Investigation of risk factors for vaginal dehiscence and development of small bowel evisceration after robot-assisted radical cystectomy for female bladder cancer and an improved vaginal reconstruction technique to prevent its onset.

Transvaginal organ prolapse, such as small bowel evisceration, is a rare complication after radical cystectomy (RC) in female patients with invasive bladder cancer, However, it often requires emergency surgical repair. Here, we describe our experience with such a case and a review of similar previously reported cases, along with evaluation of the risk factors. We also propose a vaginal reconstruction technique to prevent this complication during robot-assisted laparoscopic radical cystectomy (RARC). A total of 178 patients who underwent laparoscopic radical cystectomy (LRC) or RARC were enrolled, 34 of whom (19%) were female. One of the 34 female patients had transvaginal small bowel evisceration after RARC. We evaluated our case and six such previously reported cases, to determine vaginal reconstruction techniques during RARC to prevent this complication postoperatively. Median age of these cases was 73 (51-80) years, and all patients were postmenopausal. The median time to small bowel evisceration was 14 (6-120) weeks postoperatively. In addition, we changed the methods of the vaginal reconstruction technique during RARC from the conventional side-to-side closure technique to the improved caudal-to-cephalad closure technique. Since implementing this change, we have not experienced any cases of vaginal vault dehiscence or organ prolapse. Transvaginal small bowel evisceration after RC can easily become severe. Therefore, all possible preventive measures should be taken during RARC. We believe that our vaginal reconstruction techniques might reduce the risk of developing this complication.

Arterio-ureteral fistula from a pseudoaneurysm of the right common iliac artery after robot-assisted laparoscopic radical cystectomy: A case report.

Arterio-ureteral fistulas (AUFs), which are relatively rare but potentially life-threatening, require prompt diagnosis and treatment. We reported a case of AUFs following robot-assisted laparoscopic radical cystectomy (RARC) with extended pelvic lymph node dissection and ileal conduit urinary diversion for muscle-invasive bladder cancer, which resulted in massive hemorrhage. Urine leaked from the anastomosis between the ureter, and the end of the ileal conduit was infected, which resulted in an AUF between the pseudoaneurysm of the right common iliac artery and the ureter. The AUF was managed successfully by vascular intervention with an arterial stent graft.

[A Case of Successful Treatment of Small Cell Carcinoma of the Bladder with Pembrolizumab].

Small cell carcinoma of the bladder (SCCB) is a rare cancer that accounts for approximately 1% of primary malignant bladder tumors. It is highly malignant and has a poor prognosis. Similar to small cell lung cancer, platinum-based chemotherapy is recommended as the first-line therapy, and amrubicin (AMR) is recommended as the second-line therapy, but there is no established therapy after the second line. We report a case of SCCB that was refractory to multiple chemotherapies but responded to pembrolizumab. A 77-year-old male, diagnosed with clinical stage T3N0M0 small cell carcinoma and invasive urothelial carcinoma by transurethral resection of bladder tumor (TURBT), underwent robot-assisted radical cystectomy after three cycles of neoadjuvant cisplatin-irinotecan chemotherapy, and pathological examination revealed only small cell carcinoma in his cystectomy specimen. After three courses of adjuvant carboplatin-etoposide chemotherapy, the patient developed liver and bone metastases. Furthermore, after two courses of amrubicin, we started pembrolizumab due to the progression of metastases. Metastases decreased after starting pembrolizumab and continued to decrease after discontinuation because of immunerelated adverse events (irAEs). Therefore, pembrolizumab may be an option for the treatment of refractory SCCB.

[A Case of Lymphorrhea after Radical Cystectomy Treated by Ultrasound-Guided Inguinal Intranodal Lymphangiography].

