Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline: 2024 Amendment.

PURPOSE: The purpose of this American Urological Association (AUA)/Society of Urologic Oncology (SUO) guideline amendment is to provide a useful reference on the effective evidence-based treatment strategies for non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: In 2023, the NMIBC guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines in an effort to maintain currency. The amendment allowed for the incorporation of additional literature released since the previous 2020 amendment. The updated search gathered literature from July 2019 to May 2023. This review identified 1918 abstracts, of which 75 met inclusion criteria.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) in support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: Updates were made to statements on variant histologies, urine markers after diagnosis of bladder cancer, intravesical therapy, BCG maintenance, enhanced cystoscopy, and future directions. Further revisions were made to the methodology and reference sections as appropriate. CONCLUSIONS: This guideline seeks to improve clinicians' ability to evaluate and treat patients with NMIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Management Trends and Outcomes of Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder: Evolution of the University of Southern California Experience over 3,347 Cases.

PURPOSE: There are conflicting reports on outcome trends following radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS: Evolution of modern bladder cancer management and its impact on outcomes was analyzed using a longitudinal cohort of 3,347 patients who underwent RC at an academic center between 1971 and 2018. Outcomes included recurrence-free survival (RFS) and overall survival (OS). Associations were assessed using univariable and multivariable models. RESULTS: In all, 70.9% of cases underwent open RC in the last decade, although trend for robot-assisted RC rose since 2009. While lymphadenectomy template remained consistent, nodal submission changed to anatomical packets in 2002 with increase in yield (p <0.001). Neoadjuvant chemotherapy (NAC) use increased with time with concomitant decrease in adjuvant chemotherapy; this was notable in the last decade (p <0.001) and coincided with improved pT0N0M0 rate (p=0.013). Median 5-year RFS and OS probabilities were 65% and 55%, respectively. Advanced stage, NAC, delay to RC, lymphovascular invasion and positive margins were associated with worse RFS (all, multivariable p <0.001). RFS remained stable over time (p=0.73) but OS improved (5-year probability, 1990-1999 51%, 2010-2018 62%; p=0.019). Among patients with extravesical and/or node-positive disease, those who received NAC had worse outcomes than those who directly underwent RC (p ≤0.001). CONCLUSIONS: Despite perioperative and surgical advances, and improved pT0N0M0 rates, there has been no overall change in RFS trend following RC, although OS rates have improved. While patients who are downstaged with NAC derive great benefit, our real-world experience highlights the importance of preemptively identifying NAC nonresponders who may have worse post-RC outcomes.

Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial.

BACKGROUND: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer. METHODS: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849. FINDINGS: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths. INTERPRETATION: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state. FUNDING: FKD Therapies Oy.

Extended hospital stay after radical cystectomy with enhanced recovery protocol.

INTRODUCTION: To evaluate the reasons leading to an extended hospital stay (EHS) in patients undergoing radical cystectomy (RC) with postoperative enhanced recovery after surgery (ERAS) protocol. MATERIALS AND METHODS: A total of 509 patients underwent RC and urinary diversion with ERAS between May 2012 and March 2017. The protocol includes no bowel preparation, early feeding, predominantly non-narcotic pain control and µ opioid antagonists. Non-consenting/lost to follow up patients, and those with non-urothelial carcinoma were excluded. We defined EHS as ≥ 5 postoperative days and compared the cohort to those with a LOS of ≤ 4 days. Demographics including modifiable and non-modifiable factors as well as in-house complications as possible contributing factors to EHS was reviewed. RESULTS: There were 279/509 (54.8%) patients had an EHS. Median age was 73 years, 82.4% were male, and 36.6% had a Charlson comorbidity index (CCI) of > 2. Univariate analysis demonstrated that age > 65 years, CCI > 2, increased operative time, anemia requiring transfusion and non-orthotopic diversion were associated with EHS. On multivariate analysis, advanced age, operative time, postop transfusion, CCI > 2 as well as surgeon specific preferences was associated with EHS. Within EHS patients, 86% stayed due to an in-house complication; ileus (34.3%), anemia requiring transfusion (9.8%), UTIs (9.4%) and atrial fibrillation (8.5%). CONCLUSIONS: Advanced age, operative time, postop transfusion, CCI > 2 and surgeon-specific preferences are associated with an EHS following RC with ERAS. The common causes of EHS are in-house complications, mainly ileus.

