Impact of Gene Expression Classifier Testing on Adjuvant Treatment Following Radical Prostatectomy: The G-MINOR Prospective Randomized Cluster-crossover Trial.

BACKGROUND AND OBJECTIVE: Decipher is a tissue-based genomic classifier (GC) developed and validated in the post-radical prostatectomy (RP) setting as a predictor of metastasis. We conducted a prospective randomized controlled cluster-crossover trial assessing the use of Decipher to determine its impact on adjuvant treatment after RP. METHODS: Eligible patients had undergone RP within 9 mo of enrollment, had pT3-4 disease and/or positive surgical margins, and prostate-specific antigen <0.1 ng/ml. Centers were randomized to a sequence of 3-mo periods of either GC-informed care or usual care (UC). Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) recurrence risk scores were provided to treating physicians and patients in all periods. KEY FINDINGS AND LIMITATIONS: Impact of GC test results on adjuvant treatment were compared with UC alone. Longitudinal patient-reported urinary and sexual function was assessed. A total of 175 patients were enrolled in 27 periods with GC and 163 in 28 periods with UC. At 18 mo after RP, an average patient in the GC arm received adjuvant treatment 9.7% of the time compared with 8.7% for an average individual in the UC arm (0.99% mean difference, 95% confidence interval [CI] -7.6%, 9.6%, p = 0.8). While controlling for CAPRA-S score, higher GC scores tended to result in an increased likelihood of adjuvant treatment that was not statistically significant (odds ratio [OR] = 1.35 per 0.1 increase in GC score, 95% CI 0.98-1.85, p = 0.066). Using the GC risk groups, reflecting clinical use, a high GC risk was associated with significantly higher odds of receiving adjuvant treatment (OR = 6.9, 95% CI 1.8, 26, p = 0.005) compared with a low GC score, adjusted for CAPRA-S score. There were no differences in patient-reported urinary and sexual function between the study arms. As oncologic outcomes are immature, the present data cannot address whether GC testing provides any cancer control benefit. CONCLUSIONS AND CLINICAL IMPLICATIONS: GC testing impacts adjuvant therapy administration when viewed through the risk categories presented in the patient report; however, these data do not provide specific support for GC testing in the adjuvant treatment setting.

Prevalence of unnecessary kidney function exclusion criteria in urologic oncology clinical trials.

INTRODUCTION: Clinical trials play a pivotal role in advancing treatments for people with cancer, but often struggle with low enrollment. Unnecessarily including kidney function eligibility criteria when a trial's interventions do not have any potential kidney effects may contribute to this problem by needlessly limiting the pool of eligible patients, adding complexity to the patient screening process, and raising issues of inequitable access to trials. For these reasons, we applied custom natural language processing to assess renal function eligibility criteria, and the appropriateness of these exclusions, within phase 3 urologic oncology trials. METHODS: We accessed all phase 3 urologic oncology trials registered on ClinicalTrials.gov from 2007 to 2021. We used a custom natural language processing script to extract kidney function requirements (e.g., creatinine, GFR) from trial free-text records. For each trial, we manually coded whether any trial intervention affected renal function or was renally excreted. Additionally, we recorded the formula used to calculate GFR in each trial. RESULTS: Of 850 trials, 299 (35%) listed kidney function eligibility restrictions, and 432 (51%) tested an intervention with possible renal effects. Of the 299 trials with kidney function exclusions, 124 (41%) tested interventions with no kidney effects. CONCLUSION: There is a major disconnect in urologic oncology clinical trials between renal function exclusions and potential harm to the kidneys from the tested interventions. Standardizing eligibility criteria and restricting enrollment based on renal function only when necessary has the potential to increase the success, access, and applicability of clinical trials.

Association Between Kidney Stone History and Cardiovascular Event Risk in US Adults.