A 76-year-old woman was diagnosed with invasive bladder cancer and underwent cystectomy, bilateral external iliac, internal iliac and obturator lymph node dissection, and bilateral cutaneous ureterostomy. Pathological findings showed no lymph node metastasis ; however, the patient had lower abdominal pain and fever from the 14th postoperative day, and computed tomography (CT) revealed fluid retention in the pelvis. Retrograde pyelography showed no leakage from the urinary tract, and a drain was placed after percutaneous puncture of the pelvic cavity. There was copious drainage fluid and its nature and composition suggested lymphorrhea. Ultrasound-guided intranodal lymphangiography revealed contrast material leakage from the bilateral lymph node dissection sites. After lymphangiography, drainage from the drain decreased. Despite the drainage being minimal yet persistent, sclerotherapy was performed, the drain was removed and the patient was discharged. After discharge, there was leakage from the site of urethral extraction, and CT revealed recurrent lymph leakage. The patient was readmitted, and a second lymphangiography was performed. The leakage from the site of urethral extraction gradually decreased, and the patient was discharged on the 59th postoperative day. CT after discharge confirmed that the lymphorrhea had shrunk in size, and there has been no recurrence since then. Lymphangiography is a promising treatment option for lymphorrhea after pelvic surgery.

[Repair of Vaginal Cuff Dehiscence after Laparoscopic Radical Cystectomy with Gracilis Myocutaneous Flap].

Vaginal cuff dehiscence after total hysterectomy or total cystectomy had been increasing since laparoscopic or robotic surgery became a common surgery among gynecologists and urologists. A 52-yearold woman underwent laparoscopic radical total cystectomy for muscle invasive bladder carcinoma at Rakuwakai Otowa Hospital. She was emergently admitted with a fist-sized lump protruding from her vagina four months after surgery. Physical examination and her past history on admission disclosed vaginal cuff dehiscence after cystectomy. Computed tomographic scan and magnetic resonance imaging showed no bowel evisceration in the lump. We confirmed that the content of lump was peritoneal tissue and removed it by laparoscopic surgery. Simultaneously, we repaired the vaginal cuff dehiscence with a gracilis myocutaneous flap. There was no subsequent recurrence of vaginal dehiscence or bladder carcinoma in one-year follow-up.

Robotic assisted vs open radical cystectomy: an updated systematic review and meta-analysis.

Several randomized control trials (RCTs) have been published comparing open (ORC) with robot-assisted radical cystectomy (RARC). However, uncertainty persists regarding this issue, as evidences and recommendations on RARC are still lacking. In this systematic review and metaanalysis, we summarized evidence in this context. A literature search was conducted according to PRISMA criteria, using PubMed/Medline, Web Of Science and Embase, up to March 2024. Only randomized controlled trials (RCTs) were selected. The primary endpoint was to investigate health-related quality of life (QoL) both at 3 and 6 months after surgery. Secondary endpoints include pathological and perioperative outcomes, postoperative complications and oncological outcomes. Furthermore, we conducted a cost evaluation based on the available evidence. Eight RCTs were included, encompassing 1024 patients (515 RARC versus 509 ORC). QoL appeared similar among the two groups both after 3 and 6 months. No significant differences in overall and major complications at 30 days (p = 0.11 and p > 0.9, respectively) and 90 days (p = 0.28 and p = 0.57, respectively) were observed, as well as in oncological, pathological and perioperative outcomes, excepting from operative time, which was longer in RARC (MD 92.34 min, 95% CI 83.83-100.84, p < 0.001) and transfusion rate, which was lower in RARC (OR 0.43, 95% CI 0.30-0.61, p < 0.001). Both ORC and RARC are viable options for bladder cancer, having comparable complication rates and oncological outcomes. RARC provides transfusion rate advantages, however, it has longer operative time and higher costs. QoL outcomes appear similar between the two groups, both after 3 and 6 months.

Robot-assisted radical cystectomy for bladder cancer after low anterior resection: A case report.

Radical cystectomy after low anterior resection is rare, and no cases of robotic surgery have been reported. Cystectomy in patients who have undergone a previous pelvic surgery, whether open or endoscopic, requires caution to avoid damaging other organs due to anatomical changes caused by adhesions in a limited space. Additionally, the curative nature of the treatment must be maintained. We describe a 69-year-old man with a history of open low anterior resection for rectal cancer who underwent robot-assisted radical cystectomy with extracorporeal ileal conduit construction. Although this procedure is challenging, it was performed safely with the collaboration of colorectal surgeons. The patient was discharged without perioperative complications and remained recurrence-free for 5 years.

