Variation in management of lymph node positive prostate cancer after radical prostatectomy within a statewide quality improvement consortium.

BACKGROUND: Patients with lymph node positive (pN+) disease found at the time of radical prostatectomy with pelvic lymphadenectomy for clinically localized prostate cancer (CaP) are at high risk of disease persistence and progression. Contemporary management trends of pN+ CaP are not well described. MATERIALS AND METHODS: Patients in the Michigan Urologic Surgery Improvement Collaborative (MUSIC) with clinically localized prostate cancer who underwent radical prostatectomy between 2012 and 2023 with cN0/pN+ disease were identified. The primary outcome was to evaluate patient and practice-level factors associated with time to secondary post-RP treatment. Secondary outcomes included practice-level variation in management of pN+ CaP and rates of secondary treatment modality. To assess factors associated with secondary treatment, a Cox proportional hazards model of a 60-day landmark analysis was performed. RESULTS: We identified 666 patients with pN+ disease. Overall, 66% underwent secondary treatment within 12 months post-RP. About 19% of patients with detectable post-RP PSA did not receive treatment. Of patients receiving secondary treatment after 60-days post-RP, 34% received androgen deprivation therapy (ADT) alone, 27% received radiation (RT) alone, 36% received combination, and 4% received other systemic therapies. In the multivariable model, pathologic grade group (GG)3 (HR 1.5; 95%CI: 1.05-2.14), GG4-5 (HR 1.65; 95%CI: 1.16-2.34), positive margins (HR 1.46; 95%CI: 1.13-1.88), and detectable postoperative PSA ≥0.1 ng/ml (HR 3.46; 95%CI: 2.61-4.59) were significantly associated with secondary post-RP treatment. There was wide variation in adjusted practice-level 12-month secondary treatment utilization (28%-79%). CONCLUSIONS: The majority pN+ patients receive treatment within 12 months post-RP which was associated with high-risk pathological features and post-RP PSA. Variation in management of pN+ disease highlights the uncertainty regarding the optimal management. Understanding which patients will benefit from secondary treatment, and which type, will be critical to minimize variation in care.

Gender-based Disparity Exists in the Surgical Experience of Female and Male Urology Residents.

OBJECTIVE: To determine if a discrepancy exists in the number and type of cases logged between female and male urology residents. MATERIALS AND METHODS: ACGME case log data from 13 urology residency programs was collected from 2007 to 2020. The number and type of cases for each resident were recorded and correlated with resident gender and year of graduation. The median, 25th and 75th percentiles number of cases were calculated by gender, and then compared between female and male residents using Wilcoxon rank sum test. RESULTS: A total of 473 residents were included in the study, 100 (21%) were female. Female residents completed significantly fewer cases, 2174, compared to male residents, 2273 (P = .038). Analysis by case type revealed male residents completed significantly more general urology (526 vs 571, P = .011) and oncology cases (261 vs 280, P = .026). Additionally, female residents had a 1.3-fold increased odds of logging a case in the assistant role than male residents (95% confidence interval: 1.27-1.34, P < .001). CONCLUSION: Gender-based disparity exists within the urology training of female and male residents. Male residents logged nearly 100 more cases than female residents over 4years, with significant differences in certain case subtypes and resident roles. The ACGME works to provide an equal training environment for all residents. Addressing this finding within individual training programs is critical.

Antisperm Antibody Levels After Vasectomy Reversal Are Not Associated With Pregnancy Rates or Method of Conception.

OBJECTIVE: To examine the relationship between antisperm antibody (ASA), pregnancy rates, and method of conception following vasectomy reversal, given that before and after vasectomy reversal, patients wonder if ASAs will prevent them from achieving pregnancy and American Urological Association vasectomy guidelines call for additional research to answer this question. METHODS: We performed retrospective chart review and phone interview of patients who underwent vasectomy reversal at our institution from 1/1/2000 to 12/31/2018. We excluded patients who underwent vasectomy reversal for pain, or without postoperative semen analysis with ASA. We categorized patients as having low (<50%) or high (≥50%) ASA levels using the first postoperative semen analysis. Our primary outcome was pregnancy rate, including method of conception. Differences in pregnancy rates were tested using Fisher exact test. RESULTS: Two hundred and four patients were chart reviewed. Median age at time of surgery was 40years and median obstruction interval was 7.3years. Median partner age was 32years. One hundred sixty-four (80%) patients underwent bilateral vasovasostomy. Eighty-five patients (42%) had low (<50%) ASA levels and 119 (58%) had high (≥50%) ASA levels. Sixty-seven patients completed phone interviews. Of 27 men with low ASA levels, 19 (70%) achieved a pregnancy with 16 (59%) spontaneous pregnancy. Of 40 men with high ASA levels, 30 (75%) achieved a pregnancy with 16 (40%) spontaneous pregnancy. The Fisher exact test P-value was .2. CONCLUSION: ASA levels are not associated with pregnancy rate or method of conception after vasectomy reversal. These findings can improve patient counseling before and after vasectomy reversal.

