Strategies to reduce bladder tumor recurrences following surgery for upper tract urothelial carcinoma.

The incidence of upper tract urothelial carcinoma (UTUC) has been on the rise and the malignancy is more commonly managed surgically as higher proportions of in situ disease are being detected. One challenge facing urologists is the high rate of post-treatment intravesical recurrence (IVR) of UTUC (23 - 50%). Genomic research indicated that cells of recurrent bladder lesions are most often clonally derived from the primary UTUC and are likely to seed into the bladder after tumor manipulation. This calls for effective strategies to prevent the spread of UTUC. The methods we discuss here are the use of a ureteral access sheath during diagnostic ureteroscopy, application and timing of intravesical chemoprophylaxis, early ureteral ligation distal to UTUC, and formal bladder cuff excision. Urologic surgeons should aim to achieve a reduced rate of IVR when applying these techniques.

Association Between Resident In-Service Exam Scores by Post-Graduate Year and Subsequent Board Qualifying Exam.

INTRODUCTION: Prior work notes the AUA in-service exam (ISE) percentile ranking of chief residents correlates with qualifying exam (QE) performance. We present a 5-year analysis of resident performance on the ISE and subsequent QE to determine if earlier time points in training may identify those needing additional educational support. METHODS: Participant ISE scores over a 5-year period from 2014 to 2018 and subsequent QE scores in 2019 were recorded. Pearson's correlation coefficient measured the association between percentage questions correct for each ISE year and QE. Youden Index calculated the optimal cut-point for yearly ISE percentage correct that would predict scoring greater than the lowest quartile and decile on the QE. RESULTS: Median percent questions correct on ISE increased over PGY1 (47%), PGY2 (56.5%), and PGY3 (70%) years but remained stable thereafter (PGY4-5) at approximately 70%. Median QE percent correct in 2019 was 66% (Std Dev 7.6%). Correlation of percent questions correct between ISE and QE improved from 0.31 to 0.53 over training duration. The lowest decile and quartile percent correct scores on the QE were 56% and 60%, respectively. Percent correct ISE score predicting performance above the lowest decile 2019 QE score increased from 38% PGY1, 57% PGY2, and leveled off after PGY3 year (∼70%). Similar observations were noted with lowest quartile QE score. CONCLUSIONS: Scoring approximately 70% of questions correct on the ISE during PGY3 and later years was associated with low risk of failing the QE. Such information provides benchmarks for residency programs to offer targeted educational content for at-risk candidates.

Clinical significance of tumor location for ureteroscopic tumor grading in upper tract urothelial carcinoma.

BACKGROUND: Although previous literature shows tumor location as a prognostic factor in upper tract urothelial carcinoma (UTUC), there remains uninvestigated regarding the impact of tumor location on grade concordance and discrepancies between ureteroscopic (URS) biopsy and final radical nephroureterectomy(RNU) pathology. METHODS: In this international study, we retrospectively reviewed the records of 1,498 patients with UTUC who underwent diagnostic URS with concomitant biopsy followed by RNU between 2005 and 2020. Tumor location was divided into four sections: the calyceal-pelvic system, proximal ureter, middle ureter, and distal ureter. Patients with multifocal tumors were excluded from the study. We performed multiple comparison tests and logistic regression analyses. RESULTS: Overall, 1,154 patients were included; 54.4% of those with low-grade URS biopsies were upgraded on RNU. In the multiple comparison tests, middle ureter tumors exhibited the highest probability of upgrading, meanwhile pelvicalyceal tumors exhibited the lowest probability of upgrading (73.7% vs 48.5%, p=0.007). Downgrading was comparable across all tumor locations. On multivariable analyses, middle ureteral location was significantly associated with a low probability of grade concordance (OR 0.59; 95%CI, 0.35-1.00; p =0.049) and an increased risk of upgrading (OR 2.80; 95%CI, 1.20-6.52; p =0.017). The discordance did not vary regardless of caliceal location, including the lower calyx. CONCLUSIONS: Middle ureteral tumors diagnosed to be low-grade had a high probability to be undergraded. Our data can inform providers and their patients regarding the likelihood of undergrading according to tumor location, facilitating patient counselling and shared decision making regarding the choice of kidney sparing vs RNU.

