Faculty Bibliography

A 71-year-old male with history of clear cell renal cell carcinoma (RCC) 6-years status post nephrectomy presented for gross hematuria. Cystoscopy revealed a bulge of the right ureteral orifice, and transurethral resection confirmed RCC metastasis to the ureteral stump. Ureterectomy with bladder cuff excision was performed, and the patient is currently undergoing aggressive imaging surveillance. This is the 57th case of metastasis of RCC to the ureteric stump, and this case occurred beyond baseline surveillance recommendation of five years. Potential mechanisms of metastasis of RCC are reviewed, and RCC surveillance is discussed.

PURPOSE/OBJECTIVE:Patients undergoing endoscopic management for upper tract urothelial carcinoma often progress to definitive therapy with radical nephroureterectomy. This study examined the rate of progression as well as risk factors for transitions in treatment over time. METHODS:Retrospective review at two institutions identified patients undergoing endoscopic management for upper tract urothelial carcinoma. Patients were assessed for progression to radical nephroureterectomy. Baseline characteristics were compared using Chi square analysis. Kaplan-Meier method analyzed the probability of patients not progressing to radical nephroureterectomy. Cox proportional hazards identified factors associated with progression to radical nephroureterectomy. RESULTS:Eighty-one patients had endoscopic management alone and 89 progressed to radical nephroureterectomy. The two groups had similar age, histories of bladder cancer, and Charlson comorbidity index. Positive urinary cytology, ureteroscopic visualization, and biopsy grade were higher in those progressing to RNU (p < 0.001). Hazard modeling demonstrated higher rates of progression to radical nephroureterectomy with positive biopsy (HR 11.8, 95% CI 2.4-59.5, p = 0.003) or visible lesion on ureteroscopy (HR 8.4, 95% CI 3.0-23.9, p < 0.001). Patients with a higher Charlson comorbidity index were less likely to have radical nephroureterectomy. On Kaplan-Meier modeling, the probability of not undergoing radical nephroureterectomy at 2 years and 5 years was 50% and 20%, respectively. CONCLUSIONS:Patients who progress to radical nephroureterectomy after endoscopic management have fewer comorbid conditions and changes in disease status including visible lesions on ureteroscopy and positive biopsies. The high rate of progression to radical nephroureterectomy reinforces the need for long-term follow-up of these patients.

BACKGROUND:Bladder cancer affects life quality, overall health, and mortality negatively. The effect of bladder cancer on activities of daily living (ADLs) is not well established. OBJECTIVE:To examine the effect of bladder cancer diagnosis on ADLs, in addition to physical, mental, and overall health measures. DESIGN SETTING AND PARTICIPANTS/METHODS:Using data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) registry, responses regarding ADLs and overall health were evaluated in bladder cancer patients over time. The Short Form 12 health survey responses were analyzed to determine the change in physical and mental health scores following bladder cancer diagnosis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:test. RESULTS AND LIMITATIONS/CONCLUSIONS: = 0.0003, respectively). CONCLUSIONS:Patients with bladder cancer report a significant decline in functional status and overall health, including both physical and mental well-being after diagnosis. Further study is needed for factors that may be most predictive of the decline in functional independence for this population. PATIENT SUMMARY/RESULTS:There is a decreased ability to perform daily activities following bladder cancer diagnosis, and patients report a decrease in their physical and mental health. This information can help patients and their caregivers anticipate patient needs following bladder cancer diagnosis, in addition to helping manage their expectations when making decisions regarding treatment options.

Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. The advancement of UTUC research is hampered by the lack of disease-specific models. Here, we report the establishment of patient derived xenograft (PDX) and cell line models that reflect the genomic and biological heterogeneity of the human disease. Models demonstrate high genomic concordance with the corresponding patient tumors, with invasive tumors more likely to successfully engraft. Treatment of PDX models with chemotherapy recapitulates responses observed in patients. Analysis of a HER2 S310F-mutant PDX suggests that an antibody drug conjugate targeting HER2 would have superior efficacy versus selective HER2 kinase inhibitors. In sum, the biological and phenotypic concordance between patient and PDXs suggest that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients.

The engraftment of human tumor tissues into immunodeficient host mice to generate patient-derived xenograft (PDX) models has become increasingly utilized for many types of cancers. By capturing the unique genomic and molecular properties of the parental tumor, PDX models enable analysis of patient-specific clinical responses. PDX models are an important platform to address the contribution of inter-tumoral heterogeneity to therapeutic sensitivity, tumor evolution, and the mechanisms of treatment resistance. With the increasingly important role played by targeted therapies in urological malignancies, the establishment of representative PDX models can contribute to improved facilitation and adoption of precision medicine. In this review of the evolving role of the PDX in urothelial cancer and kidney cancer, we discuss the essential elements of successful graft development, effective translational application, and future directions for clinical models.

PURPOSE/OBJECTIVE:To evaluate patient satisfaction (with emphasis on preoperative education) with radical cystectomy for bladder cancer at our institution, the University of Missouri Hospital, qualitatively in order to identify specific areas where improvements can be made. MATERIALS AND METHODS/METHODS:We developed a patient survey that used open-ended questions to identify positive and negative experiences that contributed to patient satisfaction. We administered the survey to radical cystectomy patients who met inclusion criteria and agreed to participate. We recorded, transcribed and qualitatively coded the responses. We identified four themes under which both positive and negative responses were placed, and constructed two diagrams to better illustrate contributors to patient experience and satisfaction. RESULTS:We identified 25 patients who met inclusion criteria. Of those, 13 participated in the survey. Regarding overall experience, 92.3% of patients rated their care as excellent or good. Regarding preoperative education, 76.9% of patients reported they definitely or somewhat received enough information on what to expect after surgery, and 76.9% definitely received enough guidance on how to care for themselves after surgery. From qualitative coding of patient responses to open-ended questions, we identified preoperative preparation, delivery of care, caregiver availability, and patient-centered care as themes that contributed positively and negatively to patient experience. CONCLUSION/CONCLUSIONS:Although the overall patient satisfaction could be perceived as high (92.3%), qualitative analysis revealed several areas where improvements can be made to improve patient experience with radical cystectomy at our institution. As previously expected, preoperative preparation was a contributor.