Perioperative and extended outcomes of patients undergoing parastomal hernia repair following cystectomy and ileal conduit.

PURPOSE: To report perioperative and long-term postoperative outcomes of cystectomy patients with ileal conduit (IC) urinary diversion undergoing parastomal hernia (PSH) repair. METHOD: We reviewed patients who underwent cystectomy and IC diversion between 2003 and 2022 in our center. Baseline variables, including surgical approach of PSH repair and repair technique, were captured. Multivariable Cox regressionanalysis was performed to test for the associations between different variables and PSH recurrence. RESULTS: Thirty-six patients with a median (IQR) age of 79 (73-82) years were included. The median time between cystectomy and PSH repair was 30 (14-49) months. Most PSH repairs (32/36, 89%) were performed electively, while 4 were due to small bowel obstruction. Hernia repairs were performed through open (n=25), robotic (10), and laparoscopic approaches (1). Surgical techniques included direct repair with mesh (20), direct repair without mesh (4), stoma relocation with mesh (5), and stomarelocation without mesh (7). The 90-day complication rate was 28%. In a median follow-up of 24 (7-47) months, 17 patients (47%) had a recurrence. The median time to recurrence was 9 (7-24) months. On multivariable analysis, 90-day complication following PSH repair was associated with an increased risk of recurrence. CONCLUSIONS: In this report of one of the largest series of PSH repair in the Urology literature, 47% of patients had a recurrence following hernia repair with a median follow-up time of 2 years. There was no significant difference in recurrence rates when comparing repair technique or the use of open or minimally invasive approaches.

Opioid prescription following radical orchiectomy associated with new persistent opioid use.

INTRODUCTION: Opioid dependence represents a public health crisis and can be observed after outpatient urologic procedures. The purpose of this study was to evaluate the risk of persistent opioid usage after radical orchiectomy for testicular cancer. MATERIALS AND METHODS: The TriNetX Research network database was queried for men between 15 and 45 years undergoing radical orchiectomy for a diagnosis of testicular cancer. All patients with N+ or M+ disease, prior opioid use, and patients who underwent chemotherapy, radiotherapy, or retroperitoneal lymph node dissection were excluded. Patients were stratified whether they were prescribed opioids or not at time of orchiectomy. The incidence of new, persistent opioid use, defined as a prescription for opioids between 3 and 15 months after orchiectomy, was evaluated. RESULTS: A total of 2,911 men underwent radical orchiectomy for testicular cancer, of which 89.8% were prescribed opioids at time of orchiectomy. After propensity score matching for age, race, and history of psychiatric diagnosis, 592 patients were included (296 received opioids, 296 did not). Overall, 0% of patients who did not receive postoperative opioids developed new persistent opioid use, whereas 10.5% of patients who received postoperative opioids developed new persistent opioid use. Patients prescribed postoperative opioids for orchiectomy had statistically higher risk difference of developing new persistent opioid use (Risk Difference: 10.5%; 95% CI: 7.0-14.0; Z: 5.7; P < 0.01). CONCLUSIONS: Postoperative opioid prescription following radical orchiectomy is significantly associated with developing new persistent opioid use, with 1 in 10 young men who received postoperative opioids obtaining a new prescription for opioids well beyond the postoperative period. Future efforts should emphasize nonopioid pathways for pain control following this generally minor procedure.

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.

Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/SUO Guideline (2017; Amended 2020, 2024).

PURPOSE: Although representing approximately 25% of patients diagnosed with bladder cancer, muscle-invasive bladder cancer (MIBC) carries a significant risk of death that has not significantly changed in decades. Increasingly, clinicians and patients recognize the importance of multidisciplinary collaborative efforts that take into account survival and quality of life concerns. This guideline provides a risk-stratified, clinical framework for the management of muscle-invasive urothelial bladder cancer. METHODOLOGY/METHODS: In 2024, the MIBC 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 May 2020 to November 2023. This review identified 3739 abstracts, of which 46 met inclusion criteria.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for 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 regarding neoadjuvant/adjuvant chemotherapy, radical cystectomy, pelvic lymphadenectomy, multi-modal bladder preserving therapy, 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 MIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

Prophylactic Use of Biologic Mesh in Ileal Conduit (PUBMIC): A Randomized Clinical Trial.

PURPOSE: We assessed the effect of prophylactic biologic mesh on parastomal hernia (PSH) development in patients undergoing cystectomy and ileal conduit (IC). MATERIALS AND METHODS: This phase 3, randomized, controlled trial (NCT02439060) included 146 patients who underwent cystectomy and IC at the University of Southern California between 2015 and 2021. Follow-ups were physical exam and CT every 4 to 6 months up to 2 years. Patients were randomized 1:1 to receive FlexHD prophylactic biological mesh using sublay intraperitoneal technique vs standard IC. The primary end point was time to radiological PSH, and secondary outcomes included clinical PSH with/without surgical intervention and mesh-related complications. RESULTS: The 2 arms were similar in terms of baseline clinical features. All surgeries and mesh placements were performed without any intraoperative complications. Median operative time was 31 minutes longer in patients who received mesh, yet with no statistically significant difference (363 vs 332 minutes, P = .16). With a median follow-up of 24 months, radiological and clinical PSHs were detected in 37 (18 mesh recipients vs 19 controls) and 16 (8 subjects in both arms) patients, with a median time to radiological and clinical PSH of 8.3 and 15.5 months, respectively. No definite mesh-related adverse events were reported. Five patients (3 in the mesh and 2 in the control arm) required surgical PSH repair. Radiological PSH-free survival rates in the mesh and control groups were 74% vs 75% at 1 year and 69% vs 62% at 2 years. CONCLUSIONS: Implementation of biologic mesh at the time of IC construction is safe without significant protective effects within 2 years following surgery.

