Investigation of intradetrusor onabotulinum toxin A efficacy and safety in older adults with urge urinary incontinence.

PURPOSE: Intradetrusor onabotulinum toxin A (BTX-A) has been demonstrated to be an effective treatment option for overactive bladder (OAB). However, concerns about frailty and frequent injections may deter its use in the elderly. This study aims to assess the safety, efficacy, and treatment duration of BTX-A in managing OAB in elderly women. METHODS: We retrospectively reviewed female patients aged 70 and above who were diagnosed with OAB with predominant urge urinary incontinence and underwent intravesical BTX-A treatment. We collected demographic and clinical data, with repeat BTX-A injections re-administered upon patient-reported symptom recurrence. RESULTS: Twenty-one female patients, median age 77 (range 71-92), were included. The median time between the first and second injection was 185 (84-448) days, 186 (105-959) days between the second and third injection, and increased to 206.5 (84-256) days between the third and fourth injection. However, the median interval trended downward after the fourth injection (Fig. 1). Patients with four or more injections had a shorter median interval between injections, 154 days, compared to those with fewer injections, 210 days. Two patients (6.9%) experienced urinary retention after the initial treatment, with 1 (2.2%) among a total of 46 subsequent treatments (Table 3). There were ten (13.3%) episodes of UTIs within 2 weeks of treatment. Patients reported improvement in symptoms following 93.3% of the injections. CONCLUSION: This real-world study demonstrates that BTX-A effectively controls OAB symptoms in elderly women, with just two injections annually. BTX-A appears safe and efficacious for treating OAB in elderly females.

Adjuvant therapy for renal cell carcinoma in 2023: hopes and disappointments.

PURPOSE: It is known that 30% of clear cell renal cell carcinomas (ccRCC) will develop progressive disease after surgical treatment. These patients with high-risk ccRCC require adjuvant therapy after nephrectomy or resection of metastases. The article presents an overview of the results of recent studies in adjuvant therapy. METHODS: We analyzed the results of randomized trials of targeted therapy and checkpoint inhibitors in high-risk ccRCC patients. RESULTS: Targeted therapy did not significantly reduce this risk or/and did not affect overall survival. Three randomized studies investigating nivolumab, ipilimumab, and atezolizumab in the adjuvant setting also failed without improving disease-free survival. Pembrolizumab had a significant impact on the disease-free survival in the entire population, with the greatest effect in patients after metastasectomy, but mature overall survival data are not yet available. CONCLUSIONS: In conclusion, it must be noted that, at present, it has not been possible to achieve magnificent success in adjuvant therapy of RCC in patients at high risk of relapse after surgical treatment. There remains hope for adjuvant pembrolizumab, which has been used for high-risk population including patients with removed metastases who may benefit more from therapy.

Disparities Associated with Shared Decision-making in Prostate Cancer Screening.

BACKGROUND: Prostate cancer screening guidelines recommend shared decision-making (SDM) regarding prostate-specific antigen (PSA) testing. However, it is unclear who undergoes SDM and whether any disparities exist. OBJECTIVE: To examine sociodemographic differences in participation of SDM and its association with PSA testing in prostate cancer screening. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cross-sectional study was conducted among men aged 45-75 yr undergoing PSA screening, using the 2018 National Health Interview Survey database. The evaluated sociodemographic features included age, race, marital status, sexual orientation, smoking status, working status, financial difficulty, US geographic regions, and cancer history. Questions regarding self-reported PSA testing and whether respondents discussed its advantages and disadvantages with their healthcare provider were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Our primary outcome was to evaluate the possible associations between various sociodemographic factors and undergoing PSA screening and SDM. We used multivariable logistic regression analyses to detect potential associations. RESULTS AND LIMITATIONS: A total of 59596 men were identified, of whom 5605 answered the question regarding PSA testing, with 2288 (40.6%) undergoing PSA testing. Of these men, 39.5% (n = 2226) discussed the advantages and 25.6% (n = 1434) discussed the disadvantages of PSA testing. On a multivariable analysis, older (odds ratio [OR] 1.092; 95% confidence interval [CI] 1.081-1.103, p < 0.001) and married (OR 1.488; 95% CI 1.287-1.720, p < 0.001) men were more likely to undergo PSA testing. Although Black men were more likely to discuss PSA advantages (OR 1.421; 95% CI 1.150-1.756, p = 0.001) and disadvantages (OR 1.554; 95% CI 1.240-1.947, p < 0.001) than White men, this did not correlate with higher rates of PSA screening (OR 1.086; 95% CI 0.865-1.364, p = 0.477). The lack of important clinical data remains a limitation. CONCLUSIONS: Overall, SDM rates were low. Older and married men had an increased likelihood of SDM and PSA testing. Despite higher rates of SDM, Black men had similar rates of PSA testing to White men. PATIENT SUMMARY: We evaluated sociodemographic differences in shared decision-making (SDM) in prostate cancer screening using a large national database. We found that SDM had varying results in different sociodemographic groups.

