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Introduction Bladder cancer is one of the most prevalent cancers worldwide, with significant morbidity and mortality rates. Treatment options for metastatic urothelial carcinoma (mUC) primarily include platinum-based chemotherapy. Cisplatin-based chemotherapy is conventionally used for treating mUC, but many patients are ineligible due to various factors such as poor performance status, creatinine clearance, neuropathy, and cardiac function. Carboplatin-based therapy is another alternative, which typically yields less favorable outcomes. Some centers use split-dose cisplatin for treating patients with comorbidities and impaired renal function, broadening cisplatin's spectrum. While eligibility criteria for full-dose cisplatin are well-established, those for split-dose cisplatin and carboplatin lack strong evidence. This study aims to assess the recommended criteria for full-dose cisplatin, split-dose cisplatin, and carboplatin regimens in real-world settings, including hematological parameters for patients with mUC. Methods  A cross-sectional web-based survey was conducted among 136 oncologists from 21 countries, assessing criteria such as creatinine clearance, Eastern Cooperative Oncology Group (ECOG) performance status (PS), neurotoxicity, hearing loss, heart failure classification, and hematological parameters. Results The survey revealed diverse preferences among 113 oncologists treating mUC, regarding the eligibility criteria for each chemotherapy regimen with 81% prioritizing full-dose cisplatin, 21% split-dose cisplatin, and 14% carboplatin regimens. Criteria for all three regimens included specific thresholds. For full-dose cisplatin, the preferred criteria included creatinine clearance ≥60 mL/min, ECOG PS ≤1, grade 1 neuropathy, grade 1 deafness, New York Heart Association (NYHA) heart failure ≤class II with ≥50% cardiac ejection fraction, and normal blood parameters. Split-dose cisplatin criteria were creatinine clearance ≥40 mL/min, ECOG PS ≤2, grade 1 neuropathy, grade 1 deafness, NYHA heart failure ≤class II with ≥50% cardiac ejection fraction, and normal blood parameters. Carboplatin eligibility criteria were creatinine clearance ≥30, ECOG PS ≤2, grade ≤2 neuropathy, grade ≤2 deafness, NYHA heart failure ≤class II with ≥50% cardiac ejection fraction, and normal blood parameters. Hematological parameters were deemed crucial for all regimens, particularly stringent for carboplatin-based chemotherapy. Conclusion The study underscores the importance of renal function and hematological parameters in determining chemotherapy eligibility for patients with mUC. It highlights the importance of precise treatment criteria in mUC management, with hematological factors playing a significant role. Standardized criteria and further research are warranted to optimize treatment outcomes and minimize adverse events associated with chemotherapy regimens. Understanding the preferences of oncologists globally can facilitate tailored treatment approaches and improve patient care in the management of mUC.

