Perelman School of Medicine at the University of Pennsylvania, will receive the John W. Duckett, Jr., MD Pediatric Urology Research Excellence Award. Established in 2009, this award honors a physician-scientist or researcher for their outstanding work in pediatric urology. Dr. Kolon was nominated by the Societies for Pediatric Urology for this award, and was selected by a review committee. The award is provided through a fund established by Mrs. Peggy Duckett-Drach and the Societies for Pediatric Urology.

Richard D. Williams, MD Prostate Cancer Research Excellence Award

Eric A. Klein, MD, Professor of Surgery at Case Western University and Chairman of the Glickman Urological & Kidney Institute at the Cleveland Clinic, will be honored with the Richard D. Williams, MD Prostate Cancer Research Excellence Award. This award, established in 2013, is presented annually to recognize outstanding and impactful work in prostate cancer research over the past 10 years. Dr. Klein was nominated for this honor by the Society of Urologic Oncology and was selected by a review committee. The award is made possible through a fund established by Mrs. Beverly Williams.

Urology Care Foundation Distinguished Mentor Award

Margot S. Damaser, PhD, Professor of Molecular Medicine at the Cleveland Clinic Lerner College of Medicine and Biomedical Engineering at Case Western Reserve, will be awarded with this year’s Urology Care Foundation Distinguished Mentor Award. The award reflects Dr. Damaser’s outstanding track record of fostering the next generation of urologic research leaders by continually providing an excellent training environment and guidance to early-career investigators. Recipients of this award are nominated by their peers and selected by the AUA Research Council and Committees.

Urology Care Foundation Distinguished Scholar Alumnus Award

Stephen A. Zderic, MD, Professor of Urology in Surgery at the Perelman School of Medicine at the University of Pennsylvania, will be recognized with the Urology Care Foundation Distinguished Alumnus Award. This award honors former Urology Care Foundation Research Scholars who have achieved a substantial body of impactful research and demonstrate an unwavering commitment to scholarship and academic leadership in the field. Dr. Zderic was nominated for this award by his peers and selected by the AUA Research Council and Committees.

Outstanding Graduate Scholar Award

Each year, a one- and two-year Urology Care Foundation Research Scholar are chosen to receive the Outstanding Graduate Scholar Award based on the quality and potential impact of their studies, overall research productivity and publications generated during the award period, and the Scholars’ potential as a future research leader.

Brandon J. Manley, MD, a two-year Research Scholar Awardee from the Moffitt Cancer Center, will be granted with one of these awards. Dr. Manley’s two-year study, titled “Employing Multiparametric Profiling to Characterize Immunotherapy Responders in Clear Cell Renal Cell Carcinoma,” was conducted under the mentorship of James Mule, MD.

Naveen Kachroo, MD, PhD will also receive a Urology Care Foundation Outstanding Graduate Scholar Award. Dr. Kachroo’s one-year study, titled “Elucidating the Microbial Mechanisms Associated with Urinary Stone Disease,” was conducted at the Cleveland Clinic Foundation under the mentorship of Aaron Miller, PhD and Manoj Monga, MD.

Please contact with any questions about the selection process.

Advancing Bladder Preservation: Biomarkers, Decision-Making, and Therapy

The third annual Johns Hopkins Greenberg Bladder Cancer Institute/American Urological Association (AUA) translational bladder cancer research symposium, “Advancing Bladder Preservation: Biomarkers, Decision-Making, and Therapy,” was held on March 6-7, 2020 at the Johns Hopkins campus in Baltimore, Maryland. Due to travel restrictions related to the COVID-19 pandemic, approximately half of the 95 meeting registrants and speakers participated remotely via video conferencing. Despite the last-minute integration of the video platform, and thanks to the dedication and professionalism of the AUA and Johns Hopkins Kimmel Cancer Center conference management teams, there was consensus among those participating in-person and remotely that the meeting was an unqualified success, demonstrating that great science to help patients can always move forward with the will of the scientists and those who support them.

The meeting opened with a panel discussion led by Stephanie Chisholm, PhD of the Bladder Cancer Advocacy Network (BCAN), involving five patient stakeholders who had opted either bladder preservation or cystectomy as definitive treatment for their muscle-invasive bladder cancer. The discussion revealed that each survivor was satisfied with his/her decision, although it was unclear whether each received a balanced presentation of the risks and benefits of each approach, and some survivors were convinced that cystectomy was the only truly “definitive” approach. The panel discussion effectively focused the rest of the meeting on patient-centered outcomes, and the continuous input from the stakeholders through the rest of the meeting raised the level of discussion overall.

The scientific program continued with a remote presentation by Jason Efstathiou, MD, DPhil, entitled, “Setting the Stage: Current Criteria for Bladder Preservation, Disqualifiers, and Other Considerations,” in which Dr. Efstathiou discussed 10 common misconceptions about the approach. Seth Lerner, MD, then led a speaker panel that included Leslie Ballas, MD and Parminder Singh, MD, and focused on targeting barriers to wider use of trimodal therapy with maximal TURBT plus chemoradiation. Dr. Ballas also discussed special considerations related to pursuing bladder preservation in women. Rounding out the first day of talks were remote presentations by Stephen Williams, MD on costs of cystectomy versus bladder preservation, and Anna Gagliardi, PhD on breaking down barriers in knowledge translation.

