The Use of Genetic Testing in Nephrolithiasis Evaluation: A Retrospective Review from a Multidisciplinary Kidney Stone Clinic.

OBJECTIVES: To describe genetic and clinical characteristics for patients undergoing genetic testing at our multidisciplinary kidney stone clinic. METHODS: A retrospective review was performed on patients evaluated in our stone clinic and referred to genetics between 2018 and 2022. Patient demographic, clinical, stone, and genetic data were included. We assessed the specific variants identified in our cohort, both those with a pathogenic association and variants of unknown significance (VUS). RESULTS: Of 825 patients seen in our stone clinic from 2018-2022, 50 patients were referred to genetics. Among these patients, 33/50 (66%) underwent genetic testing and were included in the analysis. Of those who underwent genetic testing, a variant was identified in 19/33 (58%) patients, and 9/33 (27%) of these were a known pathogenic variant. Among patients with a pathogenic variant identified, the majority had a family history of stones (55.6%), calcium-based stones (77.8%), had their first stone prior to age 18 (66.7), were recurrent stone formers (100%), and had been managed medically (88.9%) or surgically (88.9%) prior to testing. When comparing patients with a pathogenic variant, VUS, and no variant, there were no significant differences in demographic or clinical parameters. CONCLUSION: In our stone practice, more than half of patients who underwent genetic testing were found to have a variant. However, the majority of these variants were of unknown significance. Further evaluation regarding how genetic testing can impact nephrolithiasis management is needed.

Trends in patient complexity, practice setting, and surgeon reimbursement for urolithiasis: do rural urologists pay the price?

OBJECTIVES: To evaluate the relationship between patient complexity, practice setting, and surgeon reimbursement for ureteroscopy and percutaneous nephrolithotomy (PCNL). METHODS: The "2021 Medicare Physician and Other Provider" file was used to collect Rural-Urban Commuting Area (RUCA) codes and hierarchical condition category (HCC) scores of urologists. Higher HCC score corresponds to higher medical complexity and higher RUCA code corresponds to a more rural area. Medicare reimbursement for ureteroscopy and PCNL were collected. Linear regressions were performed to predict change in reimbursement based on RUCA and HCC scores. RESULTS: In 2021, 52,816 procedures under CPT code 52356 (ureteroscopy) and 1649 procedures under 50080 or 50081 (PCNL) were billed to Medicare. Mean reimbursement was $338.24 for ureteroscopy and $957.89 for PCNL. For ureteroscopy, higher HCC score predicted lower reimbursement (p<0.001). Higher HCC score predicted higher reimbursement for PCNL (p<0.01). Average RUCA for ureteroscopy was higher than for PCNL (p=0.02). Rural location predicted lower reimbursement for ureteroscopy (p<0.001), however there was no association for PCNL. CONCLUSIONS: For ureteroscopy, higher-risk patients are associated with lower reimbursement while the opposite holds true for PCNL. Rural practices were associated with lower reimbursement for ureteroscopy, but there was no association between location and PCNL reimbursement. Together, these findings suggest practice pattern variation between ureteroscopy and PCNL and highlight gaps in reimbursement policy. Risk-adjusted reimbursement should be considered to incentivize urologists to treat complex patients within their practice scope.

Lifetime Health and Economic Outcomes of Biparametric Magnetic Resonance Imaging as First-Line Screening for Prostate Cancer : A Decision Model Analysis.