90-Day complication rate in patients undergoing radical cystectomy with enhanced recovery protocol: a prospective cohort study.

PURPOSE: To report 90-day complication rates following radical cystectomy (RC) with enhanced recovery after surgery (ERAS) protocol. METHODS: All consecutive patients who underwent open RC with ERAS protocol from 2012 to 2014 were included. The protocol includes no bowel preparation or NGT, early feeding, predominantly non-narcotic pain management and µ-opioid antagonists. Non-consenting and lost to follow-up patients were excluded. All patients were closely followed up, and 90-day complication (Clavien-Dindo grading), readmission and emergency room (ER) visits were prospectively recorded. RESULTS: One hundred and sixty-nine cases with a median age of 71 years were included in the study. 90-Day major and minor complication rates were 24.3 and 53.9 %, respectively. The most common complications were infectious and gastrointestinal. The 90-day ER visit rate was 37.9 %, whereas the readmission rate was 29.6 %. The most common cause of hospital readmission and ER visits was infections. CONCLUSION: Radical cystectomy and urinary diversion with enhanced recovery protocol is a morbid surgery. The most common complication, cause of ER visit and readmission is yet infections. Further studies on methods to decrease these rates are underway.

Current Management Strategy for Penile Cancer and Future Directions.

PURPOSE OF REVIEW: The aim of this review is to evaluate the trends in multidisciplinary management of localized penile cancer and systemic therapy for advanced disease in the evolving era of targeted and immune checkpoint therapy. RECENT FINDINGS: Organ preservation (surgical or incorporating radiation) and reconstructive techniques are important considerations for quality of life in penile cancer survivors. Although local recurrence may be higher with organ preservation, salvage therapy appears successful. Inguinal and pelvic node management requires multidisciplinary care, including chemotherapy; optimal use of radiation has not been fully defined. Advanced in understanding the biology of penile cancer, particularly with regard to epidermal growth factor receptor (EGFR) and HPV status, have led to clinical trials of targeted and immune therapy for patients with refractory disease. Refinements in the management of penile cancer are occurring, though level 1 evidence remains scarce. Referral to specialized centers will facilitate successful completion of clinical trials to advance standard care in this disease.

Prospective Evaluation of Continence Following Radical Cystectomy and Orthotopic Urinary Diversion Using a Validated Questionnaire.

PURPOSE: We evaluated continence outcomes in male patients undergoing orthotopic neobladder diversion after radical cystectomy using a validated questionnaire. MATERIALS AND METHODS: Using our institutional review board approved bladder cancer database we identified 1,269 patients who underwent open radical cystectomy from 2002 to 2015. Orthotopic neobladder was constructed in 935 (74%) patients, of whom 798 (85%) were male. Beginning in 2012 the patients completed a validated pictorial pad use questionnaire at each followup visit. The questionnaire assessed pad number, size and wetness as well as catheter use. Continence was defined as use of no pads or pads that are almost dry. Questionnaires were stratified into distinct postoperative intervals for analysis. Female patients, or patients with artificial urinary sphincters or prior radiotherapy were excluded from the study. RESULTS: A total of 188 male patients with available questionnaires were followed from September 2012 to August 2015. Overall 447 questionnaires were collected, with 351 interval distinct questionnaires separated into intervals of less than 3, 3 to 6, more than 6 to 12, more than 12 to 18, more than 18 to 36 and more than 36 months after surgery (64, 61, 58, 49, 61 and 58 questionnaires, respectively). Daytime continence increased from 59% at less than 3 months postoperatively to 92% by more than 12 to 18 months. Nighttime continence increased from 28% at less than 3 months postoperatively to 51% by more than 18 to 36 months. Nearly 50% of patients reported daytime and nighttime continence by 18 to 36 months. CONCLUSIONS: After orthotopic neobladder diversion in male patients, continence improves significantly by 6 months and subsequently plateaus with 92% daytime continence by more than 12 to 18 months. Orthotopic neobladder represents an excellent functional option for urinary diversion.

Postoperative Pain Management after Radical Cystectomy: Comparing Traditional versus Enhanced Recovery Protocol Pathway.

