There were a lot of reasons to focus on urothelial cancer of the bladder and upper tracts at this year’s meeting in Chicago. There were at least 85 podium abstracts, 160 poster abstracts, and 7 late-breaking abstracts involving research in urothelial cancer, and there were multiple courses and even a 4-hour Bladder Cancer Forum for AUA2023 attendees to gain new insights into urothelial cancer and the changing landscape of treatment. A few of the many significant presentations are summarized herein.

Importantly, this year’s meeting provided a summary of new AUA/Society of Urologic Oncology guidelines for diagnosis and management of nonmetastatic upper tract urothelial carcinoma,¹ consisting of 36 principles of staging, standardized reporting, testing, and treatment. These guidelines should be utilized in daily practice to incorporate new evidence-based strategies, especially around multimodal treatment and recognition of risk factors for Lynch syndrome.

Genomic characterization of several populations of patients with urothelial bladder cancer highlighted subtypes that may help identify pharmacologic targets and may better risk stratify patients. Anurag et al² performed sequencing on carcinoma in-situ (CIS) tumors and developed a gene signature with potential treatment targets; CIS tumors were characterized by high tumor mutational burden and mutations in genes KDM6A and CCDC138. Chu et al³ examined genomic alternations in HG T1 tumors and observed that “very high risk” T1 tumors were similar to T2 tumors genomically. Yu et al⁴ sequenced treatment naïve nonmuscle-invasive baldder cancer (NMIBC) tumors and identified tumor mutational burden and mutations in TERT and EGFR as predictive of early recurrence. In trying to stratify muscle-invasive bladder cancer (MIBC) tumors based on proteomic profiling, Contreras-Sanz et al⁵ identified clusters that were predictive of response to chemotherapy and worse prognosis.

An effort representing years of work by a large collaboration of investigators, published 1 week before the meeting in Nature Communications,⁶ was summarized at the Society for Basic Urologic Research session on April 29 by Dr Josh Meeks. The authors confirmed that expression-based subtypes of MIBC cases correlate with prognosis and immunotherapy response, bringing the field one step closer toward genetic profile-based treatment selection. We are anticipating exciting future clinical trials examining these characteristics.

Trials around treatment of bacillus Calmette-Guérin–unresponsive NMIBC with several agents and novel strategies are maturing and presented data showed promising results. A phase 2 study of combination pembrolizumab and intravesical cretostimogene grenadenorepvec (CG0070), an adenoviral gene therapy, for CIS with or without papillary NMIBC⁷ demonstrated an overall complete response (CR) of 85% and 68% sustained CR at 12 months. The first data from the SunRISe-1 trial,⁸ of the monotherapy arms with TAR-200, an intravesical gemcitabine sustained-release delivery system, or cetrelimab, a PD1-directed monoclonal antibody, observed a 72% CR in those treated with TAR-200, with further results forthcoming from a combination treatment arm. A novel laser-based photodynamic therapy trial⁹ for bacillus Calmette-Guérin–unresponsive CIS was presented with early encouraging response rates of up to 55% and additional testing in progress.

Milowsky et al¹⁰ reported longer-term results (median 3 years follow-up) of treatment of resected high-risk MIBC with adjuvant nivolumab, confirming durable cancer control regardless of tumor PD-L1 expression.

The level of science and innovation around urothelial cancer grows every year and this year at AUA was no exception!