Urine Biopsy as Dynamic Biomarker to Enhance Clinical Staging of Bladder Cancer in Radical Cystectomy Candidates.

PURPOSE: There is significant interest in identifying complete responders to neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) to potentially avoid removal of a pathologically benign bladder. However, clinical restaging after NAC is highly inaccurate. The objective of this study was to develop a next-generation sequencing-based molecular assay using urine to enhance clinical staging of patients with bladder cancer. METHODS: Urine samples from 20 and 44 patients with bladder cancer undergoing RC were prospectively collected for retrospective analysis for molecular correlate analysis from two clinical trials, respectively. The first cohort was used to benchmark the assay, and the second was used to determine the performance characteristics of the test as it correlates to responder status as measured by pathologic examination. RESULTS: First, to benchmark the assay, known mutations identified in the tissue (MT) of patients from the Accelerated Methotrexate, Vinblastine, Doxorubicin, Cisplatin trial (ClinicalTrials.gov identifier: NCT01611662, n = 16) and a cohort from University of California-San Francisco (n = 4) were cross referenced against mutation profiles from urine (MU). We then determined the correlation between MU persistence and residual disease in pre-RC urine samples from a second prospective clinical trial (The pT0 trial; ClinicalTrials.gov identifier: NCT02968732). Residual MU status correlated strongly with residual disease status (pT0 trial; n = 44; P = .0092) when MU from urine supernatant and urine pellet were assessed separately and analyzed in tandem. The sensitivity, specificity, PPV, and NPV were 91%, 50%, 86%, and 63% respectively, with an overall accuracy of 82% for this second cohort. CONCLUSION: MU are representative of MT and thus can be used to enhance clinical staging of urothelial carcinoma. Urine biopsy may be used as a reliable tool that can be further developed to identify complete response to NAC in anticipation of safe RC avoidance.

Racial Disparities in Diagnosis and Treatment of Depression Associated with Androgen Deprivation Therapy for Prostate Cancer.

OBJECTIVE: To analyze potential racial disparities in the diagnosis and management of depression associated with androgen deprivation therapy. METHODS: TriNetX health record network was queried for prostate cancer patients treated with androgen deprivation therapy from 2003-2023. Differences in rates of depression diagnosis and treatment were compared between White and Black patients. Means, odds ratios, and t tests were calculated in univariate analysis with 95% confidence intervals (CI). RESULTS: Data were queried from 93 health care organizations to yield 78,313 prostate cancer patients treated with androgen deprivation therapy. Patients on androgen deprivation therapy had 60% greater odds of developing depression vs other patients [9% vs 6%; odds ratio (OR) 1.6; 95% CI (1.5-1.7); P <.0001]. Of those with depression secondary to androgen deprivation therapy, only 35% were treated with antidepressants. After starting androgen deprivation therapy, White patients had 30% greater odds of being diagnosed with depression, compared to Black patients [10% vs 8%; OR 1.3; 95% CI (1.2-1.4); P <.001]. White patients also had higher odds of being treated with a first line antidepressant than Black patients [56% vs 48%; OR 1.4, 95% CI (1.2-1.6), P <.001]. CONCLUSION: This analysis confirms a significant association between androgen deprivation therapy and the development of clinical depression, and highlights its medical undertreatment. Importantly, our findings also indicate significant racial disparities in the identification and treatment of depression. Routine screening initiatives that account for social determinants of health may alleviate this disparity. Limitations of this study include retrospective design and lack of data describing severity of depression, which might correlate with need for medication.

Gender Diversity in Urology Residency Program Leadership Is Associated With Gender Diversity in Residency Cohort.