PURPOSE: Opioids have traditionally been the mainstay of pain management after radical cystectomy for bladder cancer but they have many side effects. The efficacy of opioid sparing analgesics after cystectomy as part of a protocol of enhanced recovery after surgery has yet to be proved. We compared opioid use, pain score and postoperative ileus in consecutive patients on a protocol of enhanced recovery after surgery and those on a traditional protocol after radical cystectomy. MATERIALS AND METHODS: Using our institutional review board approved bladder cancer database we retrospectively reviewed the records of patients who underwent open radical cystectomy using a traditional protocol or a protocol of enhanced recovery after surgery for pain management. A total of 205 patients were ultimately enrolled in study, including 81 on a traditional protocol and 124 on the enhanced protocol. Opioid use and pain scores were analyzed and compared up to postoperative day 4. All routes of opioid use were recorded and converted to the morphine equivalent dose for comparison. Postoperative pain was recorded using a visual analog scale. Postoperative records were reviewed for the incidence of ileus. RESULTS: Patients on the enhanced recovery after surgery protocol and those on a traditional protocol were similar demographically. When analyzing data up to the median hospital stay on the case group, patients on enhanced recovery used significantly less opioids per day (4.9 mg vs 20.67 mg morphine equivalents, p <0.001) and reported more pain (visual analog scale 3.1 vs 1.14, p <0.001). They also experienced a significantly lesser incidence of postoperative ileus (7.3% vs 22.2%, p = 0.003) and had a significantly shorter median length of hospital stay (4 vs 8 days, p <0.001). CONCLUSIONS: Patients on the protocol of enhanced recovery after surgery used significantly less opioid analgesics, possibly contributing to decreased postoperative ileus and shorter length of hospital stay.

Enhanced recovery protocol after radical cystectomy for bladder cancer.

PURPOSE: Enhanced recovery after surgery protocols aim to improve patient care and decrease complications and hospital stay. We evaluated our enhanced recovery after surgery protocol, focusing on length of stay, early complication and readmission rates after radical cystectomy for bladder cancer. MATERIALS AND METHODS: From May 2012 to July 2013 a perioperative protocol was applied in 126 consecutive patients who underwent open radical cystectomy and urinary diversion. Nonconsenting patients (2), those with previous diversion (2) and prolonged postoperative intubation (3), and those who underwent additional surgery (9) were excluded from study. The protocol focuses on avoiding bowel preparation and nasogastric tube, early feeding, nonnarcotic pain management and the use of cholinergic and µ-opioid antagonists. Outcomes were compared to those in matched controls from our bladder cancer database. RESULTS: A total of 110 patients with a median age of 69 years were included in analysis, of whom 68% underwent continent urinary diversion. Of the patients 82% had a bowel movement by postoperative day 2. Median length of stay was 4 days. The 30-day minor and major complication rates were 64% and 14%, respectively. The most common minor complication was anemia requiring transfusion in 19% of patients, urinary tract infection in 13% and dehydration in 10%. The latter 2 complications were the most common etiologies for readmission. The 30-day readmission rate was 21% (23 patients). Patients 75 years old or older had a longer length of stay (5 vs 4 days, p = 0.03) and a higher minor complication rate (72% vs 51%, p = 0.04) than younger patients. CONCLUSIONS: Our enhanced recovery after surgery protocol expedites bowel function recovery and shortens hospital stay after RC and urinary diversion without an increase in the hospital readmission rates.

Factors influencing post-recurrence survival in bladder cancer following radical cystectomy.