An evaluation of mitomycin-containing reverse thermal gel for the treatment of low-grade upper tract urothelial carcinoma.

INTRODUCTION: Endoscopic management of upper tract urothelial carcinoma (UTUC) is increasingly relevant with greater detection of low-grade disease and guidelines recommending kidney preservation for low-risk disease. Historically, laser or thermal ablation has served as the primary tool for endoscopic management of UTUC, however, chemoablation is rapidly being developed to serve as a primary or adjuvant treatment option, which warrants review. AREAS COVERED: The current literature was reviewed to compare the outcomes and clinical utility of endoscopic treatment modalities for low-grade UTUC, with a focus on mitomycin-containing reverse thermal gel (UGN-101). EXPERT OPINION: The overall outcomes of mitomycin-containing gel therapy are promising, but adverse effects such as ureteral stricture call for careful consideration when using this treatment. We believe it is reasonable to consider use of mitomycin-containing gel as an adjuvant chemotherapy with endoscopic laser resection of low-grade upper tract urothelial carcinoma.

Prior Negative Biopsy, PSA Density, and Anatomic Location Impact Cancer Detection Rate of MRI-Targeted PI-RADS Index Lesions.

BACKGROUND: MRI fusion prostate biopsy has improved the detection of clinically significant prostate cancer (CSC). Continued refinements in predicting the pre-biopsy probability of CSC are essential for optimal patient counseling. We investigated potential factors related to improved cancer detection rates (CDR) of CSC in patients with PI-RADS ≥ 3 lesions. METHODS: The pathology of 980 index lesions in 980 patients sampled by transrectal mpMRI-targeted prostate biopsy across four medical centers between 2017-2020 was reviewed. PI-RADS lesion distribution included 291 PI-RADS-5, 374 PI-RADS-4, and 315 PI-RADS-3. We compared CDR of index PI-RADS ≥ 3 lesions based on location (TZ) vs. (PZ), PSA density (PSAD), and history of prior negative conventional transrectal ultrasound-guided biopsy (TRUS). RESULTS: Mean age, PSA, prostate volume, and level of prior negative TRUS biopsy were 66 years (43-90), 7.82 ng/dL (5.6-11.2), 54 cm3 (12-173), and 456/980 (46.5%), respectively. Higher PSAD, no prior history of negative TRUS biopsy, and PZ lesions were associated with higher CDR. Stratified CDR highlighted significant variance across subgroups. CDR for a PI-RADS-5 score, PZ lesion with PSAD ≥ 0.15, and prior negative biopsy was 77%. Conversely, the CDR rate for a PI-RADS-4 score, TZ lesion with PSAD < 0.15, and prior negative biopsy was significantly lower at 14%. CONCLUSIONS: For index PI-RADS ≥ 3 lesions, CDR varied significantly based on location, prior history of negative TRUS biopsy, and PSAD. Such considerations are critical when counseling on the merits and potential yield of prostate needle biopsy.

Appropriateness of Imaging for Low-Risk Prostate Cancer-Real World Data from the Pennsylvania Urologic Regional Collaboration (PURC).