Management of Localized T1c Prostate Cancer Among Men 75 Years and Older: A National Cancer Database Study.

INTRODUCTION: Elderly men are underrepresented in prostate cancer (PCa) literature, with management based on individualized care pathways and life expectancy. Reports have shown survival benefit with radiation (XRT), surgery, and hormone (ADT) in localized disease. The objective of this study was to assess treatment trends and overall survival (OS) among men 75 years of age and older with cT1c PCa. METHODS: The National Cancer Database was queried to identify patients with cT1c PCa, aged 75 years and older, between 2004 and 2016. We excluded individuals with N1/NX or M1/MX disease, unknown treatment, treatment with both XRT and surgery, surgery other than radical prostatectomy (RP), or PSA > 10 ng/ml. We described 4 treatment cohorts: observation, XRT, surgery, and ADT alone. Treatment trends and OS were analyzed using SPSS. RESULTS: Among 49,843 patients, 7% had surgery, 66% had XRT, 5% had ADT alone, and 22% were observed. From 2004-2016, a large decline in XRT was noted, with an increase in surgery and observation. Men receiving ADT alone were significantly older, with higher Gleason's score, and lower incomes. Cox regression revealed survival benefit for surgery and XRT (HR 0.44 and 0.69, P < .001 respectively); ADT had worse survival than observation (HR 1.23, P < .001). CONCLUSION: Fewer men 75 years of age and older with cT1c PCa are being diagnosed and treated. Rates of XRT have declined, with rises in surgery and observation. Survival benefit was seen for surgery and XRT among elderly men, which highlights the importance of proper patient selection for improved outcomes in a highly individualized sphere.

Novel synthetic lethality drug target in urothelial bladder cancer based on MTAP genomic loss.

BACKGROUND: When urothelial carcinoma of the bladder (UCB) presents or progresses to chemo-refractory metastatic disease, the search for new therapeutic targets is paramount. Targeting protein arginine methyltransferase 5 accumulation in tumors with methylthioadenosine phosphorylase (MTAP) genomic loss has been proposed as a new anti-tumor strategy. We evaluated the incidence of patients with MTAP loss and correlate to treatment-guiding targets and biomarkers. METHODS: Two thousand six hundred eighty-three cases of advanced UCB underwent hybrid-capture based comprehensive genomic profiling using the FDA-approved F1CDx assay to evaluate all classes of genomic alterations (GA) among 324 genes. Tumor mutational burden was determined on at least 0.8 Mbp of sequenced DNA and microsatellite instability was determined on at least 95 loci. RESULTS: 650 (24%) of UCB featured MTAP loss mutations (MTAP-). The gene and age distributions were similar in MTAP intact (MTAP+) and MTAP- UCB. MTAP- UCB contained higher GA/tumor frequency than MTAP+ UCB likely reflecting the frequent co-deletions of cyclin-dependent kinase inhibitor 2A/B. Of potential therapeutic targets, fibroblast growth factor receptor 3, and phosphatase and tensin homolog GA were more frequent in MTAP- UCB. In contrast, biomarkers of immunotherapy response, including higher frequencies of high tumor mutational burden and high programmed death-ligand 1 IHC staining, were observed in the MTAP+ UCB. CONCLUSIONS: When compared with MTAP+ UCB, MTAP- UCB differs in genomic signatures including an increase in potentially targetable alterations but a lower frequency of immunotherapy drug biomarkers. Thus, the genomic landscape in MTAP- UCB may play a role in the design of clinical trials incorporating combination treatment strategies when targeting protein arginine methyltransferase 5 in MTAP- tumors.