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Background: For patients with locally advanced or metastatic urothelial carcinoma (la/mUC), prognosis is poor and effective treatment options are limited. Erdafitinib is an oral fibroblast growth factor receptor (FGFR) kinase inhibitor approved by the FDA for the treatment of adults with la/mUC harboring FGFR alterations whose disease progressed following at least 1 prior line of therapy, including a PD-1 or PD-L(1) inhibitor, based on the phase 3, randomized THOR trial (NCT03390504, Cohort 1). Objective: To compare the efficacy and safety of erdafitinib vs enfortumab vedotin-ejfv (EV) in the absence of head-to-head comparison via an anchored matching-adjusted indirect comparison (MAIC). Methods: An anchored MAIC was conducted according to the National Institute for Health and Care Excellence Decision Support Unit guidance, with physician's choice of chemotherapy (docetaxel/paclitaxel and vinflunine) as the common comparator. Individual patient data from THOR were adjusted to match published key eligibility criteria and average baseline characteristics of EV-301, such as Bellmunt risk score, liver or visceral metastases, primary site, among others. Erdafitinib was then indirectly compared with EV using the relative treatment effects for the reweighted THOR population and those published for EV-301. Results: After matching, the effective sample size for THOR was 126 patients. The MAIC-recalculated hazard ratio (95% credible interval) for erdafitinib vs EV was 0.92 (0.54, 1.57) for overall survival and 0.93 (0.55, 1.56) for progression-free survival, yielding Bayesian probabilities of erdafitinib being better than EV of 62.1% and 60.5%, respectively. For response outcomes, the MAIC-recalculated risk ratio was 1.49 (0.56, 3.90) for confirmed objective response rate and 2.89 (0.27, 30.33) for confirmed complete response with probabilities of 72.6% and 81.3% for erdafitinib being better than EV, respectively. For safety, MAIC-yielded risk ratios of 1.09 (0.99, 1.21) for any treatment-related adverse events, 0.86 (0.57, 1.28) for grade 3+ TRAEs, and 1.02 (0.98, 1.06) for any treatment-emergent adverse events. Conclusion: The MAIC indicates comparable efficacy of erdafitinib vs EV for overall survival and progression-free survival, with erdafitinib showing a higher probability of achieving deep responses. While erdafitinib is associated with slightly more adverse events compared with EV, these events seem to be less severe.

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Metastatic urothelial carcinoma (muC) has historically had few effective therapeutic options. Recently, immune checkpoint inhibitors (ICIs), were introduced as therapeutic options for cisplatin-ineligible patients, however, direct head-to-head trials comparing these treatments are lacking. To address this gap, this study employs a Bayesian framework to indirectly compare the performance of ICIs as first-line agents for muC. A systematic review was performed to identify randomized controlled trials evaluating different ICI for mUC. Data was inputted into Review Manager 5.4 for pairwise meta-analysis. Data was then used to build a network in R Studio. These networks were used to model 200,000 Markov Chains via MonteCarlo sampling. The results are expressed as hazard ratios (HR) with 95% credible intervals (CrI). Six studies with 5,449 patients were included, 3,255 received ICI monotherapy or combination. Moreover, a total of 3,006 had PD-L1 positive tumors and 2,362 were PD-L1 negative. Median overall survival (OS) ranged from 12.1 to 31.5 months across the studies, with the combination of enfortumab vedotin and pembrolizumab demonstrating the most substantial reduction in the risk of death (HR 0.47 [95% CrI: 0.38, 0.58]), followed by avelumab monotherapy (HR 0.69 [95% CrI: 0.56, 0.86]). The limitations of this network meta-analysis include variability in study follow-up duration, lack of standardized methods for assessing PD-L1 positivity, and potential bias introduced by control arms with poorer survival outcomes across included trials. The enfortumab vedotin/pembrolizumab combination significantly improved survival and response rates. Avelumab showed notable single-agent activity. These findings provide a valuable framework to guide clinical decision-making and highlight priority areas for future research, including biomarker refinement and novel combination strategies to enhance antitumor immunity in this challenging malignancy.

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BACKGROUND: Platinum-based chemotherapy (ChT) has been the standard first-line treatment for metastatic urothelial carcinoma (mUC). The purpose of this study was to evaluate the use of induction avelumab followed by avelumab in combination with carboplatin-gemcitabine (carbo/gem) followed by avelumab maintenance. We tested the hypothesis that induction immunotherapy (IO) could enhance the response to ChT and prevent its detrimental effect on immune cells. MATERIALS AND METHODS: INDUCOMAIN is a multicenter, randomized, investigator-initiated, open-label phase II study evaluating the safety and efficacy of induction avelumab before carboplatin-gemcitabine-avelumab, followed by avelumab maintenance (arm A), compared to carbo/gem (arm B). Eligibility criteria included patients with mUC, no prior systemic therapy, and ineligibility for cisplatin by Galsky criteria. Patients were stratified by the presence/absence of visceral metastasis and Eastern Cooperative Oncology Group performance status 0-1 versus 2. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Eighty-five patients were included and randomized to arm A (n = 42) and arm B (n = 43), respectively. ORR was similar between treatment arms: 59.5% in arm A and 53.5% in arm B (P = 0.57). Fourteen patients (33%) in arm A early progressed/died before or at first response assessment, compared to three patients (7%) in arm B. Median OS was 11.1 months in arm A and 13.2 months in arm B [hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.57-1.46, P = 0.69]. Median PFS was 6.9 months in arm A versus 7.4 months in arm B (HR 0.99, 95% CI 0.61-1.60, P = 0.95). Treatment-related adverse events of grade 3-4 occurred in 70.7% of patients in arm A and in 72.1% in arm B. No predictive role of programmed death-ligand 1 expression was found. CONCLUSIONS: The hypothesis that induction avelumab could enhance the efficacy of subsequent ChT was not proven. Administering IO alone as induction before ChT is not an adequate strategy.