BACKGROUND: Contemporary prostate cancer (PCa) screening uses first-line prostate-specific antigen (PSA) testing, possibly followed by multiparametric magnetic resonance imaging (mpMRI) for men with elevated PSA levels. First-line biparametric MRI (bpMRI) screening has been proposed as an alternative. OBJECTIVE: To evaluate the comparative effectiveness and cost-effectiveness of first-line bpMRI versus PSA-based screening. DESIGN: Decision analysis using a microsimulation model. DATA SOURCES: Surveillance, Epidemiology, and End Results database; randomized trials. TARGET POPULATION: U.S. men aged 55 years with no prior screening or PCa diagnosis. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. health care system. INTERVENTION: Biennial screening to age 69 years using first-line PSA testing (test-positive threshold, 4 µg/L) with or without second-line mpMRI or first-line bpMRI (test-positive threshold, PI-RADS [Prostate Imaging Reporting and Data System] 3 to 5 or 4 to 5), followed by biopsy guided by MRI or MRI plus transrectal ultrasonography. OUTCOME MEASURES: Screening tests, biopsies, diagnoses, overdiagnoses, treatments, PCa deaths, quality-adjusted and unadjusted life-years saved, and costs. RESULTS OF BASE-CASE ANALYSIS: For 1000 men, first-line bpMRI versus first-line PSA testing prevented 2 to 3 PCa deaths and added 10 to 30 life-years (4 to 11 days per person) but increased the number of biopsies by 1506 to 4174 and the number of overdiagnoses by 38 to 124 depending on the biopsy imaging scheme. At conventional cost-effectiveness thresholds, first-line PSA testing with mpMRI followed by either biopsy approach for PI-RADS 4 to 5 produced the greatest net monetary benefits. RESULTS OF SENSITIVITY ANALYSIS: First-line PSA testing remained more cost-effective even if bpMRI was free, all men with low-risk PCa underwent surveillance, or screening was quadrennial. LIMITATION: Performance of first-line bpMRI was based on second-line mpMRI data. CONCLUSION: Decision analysis suggests that comparative effectiveness and cost-effectiveness of PCa screening are driven by false-positive results and overdiagnoses, favoring first-line PSA testing with mpMRI over first-line bpMRI. PRIMARY FUNDING SOURCE: National Cancer Institute.

High-Risk Patients Undergoing Holmium Laser Enucleation of the Prostate Have Fewer Infections with a Longer Course of Preoperative Antibiotics.

Introduction: There are minimal data to guide antibiotic management of patients undergoing holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia. Specifically, management of high-risk patients who are catheter dependent or have positive preoperative urine cultures varies widely. We aimed to evaluate the effect of preoperative antibiotic duration on infectious complications in high-risk patients undergoing HoLEP. Methods: A multi-institutional retrospective review of patients undergoing HoLEP between 2018 and 2023 at five institutions was performed. Patients were defined as high risk if they were catheter-dependent (indwelling urethral catheter, self-catheterization, or suprapubic tube) or had a positive preoperative urine culture. These patients were categorized into long course (>3 days) or short course (≤3 days) of preoperative antibiotics. The primary outcome was 30-day infectious complications defined as a positive urine culture with symptoms. A t-test or Wilcoxon rank-sum test was used for continuous variables and Fisher's exact test was used for categorical variables. Logistic regression analysis was conducted to identify associations with infectious complications. Results: Our cohort included 407 patients, of which 146 (36%) and 261 (64%) were categorized as short course and long course of preoperative antibiotics, respectively. Median preoperative antibiotic duration was 1 day (interquartile range [IQR]: 0, 3 days) and 7 days (IQR: 5, 7 days) in the short and long cohorts, respectively. Thirty-day postoperative infectious complications occurred in 11 (7.6%) patients who received a short course of antibiotics and 5 (1.9%) patients who received a long course of antibiotics (odds ratio 0.24, 95% confidence interval 0.07-0.67; p = 0.009). Variables such as age, positive urine culture, and postoperative antibiotic duration were not significantly associated with postoperative infection after propensity score weighting. Conclusion: In high-risk patients undergoing HoLEP, infectious complications were significantly lower with a long course vs short course of antibiotics. Further prospective trials are needed to identify optimal preoperative antibiotic regimens.

Access to Care and Health Care Utilization Among Patients With Nephrolithiasis.

