Urology Basic Science Clinical Research

SCHIEWER UROLOGY LAB

As we close out another calendar year still mired in a pandemic, Dr. Schiewer notes: “I am reminded about why we do what we do in the lab: to try to positively impact the lives of cancer patients and their family members. The students in the lab are both thriving and striving towards the goal of benefitting human health.”

Moriah Cunningham, who is a PhD student in the Cell Biology and Regenerative Medicine Program, is making progress on better understanding the mechanisms that underlie response to PARP inhibitors in prostate cancer. Her work has the potential to uncover strategies to use this class of drug with greater precision. Moriah is in the midst of putting together her thesis committee, and is nearly finished with all required coursework, which will give her increased time to pursue her research.

Latese Evans, who is both a Master of Science student and a Research Technician in the lab, is making progress on understanding the molecular underpinnings that lead to differences between male and female bladder cancer patients. She is investigating the roles that hormones play in bladder tumors, and whether these mechanisms could be taken advantage of for therapeutic benefit. We are also excited that Latese has made the decision to continue her studies in the lab and pursue her PhD degree beginning next year.

Candice Bizzaro, who is a PhD student in the Biochemistry and Molecular Pharmacology Program, is currently rotating in our lab as part of the process in deciding which lab to conduct her thesis research. She has spent the last several weeks investigating a novel combination treatment strategy for bladder cancer management that builds on the standard of care. The initial results seem promising!

Moriah and Latese are also working on a collaborative project where they are investigating the potential of novel therapeutic strategy in the context of advanced prostate cancer. The preliminary results to uncover the mechanisms by which this combination is effective, and identify which patients might benefit have excited us. Work continues on the identification of genomic signatures that may provide insight into why certain patients develop muscle invasive bladder cancer following pelvic radiation therapy.

This past year has been an exciting time of discovery in the lab, and we are excited about what the future will bring. Dr. Scheiwer is currently in the midst of recruiting a postdoctoral fellow, and, as always, the lab is in pursuit of grant funding. We are grateful for the support of the Department of Urology and the SKCC. Schiewer Urology Lab in the Bleumle Life Science Building team members: Candice Bizzaro (PhD Rotating Student), Matt Schiewer, PhD (Lab Principal Investigator), Moriah Cunningham (PhD Student), Latese Evans (MS/Research Assistant)

VPAC PROJECT UPDATE

Funded by the NIH, our joint UrologyRadiology research group is continuing work to develop a simple and reliable method that uses voided urine and targets a genomic biomarker, VPAC, to detect prostate cancer. VPAC (combined vasoactive intestinal peptide and pituitary adenylate cyclase-activating peptide family of cell surface receptors) is expressed in high density only on malignant prostate cancer cells shed in urine, using a specific biomolecule developed in our laboratory. A microscopic examination of the shed cells distinguishes malignant cells from normal epithelial cells efficiently and depicts prostate cancer with >95% accuracy. The Co-PI’s are Drs. Thakur and Trabulsi. Drs. Tripathi and Manisha Kumari in Dr. Thakur’s lab perform these innovative studies and urology research fellow Dr. Cass Clark is primarily assigned to the clinical component of the study. Dr. Thakur is Director, Laboratories of Radiopharmaceutical Research, Molecular Imaging and Biofluid Diagnostics and Professor of Radiology, Radiation Oncology and Urology and Dr. Trabulsi is Professor of Urology and Vice Chair for research.

We are pleased to also report some new findings from our Jefferson India Center collaborators at KLE in Belgaum, India. Following Dr. Thakur’s visits to KLE and reviewing their techniques, they have been able to validate clinically our VPAC prostate cancer detection work and have also identified that bladder cancer shed cells can also be detected in the urine using the VPAC shed cell assay. The concept of VPAC shed cell detection on a wide variety of epithelial malignancies was developed by Drs. Mat Thakur and Leonard

Gomella, Chair of the Department of Urology, and the technology has been licensed by Thomas Jefferson University. The latest VPAC publications are: Nerli RB, Ghagane SC, Bidi SR, Thakur ML, Gomella L. Voided urine test to diagnose prostate cancer: Preliminary report. Cytojournal. 2021 Oct 2;18:26. Nerli RB, Ghagane SC, Rangrez S, Chandra S, Thakur ML, Gomella L. Detection of bladder cancer using voided urine sample and by targeting genomic VPAC receptors. Indian J Urol. 2021 Oct-Dec;37(4):345-349.

PURC (PENNSYLVANIA UROLOGIC RESEARCH COLLABORATIVE)

As one of the original five founding members of PURC, Jefferson Urology remains at the forefront of collaborative multi-institutional urologic outcomes research in Philadelphia. As a result of the prolific success of the endeavor, after a rapid expansion to include all academic institutions in Pennsylvania, as well as institutions from New Jersey (Cooper, CINJ) and pending groups from Connecticut (Yale) and Virginia (UVA), it has been renamed USCOPE (Urologic Surgeons Comparing Outcomes Pursuing Excellence). This physician-led prostate cancer quality improvement collaborative effort strives to reduce variation in care; measure, understand, and influence treatment outcomes; improve patientcentered decision-making; and provide reliable, sustainable platform for data collection for benchmarking and practice level quality improvement initiatives. Dr. Ed Trabulsi has served as the Jefferson Physician champion and has been in a leadership position of the group since its inception, serving on the executive council and various subcommittees. Together with Drs. Mark Mann and Thenu Chandrasekar, as well as the student research scholars who abstract and input data on our prostate cancer patients, Jefferson Urology maintains a prominent role in USCOPE. From this initiative, Jefferson has been named in multiple published manuscripts as well poster and podium presentations regionally and nationally. The most prominent of recent publications was published in JAMA Oncology in July 2021 on Prostate Cancer Racial Treatment Disparities during the COVID crisis (https://hcifonline.org/ wp-content/uploads/2021/07/Assessmentof-Prostate-Cancer-Treatment-AmongBlack-and-White-Patients-during-theCOVID-19-Pandemic.pdf.) (See page 18.)