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Skeletal muscle metastases are uncommon, and metastases of urothelial carcinoma to the skeletal muscle are particularly rare. The most common presentation of skeletal muscle metastases is a focal mass, but their clinical and radiographic findings can be diverse. We present an unusual case of a 71-year-old male without prior known history of malignancy who presented with skeletal muscle pain with imaging most consistent with an inflammatory or infectious process but was ultimately determined to be metastatic urothelial carcinoma from the bladder. This case demonstrates the need to keep an expanded differential for muscular pain, particularly when initial treatments are ineffective.

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A 76-year-old man who was diagnosed with urothelial carcinoma (UC) in the bladder diverticulum was referred to our institution. The patient was diagnosed with muscle-invasive bladder cancer, which was confirmed by magnetic resonance imaging that showed tumor invasion into the fatty tissue surrounding the diverticulum. After two cycles of neoadjuvant gemcitabine and cisplatin, he underwent robot-assisted radical cystectomy (RARC) with pelvic lymph node dissection followed by intracorporeal ileal conduit. The histopathologic diagnosis of the bladder tumor was UC with squamous differentiation and sarcomatoid subtype and ypT3bN0M0 without positive surgical margins. The patient refused any adjuvant therapy. Six months after RARC, the patient visited our institution with a complaint of suddenly occurring generalized pain. Because 18F-fluorodeoxyglucose positron emission tomography-CT showed multiple metastases, including bone, para-aortic lymph nodes, and pleura, pembrolizumab was initiated as a second-line treatment. After two courses of pembrolizumab, the patient's symptoms remarkably improved, and the abnormal systemic accumulation on PET-CT almost disappeared. After 26 months of continuous treatment with pembrolizumab, the patient remains disease-free. Several studies have been reported that focused on tumor subtypes and programmed cell death ligand 1 (PD-L1)-positive tumor cells as candidate biomarkers in relation to the efficacy of pembrolizumab. The higher proportion of PD-L1-positive cells in the sarcomatoid subtype may have resulted in favorable oncological outcomes compared with pure UC.

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Introduction: Few studies have reported on administering enfortumab vedotin to patients with metastatic urothelial carcinoma and end-stage renal disease requiring hemodialysis. Case presentation: Case 1: An 85-year-old man underwent hemodialysis for progressive renal failure 4 months after right laparoscopic radical nephroureterectomy. Case 2: A 73-year-old man underwent hemodialysis after two laparoscopic radical nephroureterectomies for recurrent urothelial carcinoma. In both cases, enfortumab vedotin was administered due to postoperative recurrence and progression despite platinum-based chemotherapy and pembrolizumab. Partial response and disease progression were observed in cases 1 and 2, respectively. Adverse events included a mild skin rash in both patients and neutropenia in Case 1, both of which resolved with symptomatic treatment. Conclusion: The efficacy and safety of enfortumab vedotin in patients with metastatic urothelial carcinoma, and end-stage renal disease undergoing hemodialysis, were confirmed.