OBJECTIVE: To identify prognostic indicators that influence post-recurrence survival following radical cystectomy for bladder cancer. PATIENTS AND METHODS: In all, 2029 patients with bladder cancer underwent radical cystectomy with intent to cure between 1971 and 2005 at our institution. Of these, 447 patients (22%) developed non-urinary tract recurrence and were chosen for further analysis. Clinicopathological characteristics were analysed by univariate and multivariate analysis to identify factors prognostic for post-recurrence survival. RESULTS: Median time to recurrence was 13.21 months and median post-recurrence overall survival was 5.59 months. Pathological stage (P < 0.001), intravesical therapy (P= 0.035), tumour upstaging (P < 0.001), lymph node density (P < 0.001) and recurrence site (P= 0.017) were associated with time to recurrence. Age (P= 0.042), type of urinary diversion (P < 0.014), surgical margin status (P= 0.049), pathological stage (P < 0.001), lymph node density (P < 0.001), time to recurrence (P < 0.001), recurrence site (P < 0.001) and post-recurrence chemotherapy administration (P < 0.001) were univariately prognostic for post-recurrence overall survival. Multivariate analysis confirmed the associations of pathological stage, type of urinary diversion, lymph node density, time to recurrence after cystectomy, site of recurrence and post-recurrence chemotherapy administration with outcome following bladder cancer recurrence. Median post-recurrence survival with either local or distant recurrence was 7.95 months and 5.95 months, respectively, whereas patients with both local and distant recurrences had median post-recurrence survival of 3.98 months. CONCLUSIONS: Bladder cancer recurrence forebodes poor prognosis, with 6 months' median survival following recurrence. Advanced pathological stage, positive surgical margins, high lymph node density and early recurrence portends poorer outcome. Although patients with local recurrence have a slightly better prognosis, those with disease recurrence at local and distant sites perform very poorly; nearly 97% of all patients with recurrence eventually succumb to the disease. Chemotherapy administration following recurrence may improve survival, although further studies are needed to exclude selection bias.

Chronic kidney disease and radical cystectomy for bladder cancer: perioperative and oncologic outcomes in 1,214 patients.

INTRODUCTION AND OBJECTIVE: To assess the impact of chronic kidney disease (CKD) on outcomes after radical cystectomy (RC) in patients with bladder cancer treated within a high-volume tertiary referral center. METHODS: We identified 1,214 patients who underwent RC with intent to cure from 2009 to 2019. The Modification of Diet in Renal Disease (MDRD) GFR (ml/min/1.73 m²) was calculated and patients were categorized by baseline GFR: Group A = GFR > 60, Group B = GFR > 30-59 and Group C = GFR < 30. Pre-, intra- and postoperative characteristics, oncological outcomes, and 90-day perioperative outcomes were compared. Multivariable logistic regression was used to control for confounding variables. RESULTS: We identified 722 (59.5%) patients in Group A, 448 (36.9%) in Group B, and 44 (3.6%) in Group C. Patients with worse CKD were older and had significantly worse overall comorbidity (all P < 0.001). Neoadjuvant chemotherapy was used in 352 patients (29%), including 182 (25.2%) in Group A, 153 in Group B (35.3%), and 12 in Group C (27.3%). On univariate analysis, worse CKD was associated with higher pathologic stage, lymph node metastases and positive soft tissue margins (all P < 0.0001). The rates of blood transfusion, 90-day complications and readmissions were higher in patients with worse CKD (P < 0.0001, P = 0.02, P = 0.04, respectively). Patients with worse CKD had worse overall survival (77% vs. 73% vs. 55%, P < 0.0001). On multivariable analysis, worse CKD was independently associated with adverse pathology (≥pT3 or node positive) (OR = 6.96, 95%CI 3.20-15.12), 90-day readmissions (OR 2.09, 95%CI 1.11-3.94) and perioperative transfusion (OR 2.08, 95%CI 1.05-4.11). Receipt of neoadjuvant chemotherapy was significantly associated with a decreased risk of adverse pathology (OR 0.51, 95%CI 0.36-0.74) and increased risk of transfusion (OR 2.24, 95%CI 1.70-2.96), but not with mortality, complications, readmissions or length or stay. CONCLUSION: CKD is prevalent in patients undergoing radical cystectomy. We found CKD to be independently associated with a higher likelihood of adverse pathology, 90-day readmissions, and transfusion.

An Assessment Tool to Provide Targeted Feedback to Robotic Surgical Trainees: Development and Validation of the End-To-End Assessment of Suturing Expertise (EASE).