Epididymectomy Is an Effective Treatment for Chronic Epididymal Pain.

INTRODUCTION: Chronic scrotal pain is difficult to manage, and epididymectomy is a treatment option for a subset of men with pain localized to the epididymis. We sought to evaluate the efficacy of epididymectomy at our institution. METHODS: Between 2000 and 2020, 225 men underwent epididymectomy at our institution for pain localized to the epididymis and not part of a greater constellation of pelvic pain or urinary symptoms. Our primary outcome measure was change in pain after epididymectomy, categorized as cured/improved or no change/worsened. Multivariable logistic regression compared the impact of pain duration, and surgical and psychiatric histories on postoperative pain. RESULTS: Patients in both outcome categories-cured/improved and no change/worsened-were similar in age and BMI. Overall, 162 patients (72%) reported cured/improved pain at the last documented follow-up visit. Median follow-up time was 12 (IQR 1-364) weeks. About half of the cohort (n = 117, 52%) had a prior vasectomy, and there was no difference in outcome based on vasectomy history on multivariate analysis (OR 0.625, P = .3). Men with pain duration > 1 year (OR 0.46, P = .03), diagnosed psychiatric conditions (OR 0.44, P = .04), or prior scrotal/inguinal/abdominal surgeries other than vasectomy (OR 0.47, P = .03) had decreased odds of pain relief after epididymectomy. CONCLUSIONS: This 20-year analysis is the largest review of postepididymectomy outcomes reported. Among carefully screened men, 72% had resolution or improvement of scrotal pain. Epididymectomy is most effective for men with < 1 year of focal epididymal pain, with no history of psychiatric conditions or scrotal/inguinal/abdominal surgery other than vasectomy.

Antibiotic use, best practice statement adherence, and UTI rate for intradetrusor onabotulinumtoxin-A injection for overactive bladder: A multi-institutional collaboration from the SUFU Research Network (SURN).

INTRODUCTION: Onabotulinumtoxin A (BTX-A) is a well-established treatment for overactive bladder (OAB). The American Urological Association (AUA) 2008 Antibiotic Best Practice Statement (BPS) recommended trimethoprim-sulfamethoxazole or fluoroquinolone for cystoscopy with manipulation. The aim of the study was to evaluate concordance with antibiotic best practices at the time of BTX-A injection and urinary tract infection (UTI) rates based on antibiotic regimen. METHODS: Men and women undergoing first-time BTX-A injection for idiopathic OAB with 100 units in 2016, within the SUFU Research Network (SURN) multi-institutional retrospective database were included. Patients on suppressive antibiotics were excluded. The primary outcome was concordance of periprocedural antibiotic use with the AUA 2008 BPS antimicrobials of choice for "cystoscopy with manipulation." As a secondary outcome we compared the incidence of UTI among women within 30 days after BTX-A administration. Each outcome was further stratified by procedure setting (office vs. operating room; OR). RESULTS: Of the cohort of 216 subjects (175 women, 41 men) undergoing BTX-A, 24 different periprocedural antibiotic regimens were utilized, and 98 (45%) underwent BTX-A injections in the OR setting while 118 (55%) underwent BTX-A injection in the office. Antibiotics were given to 86% of patients in the OR versus 77% in office, and 8.3% of subjects received BPS concordant antibiotics in the OR versus 82% in office. UTI rates did not vary significantly among the 141 subjects who received antibiotics and had 30-day follow-up (8% BPS-concordant vs. 16% BPS-discordant, CI -2.4% to 19%, p = 0.13). A sensitivity analysis of UTI rates based on procedure setting (office vs. OR) did not demonstrate any difference in UTI rates (p = 0.14). CONCLUSIONS: This retrospective multi-institutional study demonstrates that antibiotic regimens and adherence to the 2008 AUA BPS were highly variable among providers with lower rates of BPS concordant antibiotic use in the OR setting. UTI rates at 30 days following BTX-A did not vary significantly based on concordance with the BPS or procedure setting.

Assessment of neophallus length following metoidioplasty.

