Functional and oncologic outcomes of prostate capsule-sparing radical cystectomy: A systematic review and meta-analysis.

Radical cystectomy (RC) is the gold standard treatment for patients with organ-confined bladder cancer. However, despite the success of this treatment, many men who undergo orthotopic neobladder substitution develop significant erectile dysfunction and urinary symptoms, including daytime and nighttime urinary incontinence. Prostate-capsule-sparing radical cystectomy (PCS-RC) with orthotopic neobladder (ONB) has been described in the literature as a surgical technique to improve functional outcomes in appropriately selected patients. We performed a systematic review and meta-analysis of manuscripts on PCS-RC with ONB published after 2000. We included retrospective and prospective studies with more than 25 patients and compared PCS-RC with nerve-sparing or conventional RC. Studies in which the entire prostate was spared (including the transitional zone) were excluded. Comparative studies were analyzed to assess rates of daytime continence, nighttime continence, and satisfactory erectile function in patients undergoing PCS-RC compared with those undergoing conventional RC. Fourteen reports were included in the final review. Our data identify high rates of daytime (83%-97%) and nighttime continence (60%-80%) in patients undergoing PCS-RC with ONB. In comparative studies, meta-analysis results demonstrate no difference in daytime continence (RR:1.12; 95% CI: 0.72-1.73) in those undergoing PCS-RC compared to those undergoing conventional RC. Similarly, nighttime continence was similar between the 2 groups (RR:1.85; 95% CI: 0.57-6.00. Erectile function was improved in those undergoing PCS-RC (RR 5.35; 95% CI: 1.82-15.74) in the PCS-RC series. Bladder cancer margin positivity and recurrence rates were similar to those reported in the literature with conventional RC with an average weighted follow-up of 52.2 months. While several studies utilized different prostate cancer (CaP) screening techniques, the rates of CaP were low (incidence 0.02; 95% CI:0.01-0.04), and oncologic outcomes were similar to standard RC. PCS-RC is associated with improved nighttime continence and erectile function compared to conventional RC techniques. Further work is needed to standardize CaP screening before surgery, but the data suggest low rates of CaP with similar oncologic outcomes when compared to RC.

Preoperative anemia is associated with increased radical cystectomy complications.

PURPOSE: The impact of anemia in postoperative complications following radical cystectomy (RC) is not completely elucidated and its association with direct hospital costs has not been characterized in depth. Our goal is to determine the association between anemia, 90-day surgical complications and the expenditure attributed to preoperative anemia in patients undergoing RC. MATERIALS AND METHODS: We captured all patients who underwent RC between 2003 and 2017 using the Premier Hospital Database (Premier Inc, Charlotte, NC). Patient, hospital and surgical characteristics were evaluated. Anemia was defined by a corresponding diagnostic code that was present on admission prior to RC. Unadjusted patients' demographic characteristics with and without anemia, hospital and surgeon characteristics were compared, and multivariable regression models were developed to evaluate 90-day complications and total direct hospital costs. RESULTS: The cohort included 83,470 patients that underwent RC between 2003 and 2017 and 11% were found to be anemic. On multivariable analysis, preoperative anemia more than doubled the odds of having a complication (odds ratio 2.19 (1.89-2.53)) and significantly increased the risk of major complications (odds ratio 1.51 (1.31-1.75)) at 90-days after RC. Anemic patients had significantly higher 90-days total direct costs due to higher laboratory, pharmacologic, radiology and operating room costs. CONCLUSIONS: Anemic cystectomy patients face a 50% increase in the risk of major complications within the first 90-days after surgery. This increased risk persisted after adjusting for patient, hospital and surgical factors. Our study suggests hematocrit level prior to RC may be used as a pre-exisitng condition for increased risk of surgical complications.

Prognostic factors for overall survival in malignant ureteral obstruction.