OBJECTIVE: To determine the association between kidney stone history and predicted 10-year risk of atherosclerotic cardiovascular disease (CVD) events in a nationally representative US adult sample without existing CVD. METHODS: This was a cross-sectional study of the 2017-2020 National Health and Nutrition Examination Survey that included a nationally representative sample of 3842 adults aged 40-79 free from CVD. Kidney stone history was assessed through self-reporting. The 10-year risk of an atherosclerotic CVD event was predicted using the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Equations. RESULTS: The weighted prevalence of kidney stones was 12.2% (95% CI: 10.5% to 14.1%). In unadjusted analysis, the odds of borderline or higher (≥5%) atherosclerotic CVD risk were higher in stone formers (odds ratio=1.56; 95% CI 1.01-2.40; P = .046). This association persisted after adjustment for demographics and clinical covariates (adjusted odds ratio=1.57; 95% CI=1.02 to 2.43; P = .04). A significant interaction by biological sex was identified (P = .002), with excess risk conferred by kidney stones in males but not females. CONCLUSION: Kidney stone history was independently associated with increased 10-year predicted atherosclerotic CVD event risk, with excess risk observed among males but not females. Intensified CVD screening may be warranted among stone formers given their increased cardiovascular risk.

Renal Mass Biopsy is Associated With Fewer Radical Nephrectomies for Benign or Indolent Disease, Particularly for T1b Renal Masses.

INTRODUCTION: How renal mass biopsy (RMB) impacts patient management with T1 renal masses (T1RM) is unclear. We explore the association between RMB and utilization of active surveillance (AS), nephron-sparing interventions (NSI), and radical nephrectomy (RN). METHODS: Data were analyzed retrospectively using the MUSIC-KIDNEY registry. Treatment received was analyzed using a fitted mixed-effects multinomial logistic-regression model. RESULTS: Of 4062 patients, 19.6% underwent RMB. Factors associated with RMB included younger age, higher Charlson comorbidity score, tumor size > 2.0 cm and higher complexity tumors. AS was selected by 88%, 68%, and 27% of patients with benign, indeterminate, and malignant RMB findings. Non-malignant pathology at surgery was significantly (P < .0001) more common without RMB (vs after RMB): 14.8% vs 7.2% of PN and 10.2% vs 1.7% of RN. Patients with T1bRM managed without or with RMB, AS was chosen by 22% vs 34%, NSI by 31% vs 35%, and RN by 47% vs 32% (P = .0027). An interaction between tumor stage (T1a vs T1b) and RMB remained in multivariable analyses accounting for practice-level variation and other confounding variables. The risk-adjusted RN rate for T1bRM was 41.4% without RMB vs 27.8% with RMB; 7.4 RMB are needed to avoid one RN (number needed to treat) for benign or indolent disease. CONCLUSIONS: Treatments received by T1RM patients undergoing RMB are different than when RMB is omitted, based on RMB results and several confounders. T1RM patients benefit from reduction in intervention for non-malignant disease, particularly when RN is planned. For every 7 biopsies of T1bRM performed, one RN was avoided.

The impact of siphoning effect on renal pelvis pressure during ureteroscopy using an in vitro kidney and ureter model.

PURPOSE: To experimentally measure renal pelvis pressure (PRP) in an ureteroscopic model when applying a simple hydrodynamic principle, the siphoning effect. METHODS: A 9.5Fr disposable ureteroscope was inserted into a silicone kidney-ureter model with its tip positioned at the renal pelvis. Irrigation was delivered through the ureteroscope at 100 cm above the renal pelvis. A Y-shaped adapter was fitted onto the model's renal pelvis port, accommodating a pressure sensor and a 4 Fr ureteral access catheter (UAC) through each limb. The drainage flowrate through the UAC tip was measured for 60 s each run. The distal tip of the UAC was placed at various heights below or above the center of the renal pelvis to create a siphoning effect. All trials were performed in triplicate for two lengths of 4Fr UACs: 100 cm and 70 cm (modified from 100 cm). RESULTS: PRP was linearly dependent on the height difference from the center of the renal pelvis to the UAC tip for both tested UAC lengths. In our experimental setting, PRP can be reduced by 10 cmH20 simply by lowering the distal tip of a 4 Fr 70 cm UAC positioned alongside the ureteroscope by 19.7 cm. When using a 4 Fr 100 cm UAC, PRP can drop 10 cmH20 by lowering the distal tip of the UAC 23.3 cm below the level of the renal pelvis. CONCLUSION: Implementing the siphoning effect for managing PRP during ureteroscopy could potentially enhance safety and effectiveness.