Background: An increasing number of gender diverse individuals are presenting for gender affirming care. An option for genital gender affirming surgery (gGAS) in transmasculine individuals is metoidioplasty, creating a small neophallus from enlarged clitoral tissue following prolonged testosterone exposure. The goal of this study is to understand factors which contribute to greater exposed neophallus length following metoidioplasty. Methods: We performed a retrospective chart review on patients presenting to a single academic institution who underwent a metoidioplasty. All operations were performed using the Belgrade technique with or without urethral lengthening depending on patient preference. Results: Twenty-seven patients underwent metoidioplasty from 2017-2022. Sixteen had recorded stretched clitoral length (pre-operatively) and exposed neophallus length (post-operatively). The median length of time on testosterone therapy was 4.6 years. The median stretched clitoral length was 5.8 cm, and exposed neophallus length was 6 cm. There was a strong correlation between pre-operative length and post-operative length (ρ=0.9; P<0.0001). There were no correlations between pre-operative length or exposed neophallus length and BMI (ρ=-0.02, P=0.93; ρ=0.05, P=0.83, respectively). Time on testosterone does not correlate with stretched clitoral length nor exposed neophallus length (ρ=-0.28, P=0.15; ρ=-0.35, P=0.18, respectively). Conclusions: Patients considering metoidioplasty often wonder how large their neophallus will be. We found that patients can expect exposed neophallus length to be about 0.6 cm longer than their pre-operative stretched clitoral length. No evidence of association of time on testosterone nor BMI with exposed neophallus length was found. This information is crucial for gender diverse patients to make informed decisions about gGAS.

A pooled long-term follow-up after radiotherapy for prostate cancer with and without a rectal hydrogel spacer: impact of hydrogel on decline in sexual quality of life.

Purpose: The purpose of this study was to analyze the impact of prostate rectal spacers on sexual quality of life (QOL) following external beam radiation therapy (RT). Methods and materials: Patient- reported QOL was evaluated using the Expanded Prostate Cancer Index Composite (EPIC). Patients were pooled from two sources: a randomized controlled trial and a non-randomized cohort of patients from a single institution. Both cohorts used the same spacing product and QOL instrument. Analysis was limited to those with good baseline pre-treatment sexual QOL (EPIC >/= 60). Differences in QOL summary score and individual items were assessed compared with baseline and between treatment arms. Results: A total of 128 men had good baseline sexual function and were evaluated (64% with spacer and 36% without) with QOL data available for median 33 months (range: 2.5-69.4 months). Men without spacer were more likely to have declines in sexual function (p < 0.0001), bother (p = 0.0002), and sexual summary score (p < 0.0001). A minimally important difference of 10 points (1xMID) and 20 point (2xMID) was more likely without rectal spacer [10 points: odds ratio 3.53, (95% confidence interval 1.11-11.2), p = 0.032; 20 points: odds ratio 3.29, (95% confidence interval 1.16-9.33), p = 0.025]. Seven of 13 QOL items were statistically superior with hydrogel (six of nine functional and one of four bother), while no items were statistically superior for control. At baseline, more men treated with hydrogel had erections sufficient for intercourse; however, when analyzed only by the men with best baseline erectile potential and excluding those with worse function, the benefit of rectal spacing was maintained with a higher likelihood of preservation of erections sufficient for intercourse in those treated with hydrogel. Conclusion: In this pooled analysis of QOL after prostate RT, the utilization of a hydrogel spacer was associated with better sexual QOL, less men with measurable declines in sexual QOL, and higher rates of adequate erectile function.

Testicular catch-up growth in the non-operative management of the adolescent varicocele.