INTRODUCTION: To identify prognostic factors for overall survival (OS) in patients with malignant ureteral obstruction (MUO) from gynecologic malignancy (GM), with the goal of improving patient selection for urinary diversion. MATERIALS AND METHODS: Retrospective review of 126 patients with MUO from GM at two academic centers from 2011-2019. Factors related to OS identified by Cox regression proportional hazard model. In patients with incomplete survival data (n = 30), hospice was used as a surrogate for death. Multivariate models and receivers operating characteristics (ROC) curves were created for hemoglobin and albumin values. RESULTS: Overall median survival was 6.2 months. On univariate analysis, age at diagnosis, Charlson Comorbidity Index (CCI) ≥ 8, advanced clinical stage, ascites, pleural effusion, albumin, and hemoglobin were associated with poor OS. OS was higher for those receiving ureteral stenting as compared with no intervention. There was no survival difference based on hydronephrosis grade, stent failure (SF), or creatinine at the time of intervention. On multivariate analysis, albumin < 2.85 g/dL and hemoglobin < 9.6 g/dL were predictive of poor OS. CONCLUSIONS: OS in patients with MUO due to GM is poor. Several prognostic factors for poor survival including low serum albumin and hemoglobin were identified. Ureteral stenting was associated with improved OS compared to observation, but selection bias likely contributed to this result. Additional studies are needed to clarify this finding. These data can be utilized to counsel patients regarding outcomes after urinary diversion in the setting of MUO and perhaps avoid additional procedures in some of these patients who will not derive meaningful benefit.

Bladder diverticulum caused by primary bladder neck obstruction.

Here, we report a case of a patient in their mid 30s who presented with an elevated creatinine and was found to have a massive bladder diverticulum. The patient underwent a robotic-assisted diverticulectomy. They were later found to have a primary bladder neck obstruction on video urodynamics, and subsequently, underwent bladder neck incision, leading to significant improvement in urinary symptoms. Primary bladder neck obstruction is an overlooked cause of bladder diverticulum. While cystoscopy and cross-sectional imaging are frequently used in the initial evaluation of bladder diverticula, in the absence of an anatomic obstruction such as prostate enlargement, video urodynamics should be performed to assess for primary bladder neck obstruction.

Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences.

Racial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P < 0.001) and ETS (P = 0.02) expression, decreased SPINK1 expression (P < 0.001), and basal-like (P < 0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p < 0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM.

Sex and Racial Disparities in the Treatment and Outcomes of Muscle-invasive Bladder Cancer.

OBJECTIVE: To identify racial and sex disparities in the treatment and outcomes of muscle-invasive bladder cancer (MIBC) using a nationwide oncology outcomes database. METHODS: Using the National Cancer Database, we identified patients with muscle invasive bladder cancer from 2004 to 2014. Treatments analyzed included no treatment, cystectomy, neoadjuvant chemotherapy plus cystectomy ("optimal treatment"), cystectomy plus adjuvant chemotherapy, and chemoradiation. Propensity matching compared mortality outcomes between sexes. Logistic models evaluated predictors of receiving optimal treatment, as well as mortality. RESULTS: Forty seven thousand two hundred and twenty nine patients were identified. Most patients were male (73.4%) and underwent cystectomy alone (69.0%). Propensity score matching demonstrated increased 90-day mortality in women vs men (13.0% vs 11.6%, P = .009), despite adjusting for differences in treatments between sexes. Logistic regression models showed no difference in receipt of optimal treatment between sexes (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.83-1.22) although black patients were less likely to receive optimal treatment (OR 0.15, 95% CI 0.05-0.48). Logistic regression models confirmed increased 90-day mortality in female (OR 1.17, CI 1.08-1.27, P < .001) and black (OR 1.29, CI 1.11-1.50, P = .001) patients. Females had a lower overall survival on Cox regression analysis (Hazard Ratio 0.92, 95% CI 0.87-0.97). CONCLUSION: While there do not appear to be significant treatment disparities between sexes, women experience higher 90-day mortality and lower overall survival. Black patients are less likely to receive optimal treatment and have a higher risk of 90-day mortality. Additional research is needed to determine the variables leading to worse outcomes in females and identify impediments to black patients receiving optimal treatment.

Practice patterns for extended venous thromboembolism chemoprophylaxis among urologic oncologists after radical cystectomy.

