Faculty Bibliography

Upper tract urothelial carcinoma (UTUC) is a rare malignancy that accounts for a small minority of all urothelial cancers. Historically, treatment recommendations for UTUC have been extrapolated from bladder cancer trials due to limited high-quality, UTUC-specific evidence. However, emerging data has shown how UTUC exhibits distinct biological, molecular, and clinical features compared to bladder cancer. In this piece, we provide an analysis of the current evidence supporting adjuvant chemotherapy and immunotherapy for UTUC. We discuss landmark trials such as the POUT trial for adjuvant chemotherapy, as well as pivotal trials such as CheckMate 274, IMvigor 010 and AMBASSADOR that examine the role of adjuvant immunotherapy for UTUC. Additionally, we briefly highlight advances in cancer genetics and the emerging use of circulating tumor DNA as a potential biomarker. While there has been significant progress made in adjuvant treatments for UTUC, substantial knowledge gaps remain. Clinical trials using UTUC-specific populations will be critical in improving outcomes and personalizing care for this patient population.

PURPOSE/OBJECTIVE:TAR-200 is a first-in-class intravesical drug-releasing system designed to provide sustained delivery of gemcitabine in the bladder. TAR-200 alone or in combination with cetrelimab (PD-1 inhibitor) could improve outcomes in patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC) ineligible for or refusing radical cystectomy. PATIENTS AND METHODS/METHODS:In this phase IIb parallel cohort study, patients with BCG-unresponsive carcinoma in situ (CIS) with/without papillary disease received TAR-200 monotherapy (Cohort 2 [C2]), TAR-200 plus cetrelimab (C1), or cetrelimab monotherapy (C3). Patients with BCG-unresponsive high-risk papillary disease-only NMIBC received TAR-200 monotherapy (C4). TAR-200 was dosed through month 24; cetrelimab through month 18. Primary end points were centrally-confirmed overall complete response (CR) rate (C1-3) or disease-free survival (DFS) rate (C4). (ClinicalTrials.gov number, NCT04640623.). RESULTS:At data cutoff (March 31, 2025), 53, 85, 28, and 52 patients were treated in C1-4, respectively. In C2, CR rate and median duration of response were 82.4% (95% CI, 72.6-89.8) and 25.8 months (95% CI, 8.3-not estimable), respectively. In C4, 6-, 9-, and 12-month DFS rates were 85.3% (95% CI, 71.6-92.7), 81.1% (95% CI, 66.7-89.7), and 70.2% (95% CI, 51.6-82.8), respectively. In C1 and C3, CR rates were 67.9% (95% CI, 53.7-80.1) and 46.4% (95% CI, 27.5-66.1), respectively. Rates of grade ≥3 treatment-related adverse events were 12.9%, 13.5%, 37.7%, and 7.1% in C2, C4, C1, and C3, respectively, and of serious treatment-related adverse events, 5.9%, 5.8%, 15.1%, and 3.6%. No treatment-related deaths occurred. CONCLUSIONS:TAR-200 monotherapy was well tolerated, with a high CR rate, durable responses, and prolonged DFS in patients with BCG-unresponsive high-risk NMIBC. TAR-200 monotherapy offered a more favorable risk-benefit profile versus TAR-200 plus cetrelimab or cetrelimab alone in BCG-unresponsive CIS.

PURPOSE/OBJECTIVE:UGN-101, a reverse thermal mitomycin gel for upper tract instillation, recently became the first FDA approved treatment for upper tract urothelial carcinoma (UTUC). However, the durability of UGN-101 treatment has not been well described. Here we present long term outcomes from our multi-institutional cohort for patients who initially responded to treatment. MATERIALS AND METHODS/METHODS:We identified patients from a multi-institutional database with UTUC who had a negative endoscopic evaluation following either adjuvant or chemoablative UGN-101 induction. Recurrence and progression data for those patients was reviewed. Kaplan-Meier survival analysis was performed, stratified by relevant clinical features. RESULTS:We identified 56 renal units that met the inclusion criteria of which 93% had low-grade disease while 4 cases had high-grade UTUC. With a median follow-up of 23.5 months, 21.4% of renal units experienced a recurrence, with 65% of renal units recurrence-free at 36 months. Three patients experienced eventual progression of disease leading to mortality, however only 1 of these patients had presumed low-grade UTUC and did not undergo nephroureterectomy on recurrence due to solitary kidney. CONCLUSIONS:UGN-101 treatment has excellent durability in patients who initially respond to the treatment. Further study is needed to better understand the long term outcomes of this novel therapy and also the risks/benefits of maintenance therapy in this setting. Caution should be used in patients with high-grade disease who appear to be at higher risk of relapse and death despite initial response.