INTRODUCTION: Adolescent varicocele is a common urologic condition with a spectrum of outcomes, leading to variations in management. Testicular hypotrophy is a common indication for surgery Routine monitoring may be an appropriate form of management for many adolescents with testicular hypotrophy, as studies have shown that a large proportion of these patients may experience catch-up growth of the ipsilateral testis. Furthermore, there are few longitudinal studies which have correlated patient specific factors to catch-up growth. We aimed to determine the frequency of testicular catch up-growth in adolescents with varicocele while also examining if patient specific factors such as BMI, BMI percentile, or height correlated with testicular catch-up growth. METHODS: A retrospective chart review found adolescent patients who presented to our institution with varicocele from 1997 to 2019. Patients between the ages of 9 and 20 years with left-sided varicocele, a clinically significant testicular size discrepancy, and at least two scrotal ultrasounds at least one year apart were included in analysis. Testicular size discrepancy of greater than 15% on scrotal ultrasound was considered clinically significant. Testicular size was estimated in volume (mL) via the Lambert formula. Statistical relationships between testicular volume differential and height, body mass index (BMI), and age were described with Spearman correlation coefficients (ρ). RESULTS: 40 patients had a testicular volume differential of greater than 15% at some point during their clinical course and were managed non-operatively with observation and serial testicular ultrasounds. On follow-up ultrasound, 32/40 (80%) had a testicular volume differential of less than 15%, with a mean age of catch up growth at 15 years (SD 1.6, range 11-18 years). There were no significant correlations between baseline testicular volume differential and baseline BMI (ρ = 0.00, 95% CI [-0.32, 0.32]), baseline BMI percentile (ρ = 0.03, 95% CI [-0.30, 0.34]), or change in height over time (ρ = 0.05, 95% CI [-0.36, 0.44]). DISCUSSION: The majority of adolescents with varicocele and testicular hypotrophy exhibited catch-up growth with observation, suggesting that surveillance is an appropriate form of management in many adolescents. These findings are consistent with previous studies and further indicate the importance of observation for the adolescent varicocele. Further research is warranted to determine patient specific factors that correlate with testicular volume differential and catch up growth in the adolescent varicocele.

What Is the Optimal Stenting Duration After Ureteroscopy and Stone Intervention? Impact of Dwell Time on Postoperative Emergency Department Visits.

PURPOSE: AUA stone management guidelines recommend stenting duration following ureteroscopy be minimized to reduce morbidity; stents with extraction strings may be used for this purpose. However, an animal study demonstrated that short dwell time results in suboptimal ureteral dilation, and a pilot clinical study showed this increases postprocedure events. Using real-world practice data we examined stent dwell time after ureteroscopy and its association with postoperative emergency department visits. MATERIALS AND METHODS: We used the Michigan Urological Surgery Improvement Collaborative registry to identify ureteroscopy and stenting procedures (2016-2019). Pre-stented cases were excluded. Stenting cohorts with and without strings were analyzed. Using multivariable logistic regression we evaluated the risk of an emergency department visit occurring on the day of, or day after, stent removal based on dwell time and string status. RESULTS: We identified 4,437 procedures; 1,690 (38%) had a string. Median dwell time was lower in patients with a string (5 vs 9 days). Ureteroscopy in younger patients, smaller stones, or renal stone location had a higher frequency of string use. The predicted probability of an emergency department visit was significantly greater in procedures with string, compared to without string, when dwell times were less than 5 days (P < .01) but were not statistically significant after. CONCLUSIONS: Patients who had ureteroscopy and stenting with a string have short dwell times. Patients are at increased risk of a postoperative emergency department visit around the time of stent removal if dwell time is ≤4 days. We recommended stenting duration of at least 5 days in nonpre-stented patients.

Development and Validation of a Model to Predict Ureteral Stent Placement Following Ureteroscopy: Results From a Statewide Collaborative.

OBJECTIVE: To develop and validate a model to predict whether patients undergoing ureteroscopy (URS) will receive a stent. METHODS: Using registry data obtained from the Michigan Urological Surgery Improvement Collaborative Reducing Operative Complications from Kidney Stones initiative, we identified patients undergoing URS from 2016 to 2020. We used patients' age, sex, body mass index, size and location of the largest stone, current stent in place, history of any kidney stone procedure, procedure type, and acuity to fit a multivariable logistic regression model to a derivation cohort consisting of a random two-thirds of episodes. Model discrimination and calibration were evaluated in the validation cohort. A sensitivity analysis examined urologist variation using generalized mixed-effect models. RESULTS: We identified 15,048 URS procedures, of which 11,471 (76%) had ureteral stents placed. Older age, male sex, larger stone size, the largest stone being in the ureteropelvic junction, no prior stone surgery, no stent in place, a planned procedure type of laser lithotripsy, and urgent procedure were associated with a higher risk of stent placement. The model achieved an area under the receiver operating characteristic curve of 0.69 (95% CI 0.67, 0.71). Incorporating urologist-level variation improved the area under the receiver operating characteristic curve to 0.83 (95% CI 0.82, 0.84). CONCLUSION: Using a large clinical registry, we developed a multivariable regression model to predict ureteral stent placement following URS. Though well-calibrated, the model had modest discrimination due to heterogeneity in practice patterns in stent placement across urologists.

Real-world Practice Stone-free Rates After Ureteroscopy: Variation and Outcomes in a Surgical Collaborative.