Sociodemographic differences in opioid use and recovery following ambulatory pediatric urologic procedures.

Our aim was to examine associations between sociodemographic factors and postoperative opioid use and recovery among pediatric patients undergoing outpatient urologic procedures. We retrospectively evaluated 831 patients undergoing ambulatory urologic procedures from 2013 to 2017 at an urban pediatric hospital. Patients were evaluated for days of opioid use and days until return to baseline behavior. Differences in outcomes by race/ethnicity, primary language, median neighborhood household income, and health insurance type were analyzed using negative binomial regression models. Overall, patients reported a median of 1.0 day (IQR: 2.0) of postoperative opioid use and 3.0 days (IQR: 6.0) of recovery time. After controlling for covariates, patients with non-English speaking parents took opioids for 26.5% (95% CI: 11.4-41.7%) longer and had 27.8% (95% CI: 8.1-51.0%) longer recovery time than patients with English-speaking parents. Hispanic patients took opioids for 27.5% (95% CI: 0.1-54.9%) longer than White patients. Patients with public insurance used opioids for 47.6% (95% CI: 5.0-107.4%) longer than privately insured patients. Non-English speaking, Hispanic, and publicly insured patients had a longer duration of postoperative opioid use than primarily English-speaking, White, and privately insured patients, respectively. Identifying these disparities is important for designing equitable postoperative care pathways.

Perioperative outcomes of goal-directed versus conventional fluid therapy in radical cystectomy with enhanced recovery protocol.

PURPOSE: The aim of this study is to evaluate the intra/perioperative fluid management and early postoperative outcomes of patients who underwent radical cystectomy with Enhanced Recovery After Surgery protocol, using goal-directed fluid therapy compared to conventional fluid therapy. METHODS: This cohort study included patients who underwent open RC for urothelial bladder carcinoma with intent to cure and Enhanced Recovery After Surgery protocol between May 2012 and August 2019. Patients who had palliative or salvage cystectomy and/or adjunct procedures, as well as those with missing detailed perioperative data were excluded. Data were compared between patients who received goal-directed fluid therapy using stroke volume variation by FloTrac™/Vigileo system (n = 119) and conventional fluid therapy based on the anesthesiologist discretion (n = 192). Primary outcome variable was 90-day complications and secondary outcome measures included in-hospital GFR trend, length of stay, and 90-day readmission. RESULTS: The goal-directed fluid therapy group received less total and net intra/perioperative fluid, yet early postoperative glomerular filtration rate trends were similar between both groups (p = 0.7). Estimated blood loss, blood transfusion, index hospital stay, 90-day complication and readmission rates were also comparable between the two groups. Multivariable logistic regression showed no significant association between perioperative fluid management method and 90-day complication rate (OR 1.4, 95% CI 0.8-2.4, p = 0.2). CONCLUSION: Stroke volume variation guided goal-directed fluid therapy is safe in radical cystectomy without compromising the renal function. It is associated with less intra- and perioperative fluid infusion; however, no association with hospital stay, 90-day complication or readmission rates were noted.

The impact of patient age and procedure type on postoperative opioid use following ambulatory pediatric urologic procedures.

PURPOSE: The aim of this study is to determine whether patient age and procedure type are associated with duration of opioid use in pediatric patients undergoing ambulatory urologic procedures. METHODS: We retrospectively reviewed pediatric patients who underwent outpatient urologic procedures from 2013 to 2017. At postoperative visits, parents reported the number of days their child took opioid pain medication. Factors associated with duration of opioid use were evaluated using negative binomial regression models. RESULTS: 805 patients were included: 320 infants (39.8%), 430 children (53.4%), and 55 adolescents (6.8%). Overall mean length of opioid use was 1.7 (± 2.6) days. On average, infants used opioids for the shortest duration: 1.5 (± 2.3) days, followed by children: 1.7 (± 2.5) days, and adolescents: 3.1 (± 4.6) days. In adjusted models, adolescents used opioids for 85.2% longer (95% CI 13.1-161.8%; p < 0.001) than children and infants used opioids for 19.4% shorter duration (95% CI 0.4-34.7%; p = 0.05) than children. Each 1-year increase in age was associated with 6.1% increased duration of opioid use (95% CI 3.9-8.5%; p < 0.0001). Patients who underwent circumcision, hypospadias repair, and penile reconstruction took opioids for 75.9% (95% CI 42.6-117.1%; p < 0.001), 144.2% (95% CI 76.4-238.0%; p < 0.001), and 126.7% (95% CI 48.8-245.3%; p < 0.001) longer respectively than patients who underwent inguinal procedures. CONCLUSIONS: Increasing age, circumcision, hypospadias repair, and penile reconstruction are associated with increased duration of opioid use.