OBJECTIVE: To evaluate the association of program director (PD) gender on the proportion of female residents in urology residency programs. METHODS: Demographics for program faculty and current residents matched in the 2017-2022 cycles at United States' accredited urology residency programs were collected from institutional websites. Data verification was completed using the American Urological Association's (AUA) list of accredited programs and the programs' official social media channels. Proportion of female residents across cohorts was compared using two-tailed Student's t-tests. RESULTS: One hundred forty-three accredited programs were studied, and 6 were excluded for lack of data. Thirty (22%) of the 137 programs studied have female PDs. Of 1799 residents, 571 (32%) are women. There has been an upward trend in the proportion of females matched from 26% in 2018 to 30% in 2019, 33% in 2020, 32% in 2021, to 38% in 2022. When compared to programs with male PDs, those with female PDs had a significantly higher proportion of female residents (36.2% vs 28.8%, p = .02). CONCLUSION: Nearly one-quarter of urology residency PDs are female, and approximately one-third of current urology residents are women, a proportion that has been increasing. Programs with female PDs are more likely to match female residents, whether those programs with female leadership rank female applicants more favorably or female applicants rank those programs higher. Given the ongoing gender disparities in urology, these findings indicate notable benefit in supporting female urologists in academic leadership positions.

The Impact of COVID-19 on the Urology Residency Match and Geographic Proximity of Applicants.

OBJECTIVE: To determine the impacts of COVID-19 pandemic-related changes and program-specific characteristics on the geographic diversity of the 2021 and 2022 urology match classes. METHODS: We gathered publicly available information to compare match outcomes in 2021 and 2022 to the previous 5 application cycles (2016-2020). Variables included residency program class size, program and resident AUA section, and program and resident medical school. Univariate comparisons were made with Fisher's t-tests. Odds ratios were calculated following multivariable analysis. RESULTS: Comparing the previous 5 application cycles to the 2 pandemic years individually and together showed no significant changes in home or in-section matches. However, when comparisons were stratified by small (1-2 residents) vs large (3+ residents) programs, a significant increase in at-home and in-section matches was observed for small programs in 2021. Large programs did not experience significant changes in match patterns. Multivariate analysis showed that small programs had significantly lower odds of matching applicants from home institutions and within AUA sections. Additionally, certain AUA sections demonstrated significantly increased likelihood of accepting in-section applicants. CONCLUSION: The changes from in-person to virtual application cycles during the pandemic particularly affected small residency programs in 2021. With easing restrictions and logistical improvements in the 2022 cycle, locoregional match rates partially shifted back to prepandemic patterns, though not completely. Although the pandemic did not affect geographic diversity in urology as much as in other surgical subspecialties, these findings and further study should be considered to optimize upcoming cycles.

Pretest Genetic Education Video Versus Genetic Counseling for Men Considering Prostate Cancer Germline Testing: A Patient-Choice Study to Address Urgent Practice Needs.

PURPOSE: Germline testing (GT) for prostate cancer (PCA) is now central to treatment and hereditary cancer assessment. With rising demand for and shortage of genetic counseling (GC), tools to deliver pretest informed consent across practice settings are needed to improve access to GT and precision care. Here, we report on Evaluation and Management for Prostate Oncology, Wellness, and Risk (EMPOWER), a patient-choice study for pretest video-based genetic education (VBGE) versus GC to inform urgent practice needs. PATIENTS AND METHODS: Men with PCA or at risk for PCA (family history of PCA) were eligible and could choose pretest VBGE or GC. Outcomes included decisional conflict for GT, change in genetics knowledge, satisfaction, and intention to share results with family and/or providers. Descriptive statistics summarized results with counts and percentages for categorical variables and mean ± standard deviation for continuous variables. Data were compared with Fisher's exact, chi-squared, or Wilcoxon two-sample tests. Mean change in genetics knowledge was compared with t tests. The significance level was set a priori at .05. RESULTS: Data on the first 127 participants were analyzed. Characteristics were White (85.8%), bachelor's degree (66.9%), and PCA diagnosis (90.6%). The majority chose VBGE (71%) versus GC (29%; P < .001). No differences were observed in decisional conflict for GT or satisfaction. Cancer genetics knowledge improved in both groups without significant difference (+0.9 VBGE, +1.8 GC, P = .056). Men who chose VBGE had higher intention to share GT results (96.4% VBGE v 86.4% GC, P = .02). Both groups had high rates of GT uptake (VBGE 94.4%, GC 92%). CONCLUSION: A substantial proportion of men opted for pretest VBGE, with comparable patient-reported outcomes and uptake of GT. The results support the use of pretest video to address the critical GC shortage in the precision era.