BACKGROUND: Studies assessing the stone-free rate (SFR) after ureteroscopy are limited to expert centers with varied definitions of stone free. Real-world data including community practices related to surgeon characteristics and outcomes are lacking. OBJECTIVE: To evaluate the SFR for ureteroscopy and its predictors across diverse surgeons in Michigan. DESIGN, SETTING, AND PARTICIPANTS: We assessed the Michigan Urological Surgery Improvement Collaborative (MUSIC) clinical registry for patients with renal or ureteral stones treated with ureteroscopy between 2016 and 2021 who had postoperative imaging. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Stone free was defined as no fragments on imaging reports within 60 d entered by independent data abstractors. Factors associated with being stone free were examined using logistic regression, including annual surgeon volume. We then assessed variation in surgeon-level SFRs adjusted for risk factors. RESULTS AND LIMITATIONS: We identified 6487 ureteroscopies from 164 surgeons who treated 2091 (32.2%) renal and 4396 (67.8%) ureteral stones. The overall SFRs were 49.6% (renal) and 72.7% (ureteral). Increasing stone size, lower pole, proximal ureteral location, and multiplicity were associated with not being stone free. Female gender, positive urine culture, use of ureteral access sheath, and postoperative stenting were associated with residual fragments when treating ureteral stones. Adjusted surgeon-level SFRs varied for renal (26.1-72.4%; p < 0.001) and ureteral stones (52.2-90.2%; p < 0.001). Surgeon volume was not a predictor of being stone free for renal stones. Limitations include the lack of imaging in all patients and use of different imaging modalities. CONCLUSIONS: The real-world complete SFR after ureteroscopy is suboptimal with substantial surgeon-level variation. Interventions focused on surgical technique refinement are needed to improve outcomes for patients undergoing ureteroscopy and stone intervention. PATIENT SUMMARY: Results from a diverse group of community practicing and academic center urologists show that for a large number of patients, it is not possible to be completely stone free after ureteroscopy. There is substantial variation in surgeon outcomes. Quality improvement efforts are needed to address this.

Improving the Quality of Upper Urinary Tract Stone Surgery: External Validation of a Statewide Collaborative's Efforts to Reduce Emergency Department Visits After Ureteroscopy.

PURPOSE: The ROCKS (Reducing Operative Complications from Kidney Stones) program in MUSIC (Michigan Urological Surgery Improvement Collaborative) was created to optimize ureteroscopy outcomes. Through data collection, distribution of reports, patient education, and standardization of medication, post-ureteroscopy emergency department visits in Michigan have declined. It is unclear whether this is because of statewide quality efforts or due to national trends. We therefore sought to understand emergency department visit rates in Michigan compared to a national data set. MATERIALS AND METHODS: We compared the MUSIC ROCKS clinical registry in Michigan against a national cohort, Optum's de-identified Clinformatics Data Mart, from 2016-2021 (excluding Michigan). We identified patients who underwent ureteroscopy and the proportion who had a postoperative emergency department visit within 30 days. Emergency department rates were modeled over time, adjusting for age, gender, comorbidity, and ureteral stenting. RESULTS: We identified 24,688 patients in MUSIC ROCKS and 99,340 in the Clinformatics Data Mart database who underwent ureteroscopy. The risk-adjusted emergency department visit rate in MUSIC ROCKS significantly declined over the study period (10.5% in 2016 to 6.9% in 2021, P < 0.001) while the mean emergency department visit rate in the Clinformatics Data Mart cohort was 9.9% and did not change over time (9.6% in 2016 to 10% in 2021). Comparing emergency department visits between the cohorts, the MUSIC ROCKS rate significantly declined relative to the Clinformatics Data Mart (P < 0.001) over the study period. CONCLUSIONS: Postoperative emergency department visit rates in Michigan have declined significantly after ureteroscopy since the establishment of MUSIC ROCKS. This decline outpaced national rates, providing evidence that systematic quality initiatives can improve urological care.

Stent Omission in Pre-stented Patients Undergoing Ureteroscopy Decreases Unplanned Health Care Utilization.