OBJECTIVE: To characterize the impact of nephrolithiasis diagnosis and treatment on health care utilization and identify predictors of barriers to care in the patient population. METHODS: We conducted a retrospective cohort study using the All of Us Database, a National Institutes of Health database targeting recruitment of underrepresented populations. Patients with a diagnosis of kidney stones were included and matched to a control group. Primary outcomes were patients' self-reported health care access and utilization. Univariable and multivariable regression analyses were performed. RESULTS: 9173 patients with a diagnosis of nephrolithiasis were included and matched to 9173 controls without a diagnosis of nephrolithiasis. Patients with kidney stones were less likely to have had >1 year since last provider visit (1.7% vs 3.8%, P <.001), but did not report increased delays obtaining care (31%), inability to afford care (11.4%), or higher likelihood of skipping medications (12.9%). Among patients with stones, 1208 (13.2%) had been treated surgically. On multivariable analysis, younger age, female sex, lower income, lower education, non-insured status, and lower physical and mental health were all associated with delays obtaining care, difficulty affording care, skipping medications, and/or prolonged time since seeing a provider. CONCLUSION: A diagnosis of nephrolithiasis and subsequent surgical intervention were not associated with an increase in patient-reported barriers to care. However, among patients with nephrolithiasis, younger, comorbid, female patients from lower socioeconomic status are at significant risk of being unable to access and utilize treatment.

The Impact of Standard vs Early Apical Release Holmium Laser Enucleation of the Prostate Technique on Postoperative Incontinence and Quality of Life.

OBJECTIVE: To investigate the difference in postoperative incontinence and quality of life comparing standard vs early apical release (EAR) Holmium Laser Enucleation of the Prostate (HoLEP). METHODS: A retrospective review was performed to identify patients who underwent HoLEP from December 2021 to December 2022 at a single tertiary referral center with two participating consultant urologists. Patients were assessed with questionnaires and evaluated clinically. We performed propensity score matching with a logistic regression and a 1:1 matching method. A propensity score-adjusted logistic regression (PSRM) was performed to compare the pads per day between surgical techniques controlling for age, prostate size, preoperative survey data, uroflow, and postvoid residual. RESULTS: One hundred fourteen patients underwent HoLEP, of which 60 patients were treated with EAR and 54 patients with standard technique. EAR technique demonstrated shorter operative times (P = .046). The EAR cohort demonstrated improved AUASS (P = .034, P = .001), QOL (P = .001, P <.001), and continence rates (P <.001, P <.001) at 6 and 12weeks postoperatively. PSRM showed that the standard HoLEP increased the risk of requiring ≥2 pads per day 4.2x (P = .031, HR 95%, CI=1.16, 15.35) and 8.3x (P <.001, HR 95% CI 3.17, 21.6) at 6 and 12weeks postoperatively. CONCLUSION: EAR technique promoted earlier return of continence and improved quality of life within 6weeks of surgery.

Are adverse events during surgery for benign prostatic hyperplasia device related? A review of the MAUDE database.

PURPOSE: The Manufacturer and User Facility Device Experience database contains anonymous, voluntary medical device reports. A review of device-related adverse events associated with Benign Prostatic Hyperplasia surgeries was completed. The objective was to evaluate the occurrence and contributing factors to clinically significant complications in a cohort of patients electing to undergo surgical intervention for Benign Prostatic Hyperplasia. METHODS: The Manufacturer and User Facility Device Experience database was queried for "Aquablation, Greenlight Laser, Holmium Laser, Morcellator, Water Vapor Thermal Therapy, Loop Resection, and Prostatic Urethral Lift" from 2018 through 2021. A complication classification system (Level I-IV) based on the Clavien-Dindo system was used to categorize events. These events were then correlated with procedural technology malfunctions and classified as "device related" and "non-device related." Chi squared analysis was performed to identify associations between procedural technology and complication classification distribution. RESULTS: A total of 873 adverse events were identified. The adverse events were classified into level I (minimal harm) versus levels II-IV (clinically significant). Aquablation (p < 0.017) and Water Vapor Thermal Therapy (p < 0.012) were associated with a higher proportion of reports with Level II-IV complications compared with other procedure types. Level II-IV complications were not associated with a reported device related malfunction. CONCLUSIONS: Aquablation and water vapor thermal therapy demonstrated noteworthy clinically significant complications which were not driven by device-related malfunctions.