Imaging for prostate cancer defines the extent of disease. Guidelines recommend against imaging low-risk prostate cancer patients with a computed tomography (CT) scan or bone scan due to the low probability of metastasis. We reviewed imaging performed for men diagnosed with low-risk prostate cancer across the Pennsylvania Urologic Regional Collaborative (PURC), a physician-led data sharing and quality improvement collaborative. The data of 10 practices were queried regarding the imaging performed in men diagnosed with prostate cancer from 2015 to 2022. The cohort included 13,122 patients with 3502 (27%) low-risk, 2364 (18%) favorable intermediate-risk, 3585 (27%) unfavorable intermediate-risk, and 3671 (28%) high-risk prostate cancer, based on the AUA guidelines. Amongst the low-risk patients, imaging utilization included pelvic MRI (59.7%), bone scan (17.8%), CT (16.0%), and PET-based imaging (0.5%). Redundant imaging occurred in 1022 patients (29.2%). There was variability among the PURC sites for imaging used in the low-risk patients, and iterative education reduced the need for CT and bone scans. Approximately 15% of low-risk patients had staging imaging performed using either a CT or bone scan, and redundant imaging occurred in almost one-third of men. Such data underscore the need for continued guideline-based education to optimize the stewardship of resources and reduce unnecessary costs to the healthcare system.

Practice Readiness? Trends in Chief Resident Case Logs vs Subsequent Case Log Data in Clinical Practice.

INTRODUCTION: Limited information exists regarding the association between resident surgical case experience and subsequent case mix in practice. We compare the case log distribution residents completed during their chief year to those completed by these graduates in their first 2 years in independent practice. METHODS: Resident chief year case logs from 10 institutions were analyzed across 4 categories of index procedures: (1) general urology, (2) endourology, (3) reconstructive urology, and (4) urologic oncology. Current Procedural Terminology codes for associated index procedures were used to query case log data during their first 2 years in practice collected by the American Board of Urology. Interactions were tested between the trends of chief year case logs relative to trends in practice case logs. RESULTS: Amongst 292 residents, a total of 104,827 cases were logged during chief year and 77,976 cases in the first 2 years as an attending. Most cases completed during chief year were in oncology followed by general urology, endourology, and reconstructive urology. As attendings, most cases completed were in general urology, followed by endourology, reconstructive urology, and oncology. Chief year case logs showed decreasing trends in the median number of case logs in reconstructive urology, endourology, and general urology, while case logs in independent practice noted increasing trends in all index procedure categories over time. CONCLUSIONS: Urology residents perform more cases during their chief year compared to their first 2 years of independent practice. Case types completed as chief residents vs subsequent clinical practice also differ significantly. These observations may have implications for residency training, particularly regarding curriculum design.

Long-term outcomes of bladder-sparing therapy vs radical cystectomy in BCG-unresponsive non-muscle-invasive bladder cancer.

OBJECTIVE: To quantify the oncological risks of bladder-sparing therapy (BST) in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) compared to upfront radical cystectomy (RC). PATIENTS AND METHODS: Pre-specified data elements were collected from retrospective cohorts of patients with BCG-unresponsive NMIBC from 10 international sites. After Institutional Review Board approval, patients were included if they had BCG-unresponsive NMIBC meeting United States Food and Drug Administration criteria. Oncological outcomes were collected following upfront RC or BST. BST regimens included re-resection or surveillance only, repeat BCG, intravesical chemotherapy, systemic immunotherapy, and clinical trials. RESULTS: Among 578 patients, 28% underwent upfront RC and 72% received BST. The median (interquartile range) follow-up was 50 (20-69) months. There were no statistically significant differences in metastasis-free survival, cancer-specific survival, or overall survival between treatment groups. In the BST group, high-grade recurrence rates were 37% and 52% at 12 and 24 months and progression to MIBC was observed in 7% and 13% at 12 and 24 months, respectively. RC was performed in 31.7% in the BST group and nodal disease was found in 13% compared with 4% in upfront RC (P = 0.030). CONCLUSION: In a selected cohort of patients, initial BST offers comparable survival outcomes to upfront RC in the intermediate term. Rates of recurrence and progression increase over time especially in patients treated with additional lines of BST.

Getting it Across the Finish Line - Publication Rates of Abstracts Presented at a Major Urologic Conference.