CLINICAL TRIALS

This past year, 2021, has been another challenging year for healthcare. Staffing, equipment, and medication shortages have met a surging backlog of patients as the Jefferson community has confronted the reality of the continued Covid-19 pandemic. Despite these hurdles, the Department of Urology has continued its commitment to clinical research and has enrolled a large number of patients in clinical trials as we ourselves gain familiarity with novel technologies. Our partnership with medical oncology, radiation oncology and others in the Sidney Kimmel Cancer Center allows a wide array of therapeutic clinical trial opportunities outside of the Departments portfolio to be made available to our patients. Our multidisciplinary GU Oncology team meets several times a month with our SKCC partners including, Dr. Kevin Kelly, Director, Division of Solid Tumor Oncology and Associate Director of Clinical Research, SKCC and Dr. Bobby Den Associate Professor of Radiation Oncology, Cancer Biology and Urology. Christine Hubert Assistant Director, Clinical Trials Office assists in urology centric clinical trials coordination across departments.

The unique challenges this year has presented has allowed our faculty to focus mainly on our investigator initiated clinical trials. Dr. Lallas completed enrollment for his study using 3D printed models of patients’ kidney and renal masses for surgical planning prior to partial nephrectomy. Dr. Chandrasekar met his enrollment goal evaluating the ability of different contrast enhanced ultrasound techniques to predict histologic grade of renal cell carcinoma, and Anne Lizardi-Calvaresi, DNP, CRNP, RNFA Director of Clinical Operations, doubled enrollment in her IIT therapeutic trial of Vitamin B6 for men suffering from hot flashes secondary to androgen deprivation. The work on the VPAC urine test for prostate cancer continues with more than 180 patients enrolled this year on our NCIfunded grant.

This year we also had the unique experience as the first center in the area to offer PSMA PET CT to men with prostate cancer. Access to this exciting new imaging modality provided the unique opportunity to be one of 6 sites selected to partner with the National Cancer Institute (NCI) examining the role of PSMA imaging to predict recurrence after prostatectomy for high-risk prostate cancer (NCT03976843). In 2021, 14 of our patients were able to access this novel prostate specific PET imaging modality before the FDA formally approved piflufolastat-F18 in May (for more on PSMA PET for prostate cancer see page 33).

Our involvement in cutting edge, novel medical technologies will continue in 2022. SunRISE 1 (NCT04640623), combining PD-1 inhibition with a novel chemotherapeutic intravesical implant for patients with BCG-unresponsive NMIBC, has just opened for enrollment. We also are looking forward to studying an innovative way to use a light activated therapeutic agent for endoscopic management of upper tract urothelial cancer (NCT04620239). This is a phase 3, open label, single arm study of padeliporfin (TOOKAD® a vascular-targeted photodynamic therapy) in the treatment of Upper Tract Urothelial Carcinoma (UTUC). The ENLIGHTED study will recruit patients with low-grade noninvasive upper tract urothelial carcinoma in either the kidney or the ureter.

While this has been a rough year in healthcare, we have been fortunate to benefit from a strong department and a Jefferson Health system wide commitment to the clinical research mission which has allowed us to weather personnel and supply shortages outside of our own department’s control. As our Jefferson community gets closer to business as usual, we have many exciting and novel treatment strategies that we will soon be able to share with our patients. I encourage you to review the searchable list of our available clinical trials at Jefferson’s Study Information Portal (SIP, for short http://ctmssip.tju.edu/sip/SIPMain). If you have a patient you would like to refer or require more information on a particular trial, contact Dr. J. Ryan Mark (james.mark@ jefferson.edu), Director of Clinical Trials for the Department of Urology, or our department clinical trials coordinator Olivia Dahlgren (Olivia.Dahlgren@jefferson.edu).

Dr. Ryan Mark and Olivia Dahlgren are responsible for the oversight of clinical trials in the Department of Urology. Many of the Department of Urology clinical trials are carried out in collaboration with the Sidney Kimmel Cancer Center specific protocols.

DEPARTMENT OF UROLOGY AND SIDNEY KIMMEL CANCER CENTER GU CLINICAL TRIALS FOR CALENDAR YEAR 2021

CRPC: Castration resistant prostate cancer; MIBC: Muscle Invasive Bladder Cancer; NMIBC: Non-Muscle Invasive Bladder Cancer; PCCTC: Prostate Cancer Clinical Trial Consortium; PCORI: Patient-Centered Outcomes Research Institute. Thanks to Christine Hubert for assisting with this table.