Prophylactic surgical mesh placement as a prevention of parastomal hernia in open radical cystectomy with ileal conduit diversion - pilot study.

INTRODUCTION: This study examines the efficacy of prophylactic mesh implantation during open radical cystectomy with ileal conduit diversion in preventing parastomal hernias (PH). Despite PH being a common complication, prophylactic methods have been underexplored. METHODS: A pilot, single-center, prospective cohort study was conducted involving five patients undergoing surgery with mesh implantation. Demographic and clinical characteristics were monitored, including the incidence of PH, operation time, blood loss, and hospitalization duration. RESULTS: During the mean follow-up period of 9.1±3.2 months post-operation, no occurrences of PH were observed in the patient group. Despite the risks associated with implanting foreign material in an area of surgery involving open small intestine, no infectious complications were noted. CONCLUSION: Prophylactic mesh implantation in radical cystectomy with ileal conduit diversion appears to be an effective preventive measure against PH. Further extensive studies are required to definitively confirm the efficacy and safety of mesh use in this context.

Is Stent-Free Ureteroenteric Anastomosis Associated With Lower Ureteroenteric Strictures After Robot-Assisted Radical Cystectomy and Ileal Conduit?

INTRODUCTION: We aimed to investigate the differences in perioperative outcomes, especially ureteroenteric strictures, between patients who underwent a stented ureteroenteric anastomosis at the time of robot-assisted radical cystectomy (RARC) and ileal conduit vs those who did not. METHODS: A retrospective review of our RARC database was performed (2009-2023). Patients were divided into those who received stented ureteroenteric anastomosis vs those who did not. Propensity score matching was performed in the ratio of 3 (stented ureteroenteric anastomosis) to 1 (stent-free) in terms of age, gender, BMI, race, American Society of Anesthesiologists score, neoadjuvant chemotherapy, Charlson Comorbidity Index, prior radiation therapy, previous abdominal surgery history, clinical T3/clinical T4 stage, preoperative metastasis, and preoperative hydronephrosis. A cumulative incidence curve was used to depict ureteroenteric strictures and a Cox regression model was used to identify variables associated with ureteroenteric strictures. RESULTS: Four hundred eighty-eight patients underwent RARC, 366 individuals underwent a stented ureteroenteric anastomosis, and 122 patients underwent a stent-free approach. There was no significant difference in 90-day overall complications, high-grade complications, readmissions, UTIs, leakage, and ileus (P > .05). Ureteroenteric strictures occurred at a rate of 13% and 18% at 1 and 2 years, respectively in the stented group, vs 7% and 10% in the stent-free group (P = .05). Stent placement was significantly associated with ureteroenteric strictures. CONCLUSIONS: Stent-free ureteroenteric anastomosis was associated with fewer strictures following RARC and ileal conduit.

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.

ERAS for Ambulatory TURBT: Enhancing Bladder Cancer Care (EMBRACE) randomised controlled trial protocol.

INTRODUCTION: Transurethral resection of bladder tumour (TURBT) is one of the more common procedures performed by urologists. It is often described as an 'incision-free' and 'well-tolerated' operation. However, many patients experience distress and discomfort with the procedure. Substantial opportunity exists to improve the TURBT experience. An enhanced recovery after surgery (ERAS) protocol designed by patients with bladder cancer and their providers has been developed. METHODS AND ANALYSIS: This is a single-centre, randomised controlled trial to investigate the effectiveness of an ERAS protocol compared with usual care in patients with bladder cancer undergoing ambulatory TURBT. The ERAS protocol is composed of preoperative, intraoperative and postoperative components designed to optimise each phase of perioperative care. 100 patients with suspected or known bladder cancer aged ≥18 years undergoing initial or repeat ambulatory TURBT will be enrolled. The change in Quality of Recovery 15 score, a measure of the quality of recovery, between the day of surgery and postoperative day 1 will be compared between the ERAS and control groups. ETHICS AND DISSEMINATION: The trial has been approved by the Johns Hopkins Institutional Review Board #00392063. Participants will provide informed consent to participate before taking part in the study. Results will be reported in a separate publication. TRIAL REGISTRATION NUMBER: NCT05905276.