Single-use flexible ureteroscopes: practice patterns, attitudes, and preferences for next-generation concepts.

Background: Single use flexible ureteroscopes (su-fURS) have emerged as an alternative to reusable flexible ureteroscopes (r-fURS) for the management of upper urinary tract calculi. However, little is known about urologist usage and attitudes about this technology. Through a worldwide survey of endourologists, we assessed practice patterns and preferences for su-fURS. Methods: An online questionnaire was sent to Endourology Society members in January 2021. The survey explored current su-fURS practice patterns, reasons for/against adoption, and preferences for next generation models including developments in imaging, intra-renal pressure, heat generation, and suction. Responses were collected through QualtricsXM over a 1-month period from surgeons in North America, Latin America, Europe, Asia, Africa, and Oceania. The study was conducted according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Results: 208 (13.9%) members responded to the survey. Most respondents (53.8%) performed >100 ureteroscopies per year. 77.9% of all respondents used su-fURS for less than half of all procedures while only 2.4% used su-fURS for every procedure. 26.0% had never used a su-fURS. Overall, usage was not influenced by a surgeon's geographic region, practice environment, or years of experience. Top reasons for not adopting su-fURS were cost (59.1%) and environmental impact (12.5%). The most desired improvements in design were smaller outer shaft size (19.4%), improved optics and vision (15.9%), and wireless connectivity (13.6%). For next generation concepts, the functions most commonly described as essential or important by respondents was the ability to suction fragments (94.3%) while the function most commonly noted as not important or unnecessary was incorporation of a temperature sensor (40.4%). Conclusions: su-fURS are not commonly used, even among urologists who perform a high number of fURS. The primary concern for adoption is cost and environmental impact. Suction capability was considered the most important future development.

Effect of preoperative alpha-blockers on ureteroscopy outcomes: A meta-analysis of randomised trials.

Objectives: This work aims to determine the efficacy and safety of preoperative alpha-blocker therapy on ureteroscopy (URS) outcomes. Methods: In this systematic review and meta-analysis of randomised trials of URS with or without preoperative alpha-blocker therapy, outcomes included the need for ureteral dilatation, stone access failure, procedure time, residual stone rate, hospital stay, and complications. Residual stone rates were reported with and without adjustments for spontaneous stone passage, medication noncompliance, or adverse events leading to patient withdrawal. Data were analysed using random-effects meta-analysis and meta-regression. Certainty of evidence was assessed using the GRADE criteria. Results: Among 15 randomised trials with 1653 patients, URS was effective and safe with a stone-free rate of 81.2% and rare (2.3%) serious complications. The addition of preoperative alpha-blockers reduced the need for ureteral dilatation (risk ratio [RR] = 0.48; 95% CI = 0.30 to 0.75; p = 0.002), access failure rate (RR = 0.36; 95% CI = 0.23 to 0.57; p < 0.001), procedure time (mean difference [MD] = -6 min; 95% CI = -8 to -3; p < 0.001), risk of residual stone in the primary (RR = 0.44; 95% CI = 0.33 to 0.66; p < 0.001) and adjusted (RR = 0.52; 95% CI = 0.40 to 0.68; p < 0.001) analyses, hospital stay (MD = -0.3 days; 95% CI = -0.4 to -0.1; p < 0.001), and complication rate (RR = 0.46; 95% CI = 0.35 to 0.59; p < 0.001). Alpha-blockers increased ejaculatory dysfunction risk and were less effective for renal/proximal ureter stones. The certainty of evidence was high or moderate for all outcomes. The main limitation of the review was inconsistency in residual stone assessment methods. Conclusion: While URS is an effective and safe treatment for stone disease, preoperative alpha-blocker therapy is well tolerated and can further improve patient outcomes.

Surgeon Skill and Perioperative Outcomes in Robot-Assisted Partial Nephrectomy.