Peter Black, MD launched the scientific program on the second day with a recap of the previous day’s discussion and goal setting for the rest of the meeting. Seth Lerner then led a session on surgical issues that highlighted standardizing TURBT (Wes Kassouf, MD), use of fiducial markers (Girish Kulkarni, MD, PhD), the need for re-TURBT/biopsy during follow-up (Adam Feldman, MD, MPH), radical cystectomy and diversion options after TMT failure (Trinity Bivalacqua, MD, PhD), and bladder preservation in advanced disease (Ashish Kamat, MD, MBBS and Peter Black, MD). The surgical panel was followed by a session focused on systemic therapy, moderated by Andrea Apolo, MD. The session opened with a debate between Srikala Sridhar, MD and Parminder Singh, MD on the merits of neoadjuvant versus concomitant chemotherapy, followed by presentations by Pooja Ghatalia, MD, Noah Hahn, MD, Gopa Iyer, MD, and Joaquim Bellmunt, MD, PhD on the integration of immunotherapy and chemotherapy in bladder-sparing approaches and their potential to serve as bladder-sparing approaches on their own. This discussion was timely given that two different clinical trials combining immune checkpoint blockade with radiation are currently accruing patients with muscle-invasive bladder cancer (SWOG’s S1806) or BCG-relapsing high-risk non-muscle invasive bladder cancer (ADAPT BLADDER), and two others (Alliance A031701 and the Fox-Chase RETAIN trial) are investigating whether the presence of inactivating mutations in DNA damage and repair (DDR) genes can be used as biomarkers to identify patients who can be rendered free of disease by neoadjuvant cisplatin-based chemotherapy alone.

The final session of the meeting was moderated by Kent Mouw, MD, PhD and was focused on translational science. Chuck Drake, MD, PhD led with a critical scientific appraisal of the abscopal effect, where radiation-induced cell killing is assumed to increase T-cell-mediated recognition of tumor antigens (he argued that it often does not). Catharine West, PhD then presented the evidence supporting a role for hypoxia in radiation resistance and hypoxia modification with carbogen plus nicotinamide in tumors characterized by hypoxia-associated gene expression signatures. David Miyamoto, MD, PhD continued with a discussion of transcriptomic biomarkers, focused on signatures of immune infiltration as potentially predictive of response, and Phil Abbosh, MD introduced the possible use of urine tumor DNA as a biomarker for residual disease in the bladder. Finally, Dr. Mouw concluded with a discussion of DNA damage and mutation repair as a source of biomarkers for radiation response. Overall, the presentations strongly supported the idea that response to each component of trimodal therapy can be monitored using “liquid biopsies” and that prognostic and predictive biomarkers are emerging that can be used to select patients for the approach. The success of this meeting left the AUA and GBCI co-organizers enthusiastic about planning the annual symposium for next year at the AUA headquarters in Linthicum, Maryland.

Making an IMPACT

Novel Concepts to Treat Urinary Stone Disease and the Power of Team Science

Benjamin K. Canales, MD, MPH learned that team science was a great way to advance simple ideas during his urology fellowship at the University of Minnesota. He had an idea to use a mass spectrometer to identify kidney stone matrix—the proteins that glue crystals together—but knew nothing about the science of proteomics. Fortunately, his Urology Care Foundation Research Scholar Award gave him the protected time and resources needed to assemble a group of scientists to study this topic in a novel way. Under the mentorship of Manoj Monga, MD and LeeAnn Higgins, PhD, Dr. Canales’s simple idea bloomed into a field where new drugs are being designed to inhibit stone matrix proteins and, as a result, kidney stones themselves.

Over the last ten years since his fellowship, Dr. Canales has tested a number of therapies for enteric (intestinal) hyperoxaluria, or over-absorption of oxalate, a nutrient in many common foods, from the gastrointestinal tract. Excessive amounts of this mineral in urine can lead to stones and even nephropathy or end-stage kidney disease, but the underlying mechanisms behind these conditions are difficult to study in humans. With support provided by a Urology Care Foundation Rising Stars in Urology Research Award, Dr. Canales worked with a team at the University of Florida to create a mouse model of enteric hyperoxaluria to understand the development of urinary stones in humans in search of a cure.

Their collaborative efforts ultimately discovered that the gut bacteria Oxalobacter formigines could bring urine oxalate back down to a normal level, thereby reducing the incidence of stone formation. According to Dr. Canales, “We found that Oxalobacter was literally forcing intestinal cells to pull oxalate out of the bloodstream and back into the gut lumen in order for this bacteria to use it as an energy source…a finding that is now being tested in human clinical trials.”

As an independent investigator now with a lab of his own, Dr. Canales is an active mentor for postdoctoral fellows and trainees conducting kidney stone research, some of whom have become Urology Care Foundation awardees as well. He is currently serving as a mentor for William L. Donelan, PhD, a 2018-2020 Research Scholar Awardee who is developing a dipstick test for urine oxalate levels. This simple and inexpensive test may revolutionize monitoring and treatment for kidney stones by providing real-time information for both patients and clinicians.

“Simple ideas, team science, and unwavering support from the Urology Care Foundation have made my career possible, and I’m excited to see how kidney stone disease research will advance over the next 10 years through their support!” he said.