Anterior enterocele after cystectomy: case report and review of the literature.

PURPOSE: Anterior enterocele is a rare but potentially serious complication after cystectomy with heterogeneous treatment options. METHODS: Here we report on the management of a 71-year-old patient with recurrence of anterior enterocele after cystectomy and provide a systematic review of the literature using the PubMed/MEDLINE database. RESULTS: The 71-year-old patient with recurrence of anterior enterocele after cystectomy was successfully treated with colpocleisis and anterior colporrhaphy at the Department of Gynecology and Gynecological Oncology, University Hospital Bonn. The use of a synthetic mesh was not needed. At 16-month follow-up postoperatively, the patient was asymptomatic and had no signs of recurrence. n = 14 publications including n = 39 patients were identified for the systematic review including case reports and reviews. The median duration of developing an anterior enterocele after cystectomy was 9 months (range 3 months to 8 years). Patients had a median age of 71 years (range 44-84). In all cases, a surgical approach was described using a wide variety of surgical procedures. In total, 36% of all patients developed a recurrence with an average time period of 7 months after primary surgery. A rare complication represents a vaginal evisceration with the need of urgent surgery. Furthermore, the occurrence of a fistula is a possible long-term complication. CONCLUSION: Anterior enterocele after cystectomy is a rare complication requiring an individual and interdisciplinary treatment.

Using machine learning to develop preoperative model for lymph node metastasis in patients with bladder urothelial carcinoma.

BACKGROUND: Lymph node metastasis (LNM) is associated with worse prognosis in bladder urothelial carcinoma (BUC) patients. This study aimed to develop and validate machine learning (ML) models to preoperatively predict LNM in BUC patients treated with radical cystectomy (RC). METHODS: We retrospectively collected demographic, pathological, imaging, and laboratory information of BUC patients who underwent RC and bilateral lymphadenectomy in our institution. Patients were randomly categorized into training set and testing set. Five ML algorithms were utilized to establish prediction models. The performance of each model was assessed by the area under the receiver operating characteristic curve (AUC) and accuracy. Finally, we calculated the corresponding variable coefficients based on the optimal model to reveal the contribution of each variable to LNM. RESULTS: A total of 524 and 131 BUC patients were finally enrolled into training set and testing set, respectively. We identified that the support vector machine (SVM) model had the best prediction ability with an AUC of 0.934 (95% confidence interval [CI]: 0.903-0.964) and accuracy of 0.916 in the training set, and an AUC of 0.855 (95%CI: 0.777-0.933) and accuracy of 0.809 in the testing set. The SVM model contained 14 predictors, and positive lymph node in imaging contributed the most to the prediction of LNM in BUC patients. CONCLUSIONS: We developed and validated the ML models to preoperatively predict LNM in BUC patients treated with RC, and identified that the SVM model with 14 variables had the best performance and high levels of clinical applicability.

Temporal Trends and Cancer-Specific Mortality in Nonmetastatic Muscle-Invasive Urothelial Carcinoma of the Urinary Bladder Treated With Trimodal Therapy.