The effect of enhanced recovery after surgery on oncologic outcome following radical cystectomy for urothelial bladder carcinoma.

INTRODUCTION: Limited data are available regarding the effect of enhanced recovery after surgery (ERAS) protocols on the long-term outcomes of radical cystectomy (RC) in bladder cancer patients. The aim of this study is to evaluate the oncological outcomes in patients who underwent RC with ERAS protocol. METHODS: We reviewed the records of patients who underwent RC for primary urothelial bladder carcinoma with curative intent from January 2003 to August 2022. The primary and secondary outcomes were recurrence-free (RFS) and overall survival (OS). Multivariable Cox regression analysis was performed to evaluate the effect of ERAS on oncological outcomes. RESULTS: A total of 967 ERAS patients and 1144 non-ERAS patients were included in this study. The RFS rates at 1, 3, and 5 years after RC were 81%, 71.5%, and 69% in the ERAS cohort, respectively. This rate in the non-ERAS group was 81%, 71%, and 67% at 1, 3, and 5 years after RC, respectively (P = 0.50). However, ERAS patients had significantly better OS with 86%, 73%, and 67% survival rates at 1, 3, and 5 years compared to 84%, 68%, and 59.5% survival rates in the non-ERAS group, respectively (P = 0.002). In multivariable analysis adjusting for other relevant factors, ERAS was no longer independently associated with recurrence-free (HR = 0.96, 95% CI 0.76-1.22, P = 0.75) or overall survival (HR = 0.84, 95% CI 0.66-1.09, P = 0.28) following RC. CONCLUSION: ERAS protocols are associated with a shorter hospital stay, yet with no impact on long-term oncologic outcomes in patients undergoing RC for bladder cancer.

Blood-based liquid biopsy: A promising noninvasive test in diagnosis, surveillance, and prognosis of patients with upper tract urothelial carcinoma.

OBJECTIVES: To assess the efficacy of blood-based liquid biopsy in the diagnosis, surveillance, and prognosis of upper tract urothelial carcinoma (UTUC). METHODS AND MATERIALS: In this prospective study, peripheral blood samples were collected from patients with primary UTUC before surgery with curative intent and follow-up visits at University of Southern California between May 2021 and September 2022. The samples were analyzed using the third-generation comprehensive high-definition single-cell assay (HDSCA3.0) to detect rare events, including circulating tumor cells (CTCs) and oncosomes, based on the immunofluorescence signals of DAPI (D), cytokeratin (CK), CD45/CD31 (CD), and vimentin (V). The findings of pre-surgery liquid biopsies were compared with those of blood samples from normal donors (NDs) and matched follow-up liquid biopsies. The association between liquid biopsy findings and clinical data, including recurrence-free survival (RFS), was also assessed. RESULTS: Twenty-eight patients with UTUC were included, of whom 21 had follow-up samples. Significant differences in specific rare analytes were detected in the preoperative samples compared to the NDs. In the post- vs. presurgery matched analysis, a significant decrease was detected in total-, CK-, and CK|V oncosomes, as well as in D-, D|V-, and D|V|CD cells. With a median follow-up of 11 months, 8 patients had disease recurrence. Survival analysis demonstrated that patients with >1.95 preoperative CK|V oncosomes (p = 0.020) and those with >4.18 D|CK|V cells (p = 0.050) had worse RFS compared to other patients. CONCLUSIONS: This study demonstrated promising initial evidence for the biomarker role of CTCs and oncosomes in the diagnosis and surveillance of patients with UTUC.

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.

Perioperative mortality for radical cystectomy in the modern Era: experience from a tertiary referral center

ABSTRACT Purpose To evaluate the perioperative mortality and contributing variables among patients who underwent radical cystectomy (RC) for bladder cancer in recent decades, with comparison between modern (after 2010) and premodern (before 2010) eras. Materials and Methods Using our institutional review board-approved database, we reviewed the records of patients who underwent RC for primary urothelial bladder carcinoma with curative intent from January 2003 to December 2019. The primary and secondary outcomes were 90- and 30-day mortality. Univariate and multivariable logistic regression models were applied to assess the impact of perioperative variables on 90-day mortality. Results A total of 2047 patients with a mean±SD age of 69.6±10.6 years were included. The 30- and 90-day mortality rates were 1.3% and 4.9%, respectively, and consistent during the past two decades. Among 100 deaths within 90 days, 18 occurred during index hospitalization. Infectious, pulmonary, and cardiac complications were the leading mortality causes. Multivariable analysis showed that age (Odds Ratio: OR 1.05), Charlson comorbidity index ≥ 2 (OR 1.82), blood transfusion (OR 1.95), and pathological node disease (OR 2.85) were independently associated with 90-day mortality. Nevertheless, the surgical approach and enhanced recovery protocols had no significant effect on 90-day mortality. Conclusion The 90-day mortality for RC is approaching five percent, with infectious, pulmonary, and cardiac complications as the leading mortality causes. Older age, higher comorbidity, blood transfusion, and pathological lymph node involvement are independently associated with 90-day mortality.