Salvage vesiculectomy for local prostate cancer recurrence: surgical technique and early post-operative outcomes.

PURPOSE: Isolated recurrence in remnants of the seminal vesicles (SV) after treatment of primary prostate cancer (PCa) has become a more frequent entity with the widespread use of more sensitive next-generation imaging modalities. Salvage vesiculectomy is hypothesized to be a worthwhile management option in these patients. The primary goal of this study is to describe the surgical technique of this new treatment option. Secondary outcomes are peri- and post-operative complications and early oncological outcomes. METHODS: Retrospective multicenter study, including 108 patients with solitary recurrence in the SV treated between January 2009 and June 2022, was performed. Patients with local recurrences outside the SVs or with metastatic disease were excluded. Both SVs were resected using a robot-assisted or an open approach. In selected cases, a concomitant lymphadenectomy was performed. RESULTS: Overall, 31 patients (29%) reported complications, all but one grade 1 to 3 on the Clavien-Dindo Scale. A median PSA decrease of 2.07 ng/ml (IQR: 0.80-4.33, p < 0.001), translating into a median PSA reduction of 92% (IQR: 59-98%) was observed. At a median follow-up of 14 months, freedom from secondary treatment was 54%. Lymphadenectomy had a significant influence on PSA reduction (p = 0.018). CONCLUSION: Salvage vesiculectomy for PCa recurrence limited to the SV is a safe procedure with excellent PSA response and is a potential curative treatment in a subset of patients. A concomitant lymphadenectomy can best be performed in all patients that did not underwent one at primary treatment.

Evaluation of Private Payer and Patient Out-of-Pocket Costs Associated With the Surgical Management of Benign Prostatic Hyperplasia.

OBJECTIVE: To evaluate and compare the financial burden of various surgical interventions for the management of benign prostatic hyperplasia (BPH). METHODS: We identified commercially insured men with a diagnosis of BPH who underwent a procedure of interest (simple prostatectomy (SP), transurethral resection of the prostate (TURP), holmium laser enucleation of the prostate (HoLEP), photovaporization of the prostate (PVP), prostatic urethral lift (PUL), or water vapor thermal therapy (WVTT)) between 2015 and 2021 with the OptumLabs Data Warehouse. Primary outcome was total health care costs (THC) which included both patient out-of-pocket (OOP) and health plan paid costs for the index procedure and combined follow-up years 1-5. A generalized linear model was used to estimate adjusted costs controlling for demographic and clinical characteristics. Patients undergoing WVTT were excluded from extended follow-up analyses due to limited data. RESULTS: Among 25,407 patients with BPH, 10,117 (40%) underwent TURP, 6353 (25%) underwent PUL, 5411 (21%) underwent PVP, 1319 (5%) underwent SP, 1243 (5%) underwent WVTT, and 964 (4%) underwent HoLEP. Index procedure costs varied significantly with WVTT being the least costly [THC: $2637 (95% confidence interval (CI): $2513-$2761)], and SP being the costliest [THC: $14,423 (95% CI: $12,772-$16,075)]. For aggregate index and 5-year follow-up costs, HoLEP ($31,926 [95% CI: $29,704-$34,148]) was the least costly and PUL ($36,596 [95% CI: $35,369-37,823]) was the costliest. CONCLUSION: BPH surgical treatment is associated with significant system-level health care costs. The level of impact varies between procedures. Minimally invasive options, such as WVTT, may offer initial cost reductions; however, HoLEP and SP are associated with lower follow-up costs.