INTRODUCTION: Trimodal therapy (TMT) is guideline-recommended for the management of organ confined urothelial carcinoma of urinary bladder (UCUB). However, temporal trends in TMT use and cancer-specific mortality free-survival (CSM-FS) between historical TMT versus contemporary TMT have not been assessed. We addressed this knowledge gap. MATERIAL AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified nonmetastatic UCUB patients with cT2-T4aN0-N2 treated with TMT, defined as the combination of transurethral resection of bladder tumor, chemotherapy and radiotherapy. Temporal trends described TMT use over time. Subsequently, patients were divided between historical (2004-2012) versus contemporary (2013-2020) cohorts. Survival analyses consisting of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM-FS. Separate analyses addressed patients with organ confined (OC: cT2N0M0) versus nonorgan confined (NOC: cT3-4a and/or cN1-2) clinical stages. RESULTS: Of 4,097 assessable UCUB TMT patients, 1744 (43%) were treated in the historical period (2004-2012) versus 2353 (58%) in the contemporary period (2013-2020). TMT use increased over time in OC patients (EAPC:+3.4%, P < .001), as well as in NOC (EAPC:+2.7%, P < .001). In OC stage, median CSM-FS was 55.3% in historical versus 49.0% in contemporary patients (HR:0.75, P < .001). Similarly, in NOC stage, 5-year median CSM-FS was 43.0% in historical versus 32.8% in contemporary patients (HR:0.78, P = .01). CONCLUSION: TMT rates have increased over time in both OC and NOC patients. Contemporary TMT patients benefit of better cancer-specific survival. Interestingly, this benefit applies equally to OC and NOC TMT-treated patients.

Nutritional Prehabilitation in Patients Undergoing Cystectomy: A Systematic Review.

BACKGROUND/AIM: Nutrition is a key element of the prehabilitation process prior to surgery. The aim of this study was to identify the clinical pathways of nutritional prehabilitation before cystectomy. METHODS: A systematic literature review was conducted in PubMed, the Cochrane Library, CINAHL, Scopus and the Web of Science databases. Quality and risk of bias assessment was conducted adhering to the JBI framework and evidence was evaluated according to the Oxford Centre for Evidence Based Medicine levels of evidence. RESULTS: Out of 586 records identified, six studies were included. Among them, only two were randomized controlled trials. Immunonutrition has been shown to improve postoperative bowel function (3.12 vs. 3.74 days; RR 0.82; CI, 0.73-0.93; p = 0.0029) and decrease postoperative complications (-36.7%; p = 0.008) and readmission rates (-15.38%; p = 0.03). Furthermore, oral nutritional supplements combined with nutritional counseling demonstrated an accelerated recovery of bowel function (-1 day; p < 0.01), a reduction in the length of hospital stay (-1.75 days; p = 0.01), an improvement in handgrip strength (+6.8%, p < 0.001), an increase in bone mass (+0.3 kg, p = 0.04), and a better BMI value (+2.3%, p = 0.001). CONCLUSIONS: Nutritional prehabilitation demonstrates potential in enhancing postoperative outcomes following radical cystectomy. Oral supplements, immunonutrition, and counseling exhibit efficacy in improving postoperative results.

The impact of venous thromboembolism before open or minimally-invasive radical cystectomy in the USA: insurance claims data on perioperative outcomes and healthcare costs.

BACKGROUND: The relationship between venous thromboembolism (VTE) and solid malignancy has been established over the decades. With rising projected rates of bladder cancer (BCa) worldwide as well as increasing number of patients experiencing BCa and VTE, our aim is to assess the impact of a preoperative VTE diagnosis on perioperative outcomes and health-care costs in BCa cases undergoing radical cystectomy (RC). METHODS: Patients ≥18 years of age with BCa diagnosis and undergoing open or minimally invasive (MIS) RC were identified in the Merative™ Marketscan® Research Databases between 2007 and 2021. The association of previous VTE history with 90-day complication rates, postoperative VTE events, rehospitalization, and total hospital costs (2021 USA dollars) was determined by multivariable logistic regression modeling adjusted for patient and perioperative confounders. Sensitivity analysis on VTE degree of severity (i.e., pulmonary embolism [PE] and/or peripheral deep venous thrombosis [DVT]) was also examined. RESULTS: Out of 8759 RC procedures, 743 (8.48%) had a previous positive history for any VTE including 245 (32.97%) PE, 339 (45.63%) DVT and 159 (21.40%) superficial VTE. Overall, history of VTE before RC was strongly associated with almost any worse postoperative outcomes including higher risk for any and apparatus-specific 90-days postoperative complications (odds ratio [OR]: 1.21, 95% CI, 1.02-1.44). Subsequent incidence of new VTE events (OR: 7.02, 95% CI: 5.93-8.31), rehospitalization (OR: 1.25, 95% CI: 1.06-1.48), other than home/self-care discharge status (OR: 1.53, 95% CI: 1.28-1.82), and higher health-care costs related to the RC procedure (OR: 1.43, 95% CI: 1.22-1.68) were significantly associated with a history of VTE. CONCLUSIONS: Preoperative VTE in patients undergoing RC significantly increases morbidity, post-procedure VTE events, hospital length of stay, rehospitalizations, and increased hospital costs. These findings may help during the BCa counseling on risks of surgery and hopefully improve our ability to mitigate such risks.