Importance: Technical skill in complex surgical procedures may affect clinical outcomes, and there is growing interest in understanding the clinical implications of surgeon proficiency levels. Objectives: To determine whether surgeon scores representing technical skills of robot-assisted kidney surgery are associated with patient outcomes. Design, Setting, and Participants: This quality improvement study included 10 urological surgeons participating in a surgical collaborative in Michigan from July 2021 to September 2022. Each surgeon submitted up to 7 videos of themselves performing robot-assisted partial nephrectomy. Videos were segmented into 6 key steps, yielding 127 video clips for analysis. Each video clip was deidentified and distributed to at least 3 of the 24 blinded peer surgeons from the collaborative who also perform robot-assisted partial nephrectomy. Reviewers rated technical skill and provided written feedback. Statistical analysis was performed from May 2023 to January 2024. Main Outcomes and Measures: Reviewers scored each video clip using a validated instrument to assess technical skill for partial nephrectomy on a scale of 1 to 5 (higher scores indicating greater skill). For all submitting surgeons, outcomes from a clinical registry were assessed for length of stay (LOS) greater than 3 days, estimated blood loss (EBL) greater than 500 mL, warm ischemia time (WIT) greater than 30 minutes, positive surgical margin (PSM), 30-day emergency department (ED) visits, and 30-day readmission. Results: Among the 27 unique surgeons who participated in this study as reviewers and/or individuals performing the procedures, 3 (11%) were female, and the median age was 47 (IQR, 39-52) years. Risk-adjusted outcomes were associated with scores representing surgeon skills. The overall performance score ranged from 3.5 to 4.7 points with a mean (SD) of 4.1 (0.4) points. Greater skill was correlated with significantly lower rates of LOS greater than 3 days (-6.8% [95% CI, -8.3% to -5.2%]), EBL greater than 500 mL (-2.6% [95% CI, -3.0% to -2.1%]), PSM (-8.2% [95% CI, -9.2% to -7.2%]), ED visits (-3.9% [95% CI, -5.0% to -2.8%]), and readmissions (-5.7% [95% CI, -6.9% to -4.6%]) (P < .001 for all). Higher overall score was also associated with higher partial nephrectomy volume (ß coefficient, 11.4 [95% CI, 10.0-12.7]; P < .001). Conclusions and Relevance: In this quality improvement study on video-based evaluation of robot-assisted partial nephrectomy, higher technical skill was associated with lower rates of adverse clinical outcomes. These findings suggest that video-based evaluation plays a role in assessing surgical skill and can be used in quality improvement initiatives to improve patient care.

Development and validation of a multicenter Cox regression model to predict all-cause mortality in patients with renal masses suspicious for renal cancer.

OBJECTIVE: Life expectancy models are useful tools to support clinical decision-making. Prior models have not been used widely in clinical practice for patients with renal masses. We sought to develop and validate a model to predict life expectancy following the detection of a localized renal mass suspicious for renal cell carcinoma. MATERIALS AND METHODS: Using retrospective data from 2 large centers, we identified patients diagnosed with clinically localized renal parenchymal masses from 1998 to 2018. After 2:1 random sampling into a derivation and validation cohort stratified by site, we used age, sex, log-transformed tumor size, simplified cardiovascular index and planned treatment to fit a Cox regression model to predict all-cause mortality from the time of diagnosis. The model's discrimination was evaluated using a C-statistic, and calibration was evaluated visually at 1, 5, and 10 years. RESULTS: We identified 2,667 patients (1,386 at Corewell Health and 1,281 at Johns Hopkins) with renal masses. Of these, 420 (16%) died with a median follow-up of 5.2 years (interquartile range 2.2-8.3). Statistically significant predictors in the multivariable Cox regression model were age (hazard ratio [HR] 1.04; 95% confidence interval [CI] 1.03-1.05); male sex (HR 1.40; 95% CI 1.08-1.81); log-transformed tumor size (HR 1.71; 95% CI 1.30-2.24); cardiovascular index (HR 1.48; 95% CI 1.32-1.67), and planned treatment (HR: 0.10, 95% CI: 0.06-0.18 for kidney-sparing intervention and HR: 0.20, 95% CI: 0.11-0.35 for radical nephrectomy vs. no intervention). The model achieved a C-statistic of 0.74 in the derivation cohort and 0.73 in the validation cohort. The model was well-calibrated at 1, 5, and 10 years of follow-up. CONCLUSIONS: For patients with localized renal masses, accurate determination of life expectancy is essential for decision-making regarding intervention vs. active surveillance as a primary treatment modality. We have made available a simple tool for this purpose.

