Phase 1b Trial Evaluating Tolerability and Activity of Targeted Fibroblast Growth Factor Receptor Inhibition in Localized Upper Tract Urothelial Carcinoma.

PURPOSE: We initiated a biomarker-informed preoperative study of infigratinib, a fibroblast growth factor receptor (FGFR) inhibitor, in patients with localized upper tract urothelial carcinoma (UTUC), a population with high unmet needs and tumor with a high frequency of FGFR3 alterations. MATERIALS AND METHODS: Patients with localized UTUC undergoing ureteroscopy or nephroureterectomy/ureterectomy were enrolled on a phase 1b trial (NCT04228042). Once-daily infigratinib 125 mg by mouth × 21 days (28-day cycle) was given for 2 cycles. Tolerability was monitored by Bayesian design and predefined stopping boundaries. The primary endpoint was tolerability, and the secondary endpoint was objective response based on tumor mapping, done after endoscopic biopsy and post-trial surgery. Total planned enrollment: 20 patients. Targeted sequencing performed using a NovaSeq 6000 solid tumor panel. RESULTS: From May 2021 to November 2022, 14 patients were enrolled, at which point the trial was closed due to termination of all infigratinib oncology trials. Two patients (14.3%) had treatment-terminating toxicities, well below the stopping threshold. Responses occurred in 6 (66.7%) of 9 patients with FGFR3 alterations. Responders had median tumor size reduction of 67%, with 3 of 5 patients initially planned for nephroureterectomy/ureterectomy converted to ureteroscopy. Median follow-up in responders was 24.7 months (14.9-28.9). CONCLUSIONS: In this first trial of targeted therapy for localized UTUC, FGFR inhibition was well tolerated and had significant activity in FGFR3 altered tumors. Renal preservation was enabled in a substantial proportion of participants. These data support the design of a biomarker-driven phase 2 trial of FGFR3 inhibition in this population with significant unmet clinical needs.

Low-Value Prostate Cancer Screening Among Young Men With Private Insurance.

INTRODUCTION: No professional society guidelines recommend PSA screening in men younger than age 40; however, data suggest testing occurs at meaningful rates in this age group. The purpose of this study was to identify the rate of PSA testing in men under 40. METHODS: This is a population-based, retrospective cohort study from 2008 to 2017. Using the MarketScan database, rates of testing for the sum of the annual population of men at risk were evaluated. Descriptive statistics and statistical analyses were performed in men continuously enrolled in the database for at least 5 year. Results were stratified by receipt of PSA testing and by age group. The association of diagnoses and Charlson Comorbidity Index with receipt of PSA test was evaluated using multivariable logistic regression models. RESULTS: We identified 3,230,748 men ages 18 to 39 who were enrolled for at least 5 years. The rate of ever receiving PSA testing was 0.6%, 1.7%, 8.5%, and 9.1% in men less than 25, 25 to 29, 30 to 34, and 35 to 39 years, respectively. Multivariable logistic regression showed that relative to all men 18 to 39, patients who received PSA testing had higher odds of a diagnosis of hypogonadism (OR 11.77) or lower urinary tract symptoms (OR 4.19). CONCLUSIONS: This study found a remarkable number of young men receive PSA testing, with a strong association with diagnoses of lower urinary tract symptoms and hypogonadism. Clinicians need to be educated that assessment and management guidelines for other urologic diagnoses now defer PSA testing to prostate cancer screening guidelines.

At-home use of parasacral transcutaneous electrical nerve stimulation for pediatric voiding dysfunction: a randomized controlled trial to assess its safety and feasibility.

Introduction: Treating pediatric voiding dysfunction involves behavioral changes that require significant time or medications that are often avoided or discontinued due to side effects. Using parasacral transcutaneous electrical nerve stimulation (PTENS) has shown to have reasonable efficacy, but the safety and feasibility of its off-label use for pediatric voiding dysfunction are not well-established. Concerns have also been raised over treatment adherence. In-home therapy might improve adherence compared with office-based therapy; however, no studies have evaluated in-home feasibility to date. This study aims to assess the safety and feasibility of off-label use of PTENS for pediatric voiding dysfunction. Materials and methods: A single-institution prospective, randomized controlled study was conducted from March 2019 to March 2020. Participants aged 6-18 years diagnosed with voiding dysfunction, overactive bladder, or urinary incontinence were eligible for the study. Those with known neurologic disorders, implanted electrical devices, anatomic lower urinary tract abnormality, and recurrent urinary tract infections and those taking bladder medications were excluded. Children with primary monosymptomatic nocturnal enuresis were also excluded due to previous work suggesting a lack of efficacy. Participants were randomly assigned to receive 12 weeks of urotherapy alone (control) or urotherapy plus at-home PTENS treatment. Families were contacted weekly to assess for adverse events (AEs) and treatment adherence. The primary and secondary outcomes were safety, defined as the absence of AEs and treatment adherence, respectively. Results: A total of 30 eligible participants were divided into two groups, with 15 participants in each arm. The median age was 9.4 years (interquartile range: 7.7-10.6). In total, 60% were male. Baseline demographics and urotherapy compliance were similar between the two groups. With PTENS use, two AEs were reported, including mild pruritus at the pad site and discomfort when removing pads, while no AEs were noted in the control group. In total, 60% of patients completed three 30-min sessions per week, and all participants were able to complete treatment sessions for at least 10 weeks, involving 30 min of PTENS treatment each time. Conclusion: This randomized controlled study confirms that at-home use of PTENS is feasible with reasonable treatment adherence and minimal AEs. Future collaborative, multi-institutional studies may better determine the efficacy of this treatment modality.