INTRODUCTION: Despite AUA guidelines providing criteria for ureteral stent omission after ureteroscopy for nephrolithiasis, stenting rates in practice remain high. Because pre-stenting may be associated with improved patient outcomes, we assessed the impact of stent omission vs placement in pre-stented and non-pre-stented patients undergoing ureteroscopy on postoperative health care utilization in Michigan. METHODS: Using the MUSIC (Michigan Urological Surgery Improvement Collaborative) registry (2016-2019), we identified pre-stented and non-pre-stented patients with low comorbidity undergoing single-stage ureteroscopy for ≤1.5 cm stones with no intraoperative complications. We assessed variation in stent omission for practices/urologists with ≥5 cases. Using multivariable logistic regression, we evaluated whether stent placement in pre-stented patients was associated with emergency department visits and hospitalizations within 30 days of ureteroscopy. RESULTS: We identified 6,266 ureteroscopies from 33 practices and 209 urologists, of which 2,244 (35.8%) were pre-stented. Pre-stented cases had higher rates of stent omission vs non-pre-stented cases (47.3% vs 26.3%). Among the 17 urology practices with ≥5 cases, stent omission rates in pre-stented patients varied widely (0%-77.8%). Among the 156 urologists with ≥5 cases, stent omission rates in pre-stented patients varied substantially (0%-100%); 34/152 (22.4%) never performed stent omission. Adjusting for risk factors, stent placement in pre-stented patients was associated with increased emergency department visits (OR 2.24, 95% CI:1.42-3.55) and hospitalizations (OR 2.19, 95% CI:1.12-4.26). CONCLUSIONS: Pre-stented patients undergoing stent omission after ureteroscopy have lower unplanned health care utilization. Stent omission is underutilized in these patients, making them an ideal group for quality improvement efforts to avoid routine stent placement after ureteroscopy.

Use of a physical activity monitor to track perioperative activity of radical cystectomy patients. Our first glimpse at what our patients are doing before and after surgery.

PURPOSE: To optimize recovery after radical cystectomy (RC), providers stress the importance of ambulation and adequate rest. However, little is known about the activity and sleep habits of patients undergoing RC. Therefore, we utilized a wearable physical activity monitor (PAM) in the perioperative period to provide the first objective data on physical activity and sleep habits for RC patients. MATERIALS AND METHODS: We prospectively identified patients ≥60 years old with planned RC. Participants completed a 4-week prehabilitation exercise program prior to surgery. They wore a PAM for 7-day intervals: at baseline, after prehabilitation, at postoperative day (POD) 30 and POD90. We tracked physical activity via metabolic equivalents (METs). METs were categorized by intensity: light (MET 1.5-<3), moderate (MET 3-<6), and vigorous (MET ≥6). We calculated daily step totals. We tracked hours slept and number of sleep awakenings. We correlated activity and sleep with self-reported quality of life (QOL). RESULTS: Forty-two patients completed prehabilitation and RC. Moderate intensity exercise decreased at POD30 (61 minutes/d at baseline, 30 minutes/d at POD30, P = 0.005). Physical activity did not significantly differ for light or vigorous activity at any timepoint. RC did not significantly affect sleep. Sleep and physical activity were associated with mental and physical QOL, respectively. CONCLUSIONS: This is the first study utilizing patient-worn monitors in RC to track physical activity and sleep. This study gives patients and providers a better understanding of postcystectomy recovery expectations. With these results in mind, interventions may be implemented to optimize activity and sleep in the perioperative period.

A Phase 2 Trial of Nab-paclitaxel in Combination With Anti-PD1 Therapy in Advanced Urothelial Cancer.

PURPOSE: Immune checkpoint inhibitor therapy and nab-paclitaxel have each shown efficacy in platinum-refractory advanced urothelial cancer. We conducted a single-arm phase 2 trial of the combination of nab-paclitaxel and pembrolizumab in platinum-refractory or cisplatin-ineligible advanced urothelial cancer (NCT03240016). MATERIALS AND METHODS: Eligible patients had RECIST 1.1 measurable and cisplatin-ineligible or platinum-refractory advanced urothelial cancer. Patients received nab-paclitaxel at starting dose of 125 mg/m2 intravenously on days 1 and 8 and pembrolizumab 200 mg intravenously on day 1 in 21-day cycles until progression, intolerable toxicity, or death. Nab-paclitaxel was permitted to be discontinued after 6 cycles. The nab-paclitaxel starting dose was reduced to 100 mg/m2 after planned interim analysis. Primary end point was overall response rate by RECIST 1.1. Secondary end points included safety/toxicity, duration of response, progression-free survival), and overall survival. RESULTS: Between February 2018 and April 2021, 36 response-evaluable patients were enrolled. There was an equal split of platinum-refractory and cisplatin-ineligible patients. Confirmed overall response rate was 50.0% (18/36) including 3 complete and 15 partial responses; 31/36 patients experienced some tumor shrinkage. At a median follow-up of 19.7 months, median duration of response was 4.4 months (95% CI: 4.0-8.6), median progression-free survival 6.8 months (95% CI: 4.4-not reached), and median overall survival 18.2 months (95% CI: 10.6-not reached). Grade ≥3 adverse events occurred in 21/36 patients including fatigue (n=6) and anemia (n=4). Ten patients had immune-mediated adverse events. CONCLUSIONS: The combination of nab-paclitaxel and pembrolizumab exhibited promising activity in advanced urothelial cancer and warrants further study in this population. After reduction in nab-paclitaxel starting dose, no unanticipated or unexpected toxicities emerged.

