Receiving the 2023 Urology Care Foundation™ Research Scholar Award is a privilege, and I was humbled to be selected. Before deciding to pursue medicine, I was a PhD student at Weill Cornell Medical College, studying epigenetics and the role of lysine methyltransferases in cancer under Dr Minkui Luo at Memorial Sloan Kettering. My career path changed when my father was diagnosed with non-alcoholic fatty liver disease and required a liver transplant. I had the opportunity to be his liver donor, and in 2012, after a successful live liver donation at the Lahey Clinic, I woke up in a hospital bed, intent on entering the field of medicine. After graduating from the Tufts University School of Medicine–Maine Track, I began my urology residency at Maine Medical Center. There I developed a new skillset and participated in clinical outcomes research under the tutelage of Drs Jesse Sammon and Matthew Hayn. I was always intent on continuing my education with a Society of Urologic Oncology fellowship, and along the interview trail, I found myself drawn back to translational research.

I was fortunate to join the Moffitt Cancer Center, where, right from the first interviews, it was evident that my research aspirations were closely aligned with the work of Dr Roger Li. His work employing liquid biopsy with circulating tumor DNA (ctDNA) in blood samples and urinary tumor DNA (utDNA) in urine samples for diagnosis, staging, and genetic profiling of urothelial cancers was an optimal way to combine my past research experience with my current interests. He has emerged as an expert in this field, and his mentorship has guided my current research projects toward their aims. Receiving the Research Scholar Award is also a recognition of the high caliber of research from Moffitt Cancer Center as an institution and Dr Li as a principal investigator and mentor. I am grateful to be a part of these efforts.

Bladder cancer encompasses a wide spectrum of disease, and there is an ongoing need for tests that improve diagnosis, ease the burden of surveillance, detect early recurrence, and predict treatment response. A significant challenge in this space has been the vast genomic heterogeneity observed in urothelial carcinoma, with multiple subtypes and molecular signatures for both nonmuscle invasive bladder cancers (NMIBC) and muscle-invasive bladder cancers.^1-3 However, technological advances, especially next-generation sequencing (NGS), provide an avenue to capture this heterogeneity while also offering valuable insight into tumor biology at a patient-specific level. We recently commented on the progress urinary biomarkers have made in recent decades and proposed several ways utDNA could improve upon current shortcomings.⁴ The rationale for this approach comes from both the pioneering work of leaders in the field and our own early experience.

The Dyrskjot group published some of the earliest results demonstrating the ability to detect mutations in utDNA and ctDNA with NGS that are concordant with the tumor of origin. Karin Birkenkamp-Demtroder utilized personalized assays based on mutations in tumor DNA for 12 NMIBC patients and detected ctDNA in 83% (10 of 12) of patients and utDNA in 100% (12 of 12) patients.⁵ Subsequently, Emil Christensen showed that clearance of plasma ctDNA following neoadjuvant chemotherapy or radical cystectomy in muscle-invasive bladder cancer patients was correlated with reduced risk of recurrence and better overall survival.⁶ From our group, Heather Huelster recently published results from a cohort of 30 patients with upper tract urothelial cancer, demonstrating those without detectable levels of ctDNA preoperatively had reduced rates of disease progression and better cancer-specific survival following extirpative surgery.⁷ In the NMIBC setting, Kyle Rose presented our initial result using utDNA to detect minimal residual disease prior to repeat transurethral bladder tumor resection for 11 high-risk NMIBC patients. In collaboration with Predicine Inc, up to 50 patient-specific mutations were combined with a 500-gene hotspot panel of actionable mutations in a hybrid capture NGS assay to detect utDNA and predict minimal residual disease with an area under the receiver operator curve of 0.85.⁸ These promising results have fueled our ongoing studies, which will be further supported by the Urology Care Foundation™ Research Scholar Award.

Research often advances incrementally, with slow steps along a winding path, rather than by leaps and bounds. To reach the end goal requires support, patience, and determination. In my career, I aspire to contribute to research that improves the care of bladder cancer patients. This award is an important step at the beginning of the path, and one that I am thrilled to have received.