Optimizing Lymph Node Dissection at the Time of Nephroureterectomy for High-risk Upper Tract Urothelial Carcinoma.

Lymph node dissection (LND) has prognostic and possible therapeutic benefits in the management of high-risk upper tract urothelial carcinoma. However, LND use is low and difficult to monitor, so it is not easy to study LND outcomes and the true rate of use. Prespecified templates for complete node dissection and detailed reporting are imperative to critically assess the benefits of LND in future studies. Barriers to LND use may include fear of complications and difficulty in predicting which patients have high-risk disease. Methods to improve LND implementation include the use of strict templates with descriptive pathology reporting, nomograms for preoperative risk stratification, and LND as a quality indicator to monitor rates of use and guideline concordance. PATIENT SUMMARY: For patients with high-risk cancer of the upper urinary tract, removal of lymph nodes during surgery improves identification of the cancer stage and may have a therapeutic effect too. Further studies are needed to confirm potential therapeutic benefits.

Increasing the value of PSA through improved implementation.

Low-value testing and treatment contribute to billions of dollars in waste to the United States health care system annually. High frequency, low-cost testing, including prostate-specific antigen (PSA) testing, is a major contributor to this inefficient health care delivery. Despite decreasing mortality of prostate cancer over the last few decades, the reputation of prostate specific antigen (PSA) for prostate cancer screening has fluctuated over the last decade due to lack of clarity of the benefits of screening and high risk for overtreatment. The value of PSA could be improved by efficient implementation of smarter testing strategies that reduce the harms and increase the benefits.

Impact of choosing wisely on imaging in men with newly diagnosed prostate cancer.

INTRODUCTION: Encouraging the appropriate use of staging imaging in patients with newly diagnosed prostate cancer remains a challenge. Assessing the effects of national efforts may help guide future initiatives in curtailing low-value care. The purpose of this study was to determine the impact of the Choosing Wisely campaign on imaging utilization among men with prostate cancer. METHODS: Surveillance, Epidemiology, and End Results - Medicare data were used to complete a longitudinal population-based study of men diagnosed with prostate cancer from 2007 to 2015. An interrupted time series analysis evaluated the impact of the Choosing Wisely campaign on trends of imaging utilization. RESULTS: From 2007 to 2015 imaging utilization in low-risk patients decreased, with computed tomography (CT) usage declining from 45.0% to 34.4% (P<0.001) and nuclear medicine bone scan (NMBS) from 27.8% to 11.7% (P<0.001). Choosing Wisely likely contributed to an absolute reduction of 2.9% (P=0.03) in utilization of NMBS in the low-risk population. Imaging usage for all modalities increased in the high-risk population, but with 32.8% continuing to not receive guideline-supported imaging. CONCLUSIONS: In 2012, the Choosing Wisely campaign sought to decrease inappropriate staging imaging for men with low-risk prostate cancer and encourage stewardship of medical resources. Overall decreases in staging imaging trends suggest a move towards higher value care. However, this study found that the Choosing Wisely recommendations had a modest impact on utilization of NMBS, but not CT or PET scans. These results may help inform future efforts to promote guideline concordant imaging.

Prostate-specific antigen testing among young men: an opportunity to improve value.

INTRODUCTION: Prostate cancer screening using prostate-specific antigen (PSA) testing remains widespread. The prevalence of PSA testing in young men is unknown and may be an appropriate target for improving health care by decreasing low-value testing in this age group. The purpose of this study was to determine PSA testing rates in men younger than current guidelines support. MATERIALS AND METHODS: Health Informational National Trends Surveys (HINTS) from 2011 to 2014 and 2017 were analyzed to establish the prevalence of PSA testing in young men and to evaluate the differences in testing rates based on race. RESULTS: The combined survey data included 5178 men, with 2393 reporting previous PSA screening. Of men ages 18-39, 7% recalled receipt of PSA testing. Twenty-two percent of men between the ages of 40 and 44 had been tested. Among men under age 40, PSA testing was more common among black men (14%) compared to white men (7%), Hispanics (6%), and men of Asian descent (8%). Logistic regression modeling demonstrates that black men under the age of 40 were more likely to undergo PSA testing than other racial or ethnic groups (odds ratio 2.14; 95% CI 1.17, 3.93). CONCLUSIONS: Current guidelines do not recommend routine PSA testing in average-risk men under the age of 40. This study found that a significant number of young men are exposed to testing, with the greatest risk among black men. This suggests that there is an opportunity to improve the value of PSA testing by decreasing testing in young men.

Primary headache disorders in the emergency department.

Headache is 1 of the 5 most common chief complaints in the United States and accounts for nearly 5 million visits in the emergency department (ED; B. Freidman, D. Serrano, M. Reed, M. Diamond, & R. Lipton, 2009). Despite the number of patients admitted to EDs with a headache, there appears to be a lack of consensus among practitioners as how best to treat primary headache disorder in this patient population. Current research has taken into consideration the specific factors that contribute to ED visits by patients with headaches. This research has identified the need for standardized practice protocols for the treatment of headaches in the ED. In addition, research has focused on new strategies of pain management that takes into account the chronicity of headaches. This article focuses on an important consideration in the management of primary headache disorders provided by ED clinicians-the prevention of headache recurrence through thorough patient education and the identification and modification of risk factors.