OBJECTIVE: To identify characteristics of published manuscripts following a regional American Urological Association (AUA) meeting and recognize trends of publication rates over a 13-year timeframe. METHODS: Abstract submissions to the Mid-Atlantic AUA (MA-AUA) conference from 2008 to 2020 were collected. Manuscripts were searched using abstract titles and authors in a standard fashion using PubMed, Google Scholar, and Google. Characteristic data was collected, including abstract type (podium or poster), abstract category, first author gender, manuscript publication date, and journal of publication. Univariate and multivariate analysis determined association of these variables with manuscript publication. RESULTS: 1257 abstracts were presented between 2008 and 2020, of which 458 (36%) were published as manuscripts and 799 (64%) were not published. Of the published manuscripts, 55 (12%) were published prior to the conference date and 403 (88%) were published after. Our analysis was limited to the 403 manuscripts published post-meeting and the 799 abstracts that were not published, with N=1202. Amongst the 403 published post-meeting, the mean time to publication was 14.8 months ± 13.2 months. Podium presentations had a higher proportion of publications than those of posters (39.4% vs 30.5%, p=0.002). There was a statistically significant difference in proportion of publications between years (p=0.002). No association was noted between abstract first author gender and publication (38.7% male vs. 39.2% female, p=0.899). CONCLUSIONS: Approximately one-third of presented abstracts from a major urologic conference were published with an average time to publication of 15 months. Publication percentage varied significantly between different years. Podium presentations had a higher publication rate compared to non-podium abstracts.

Clinicopathological risk factors associated with tumor relapse of upper tract urothelial carcinoma after radical nephroureterectomy: A single institution 20-year experience.

Upper tract urothelial carcinoma (UTUC) is a relatively rare yet aggressive malignancy. While radical nephroureterectomy (RNU) remains the cornerstone treatment, UTUC has high local and metastatic relapse rates, leading to a dismal prognosis. To identify the clinicopathological factors associated with an increased risk of local and metastatic relapse in UTUC, we conducted a retrospective analysis of 133 consecutive UTUC patients who underwent RNU from 1998 to 2018. Patients lost to follow-up or with a history of bladder cancer were excluded from the study. The remaining 87 patients were categorized into two subgroups: those with tumor recurrence/relapse (40 cases) and those without recurrence/relapse (47 cases). Clinical and pathological characteristics were compared across the two groups. Multiple factors are associated with UTUC recurrence/relapse including larger tumor size, histology divergent differentiations/subtypes, high tumor grade, advanced pathologic T stage, positive margin, lymphovascular invasion (LVI), positive lymph node status, and preoperative hydronephrosis. Multivariate Cox regression analysis revealed that squamous differentiation predicted recurrence/relapse (p = 0.012), independent of tumor stage. Moreover, compared to the conventional histology type, UTUC with squamous differentiation had a significantly higher relapse rate (p = 0.0001) and poorer survival (p = 0.0039). This observation was further validated in invasive high-grade UTUC cases. Our findings suggest that many pathological factors contribute to UTUC recurrence/relapse, particularly, squamous differentiation may serve as an independent risk predictor for relapse and a potent prognosticator for adverse cancer-specific survival in UTUC patients. Recognizing and thoroughly assessing the pathological factors is essential for better oncologic management of UTUC.

A Multicenter Prospective Randomized Controlled Trial Comparing Cxbladder Triage to Cystoscopy in Patients With Microhematuria: The Safe Testing of Risk for Asymptomatic Microhematuria Trial.