INTRODUCTION: Extended outpatient chemoprophylaxis (ECP) following radical cystectomy (RC) for bladder cancer is proven to reduce rates of venous thromboembolism (VTE). While ECP is commonly performed with enoxaparin, its cost-effectiveness and adherence rate has been called into question. Data from orthopedic literature suggest that ECP with direct oral anticoagulants (DOACs) may be as effective in VTE prevention as enoxaparin in patients undergoing joint surgery. Our goal is to determine how urologic oncologists employ ECP following RC. METHODS: Members of the Society of Urologic Oncology were surveyed on practice patterns for the use of ECP after RC. Specific questions were asked regarding the use of inpatient and outpatient VTE prophylaxis, as well as perceived barriers to DOACs and enoxaparin. RESULTS: There were 121 of 878 (13.8%) respondents and the majority were in academic practices (83%). Most respondents had at least 5 years of experience and performed greater than 10 cystectomies annually. Almost all participants utilized inpatient (97%) and extended (80%) chemoprophylaxis for VTE prevention. Of those who elected for ECP, almost all (96%) used enoxaparin. Only 3 respondents (3%) prescribed oral agents such as rivaroxaban (2) or warfarin (1). Among those using enoxaparin, financial-specific barriers to treatment such as lack of insurance coverage (38%), inability to afford the medication (51%), and need for additional insurance authorization (44%) were reported. Poor patient adherence and refusal to perform injections were reported by 20% and 18% of respondents, respectively. Among the 23 physicians who did not use ECP, cost (39%) and delivery method (26%) were cited as barriers to treatment. CONCLUSIONS: The majority of surveyed urologic oncologists are prescribing subcutaneous enoxaparin ECP following RC. Poor patient adherence due to self-injections and financial barriers were frequently reported and represent a possible opportunity for the use of oral anticoagulants in the post-operative setting. These data will be used in the development of a proposed clinical trial of a DOAC in the post-RC setting.

Determinants of neoadjuvant chemotherapy use in muscle-invasive bladder cancer.

Purpose: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is standard of care for muscle-invasive bladder cancer (MIBC). However, NAC is used in less than 20% of patients with MIBC. Our goal is to investigate factors that contribute to underutilization NAC to facilitate more routine incorporation into clinical practice. Materials and Methods: We identified 5,915 patients diagnosed with cT2-T3N0M0 MIBC who underwent RC between 2004 and 2014 from the National Cancer Database. Univariate and multivariable models were created to identify variables associated with NAC utilization. Results: Only 18.8% of patients received NAC during the study period. On univariate analyses, NAC utilization was more likely at academic hospitals, US South and Midwest (p<0.05). Higher Charlson score was associated with decrease use of NAC (p<0.05). On multivariate analysis, treatment in academic hospitals (odds ratio [OR], 1.367; 95% confidence interval [CI], 1.186-1.576), in the Midwest (OR, 1.538; 95% CI, 1.268-1.977) and South (OR, 1.424; 95% CI, 1.139-1.781) were independently associated with NAC utilization. Older age (75 to 84 years old; OR, 0.532; 95% CI, 0.427-0.664) and higher Charlson score (OR, 0.607; 95% CI, 0.439-0.839) were associated with decreased NAC utilization. Sixty-eight percent of patients did not receive NAC because it was not planned and only 2.5% of patients had contraindications for NAC treatment. Conclusions: Our study demonstrates that NAC is underutilized. Decreased utilization of NAC was associated with older patients and higher Charlson score. This underutilization may be related to practice patterns as very few patients have true contraindications.

Prostate Cancer in Men With Treated Advanced Heart Failure: Should we Keep Screening?

OBJECTIVE: To evaluate the outcomes of men diagnosed with prostate cancer (CaP) following implanted treatments for advanced heart failure. Given the increasingly favorable 10-year life expectancy, MedStar Washington Hospital Center screens heart transplant (HT) candidates for CaP and other malignancies prior to intervention. METHODS: Men aged 18-90 with available pretransplant Prostate Specific Antigen (PSA) who underwent left ventricular assist device (LVAD) and/or HT at MedStar Washington Hospital Center from 2007 to 2018 were identified. Serum PSA, CaP diagnosis, and treatment were captured and analyzed. Survival was analyzed using Kaplan-Meier curves. RESULTS: Data were available for 34 patients. Median age was 53 [IQR = 51-58]. Median follow-up was 77 months (95% CI = 40-87 months). Six men had postimplant elevated PSA (5.3; SD = 8.5) and 4 were diagnosed with CaP. Median age of CaP diagnosis was 59 [IQR = 58.5-62). As of 2018, 31 of the 34 patients were living, and none died from CaP. Five-year survival was 96% in those without CaP and 100% in those with CaP (Figure 2). CONCLUSION: Our cohort represents the largest known cohort with heart failure treated by LVAD and/or HT and CaP. Our median age of 59 at CaP diagnosis is considerably younger than the national median of 66.1 Of the 4 individuals diagnosed with CaP, 3 had high-grade disease. Given the favorable long-term survival of these patients post-LVAD and/or HT, age-appropriate treatment for CaP should be continued postimplantation.

Imaging in Localized Bladder Cancer: Can Current Diagnostic Modalities Provide Accurate Local Tumor Staging?