A Phase I Trial of Neoadjuvant Stereotactic Body Radiotherapy Prior to Radical Prostatectomy for Locally Advanced Prostate Cancer.

PURPOSE: Men with locally advanced prostate cancer who undergo radical prostatectomy (RP) often develop recurrence and require postoperative radiotherapy. We aimed to determine the safety of neoadjuvant stereotactic body radiotherapy (SBRT) before RP in this population. METHODS AND PATIENTS: A single-institution phase 1 trial (NCT02946008) of men with high-risk or node-positive prostate cancer were enrolled between March and October 2017. The primary endpoint was to determine the maximum tolerated dose of SBRT based on a composite 30-day post-RP toxicity goal of ≤28% of patients experiencing a dose-limiting toxicity (DLT). Secondary outcomes included toxicity, efficacy, and multiple quality of life (QoL) inventories. SBRT (30-35 Gy/5 fractions) was delivered to the prostate and seminal vesicles, and 25 Gy/5 fractions to the pelvic lymph nodes. RP was performed for a median of 6 weeks post-SBRT. Hormone therapy was not allowed. RESULTS: Median follow-up was 40 months (range, 33-44). Twenty-five percent of the patients (n = 4) experienced a DLT within 30 days post-RP; however, the trial was stopped early (n = 16 of planned 38 patients) owing to the proportion and severity of the late adverse events. Post-RP grade 3 genitourinary and gastrointestinal toxicities occurred in 75% (n = 12) and 25% (n = 4) of patients, respectively. Two patients required cystectomy and urinary diversion ≥2 years post-RP. At 24 months post-RP, 75% (n = 12) of men used ≥1 pad/d and 0% had erections suitable for intercourse. Surgical margins were negative in all patients and 31% (n = 5) had complete or partial (pre-RP) MRI-response to SBRT. Three-year biochemical recurrence and distant metastasis were 45% (95% CI, 5%-68%) and 28% (95% CI, 0%-49%), respectively. CONCLUSIONS: Neoadjuvant SBRT followed by RP resulted in unacceptably high toxicity and severe QoL declines.

Practice patterns and outcomes of urgent versus elective ureteroscopy in a statewide surgical collaborative.

PURPOSE: Urgent indications for nephrolithiasis treatment include obstruction with intractable pain or renal impairment without untreated infection. Patients and hospitals may benefit from urgent primary ureteroscopy. We aimed to examine variation in urgent ureteroscopy utilization and associated outcomes. METHODS: Using Reducing Operative Complications from Kidney Stones (ROCKS), we identified all ureteroscopy's between 2016 and 2019. Cases were classified by acuity (elective versus urgent). We assessed practice/urologist variation in urgent ureteroscopy performance. We characterized patients demographic, operative and outcomes data, making bivariate comparisons with elective ureteroscopy to understand implications of urgent surgery. We performed multilevel modeling to understand factors associated with unplanned healthcare encounters after urgent ureteroscopy. RESULTS: 12,859 cases were identified from 33 practices and 204 urologists, 10,854 (84.4%) elective and 2005 (15.6%) urgent. Urgent ureteroscopy was performed on younger patients (53 vs 57, p < 0.001), with higher rates of ureteral stones (72.8% vs 56.8%, p < 0.001). Urgent ureteroscopy rates varied widely by practice (2-70%) and urologist (0-98%). Urgent ureteroscopy had higher stenting rates (77.4% vs 72.5%, p < 0.001), stone free rates (66% vs 58.4%, p < 0.001), and postoperative ED visits (11% vs 7.2%, p < 0.001). There were no differences in intraoperative complications or unplanned hospitalizations. Factors predictive of ED visits in urgent ureteroscopy included concomitant ureteral/renal stone location (OR = 1.53, CI = 1.05-2.23, p = 0.035). CONCLUSIONS: In Michigan elective ureteroscopy is performed 5 times more frequently than urgent ureteroscopy with wide variation. Urgent ureteroscopy demonstrated low morbidity. Urgent ureteroscopy produced modestly higher stone free rates with a slightly increased frequency of unscheduled ED visits particularly for ureteral stones.