Comparative cost-effectiveness of contemporary treatment strategies for stage IIA seminoma.

BACKGROUND: The Surgery in Early Metastatic Seminoma (SEMS) trial examined retroperitoneal lymph node dissection as first-line treatment for patients with isolated 1-3 cm retroperitoneal lymphadenopathy. To date, the standard of care for these patients has been either chemotherapy or radiotherapy. Herein, we evaluated the relative cost-effectiveness of these management strategies. METHODS: A microsimulation model assessed the cost-effectiveness of retroperitoneal lymph node dissection, chemotherapy, and radiotherapy for stage IIA seminoma. Sensitivity analyses were performed to evaluate model robustness. Retroperitoneal lymph node dissection recurrence probabilities were obtained from the SEMS trial. All other probability and utility values were obtained from published literature. Primary outcomes included costs from a commercial insurer's perspective, effectiveness (quality adjusted life-years [QALYs]), and incremental cost-effectiveness ratios using a willingness-to-pay threshold of $100 000/QALY. RESULTS: At a lifetime horizon, the mean costs per patient for retroperitoneal lymph node dissection, radiotherapy, and chemotherapy were $58 469, $98 783, and $104 096, and the mean QALYs were 40.61, 40.70, and 39.15, respectively. Retroperitoneal lymph node dissection was found to be the most cost-effective approach because of high costs and accrued disutility of chronic toxicities associated with radiotherapy (cost-effectiveness ratios = $433 845/QALY) and chemotherapy (dominated). On 1-way sensitivity analyses, retroperitoneal lymph node dissection was no longer cost-effective if the probabilities of infertility and cardiovascular toxicity after radiotherapy were less than 13% and 16%, respectively, or if the 2-year probability of progression after retroperitoneal lymph node dissection was more than 26%. CONCLUSIONS: Retroperitoneal lymph node dissection was the most cost-effective treatment approach for stage IIA seminoma. These findings support clinical guideline consideration of including retroperitoneal lymph node dissection as a treatment option for well-selected patients with stage IIA seminoma.

Reuse and Reprocessing of Endoscopic Instruments: For.

Reusable endoscopes appear to be most environmentally sustainable when the carbon footprint of routine device maintenance is optimized. Single-use endoscopes may offer cost-savings in clinical settings that accelerate device damage, such as prolonged procedure time or complex patient anatomy. For many urology practices, a hybrid approach that integrates single-use and reusable devices may be most economically sensible and environmentally sound.

Healthcare system contact following ureteroscopy: does discharge instruction readability matter?

INTRODUCTION: We aimed to assess the impact of discharge instruction (DCI) readability on 30-day postoperative contact with the healthcare system. MATERIALS AND METHODS: Utilizing a multidisciplinary team, DCI were modified for patients undergoing cystoscopy, retrograde pyelogram, ureteroscopy, laser lithotripsy, and stent placement (CRULLS) from a 13th grade to a 7th grade reading level. We retrospectively reviewed 100 patients including 50 consecutive patients with original DCI (oDCI) and 50 consecutive patients with improved readability DCI (irDCI). Clinical and demographic data collected including healthcare system contact (communications [phone or electronic message], emergency department [ED], and unplanned clinic visits) within 30 days of surgery. Uni/multivariate logistic regression analyses used to identify factors, including DCI-type, associated with increased healthcare system contact. Findings reported as odds ratios with 95% confidence intervals and p values (< 0.05 significant). RESULTS: There were 105 contacts to the healthcare system within 30 days of surgery: 78 communications, 14 ED visits and 13 clinic visits. There were no significant differences between cohorts in the proportion of patients with communications (p = 0.16), ED visits (p =1.0) or clinic visits (p = 0.37). On multivariable analysis, older age and psychiatric diagnosis were associated with significantly increased odds of overall healthcare contact (p = 0.03 and p = 0.04) and communications (p = 0.02 and p = 0.03). Prior psychiatric diagnosis was also associated with significantly increased odds of unplanned clinic visits (p = 0.003). Overall, irDCI were not significantly associated with the endpoints of interest. CONCLUSIONS: Increasing age and prior psychiatric diagnosis, but not irDCI, were significantly associated with an increased rate of healthcare system contact following CRULLS.