Questioning the Status Quo: Should Gleason Grade Group 1 Prostate Cancer be Considered a "Negative Core" in Pre-Radical Prostatectomy Risk Nomograms? An International Multicenter Analysis.

OBJECTIVE: To assess the impact of excluding Gleason Grade Group 1 (GG1) prostate cancer (CaP) cores from current pre-radical prostatectomy (RP) nomograms. METHODS: Multi-institutional retrospective chart review was performed on all RP patients with prostate biopsy between 2008 and 2018. Patients were individually assessed using the Memorial Sloan Kettering Cancer Center (MSKCC) and Briganti nomograms using the following iterations: (1) Original [ORIG] - all available core data and (2) Selective [SEL] - GG1 cores considered negative. Nomogram outcomes - lymph node invasion (LNI), extracapsular extension (ECE), organ-confined disease (OCD), seminal vesicle invasion (SVI), were compared across iterations and stratified based on biopsy GG. Clinically significant impact on management (CSIM) was defined as change in LNI risk above or below 2% or 5% (Δ2/Δ5). Nomogram outcomes were validated with RP pathology. RESULTS: 7718 men met inclusion criteria. In men with GG2 who also had GG1 cores, SEL better predicted LNI (MSKCC - ORIG 4.97% vs SEL 3.50%; Briganti - ORIG 4.81% vs SEL 2.49%, RP outcome 2.46%), OCD (MSKCC - ORIG 40.91% vs SEL 48.44%, RP outcome: 68.46%) and ECE (MSKCC - ORIG 57.87% vs SEL 50.38%, RP outcome: 30.41%), but not SVI (MSKCC - ORIG 5.42% vs SEL 3.34%, RP outcome: 5.62%). This was also consistent in patients with GG3-5 disease. The greatest CSIM was on GG1-2 CaP; Δ2 and Δ5 in GG1 patients was 26.3%-31.0% and 1.5%-5.2%, respectively, and Δ2 and Δ5 in GG2 patients was 3.4%-22.2% and 12.3%-13.6%, respectively. CONCLUSION: Excluding GG1 CaP cores from pre-RP nomograms better predicts final RP pathologic outcomes. More importantly, this may better reflect extent of true cancer burden.

Medical evaluation and management of male and female voiding dysfunction: a review.

A significant workforce shortage of urologists available to serve the US population has been projected to occur over the next decade. Accordingly, much of the management of urologic patients will need to be assumed by other specialties and practitioners. Since primary care physicians are often first evaluate common urologic complaints, it makes sense that these physicians are in an excellent position to intervene in the management of these patients when appropriate. One of the most common complaints in urology is voiding dysfunction. The incidence of voiding dysfunction increases with age, with conservative estimates showing that over 50% of elderly patients suffer. Despite this high prevalence and its negative impact on quality of life, however, few seek or receive treatment, as many do not readily disclose these impactful yet personal symptoms. We sought to summarize the typical presentation, evaluation, assessment and therapeutic options for both male and female patients presenting with voiding dysfunction.

Long Term Surveillance of Renal Cell Carcinoma Recurrence Following Ablation using 2D and 3D Contrast-Enhanced Ultrasound.

OBJECTIVE: To evaluate efficacy of using 2D and 3D contrast enhanced ultrasound (CEUS) for surveillance of RCC recurrence in patients post-ablation and identify imaging hallmarks of recurrence. METHODS: 53 patients >8 months post ablation of RCC provided informed consent for this IRB approved study. Patients received 2D and 3D CEUS examinations with Optison (GE Healthcare). Three radiologists of varying CEUS experience described enhancement characteristics, made a diagnosis of recurrence/no-recurrence, and quantified their diagnostic confidence levels. RESULTS: Cases of RCC recurrence showed full ablation cavity enhancement with equal arrival times and intensity compared to the renal cortex. Lack of recurrence was characterized as a complete lack of enhancement within the cavity, or delayed enhancement stemming from the periphery of the ablation cavity. Sensitivity for detecting RCC recurrence was 100% for all readers and specificity was 90%-94%. Reader agreement ranged from 88% to 96%. No significant improvements were achieved with the addition of 3D CEUS, and its inclusion resulted in decreased reader confidence. CONCLUSION: Contrast-enhanced ultrasound successfully identified all cases of RCC recurrence in this study. Importantly, some patients with complete response to treatment developed delayed enhancement at the periphery of the ablation cavity over time, corresponding to fat necrosis, scarring or granulation tissue within the ablation cavity.