PURPOSE: AUA guidelines for patients with microhematuria (≥3 red blood cells [RBC]/high-power field [hpf]) include cystoscopy for most over age 40 due to risk of urothelial cancer (UC). Cxbladder Triage (CxbT) is a urinary genomic test with UC negative predictive value of 99%. In this prospective randomized controlled trial, we compared cystoscopy use in a standard of care (SOC) arm vs a marker-based approach. MATERIALS AND METHODS: All patients with hematuria provided urine for a CxbT. Those categorized as lower risk (LR), defined as 3 to 29 RBC/hpf and minimal smoking history (<10 pack-years) were randomized between the test group provided with the CxbT result vs the SOC control group. Negative CxbT patients were offered omission of cystoscopy with surveillance. "Not lower risk" (NLR) patients (>30 RBC/hpf or >10 pack-year smoking history) had a CxbT but otherwise SOC. Patient decision and outcomes were recorded. RESULTS: Of 390 eligible patients, 255 were NLR and 135 were LR randomized to CxbT informed decision or SOC. The median age was 62 years (range 18-94) and 54% were male. Overall, 63% of CxbT tests were negative. For NLR patients, 82% had cystoscopy. In the LR control group, cystoscopy was performed in 67% of SOC and 27% in the test group (relative risk 0.41 [95% CI 0.27-0.61]). Compared to cystoscopy, CxbT had 90% sensitivity, 56% specificity, and 99% negative predictive value for UC. CONCLUSIONS: In this prospective randomized controlled trial, use of CxbT in patients with LR hematuria resulted in 59% reduction of cystoscopy use. This clinical utility of CxbT can reduce the burden of unnecessary cystoscopies.

Current Perceptions, Practice Patterns, and Barriers to Adoption of Transperineal Prostate Biopsy Under Local Anesthesia.

OBJECTIVE: To assess perceptions, practice patterns, and barriers to adoption of transperineal prostate biopsy (TPBx) under local anesthesia. METHODS: Providers from Michigan urological surgery improvement collaborative (MUSIC) and Pennsylvania urologic regional collaborative (PURC) were administered an online survey to assess beliefs and educational needs regarding TPBx. Providers were divided into those who performed or did not perform TPBx. The MUSIC and PURC registries were queried to assess TPBx utilization. Descriptive analytics and bivariate analysis determined associations between provider/practice demographics and attitudes. RESULTS: Since 2019, TPBx adoption has increased more than 2-fold to 7.0% and 16% across MUSIC and PURC practices, respectively. Of 350 urologists invited to participate in a survey, a total of 91 complete responses were obtained with 21 respondents (23%) reported performing TPBx. Participants estimated the learning curve was <10 procedure for TPBx performers and non-performers. No significant association was observed between learning curve and provider age/practice setting. The major perceived benefits of TPBx were decreased risk of sepsis, improved cancer detection rate and antibiotic stewardship. The most commonly cited challenges to implementation included access to equipment and patient experience. Urologists performing TPBx reported learning curve as an additional barrier, while those not performing TPBx reported duration of procedure. CONCLUSION: Access to equipment and patient experience concerns remain substantial barriers to adoption of TPBx. Dissemination of techniques utilizing existing equipment and optimization of local anesthetic protocols for TPBx may help facilitate the continued adoption of TPBx.

Complications and Surgeon Health: Resources for individuals and institutions.

The emotional impact of surgical complications on urologists is a significant yet historically under-addressed issue. Traditionally, surgeons have been expected to cope with complications and their psychological effects in silence, perpetuating a culture of perfectionism and 'silent suffering.' This has left many unprepared to handle the emotional toll of adverse events during their training and early careers. Recognizing the gap in structured education on this matter, there is a growing movement to openly address and educate on the emotional consequences of surgical complications. This article underscores the importance of such educational initiatives in the mid-career phase, proposing strategies to promote surgeon health, and psychological safety. It advocates for utilizing Morbidity and Mortality conferences as platforms for peer support, learning from 'near miss' events, and encourages at least annual department-wide discussions to raise awareness and normalize the emotional challenges faced by surgeons. Furthermore, it highlights the role of formal peer support programs, acceptance and commitment therapy, and resilience training as vital tools for promoting surgeon well-being. Resources from various organizations, including the American Urological Association and the American Medical Association, are now available to facilitate these critical conversations. By integrating these resources and encouraging a culture of openness and support, the article suggests that the surgical community can better manage the inevitable emotional ramifications of complications, thereby fostering resilience and reducing burnout among surgeons.

Development and Validation of a Multivariable Nomogram Predictive of Post-Nephroureterectomy Renal Function.