Daily Ecological Momentary Assessments of Pain and Ability to Work After Ureteroscopy and Stenting.

Introduction: Ureteral stents can cause significant patient discomfort, yet the temporal dynamics and impact on activities remain poorly characterized. We employed an automated tool to collect daily ecological momentary assessments (EMAs) regarding pain and the ability to work following ureteroscopy with stenting. Our aims were to assess feasibility and better characterize the postoperative patient experience. Materials and Methods: As an exploratory endpoint within an ongoing clinical trial, patients undergoing ureteroscopy with stenting were asked to complete daily EMAs for 10 days postoperatively or until the stent was removed. Questionnaires were distributed through text messages and included a pain scale (0-10) and a single item from the validated Patient-Reported Outcomes Measurement Information System Ability to Participate in Social Roles and Activities instrument, as well as days missed from work or school. Results: Among the first 65 trial participants, 59 completed at least 1 EMA (overall response rate 91%). Response rates were >85% for each time point through postoperative day (POD)10. Median respondent age was 58 years (interquartile range [IQR] 50-67), and 56% were female. Stones were 54% renal and 46% ureteral, with a median diameter of 9 mm (IQR 7-10). Median stent dwell time was 7 days (IQR 6-8). Pain scores were highest on POD1 (median score 4) and declined on each subsequent day, reaching a median score of 2 on POD5. Sixty-three percent of patients on POD1 reported that they had trouble performing their usual work at least sometimes, but by POD5, this was <50% of patients. Patients who work or attend school reported a median of 1 day missed (IQR 0-2). Conclusions: An automated daily EMA system for capturing patient-reported outcomes was demonstrated to be feasible with sustained excellent engagement. Patients with stents reported the worst pain and interference with work on POD1, with steady improvements thereafter, and by POD5, the majority of patients had minimal pain or trouble performing their usual work. This work is associated with a registered clinical trial [NCT05026710].

Assessing renal tissue temperature changes and perfusion effects during laser activation in an in vivo porcine model.

INTRODUCTION: High fluid temperatures have been seen in both in vitro and in vivo studies with laser lithotripsy, yet the thermal distribution within the renal parenchyma has not been well characterized. Additionally, the heat-sink effect of vascular perfusion remains uncertain. Our objectives were twofold: first, to measure renal tissue temperatures in response to laser activation in a calyx, and second, to assess the effect of vascular perfusion on renal tissue temperatures. METHODS: Ureteroscopy was performed in three porcine subjects with a prototype ureteroscope containing a temperature sensor at its tip. A needle with four thermocouples was introduced percutaneously into a kidney with ultrasound guidance to allow temperature measurement in the renal medulla and cortex. Three trials of laser activation (40W) for 60 s were conducted with an irrigation rate of 8 ml/min at room temperature in each subject. After euthanasia, three trials were repeated without vascular perfusion in each subject. RESULTS: Substantial temperature elevation was observed in the renal medulla with thermal dose in two of nine trials exceeding threshold for tissue injury. The temperature decay time (t½) of the non-perfused trials was longer than in the perfused trials. The ratio of t½ between them was greater in the cortex than the medulla. CONCLUSION: High-power laser settings (40W) can induce potentially injurious temperatures in the in vivo porcine kidney, particularly in the medullary region adjacent to the collecting system. Additionally, the influence of vascular perfusion in mitigating thermal risk in this susceptible area appears to be limited.

The evolving management of small renal masses.