Hematologic Toxicity of Concurrent Administration of Radium-223 and Next-generation Antiandrogen Therapies.

PURPOSE/OBJECTIVES: Radium-223 is a first-in-class radiopharmaceutical recently approved for the treatment of castration-resistant prostate cancer in patients with symptomatic bone metastases. Initial studies investigating Radium-223 primarily used nonsteroidal first-generation antiandrogens. Since that time, newer antiandrogen therapies have demonstrated improved survival in patients with castration-resistant prostate cancer. It has been suggested that the rational combination of these newly approved agents with Radium-223 may lead to improved response rates and clinical outcomes. Currently, there is lack of information regarding the safety of concurrent administration of these agents with radiopharmaceuticals. Here, we report on hematologic toxicity findings from our institution in patients receiving concurrent Radium-223 and next-generation antiandrogen therapies with either enzalutamide or abiraterone. MATERIALS/METHODS: In a retrospective study, we analyzed patients who received Radium-223 as part of an early-access trial, and following FDA approval in May 2013, patients receiving Radium-223 as part of standard care. Radium-223 was given at standard dosing of 50 kBq/kg each month for 6 total cycles. Complete blood counts were performed before treatment monthly and following each injection. Blood counts from patients receiving Radium alone and concurrently with next-generation antiandrogens were compared. To date, 25 total patients were analyzed, with a median of 5 monthly doses received per patient. Fourteen patients received concurrent therapy during monthly Radium-223 with either enzalutamide (n=8) or abiraterone (n=6). RESULTS: Six patients expired due to disease progression. Two patients discontinued treatment due to grade 3 myelosuppression. For patients receiving either Radium alone and with concurrent next-generation antiandrogen therapy, there did not appear to be any statistically significant differences between initial and nadir blood counts. Mean change from initial neutrophil count to nadir was 1.9×10/L in patients receiving Radium alone, versus 2.3×10/L in patients receiving concurrent therapy (P=0.77). Mean change from initial hemoglobin value to nadir was 1.5 g/L in patients receiving Radium alone, versus 1.8 g/L in patients receiving concurrent therapy (P=0.31). Mean change from initial platelet count to nadir was 52.3×10 cells/L in patients receiving Radium alone versus 70.6×10 cells/L in patients receiving concurrent therapy (P=0.39). Individual blood counts for each measured laboratory are included in the supplemental data. PSA was stable or decreased in 22% of patients receiving Radium alone versus 35% of patients receiving combination treatment (P=0.24). CONCLUSIONS: Concurrent administration of Radium-223 and next-generation antiandrogen therapies appears to be well tolerated with similar toxicities to standard administration of Radium-223 alone. This particular cohort of patients represents a high-risk, heavily pretreated group of patients with advanced metastatic disease and significant marrow burden. Despite these risk factors, hematologic toxicity was modest and was in the range expected for this risk group based on previous trials. To date, this is the first study investigating the toxicity of combination treatment. Further studies investigating the safety and efficacy of combination treatments are warranted.

Adjuvant versus salvage radiation therapy for prostate cancer patients with adverse pathologic features: comparative analysis of long-term outcomes.