Perioperative Outcome of Suprarenal Resection of Vena Cava Without Reconstruction in Urologic Malignancies: A Case Series and Review of the Literature.

OBJECTIVE: To describe the feasibility and perioperative outcome of suprarenal resection of inferior vena cava (IVC) in urologic neoplasms without reconstruction. METHODS: We retrospectively reviewed the patients who underwent suprarenal resection of IVC without reconstruction for urologic neoplasms in our institution between September 2010 and October 2019. Patients' demographic, clinical, radiologic, and 90-day perioperative complications were recorded. RESULTS: Twenty-eight (79% male) patients with a median age of 59 (25-75) years were included in the study. Twenty-five (89%) of patients had renal cell carcinoma, 1 had renal leiomyosarcoma, and 2 had metastatic testicular teratoma. Twenty-two patients had Mayo level 3 thrombus, 3 had level 2, and 3 had level 4. The mean radiologic thrombus length was 12.6 cm. Eleven patients had radiologic bland thrombosis in the infrarenal IVC. Twenty-seven patients underwent open, and 1 robotic surgery. The median operating time was 411 (range 240-808) minutes, median blood loss was 3750 cc, and all but 1 patient received perioperative transfusion (median 11 units of packed red blood cells). Median hospital stay was 5 (3-50) days. Ninety-day complication rate was 35% (Clavien-Dindo grade I/II and III/IV were 21% and 14%, respectively). Four patients (14%) developed transient nondisabling leg edema. The 90-day mortality rate was 7%. CONCLUSION: Suprarenal inferior vena cava resection without reconstruction is feasible, yet high-risk operation that should be performed in experienced centers in selected patients with urologic malignancies.

Anterior Gradient 2 (AGR2) Induced Epidermal Growth Factor Receptor (EGFR) Signaling Is Essential for Murine Pancreatitis-Associated Tissue Regeneration.

A recently published study identified Anterior Gradient 2 (AGR2) as a regulator of EGFR signaling by promoting receptor presentation from the endoplasmic reticulum to the cell surface. AGR2 also promotes tissue regeneration in amphibians and fish. Whether AGR2-induced EGFR signaling is essential for tissue regeneration in higher vertebrates was evaluated using a well-characterized murine model for pancreatitis. The impact of AGR2 expression and EGFR signaling on tissue regeneration was evaluated using the caerulein-induced pancreatitis mouse model. EGFR signaling and cell proliferation were examined in the context of the AGR2-/- null mouse or with the EGFR-specific tyrosine kinase inhibitor, AG1478. In addition, the Hippo signaling coactivator YAP1 was evaluated in the context of AGR2 expression during pancreatitis. Pancreatitis-induced AGR2 expression enabled EGFR translocation to the plasma membrane, the initiation of cell signaling, and cell proliferation. EGFR signaling and tissue regeneration were partially inhibited by the tyrosine kinase inhibitor AG1478, but absent in the AGR2-/- null mouse. AG1478-treated and AGR2-/- null mice with pancreatitis died whereas all wild-type controls recovered. YAP1 activation was also dependent on pancreatitis-induced AGR2 expression. AGR2-induced EGFR signaling was essential for tissue regeneration and recovery from pancreatitis. The results establish tissue regeneration as a major function of AGR2-induced EGFR signaling in adult higher vertebrates. Enhanced AGR2 expression and EGFR signaling are also universally present in human pancreatic cancer, which support a linkage between tissue injury, regeneration, and cancer pathogenesis.