Lexiaochuan Wen, MD, was one of the recipients of the 2024 Urology Care Foundation™ Research Scholar Awards. These awards provide $40,000 annually for mentored research training for clinical and postdoctoral fellows or early-career faculty. AUA Southeastern Section sponsored Dr Wen’s award.

Nonmuscle-invasive bladder cancer (NMIBC) is characterized by a low likelihood of progression but a high propensity to recur. Despite the overall excellent prognosis, cancer surveillance in this population continues to contribute to significant economic and treatment burdens on patients and society.¹ Current NMIBC surveillance regimens rely almost exclusively on invasive, subjective visual cystoscopy, with or without adjunctive urine cytology. Urine cytology, first introduced in 1945, remains the only biomarker endorsed by the AUA and EAU despite its poor sensitivity, especially in the detection of low-grade disease.^2,3 Furthermore, the optimal surveillance regimen remains poorly defined, especially in those with frequent recurrences. This has resulted in wide variations in prescribing patterns, with a trend toward increasing overtreatment in this patient population.¹ I am both humbled and thrilled to receive support from the 2024 Urology Care Foundation™ Research Scholar Award to employ the latest advancements in treatment and biomarker technology to work toward shifting the current management paradigm of NMIBC.

My passion for oncology stems from a deep-rooted appreciation for the intricacy and complexity of oncogenesis, which developed during my time as a research assistant studying prostate cancer and drug resistance at the University of California, San Francisco. Subsequently, urology residency training at the Mayo Clinic in Rochester, Minnesota, afforded me the incredible privilege of managing some of the most complex bladder cancer pathologies. Perhaps just as impactful as the aggressive muscle-invasive and metastatic cancer cases were the uncertainties I faced in the treatment of NMIBC. As I weighed the utility of invasive surveillance against the risk of missing a treatable cancer recurrence, I found myself managing not only the physical but also the psychological impacts of bladder cancer. As I strengthened my personal resolve to do better for these patients, I took an interest in the latest advancements in tumor biomarker development. Following the completion of my residency training in 2024, I joined Dr Roger Li and the team at H. Lee Moffitt Comprehensive Cancer Center in Tampa, Florida, where I began my Society of Urologic Oncology (SUO) fellowship. Dr Li is a pioneer in utilizing noninvasive, cell-free DNA (cfDNA) to prognosticate and monitor urothelial cancers. His work aligned closely with my own intellectual interests, and under his superb and attentive mentorship, we developed a project to better understand and apply urinary cfDNA in the monitoring of NMIBC patients undergoing treatment with a novel intravesical drug delivery system.

The innovative TARIS intravesical drug-delivery system is a specialized semipermeable tube placed into the bladder to allow continuous, controlled release of the eluted therapeutic agent of choice. Early clinical data for TAR-200 (embedded with gemcitabine) have garnered significant interest because of both promising efficacy and excellent tolerability.⁴ The latest iteration of the TARIS system, TAR-210, is embedded with erdafitinib. As a potent and highly selective fibroblast growth factor receptor (FGFR) 1-4 tyrosine kinase inhibitor, erdafitinib (JNJ-42756493) has demonstrated impressive efficacy in metastatic and nonresectable urothelial carcinoma when delivered intravenously. However, the use of erdafitinib is limited by high systemic toxicity, with 100% of study patients reporting adverse events, 67% of which are grade 3 or 4.⁵ Intravesical delivery of erdafitinib via the TAR-210 system is of particular interest due to the controlled drug delivery mechanism that minimizes systemic toxicity. Early phase 1 application of TAR-210 in NMIBC with select FGFR alterations resulted in a clinical response rate of 87% at 3 months, with no dose-limiting toxicities.⁶ Several clinical trials with TAR-210 are currently underway, including the phase 1 study, which is actively accruing patients with both muscle-invasive and NMIBC disease (NCT0541655), and a phase 3 study comparing TAR-210 with traditional intravesical treatment in patients with intermediate-risk NMIBC (NCT06319820).

H. Lee Moffitt Cancer Center is one of the 21 sites actively accruing patients for NCT0541655. This provides us with valuable access to urine samples from study patients undergoing treatment with TAR-210. Urothelial cancer is unique in that tumor cells are continuously shed in the urine, providing an easy, noninvasive window to study and monitor the disease. Dr Li has an established partnership with Predicine Inc. (Hayward, California) and access to their proprietary next-generation sequencing (NGS) urine cfDNA diagnostic assay (PredicineCARE). His team recently presented on the clinical validation of the PredicineCARE platform in a cohort of 178 NMIBC patients, where FGFR alterations were identified in 60% of tissue and 58% of urine specimens at ASCO GU 2024.⁷ Additionally, the PredicineCARE platform allows for the detection and quantification of specific FGFR alterations, providing a framework for understanding drivers of disease and monitoring temporal changes that occur during and as a result of treatment.

With this distinguished award from the AUA and Urology Care Foundation™, along with the generous support from the H. Lee Moffitt Cancer Center in the form of institutional matched funding, we seek to evaluate the predictive value of urinary tumor-derived cell-free DNA (utDNA) using the PredicineCARE platform with boosted whole exome sequencing (PredicineWES+) to correlate utDNA kinetics with response in patients undergoing treatment with TAR-210 (Figure). Furthermore, by comparing samples at various stages of treatment, we aim to identify mechanisms and predictors of sensitivity and resistance to TAR-210. To date, we have enrolled 6 patients with the target goal of enrolling 10.

I believe this study will not only help define how NMIBC responds to TAR-210 and erdafitinib but also lay the groundwork for the implementation of noninvasive utDNA as a reliable and informative biomarker for ongoing disease surveillance. This is particularly pertinent as we move increasingly toward precision-based, personalized medicine. With the acceptance of this AUA Urology Care Foundation™ Research Scholar Award, I affirm my commitment to identifying and meeting the needs of the patients I serve and look forward to this opportunity to contribute to the evolving landscape of NMIBC management.