Purpose: To create a suturing skills assessment tool that comprehensively defines criteria around relevant sub-skills of suturing and to confirm its validity. Materials and Methods: 5 expert surgeons and an educational psychologist participated in a cognitive task analysis (CTA) to deconstruct robotic suturing into an exhaustive list of technical skill domains and sub-skill descriptions. Using the Delphi methodology, each CTA element was systematically reviewed by a multi-institutional panel of 16 surgical educators and implemented in the final product when content validity index (CVI) reached ≥0.80. In the subsequent validation phase, 3 blinded reviewers independently scored 8 training videos and 39 vesicourethral anastomoses (VUA) using EASE; 10 VUA were also scored using Robotic Anastomosis Competency Evaluation (RACE), a previously validated, but simplified suturing assessment tool. Inter-rater reliability was measured with intra-class correlation (ICC) for normally distributed values and prevalence-adjusted bias-adjusted Kappa (PABAK) for skewed distributions. Expert (≥100 prior robotic cases) and trainee (<100 cases) EASE scores from the non-training cases were compared using a generalized linear mixed model. Results: After two rounds of Delphi process, panelists agreed on 7 domains, 18 sub-skills, and 57 detailed sub-skill descriptions with CVI ≥ 0.80. Inter-rater reliability was moderately high (ICC median: 0.69, range: 0.51-0.97; PABAK: 0.77, 0.62-0.97). Multiple EASE sub-skill scores were able to distinguish surgeon experience. The Spearman's rho correlation between overall EASE and RACE scores was 0.635 (p=0.003). Conclusions: Through a rigorous CTA and Delphi process, we have developed EASE, whose suturing sub-skills can distinguish surgeon experience while maintaining rater reliability.

Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non-muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial.

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec.

Patient Reported Sexual Function Outcomes in Male Patients Following Open Radical Cystoprostatectomy and Urinary Diversion.

OBJECTIVE: To report sexual health outcomes in male patients undergoing open radical cystoprostatectomy using a validated questionnaire. MATERIALS AND METHODS: Beginning in 2017, male patients were asked to complete a validated questionnaire during scheduled post-cystectomy clinic visits that assessed sexual function using the 5 item International Index of Erectile Function (IIEF-5) and supplemental questions which evaluated libido, orgasm, partner interest, and adequacy of pre-operative counselling. Baseline data and functional outcomes were compared and multivariable analysis performed. RESULTS: A total of 134 patients who met inclusion criteria completed the questionnaire. Pre-operative IIEF-5 was available in 78 patients with a median score of 16 (IQR:5-23). In those patients, median age at cystectomy was 68.9 years (IQR:60.2-72.4) and median duration of follow-up was 17.3 months (IQR:6.3-28.7). Median IIEF-5 score at time of survey completion was 1 (IQR:1-11). Increasing age, shorter follow-up duration, insufficient counselling, and absence of partner interest were predictive of lower scores. Younger age, pre-operative erectile function, and neurovascular preservation were predictive of a higher IIEF-5 score on univariate and multivariate analysis. Median libido score was 2 "low" (IQR:1-3) and ability to orgasm was reported by 34 (43.6%) patients. Neurovascular preservation (OR:3.03 95% CI:1.10-8.26, P = .03) and sufficient preoperative counselling (OR:3.078 95% CI:1.17-8.098, P = .02) were associated with preserved ability to orgasm. Libido was influenced by partner interest (OR 11.7, 95% CI:3.793-6.14, P <.0001). CONCLUSION: Sexual dysfunction after radical cystoprostatectomy is prevalent with many contributing factors. As such, establishing appropriate expectations and goals during preoperative counseling, performing neurovascular preservation when appropriate, and readily identifying and treating dysfunction in follow-up may improve sexual recovery.

Feasibility and Outcomes of Orthotopic Ileal Neobladder Reconstruction Following Pelvic Irradiation.

OBJECTIVES: To evaluate the complications and oncologic outcomes of orthotopic ileal neobladder reconstruction (ONB) following pelvic radiotherapy (RT) compared to patients with no prior pelvic RT. METHODS: Our institutional database was queried for all patients with pT0-4bN0-3M0 urothelial carcinoma of the bladder who underwent radical cystectomy with curative intent and ONB between 1990 and 2018. We then queried this cohort for patients who had prior pelvic RT (>3900 cGy) and compared baseline characteristics, perioperative complications, and recurrence free survival between patients with and without prior pelvic RT. RESULTS: One thousand eight hundred and forty-six patients matched our inclusion criteria; 34 had prior pelvic RT with a median dose of 6280 cGy. Prior RT targeted the bladder, prostate, and cervix in 27, 6, and 1 patient, respectively. Median time from RT to cystectomy was 15.5 months. Patients with prior RT had a longer time from diagnosis to cystectomy, more frequently had ≥5 TURBT and neoadjuvant chemo, and less frequently had multifocal disease. Perioperative complications including operative time, estimated blood loss, days hospitalized, as well as 30- and 90-day complication rates, were not statistically different. There was no statistical difference in recurrence free survival between the 2 groups (P = .48). CONCLUSION: ONB in highly selected patients with prior pelvic RT is feasible with statistically similar perioperative complication rates compared to ONB without prior RT.