Effect of Cannabidiol Oil on Post-ureteroscopy Pain for Urinary Calculi: A Randomized, Double-blind, Placebo-controlled Trial.

PURPOSE: Post-ureteroscopy stent placement carries significant morbidity which can interfere with daily life. This discomfort unfortunately leads to high utilization of opioid pain medications, which have a known risk of addiction. Cannabidiol oil represents an alternative analgesic that has proven anti-inflammatory and antinociceptive effects. The purpose was to evaluate the effect of a Food and Drug Administration-approved cannabidiol oil (Epidiolex) on pain control and opioid usage in the post-ureteroscopy setting. MATERIALS AND METHODS: This was a prospective, randomized, double-blind, placebo-controlled trial at a tertiary care center. Ninety patients undergoing ureteroscopy with stent placement for urinary stone disease were randomized 1:1 to placebo or 20 mg cannabidiol oil daily for 3 days postoperatively. Both groups were prescribed a rescue narcotic, tamsulosin, oxybutynin, and phenazopyridine. Daily pain scores, medication usage, and ureteral stent symptoms using the validated Ureteral Stent Symptom Questionnaire were recorded postoperatively. RESULTS: Both the placebo and cannabidiol oil groups were not different in pre- and perioperative characteristics. There was no difference in pain scores or opioid usage between groups postoperatively. The level of discomfort with ureteral stents was also not different between groups when comparing physical activity, sleep, urination, and activities of daily life. CONCLUSIONS: This randomized, blinded, placebo-controlled trial showed that cannabidiol oil is safe but ineffective when compared to placebo in reducing post-ureteroscopic stent discomfort or opioid usage. Despite the availability of numerous analgesic agents, stent symptoms continue to be a dissatisfier for most patients, suggesting additional work needs to focus on novel interventions and pain control.

Neuromuscular Paralysis is not a Barrier to Same Day Catheter Removal After HoLEP.

OBJECTIVE: To determine if same day catheter removal is feasible in a population of holmium laser enucleation of the prostate patients who received paralysis and if bladder pressure monitoring could predict successful catheter removal. METHODS: From February 2021 to February 2022, we evaluated same day catheter removal for patients undergoing holmium laser enucleation of the prostate. Criteria for proceeding with same day catheter removal included: an uncomplicated procedure, continuous bladder irrigation weaned within 120 minutes of arrival to PACU, minimal postoperative hematuria and a bladder pressure over 30 cmH20 as measured using the VP Test device (SRS Medical). RESULTS: One hundred and eight patients were enrolled, with a median age of 68 years (IQR: 62.0-73.0) and prostate volume 80.8cc (IQR: 64.8-112.3). Criteria for catheter removal was met by 83/108 (76.9%) patients. Of those that attempted a trial of void, 69/83 passed for an effective pass rate of 83.1%. Median maximum detrusor pressure for those that passed and failed were 51.0 cmH20 (IQR: 40.5 -68.0) and 48.0 cmH20 (IQR: 38.8-61.8) [P = .53], respectively. Intraoperative Lasix administration was associated with a higher rate of trial of void (TOV) success and preoperative PVR was associated with lower TOV success, with OR (95%CI) of 5.8 (1.4, 29.5) [P = .02] and 0.6 (0.4, 0.9) [P = .01], respectively. CONCLUSION: Same day catheter removal is feasible in those who receive neuromuscular paralysis, with a success rate >80%. Bladder pressure monitoring did not assist with differentiating which patients will pass or fail a trial of void. Intraoperative Lasix administration may be helpful in increasing success for same day catheter removal while elevated preoperative PVR was associated with TOV failure.