OBJECTIVES: To compare long-term outcomes of men with adverse pathologic features after adjuvant radiation therapy (ART) versus salvage radiation therapy (SRT) after radical prostatectomy at our institution. METHODS: Patients treated with postprostatectomy radiation therapy with pT3 tumors, or pT2 with positive surgical margins, were identified. Cumulative freedom from biochemical failure (FFBF), freedom from metastatic failure (FFMF), and overall survival rates were estimated utilizing the Kaplan-Meier method. Multivariate analyses were performed to determine independent prognostic factors correlated with study endpoints. Propensity score analyses were performed to adjust for confounding because of nonrandom treatment allocation. RESULTS: A total of 186 patients with adverse pathologic features treated with ART or SRT were identified. The median follow-up time after radical prostatectomy was 103 and 88 months after completion of radiation therapy. The Kaplan-Meier estimates for 10-year FFBF was 73% and 41% after ART and SRT, respectively (log-rank, P=0.0001). Ten-year FFMF was higher for patients who received ART versus SRT (98.6% vs. 80.9%, P=0.0028). On multivariate analyses there was no significant difference with respect to treatment group in terms of FFBF, FFMF, and overall survival after adjusting for propensity score. CONCLUSIONS: Although unadjusted analyses showed improved FFBF with ART, the propensity score-adjusted analyses demonstrated that long-term outcomes of patients treated with ART and SRT do not differ significantly. These results, with decreased effect size of ART after adjusting for propensity score, demonstrate the potential impact of confounding on observational research.

Patterns of care for elderly men diagnosed with favorable-risk prostate cancer from 2004 to 2008: a population-based analysis.

OBJECTIVES: With the widespread use of prostate-specific antigen testing, an increasing number of men are diagnosed with favorable-risk prostate cancer (PC). Recently, emphasis has been placed on active surveillance for selected men with favorable-risk PC to avoid unnecessary treatment for tumors that may be clinically insignificant. We performed a population-based analysis to assess patterns of initial treatment (IT) for a contemporary cohort of elderly men diagnosed with a favorable-risk PC in the United States. METHODS: We used the Surveillance, Epidemiology, and End Results database to identify men aged more than or equal to 70 years diagnosed with a favorable-risk PC from 2004 to 2008. Multivariable logistic regression analyses were performed to determine patient, tumor, and socioeconomic factors associated with IT. RESULTS: A total of 15,108 men more than or equal to 70 years with a favorable-risk PC were identified. Prostatectomy was performed in 2.6% of patients. Fifty-nine percent of patients were recommended to undergo radiation therapy (RT). Among patients 70 to 74 years, 66.45% were recommended to undergo RT. Fifty-nine percent, 36.6%, and 15.8% of patients between 75 and 79, 80 and 84, and more than or equal to 85 years were recommended to receive RT, respectively. Factors significantly associated with IT on multivariable logistic regression analysis included: younger age, white race, Gleason Score 6 (vs.≤5), married marital status, and no history of prior malignancy. We also identified significant geographic variations in patterns of IT. CONCLUSIONS: A large percentage of elderly men diagnosed with favorable-risk PC undergo IT, most commonly with RT. Future research should be performed to identify barriers to patient and physician acceptance of active surveillance.

Enhancing prostate cancer care through the multidisciplinary clinic approach: a 15-year experience.

PURPOSE: To report on the 15-year prostate cancer experience of our multidisciplinary genitourinary cancer clinic established in 1996 at the National Cancer Institute (NCI) -designated Jefferson Kimmel Cancer Center. Patients with genitourinary cancers were evaluated weekly by multiple specialists at a single site, and we focus on the 83% of patients with prostate cancer. To our knowledge, our multidisciplinary genitourinary cancer clinic is the longest continuously operating center of its kind at an NCI Cancer Center in the United States. METHODS: Data from Jefferson's Oncology Data Services were compared to SEER prostate cancer outcomes. Data on treatment changes in localized disease, patient satisfaction, and related parameters were also assessed. RESULTS: Ten-year survival data approach 100% in stage I and II prostate cancer. Ten-year data for stage III (T3 N0M0) and stage IV (T4 N0M0) disease show that our institutional survival rate exceeds SEER. There is a shift toward robotically assisted laparoscopic radical prostatectomy and a slight decrease in brachytherapy relative to external beam radiation therapy in localized disease. Patient satisfaction is high as measured by survey instruments. CONCLUSION: Our long-term experience suggests a benefit of the multidisciplinary clinic approach to prostate cancer, most pronounced for high-risk, locally advanced disease. A high level of satisfaction with this patient-centered model is seen. The multidisciplinary clinic approach to prostate cancer may enhance outcomes and possibly reduce treatment regret through a coordinated presentation of all therapeutic options. This clinic model serves as an interdisciplinary educational tool for patients, their families, and our trainees and supports clinical trial participation.