PURPOSE OF REVIEW: Local tumor staging is paramount in the evaluation and management of bladder cancer. While neoadjuvant chemotherapy (NAC) followed by radical cystectomy and urinary diversion remains the gold standard for management of muscle-invasive bladder cancer, bladder-sparing regimens involving systemic chemotherapy and pelvic radiotherapy remain a viable option for select patients. Moreover, pre-cystectomy identification of patients with a complete response to NAC may obviate the need for radical cystectomy, but accurate post-therapy staging can be difficult to achieve. Contemporary imaging techniques may provide additional benefit in local tumor staging beyond standard imaging and cystoscopic biopsy. Our purpose is to summarize the ability of different imaging modalities to accurately stage bladder cancer patients in the treatment-naïve and post-chemotherapy settings. RECENT FINDINGS: Contemporary investigations have been studying multiparametric magnetic resonance imaging (mp-MRI) in the evaluation of bladder cancer. Its recent incorporation into bladder cancer staging is mainly being assessed in treatment-naïve patients; however, different sequences are being studied to assess their accuracy after the introduction of chemotherapy and possibly radiation. Multiple recent studies incorporating cystoscopy and biopsy are proving to be less accurate than originally predicted. Imaging has generally had a very limited role in guiding therapy in localized bladder cancer, but with the incorporation of newer sequences and techniques, imaging is poised to become vital in decision-making strategies of this cancer. Reliable local tumor staging through improved imaging may help better select patients for bladder-sparing treatments while maintaining optimized oncologic outcomes and allow this paradigm to become more acceptable in the urologic oncology community.

Fidelity of a PDX-CR model for bladder cancer.

Patient-derived xenografts (PDXs) are widely recognised as a more physiologically relevant preclinical model than standard cell lines, but are expensive and low throughput, have low engraftment rate and take a long time to develop. Our newly developed conditional reprogramming (CR) technology addresses many PDX drawbacks, but lacks many in vivo factors. Here we determined whether PDXs and CRCs of the same cancer origin maintain the biological fidelity and complement each for translational research and drug development. Four CRC lines were generated from bladder cancer PDXs. Short tandem repeat (STR) analyses revealed that CRCs and their corresponding parental PDXs shared the same STRs, suggesting common cancer origins. CRCs and their corresponding parental PDXs contained the same genetic alterations. Importantly, CRCs retained the same drug sensitivity with the corresponding downstream signalling activity as their corresponding parental PDXs. This suggests that CRCs and PDXs can complement each other, and that CRCs can be used for in vitro fast, high throughput and low cost screening while PDXs can be used for in vivo validation and study of the in vivo factors during translational research and drug development.

Survival and secondary interventions following treatment for locally-advanced prostate cancer.

INTRODUCTION: The utility of radical prostatectomy (RP) for locally-advanced prostate cancer remains unknown. Retrospective data has shown equivalent oncologic outcomes compared to radiation therapy (RT). RP may provide local tumor control and prevent secondary interventions from local invasion, and may decrease costs. MATERIALS AND METHODS: Using SEER-Medicare data from 1995-2011 we identified men with locally-advanced prostate cancer undergoing RP or RT. Rates of post-treatment diagnoses and interventions were identified using ICD-9 and CPT codes. Skeletal related events (SRE), androgen deprivation therapy (ADT) utilization, all-cause mortality, prostate cancer-specific mortality, and costs were compared. RESULTS: A total of 8367 men with locally-advanced prostate cancer were identified (6200 RP, 2167 RT). RT was associated with increased urinary obstruction, hematuria, infection, and cystoscopic intervention while RP was associated with increased urethral stricture intervention and erectile dysfunction. Compared to RT, RP was associated with decreased all-cause mortality (3.1 versus 5.2 deaths/100-person-years, p < 0.001), prostate cancer-specific mortality (0.8 versus 2.0 deaths/100-person-years, p < 0.001), SREs (2.0 versus 3.4 events/100 person-years, p < 0.001), and ADT utilization overall (7.4 versus 33.8 doses/100-person-years, p < 0.001) and > 3 years after treatment (3.6 versus 4.6 doses/100-person-years, p < 0.001). Overall and cancer specific costs were significantly lower for RP versus RT. CONCLUSIONS: RT for locally-advanced prostate cancer has a higher incidence of mortality, secondary diagnoses and interventions, SRE, and ADT utilization compared to RP. This may lead to increased costs and have implications for quality of life. Our findings support the utility of RP in appropriately selected men with locally-advanced prostate cancer given the possible decreased morbidity and survival benefit.

Bilateral Ureteroenteric Strictures: A Case of the "Reverse 7".