Evaluation of the Cost-Effectiveness of Surgical Treatment Options for Benign Prostatic Hyperplasia.

OBJECTIVE: To compare the cost-effectiveness of surgical interventions for BPH. METHODS: Using a Markov model, a cost-utility analysis was performed comparing HoLEP, B-TURP, WVTT, and PUL for prostate size <80cc (index patient 1) and HoLEP and SP for prostate size >80cc (index patient 2). Model probabilities and utility values were drawn from the literature. Analysis was performed at a 5-year time horizon with extrapolation to a lifetime horizon. Primary outcomes included quality-adjusted life years (QALYs), 2021 Medicare costs, and incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100,000/QALY. Univariate and probabilistic sensitivity analyses were performed. RESULTS: At 5 years, costs per patient for index patient 1 were $3292 (WVTT), $6532 (HoLEP), $6670 (B-TURP), and $10,257 (PUL). HoLEP resulted in the highest QALYs (4.66), followed by B-TURP (4.60), PUL (4.38), and WVTT (4.38). This translated to HoLEP being most cost-effective (ICER $11,847). For index patient 2, HoLEP was less costly ($6,585 vs $15,404) and more effective (4.654 vs 4.650) relative to SP. On sensitivity analysis for index patient 1, B-TURP became most cost-effective if cost of HoLEP increased two-fold or chronic stress incontinence following HoLEP increased ten-fold. When follow-up time was varied, WVTT was preferred at very short follow up (<1 year), and HoLEP became more strongly preferred with longer follow up. CONCLUSION: At 5 years follow up, HoLEP is a cost-effective surgical treatment for BPH- independent of gland size.

Cost-effectiveness of Adjuvant Pembrolizumab After Nephrectomy for High-risk Renal Cell Carcinoma: Insights for Patient Selection From a Markov Model.

PURPOSE: The KEYNOTE-564 trial demonstrated that adjuvant pembrolizumab after nephrectomy for clear cell renal cell carcinoma decreased the risk of disease progression and potentially overall mortality as well. Herein, we used a Markov model to weigh the costs, toxicities, and efficacy of pembrolizumab to further investigate its utility. MATERIALS AND METHODS: Decision-analytic Markov modeling was used to conduct a cost-utility analysis of adjuvant pembrolizumab versus observation after nephrectomy for high-risk clear cell renal cell carcinoma, using data from KEYNOTE-564 to inform model probabilities. Primary outcomes were quality-adjusted life years, Medicare costs, and incremental cost-effectiveness ratios. The willingness-to-pay threshold utilized was $100,000/quality-adjusted life year. RESULTS: At 5 years, adjuvant treatment with pembrolizumab resulted in 0.3 additional quality-adjusted life years at an additional cost of $99,484 relative to observation. Pembrolizumab was found not to be cost-effective at a 5-year time horizon (incremental cost-effectiveness ratio=$326,534). On sensitivity analysis, pembrolizumab became cost-effective if its per cycle cost was <$5,064 (base=$10,278) or its 5-year progression benefit was >18.8% (base 9%). Upon simulation, pembrolizumab was cost-effective for 29% of patients at 5 years. Specifically, we found that pembrolizumab would be cost-effective at 5 years for patients with at least a 59% 5 year risk of progression, which corresponds to a Mayo Progression-free Survival Score ≥10. CONCLUSIONS: At current prices, adjuvant pembrolizumab was found to be cost-effective only for the highest risk subset of clear cell renal cell carcinoma patients 5 years after treatment, including patients with complete metastasectomy, regional lymph node involvement, or ≥7cm pT3 tumors with sarcomatoid features. Longer-term trial data, including overall survival results, are necessary to confirm these extrapolations.