Small renal masses (SRMs) are a heterogeneous group of tumours with varying metastatic potential. The increasing use and improving quality of abdominal imaging have led to increasingly early diagnosis of incidental SRMs that are asymptomatic and organ confined. Despite improvements in imaging and the growing use of renal mass biopsy, diagnosis of malignancy before treatment remains challenging. Management of SRMs has shifted away from radical nephrectomy, with active surveillance and nephron-sparing surgery taking over as the primary modalities of treatment. The optimal treatment strategy for SRMs continues to evolve as factors affecting short-term and long-term outcomes in this patient cohort are elucidated through studies from prospective data registries. Evidence from rapidly evolving research in biomarkers, imaging modalities, and machine learning shows promise in improving understanding of the biology and management of this patient cohort.

Experts' recommendations in laser use for the treatment of urolithiasis: a comprehensive guide by the European Section of Uro-Technology (ESUT) and Training-Research in Urological Surgery and Technology (T.R.U.S.T.)-Group.

PURPOSE: To identify laser lithotripsy settings used by experts for specific clinical scenarios and to identify preventive measures to reduce complications. METHODS: After literature research to identify relevant questions, a survey was conducted and sent to laser experts. Participants were asked for preferred laser settings during specific clinical lithotripsy scenarios. Different settings were compared for the reported laser types, and common settings and preventive measures were identified. RESULTS: Twenty-six laser experts fully returned the survey. Holmium-yttrium-aluminum-garnet (Ho:YAG) was the primary laser used (88%), followed by thulium fiber laser (TFL) (42%) and pulsed thulium-yttrium-aluminum-garnet (Tm:YAG) (23%). For most scenarios, we could not identify relevant differences among laser settings. However, the laser power was significantly different for middle-ureteral (p = 0.027), pelvic (p = 0.047), and lower pole stone (p = 0.018) lithotripsy. Fragmentation or a combined fragmentation with dusting was more common for Ho:YAG and pulsed Tm:YAG lasers, whereas dusting or a combination of dusting and fragmentation was more common for TFL lasers. Experts prefer long pulse modes for Ho:YAG lasers to short pulse modes for TFL lasers. Thermal injury due to temperature development during lithotripsy is seriously considered by experts, with preventive measures applied routinely. CONCLUSIONS: Laser settings do not vary significantly between commonly used lasers for lithotripsy. Lithotripsy techniques and settings mainly depend on the generated laser pulse's and generator settings' physical characteristics. Preventive measures such as maximum power limits, intermittent laser activation, and ureteral access sheaths are commonly used by experts to decrease thermal injury-caused complications.

Does Urologist-level Utilization of Active Surveillance for Low-risk Prostate Cancer Correspond with Utilization of Active Surveillance for Small Renal Masses?

Active surveillance (AS) for prostate cancer (CaP) or small renal masses (SRMs) helps in limiting the overtreatment of indolent malignancies. Implementation of AS for these conditions varies substantially across individual urologists. We examined the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry to assess for correlation of AS between patients with low-risk CaP and patients with SRM managed by individual urologists. We identified 27 urologists who treated at least ten patients with National Comprehensive Cancer Network low-risk CaP and ten patients with SRMs between 2017 and 2021. For surgeons in the lowest quartile of AS use for low-risk CaP (<74%), 21% of their patients with SRMs were managed with AS, in comparison to 74% of patients of surgeons in the highest quartile (>90%). There was a modest positive correlation between the surgeon-level risk-adjusted proportions of patients managed with AS for low-risk CaP and for SRMs (Pearson correlation coefficient 0.48). A surgeon's tendency to use AS to manage one low-risk malignancy corresponds to their use of AS for a second low-risk condition. By identifying and correcting structural issues associated with underutilization of AS, interventions aimed at increasing AS use may have effects that influence clinical tendencies across a variety of urologic conditions. PATIENT SUMMARY: The use of active surveillance (AS) for patients with low-risk prostate cancer or small kidney masses varies greatly among individual urologists. Urologists who use AS for low-risk prostate cancer were more likely to use AS for patients with small kidney masses, but there is room to improve the use of AS for both of these conditions.