Effectiveness and Safety of Extended Lymph Node Dissection during Radical Surgery in Patients with Bladder Cancer: A Meta-Analysis.

OBJECTIVE: Bladder cancer (BC) is the most common malignant tumour of the urinary system, and radical cystectomy combined with pelvic lymph node dissection (LND) is the standard treatment for BC. We conducted this meta-analysis to explore the efficacy and safety of extended lymph node dissection in radical cystectomy for BC. METHODS: PubMed, Embase, ProQuest PsycINFO, CINAHL, Web of Science and The Cochrane Library databases were searched for studies on extended lymph node dissection during radical BC surgery. The search time limit was from the establishment of the database to December 2023. Screening and quality assessment of literature were conducted. This meta-analysis was conducted to evaluate the influence of different lymph node dissection methods on recurrence-free survival (RFS), overall survival (OS), operation time, 90-day readmission rate and postoperative complication rate. RESULTS: A total of 15 studies were included, including 4854 patients. All studies were of high quality. This meta-analysis showed no statistically significant difference in the operation time, postoperative complications and 90-day hospitalisation rate between the two groups of patients. The harvested volume of lymph nodes, RFS and OS rate were not statistically different. CONCLUSIONS: Among patients with BC undergoing radical cystectomy, extended lymph node dissection did not have a significant effect on operative time, 90-day readmission rates or postoperative complication rates. Thus, extended lymph node dissection is a safe treatment that does not increase the patient's surgical risk.

Natural History and Genomic Landscape of Chemotherapy-Resistant Muscle-Invasive Bladder Cancer.

PURPOSE: Patients with residual invasive bladder cancer after neoadjuvant chemotherapy (NAC) and radical cystectomy have a poor prognosis. Data on adjuvant therapy for these patients are conflicting. We sought to evaluate the natural history and genomic landscape of chemotherapy-resistant bladder cancer to inform patient management and clinical trials. METHODS: Data were collected on patients with clinically localized muscle-invasive urothelial bladder cancer treated with NAC and cystectomy at our institution between May 15, 2001, and August 15, 2019, and completed four cycles of gemcitabine and cisplatin NAC, excluding those treated with adjuvant therapies. Survival was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were used to identify predictors of recurrence-free survival (RFS). Genomic alterations were identified in targeted exome sequencing (Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets) data from post-NAC specimens from a subset of patients. RESULTS: Lymphovascular invasion (LVI) was the strongest predictor of RFS (hazard ratio, 2.15 [95% CI, 1.37 to 3.39]) on multivariable analysis. Patients with ypT2N0 disease without LVI had a significantly prolonged RFS compared with those with LVI (70% RFS at 5 years). Lymph node yield did not affect RFS. Among patients with sequencing data (n = 101), chemotherapy-resistant tumors had fewer alterations in DNA damage response genes compared with tumors from a publicly available chemotherapy-naïve cohort (15% v 29%; P = .021). Alterations in CDKN2A/B were associated with shorter RFS. PIK3CA alterations were associated with LVI. Potentially actionable alterations were identified in more than 75% of tumors. CONCLUSION: Although chemotherapy-resistant bladder cancer generally portends a poor prognosis, patients with organ-confined disease without LVI may be candidates for close observation without adjuvant therapy. The genomic landscape of chemotherapy-resistant tumors is similar to chemotherapy-naïve tumors. Therapeutic opportunities exist for targeted therapies as adjuvant treatment in chemotherapy-resistant disease.