BACKGROUND AND OBJECTIVE: The timing of perioperative nephrotoxic chemotherapy for upper tract urothelial carcinoma (UTUC) remains controversial and strongly depends on predicted platinum eligibility after radical nephroureterectomy (RNU). The study objective was to develop and validate a multivariable nomogram to predict estimated glomerular filtration rate (eGFR) following RNU. METHODS: This was a multi-institutional retrospective study of patients with UTUC treated with RNU from 2000 to 2020 at seven high-volume referral centers. Use of adjuvant chemotherapy was risk-stratified. Patients were retrospectively randomly allocated 2:1 to discovery and validation cohorts. Discovery data were used to identify independent factors associated with GFR at 1-3 mo after RNU on linear regression, and backward selection was applied for model construction. Accuracy was defined as the percentage of predicted eGFR results within 30% of the corresponding observed eGFR. KEY FINDINGS AND LIMITATIONS: We included 1100 patients, of whom 733 were in the discovery and 367 were in the validation cohort. Multivariable predictors of postoperative eGFR decline included advanced age (odds ratio [OR] -0.18, 95% confidence interval [CI] -0.28 to -0.08), diabetes (OR -2.38, 95% CI -4.64 to -0.11), and hypertension (OR -2.24, 95% CI -4.16 to -0.32). Factors associated with favorable postoperative eGFR included larger tumor size (OR 10.57, 95% CI 7.4-13.74 for tumors >5 cm vs ≤2 cm) and preoperative eGFR (OR 0.44, 95% CI 0.39-0.49). A composite nomogram predicted postoperative eGFR with good accuracy in both the discovery (80.5%) and validation (78.6%) cohorts. Limitations include exclusion of patients who received neoadjuvant chemotherapy. CONCLUSIONS: A nomogram that incorporates ubiquitous preoperative clinical variables can predict post-RNU eGFR and was validated with an independent cohort. PATIENT SUMMARY: We developed a tool that uses patient data to predict eligibility for chemotherapy after surgery to remove the kidney and ureter in patients with cancer in the upper urinary tract.

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.

Oncologic Outcomes in Patients with Residual Upper Tract Urothelial Carcinoma Following Neoadjuvant Chemotherapy.

BACKGROUND AND OBJECTIVE: Growing evidence supports the use of neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). However, the implications of residual UTUC at radical nephroureterectomy (RNU) after NAC are not well characterized. Our objective was to compare oncologic outcomes for pathologic risk-matched patients who underwent RNU for UTUC who either received NAC or were chemotherapy-naïve. METHODS: We retrospectively identified 1993 patients (including 112 NAC recipients) who underwent RNU for nonmetastatic, high-grade UTUC between 1985 and 2022 in a large, international, multicenter cohort. We divided the cohort into low-risk and high-risk groups defined according to pathologic findings of muscle invasion and lymph node involvement at RNU. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) estimates were calculated using the Kaplan-Meier method. Multivariable analyses were performed to determine clinical and demographic factors associated with these outcomes. KEY FINDINGS AND LIMITATIONS: Among patients with low-risk pathology at RNU, RFS, OS, and CSS were similar between the NAC and chemotherapy-naïve groups. Among patients with high-risk pathology at RNU, the NAC group had poorer RFS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 2.10-4.48), OS (HR 2.06, 95% CI 1.33-3.20), and CSS (subdistribution HR 2.54, 95% CI 1.37-4.69) in comparison to the pathologic risk-matched, chemotherapy-naïve group. Limitations include the lack of centralized pathologic review. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients with residual invasive disease at RNU after NAC represent a uniquely high-risk population with respect to oncologic outcomes. There is a critical need to determine an optimal adjuvant approach for these patients. PATIENT SUMMARY: We studied a large, international group of patients with cancer of the upper urinary tract who underwent surgery either with or without receiving chemotherapy beforehand. We identified a high-risk subgroup of patients with residual aggressive cancer after chemotherapy and surgery who should be prioritized for clinical trials and drug development.