Comparative cost-effectiveness of neoadjuvant chemotherapy regimens for muscle-invasive bladder cancer: Results according to VESPER data.

BACKGROUND: The VESPER trial demonstrated improved progression-free (PFS) and (preliminarily) overall survival (OS) with six cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVACx6) versus four cycles of gemcitabine and cisplatin (GCx4) before radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC), but with increased toxicity. This study compares the cost-effectiveness of these regimens. METHODS: A cost-effectiveness analysis of neoadjuvant ddMVACx6 and GCx4 was performed using a decision-analytic Markov model with 5-year, 10-year, and lifetime horizons. Probabilities were derived from reported VESPER data. Utility values were obtained from the literature. Primary outcomes were effectiveness measured in quality-adjusted life years (QALY) and incremental cost-effectiveness ratio (ICER) with a willingness to pay threshold of $100,000 per QALY. One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of the model. RESULTS: At 5 years, ddMVACx6 improved QALYs by 0.30 at an additional cost of $16,100, rendering it cost-effective relative to GCx4 (ICER: $53,284/QALY). Additionally, probabilistic sensitivity analysis found ddMVACx6 to be cost-effective in 79% and 81% of microsimulations at10-year and lifetime horizons, respectively. One-way sensitivity analysis demonstrated a minimum difference in 5-year progression of 0.9% and progression mortality of 0.7% between ddMVACx6 and GCx4 was necessary for ddMVACx6 to remain cost-effective. CONCLUSIONS: Neoadjuvant ddMVACx6 was more cost-effective than GCx4 for MIBC. These data, together with the improved PFS and (albeit preliminary) OS noted in VESPER, support use of this regimen in appropriate candidates for neoadjuvant chemotherapy before RC. LAY SUMMARY: We performed a benefit-to-cost analysis using evidence from a randomized controlled trial that compared two different chemotherapy treatments before bladder removal for bladder cancer that had invaded into the bladder muscle. Despite being more expensive and having a greater likelihood of toxicity, six cycles of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin was more cost-effective (or had higher value) than four cycles of gemcitabine and cisplatin.

A novel upper tract ureteroscopic biopsy technique: the "form tackle"

ABSTRACT Introduction and Objective: Upper tract urothelial carcinoma (UTUC) represents 5% of all urothelial malignancies (1-3). Accurate pathologic diagnosis is key and may direct treatment decisions. Current ureteroscopic biopsy techniques include cold-cup, backloaded cold-cup and stone basket (4-6). The study objective was to compare a standard cold-cup biopsy technique to a novel cold-cup biopsy technique and evaluate histopathologic results. Materials and Methods: We developed a novel UTUC biopsy technique termed the "form tackle" biopsy. Ureteroscope is passed into ureter/renal collecting system. Cold-cup forceps are opened and pressed into the lesion base (to engage the urothelial wall/submucosal tissue) then closed. Ureteroscope/forceps are advanced forward 3-10mm and then extracted from the patient. We compared standard versus novel upper tract biopsy techniques in a series of patients with lesions ≥1cm. In each procedure, two standard and two novel biopsies were obtained from the same lesion. The primary study aim was diagnosis of malignancy. IRB approved: 21-006907. Results: Fourteen procedures performed on 12 patients between June 2020 and March 2021. Twenty-eight specimens sent (14 standard, 14 novel) (Two biopsies per specimen). Ten procedures with concordant pathology. In 4 procedures the novel biopsy technique resulted in a diagnosis of UTUC (2 high-grade, 2 low-grade) in the setting of a benign standard biopsy. Significant difference in pathologic diagnoses was detected between standard and novel upper tract biopsy techniques (p=0.008). Conclusions: The "form tackle" upper tract ureteroscopic biopsy technique provides higher tissue yield which may increase diagnostic accuracy. Further study on additional patients required. Early results are encouraging.