Development of a Surgical Decision Aid for Patients with Nephrolithiasis: Shockwave Lithotripsy vs Ureteroscopy.

Introduction and Objective: Shared decision making is recommended to guide medical/surgical treatment strategies. We aimed at developing a surgical decision aid (SDA) facilitating decision making between ureteroscopy (URS) or shockwave lithotripsy (SWL) in patients with symptomatic nephrolithiasis. Methods: The SDA scope was identified through discussions with patients and urologists in the Michigan Urological Surgery Improvement Collaborative (MUSIC). A steering committee of patient advocates, MUSIC coordinating center, content experts, biostatisticians, and urologists was formed. Content domains were assessed through best available evidence and content experts. For content validation we anonymously surveyed 35 MUSIC urologists. Content validity ratios (CVR), numeric value indicating degree of expert validity, were calculated. Face validation interviews were conducted with patient advocates. Results: The SDA prototype using descriptive plain language and pictorial information was designed for nephrolithiasis patients, candidates for SWL or URS. It first provides patients procedural education whereas the second section informs urologists of patient goals. Six content domains were chosen: anesthesia type, effectiveness, number of procedures, risk, pain, and recovery. Overall, 91.4% and 85.7% of MUSIC urologists indicated that each section accomplished their goals, respectively. Anesthesia received an unacceptable CVR. High levels of face validation overall were reported with unacceptable scoring for anesthesia and recovery. Conclusions: We developed an SDA facilitating treatment choice between SWL and URS with promising content and face validity. Agreement and contradiction between anesthesia type and recovery validation results indicate the importance of shared decision making and the need for a validated SDA. Future work should focus on the SDAs value and opportunities for refinement in practice.

Pressure Measurement in a Bladder Phantom Using Contrast-Enhanced Ultrasonography-A Path to a Catheter-Free Voiding Cystometrogram.

OBJECTIVES: The long-term goal of this study is to investigate the efficacy of a novel, ultrasound-based technique called subharmonic-aided pressure estimation (SHAPE) to measure bladder pressure as a part of a cystometrogram (CMG) in a urodynamic test (ie, pressure-flow study). SHAPE is based on the principle that subharmonic emissions from ultrasound contrast microbubbles (MBs) decrease linearly with an increase in ambient pressure. We hypothesize that, using the SHAPE technique, we can measure voiding bladder pressure catheter-free. This is of importance because the CMG catheter, due to its space-occupying property and non-physiological effects, can undermine the reliability of the test during voiding and cause misdiagnosis. In this study, we tested this hypothesis and optimized the protocol in a controlled benchtop environment. MATERIALS AND METHODS: A bladder phantom was designed and built, capable of simulating clinically relevant bladder pressures. Laboratory-made lipid-shelled MBs (similar in composition to the commercial agent, DEFINITY) was diluted in 0.9% normal saline and infused into the bladder phantom using the CMG infusion system. A typical simulated CMG consists of 1 filling and 4 post-filling events. During CMG events, the bladder phantom is pressurized multiple times at different clinically relevant levels (small, medium, and large) to simulate bladder pressures. Simultaneous with pressurization, MB subharmonic signal was acquired. For each event, the change in MB subharmonic amplitude was correlated linearly with the change in bladder phantom pressure, and the SHAPE conversion factor (slope of the linear fit) was determined. In doing so, a specific signal processing technique (based on a small temporal window) was used to account for time-decay of MB subharmonic signal during a simulated CMG. RESULTS: A strong inverse linear relationship was found to exist between SHAPE and bladder phantom pressures for each of the CMG filling and post-filling events ( r2> 0.9, root mean square error < 0.3 dB, standard error <0.01 dB, and P < 0.001). SHAPE showed a transient behavior in measuring bladder phantom pressure. The SHAPE conversion factor (in dB/cm H 2 O) varied between filling and post-filling events, as well as by post-filling time. The magnitude of the SHAPE conversion factor tended to increase immediately after filling and then decreases with time. CONCLUSIONS: Microbubble subharmonic emission is an excellent indicator of bladder phantom pressure variation. The strong correlation between SHAPE signal and bladder phantom pressure is indicative of the applicability of this method in measuring bladder pressure during a CMG. Our results suggest that different SHAPE conversion factors may be needed for different events during a CMG (ie, at different time points of a CMG). These findings will help us better protocolize this method for introduction into human subjects and allow us to take the next step toward developing a catheter-free voiding CMG using SHAPE.