BACKGROUND:The relationship between body composition and bladder cancer outcomes is complex. While a higher body mass index (BMI) has been associated with an increased risk of bladder cancer development, its impact on survival outcomes is less clear. This study aimed to explore the association between BMI, survival, health-related quality of life, and the performance of ADLs in a cohort of older patients with bladder cancer. METHODS:Data were obtained from the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey, including patients diagnosed with bladder cancer who had recorded BMI values. Analysis of variance was used to assess the association between BMI categories and patient demographics as well as cancer/treatment characteristics. Generalized linear models examined the impact of BMI on health-related quality of life, as measured by the physical and mental component summary scores when controlling for confounding variables. Kaplan-Meier survival curves across BMI categories were compared using log-rank tests. RESULTS:The final cohort consisted of 8013 patients (age ≥ 65) with a mean age of 77.7 ± 7.1 years, the majority of whom were White (85.6%) and male (74.8%). We observed no significant association between BMI and cancer/treatment characteristics. The severely obese subgroup had the highest rate of disability in performing ADLs (18.3%) followed by the underweight subgroup (10.3%). Overweight patients exhibited the highest physical and mental component summary scores, indicating better health-related quality of life. BMI was a significant predictor of overall survival, with overweight, obese, and severely obese patients demonstrating improved survival compared to those with healthy or underweight BMI. These findings remained statistically significant in multivariable analysis. CONCLUSIONS:Our findings suggest a dual role of BMI in older patients with bladder cancer: higher BMI provides a survival advantage and, to an extent, a QoL advantage. At the same time, severe obesity did lead to the lowest QoL despite improved survival outcomes. These results underscore the complex interplay between BMI, survival, and QoL in this bladder cancer population.

The Society of Women in Urologic Oncology (WUO) initially began as a group that met informally at the Society of Urologic Oncology (SUO) annual winter meeting, and has since developed into a formal organization which is now recognized by the SUO Board of Directors. The core objective of the WUO is to advance recruitment, retention and promotion of women in Urologic Oncology. Herein, we will review the past, present and future of this organization.

BACKGROUND:Prediction models based on machine learning (ML) methods are being increasingly developed and adopted in health care. However, these models may be prone to bias and considered unfair if they demonstrate variable performance in population subgroups. An unfair model is of particular concern in bladder cancer, where disparities have been identified in sex and racial subgroups. OBJECTIVE:This study aims (1) to develop a ML model to predict survival after radical cystectomy for bladder cancer and evaluate for potential model bias in sex and racial subgroups; and (2) to compare algorithm unfairness mitigation techniques to improve model fairness. METHODS:-score. The primary metric for model fairness was the equalized odds ratio (eOR). We compared 3 algorithm unfairness mitigation techniques to improve eOR. RESULTS:-scores of 0.86, 0.904, and 0.824 in the full, Black male, and Asian female test sets, respectively. CONCLUSIONS:The ML model predicting survival after radical cystectomy exhibited bias across sex and racial subgroups. By using algorithm unfairness mitigation techniques, we improved algorithmic fairness as measured by the eOR. Our study highlights the role of not only evaluating for model bias but also actively mitigating such disparities to ensure equitable health care delivery. We also deployed the first web-based fair ML model for predicting survival after radical cystectomy.

OBJECTIVE:To characterize differences in the management of small renal masses among disaggregated race/ethnic subgroups. MATERIAL AND METHODS/METHODS:We used the National Cancer Database to identify patients diagnosed with clinically localized kidney cancer and tumor size ≤4cm. We studied 16 predefined racial/ethnic subgroups and compared 1) the use of surveillance for tumors <2cm and 2) the use of radical nephrectomy for tumors ≤4cm. We used multivariable logistic regression to evaluate the independent association of race/ethnicity with management, adjusting for baseline characteristics. We also compared our disaggregated analyses to the 6 National Institute of Health aggregate race categories. RESULTS:We identified 286,063 patients that met inclusion criteria. For tumors <2cm, Black Non-Hispanic (aOR 1.43) and Mexican patients (aOR 1.29) were significantly more likely to undergo surveillance compared to White patients. For tumors ≤4cm, Black Non-Hispanic (aOR 1.43), Filipino (aOR 1.28), Japanese (aOR 1.28), Mexican (aOR 1.32), and Native Indian patients (aOR 1.15) were significantly more likely to undergo radical nephrectomy compared to White patients. When comparing our disaggregated analyses to the NIH categories, we found that many disaggregated race/ethnic subgroups had associations with management strategies that were not represented by their aggregated group. CONCLUSIONS:In this study, we found that the use of surveillance for tumors <2cm and radical nephrectomy for tumors ≤4cm varied significantly among certain race/ethnic subgroups. Our disaggregated approach provides information on differences in treatment patterns in particular subgroups that warrant further study to optimize kidney cancer care for all patients.

PURPOSE OF REVIEW/OBJECTIVE:The most common definitive treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy. However, removing the bladder and surrounding organs poses risks of morbidity that can reduce quality of life, and raises the risk of death. Treatment strategies that preserve the organs can manage the local tumor and mitigate the risk of distant metastasis. Recent data have demonstrated promising outcomes in several bladder-preservation strategies. RECENT FINDINGS/RESULTS:Bladder preservation with trimodality therapy (TMT), combining maximal transurethral resection of the bladder tumor, chemotherapy, and radiotherapy (RT), was often reserved for nonsurgical candidates for radical cystectomy. Recent meta-analyses show that outcomes of TMT and radical cystectomy are similar. More recent bladder-preservation approaches include combining targeted RT (MRI) and immune checkpoint inhibitors (ICIs), ICIs and chemotherapy, and selecting patients based on genomic biomarkers and clinical response to systemic therapies. These are all promising strategies that may circumvent the need for radical cystectomy. SUMMARY/CONCLUSIONS:MIBC is an aggressive disease with a high rate of systemic progression. Current management includes neoadjuvant cisplatin-based chemotherapy and radical cystectomy with lymph node dissection. Novel alternative strategies, including TMT approaches, combinations with RT, chemotherapy, and/or ICIs, and genomic biomarkers, are in development to further advance bladder-preservation options for patients with MIBC.