Anastomotic stricture is a well-known complication of the urinary diversion that accompanies radical cystectomy. Management options range from endoscopic procedures to open surgeries, with a subset of the latter employing bowel as the interposing segment. In this report, we describe a rare patient, who successfully underwent a "Reverse 7" procedure, bypassing strictures at both anastomotic junctions between ureters and neobladder.

To oophorectomy or not to oophorectomy: Practice patterns among urologists treating bladder cancer.

OBJECTIVES: Classically, radical cystectomy (RC) involves hysterectomy and bilateral salpingo-oophorectomy (BSO). Current understanding of ovarian cancer pathogenesis and effect of premature oophorectomy has lead to a shift within gynecology toward risk-reducing salpingectomy without oophorectomy in the absence of gynecologic malignancy. The purpose of this study was to assess knowledge base and practice patterns of urologic oncologists with regard to management of the gynecological organs at the time of RC. MATERIALS AND METHODS: An anonymous and voluntary electronic survey was distributed to members of the Society of Urologic Oncology (SUO). Demographic data, training, practice setting and duration, experience, rationale for BSO, and knowledge assessment of ovarian cancer pathogenesis/risks associated with BSO was collected. RESULTS: A total of 159/660 (24%) SUO members responded of whom 110 (69%) were academic urologists and 58 (36%) involved in training urologic oncology fellows. Of all, 75% had performed an ovarian-sparing RC. Furthermore, 14% were aware that salpingectomy alone reduces the risk of ovarian cancer, whereas 95%, 66%, and 26% were aware that BSO increases the risk of osteoporosis, cardiovascular disease, and all-cause mortality, respectively. Reasons for BSO at the time of RC included concern for urothelial carcinoma metastasis (54%), development of future gynecologic pathology (50%), and facilitation of pelvic lymph node dissection (36%). CONCLUSIONS: Many urologic oncologists remain unaware of the benefits of risk-reducing salpingectomy and the risks associated with BSO, identifying a potential area for further education in the urologic community.

Embryonal carcinoma presenting as a calcified solitary testicular mass on ultrasound.

A 24-year-old man presented with a 2-week history of a painless right testicular mass; ultrasound demonstrated a dense, solitary calcified mass. The patient elected observation after further workup showed no evidence of metastasis.A repeat ultrasound 3 months later showed interval growth and the patient underwent right radical orchiectomy. Pathology was consistent with pure embryonal carcinoma of the testis. Calcified testicular masses are typically benign but do carry a differential of spermatic granuloma, large-cell calcifying Sertoli cell tumour, trauma, tuberculosis, filariasis, calcified Leydig cell tumour and burned-out testicular tumour.To our knowledge, this is the first case report of pure embryonal carcinoma presenting as a solitary calcified testicular mass.

Magnetic Resonance Imaging/Transrectal Ultrasonography Fusion Prostate Biopsy Significantly Outperforms Systematic 12-Core Biopsy for Prediction of Total Magnetic Resonance Imaging Tumor Volume in Active Surveillance Patients.

OBJECTIVE: To correlate the highest percentage core involvement (HPCI) and corresponding tumor length (CTL) on systematic 12-core biopsy (SBx) and targeted magnetic resonance imaging/transrectal ultrasonography (MRI/TRUS) fusion biopsy (TBx), with total MRI prostate cancer (PCa) tumor volume (TV). PATIENTS AND METHODS: Fifty patients meeting criteria for active surveillance (AS) based on outside SBx, who underwent 3.0T multiparametric prostate MRI (MP-MRI), followed by SBx and TBx during the same session at our institution were examined. PCa TVs were calculated using MP-MRI and then correlated using bivariate analysis with the HPCI and CTL for SBx and TBx. RESULTS: For TBx, HPCI and CTL showed a positive correlation (R(2)=0.31, P<0.0001 and R(2)=0.37, P<0.0001, respectively) with total MRI PCa TV, whereas for SBx, these parameters showed a poor correlation (R(2)=0.00006, P=0.96 and R(2)=0.0004, P=0.89, respectively). For detection of patients with clinically significant MRI derived tumor burden greater than 500 mm(3), SBx was 25% sensitive, 90.9% specific (falsely elevated because of missed tumors and extremely low sensitivity), and 54% accurate in comparison with TBx, which was 53.6% sensitive, 86.4% specific, and 68% accurate. CONCLUSIONS: HPCI and CTL on TBx positively correlates with total MRI PCa TV, whereas there was no correlation seen with SBx. TBx is superior to SBx for detecting tumor burden greater than 500 mm(3). When using biopsy positive MRI derived TVs, TBx better reflects overall disease burden, improving risk stratification among candidates for active surveillance.