Perioperative outcomes of goal-directed versus conventional fluid therapy in radical cystectomy with enhanced recovery protocol.

PURPOSE: The aim of this study is to evaluate the intra/perioperative fluid management and early postoperative outcomes of patients who underwent radical cystectomy with Enhanced Recovery After Surgery protocol, using goal-directed fluid therapy compared to conventional fluid therapy. METHODS: This cohort study included patients who underwent open RC for urothelial bladder carcinoma with intent to cure and Enhanced Recovery After Surgery protocol between May 2012 and August 2019. Patients who had palliative or salvage cystectomy and/or adjunct procedures, as well as those with missing detailed perioperative data were excluded. Data were compared between patients who received goal-directed fluid therapy using stroke volume variation by FloTrac™/Vigileo system (n = 119) and conventional fluid therapy based on the anesthesiologist discretion (n = 192). Primary outcome variable was 90-day complications and secondary outcome measures included in-hospital GFR trend, length of stay, and 90-day readmission. RESULTS: The goal-directed fluid therapy group received less total and net intra/perioperative fluid, yet early postoperative glomerular filtration rate trends were similar between both groups (p = 0.7). Estimated blood loss, blood transfusion, index hospital stay, 90-day complication and readmission rates were also comparable between the two groups. Multivariable logistic regression showed no significant association between perioperative fluid management method and 90-day complication rate (OR 1.4, 95% CI 0.8-2.4, p = 0.2). CONCLUSION: Stroke volume variation guided goal-directed fluid therapy is safe in radical cystectomy without compromising the renal function. It is associated with less intra- and perioperative fluid infusion; however, no association with hospital stay, 90-day complication or readmission rates were noted.

Enhanced recovery after cystectomy in patients with preoperative narcotic use.

INTRODUCTION: The aim of this study was to evaluate the outcomes of radical cystectomy with an enhanced recovery after surgery (ERAS) protocol in patients with a history of chronic preoperative narcotic use compared to narcotic-naive patients. METHODS: We identified 553 patients who underwent open radical cystectomy with ERAS. Preoperative narcotic use was identified in 34 patients who were then matched to 68 narcotic-naive patients. Postoperative outcomes, opioid use, and visual analog scale (VAS) pain scores were analyzed and compared. All routes of opioid use were recorded and converted to a morphine equivalent dose (MED). RESULTS: Patients with preoperative narcotic use reported higher median VAS pain scores per day (postoperative day [POD1]: 5.2 vs. 3.9, p=0.003; POD2: 5.1 vs. 3.6, p<0.001; POD3: 4.6 vs. 3.8, p=0.004) and used significantly more opioids (median MED) per day (POD1: 13.2 vs. 10.0, p=0.02; POD2: 11.3 vs. 6.4, p=0.003; POD3: 10.2 vs. 5.0, p=0.005) following surgery. Preoperative narcotic users were noted to have a significantly higher incidence of 90-day re-admissions (41.2% vs. 20.6%, p=0.03). There was no difference in median hospital stay (4 vs. 4 days, p=0.6), 30-or 90-day complications (64.7% vs. 60.3%, p=0.8 and 82.4% vs. 75.0%, p=0.4, respectively) or gastrointestinal complications (29.4% vs. 26.5%, p=0.8), including postoperative ileus (11.8% vs. 20.6%, p=0.2). CONCLUSIONS: Patients with preoperative narcotic exposure report higher pain scores and require more opioid use following radical cystectomy with ERAS and are more likely to be re-admitted within 90 days. However, there was no observed difference in hospital stay or complications.

Heterotopic Bone Formation in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma is associated with calcium deposition in a significant percentage of patients. However, frank ossification within a tumor is extremely rare. We report a case of a 41-year-old male with a slow-growing left renal mass who underwent minimally invasive nephron-sparing surgery. Final pathology revealed clear cell renal cell carcinoma with focal areas of heterotopic bone formation. While prognostic implications of this variant are unclear, patients with renal cell carcinoma with osseous metaplasia can present with slow growth kinetics and early-stage disease.