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BACKGROUND: In the THOR trial (NCT03390504) Cohort 1, erdafitinib demonstrated significantly prolonged overall survival (OS) (median 12.1 versus 7.8 months) and reduced risk of death by 36% (hazard ratio 0.64, P = 0.005) compared with chemotherapy in metastatic urothelial carcinoma (mUC) patients with FGFR alterations who progressed after ≥ 1 prior treatments, including anti-PD-(L)1. There have been no reports of the Japanese subgroup results yet. METHODS: THOR Cohort 1 randomized patients to erdafitinib once daily or docetaxel/vinflunine once every 3 weeks. Primary endpoint was OS. Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). No specific statistical power was set for this Japanese subgroup analysis. RESULTS: Of 266 patients randomized, 27 (14 erdafitinib; 13 chemotherapy) were Japanese. Baseline characteristics were generally similar between treatments and to the overall population, except for more males, lower body weight, and more upper tract primary tumors among Japanese patients. Compared with chemotherapy, erdafitinib showed improved OS (median 25.4 versus 12.4 months), PFS (median 8.4 versus 2.9 months) and ORR (57.1% versus 15.4%). Any grade treatment-related adverse events (AEs) occurred in all patients from both arms but Grade 3/4 AEs and AEs leading to discontinuation were lower in the erdafitinib arm. No new safety signals were observed in the Japanese subgroup. CONCLUSION: In the Japanese subgroup, erdafitinib showed improved survival and response compared to chemotherapy, with no new safety concerns. These results support erdafitinib as a treatment option for Japanese mUC patients with FGFR alterations, and early FGFR testing after diagnosis of mUC should be considered.

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Urothelial cell carcinoma (UCC) is a type of malignant cancer that affects thousands of people worldwide, especially those who smoke and have certain occupational exposures. Plasmacytoid urothelial carcinoma (PUC) is a rare histological variant of UCC that can present aggressively and insidiously. Small bowel obstruction secondary to malignancy is a rare presentation of UCC because the small bowel is a rare site of metastasis. We showcase a patient who presented with small bowel obstruction secondary to high-grade metastatic UCC with plasmacytoid features, exhibiting minimal urologic symptoms and no apparent risk factors. This case highlights the importance of high clinical suspicion for patients with possible malignancies that present with limited or unusual symptomatology and no risk factors. Further research into PUC to understand its symptoms and metastatic pattern is warranted to advance current early diagnostic criteria and further improve patient outcomes.

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OBJECTIVES: Enfortumab vedotin (EV) is an established pharmacotherapy for metastatic urothelial carcinoma (mUC); however, its adverse events (AEs) cannot be overlooked. The study investigated the efficacy and safety of biweekly EV administration. METHODS: Patients with mUC who received EV at our institution were included in the study. Eligible patients were classified into two groups as follows: those who received EV on a standard schedule (standard group) and those who received EV on a biweekly schedule (biweekly group); the treatment outcomes and AEs between the two groups were compared. RESULTS: Nine and 19 patients were in the standard group and biweekly groups, respectively. The progression-free survival, overall survival, and overall response rate were not significantly different between the two groups. AEs following EV administration, such as decreased appetite (P < .01), pruritus (P < .01), rash maculopapular (P < .01), anemia (P = .04), and liver dysfunction (P = .04), were significantly more frequent in the standard group. Grade 3 or higher AEs, such as pruritus (P = .03) and rash maculopapular (P < .01), were significantly more frequent in the standard group. Furthermore, significantly more patients in the standard group had to be given a reduced dose due to adverse events (P = .02). CONCLUSIONS: Biweekly administration of EV may be safer without compromising therapeutic efficacy than the standard schedule.

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INTRODUCTION: Avelumab (Ave) is approved for metastatic urothelial carcinoma (mUC) maintenance therapy and prolongs overall survival (OS). We explored trends related to Ave treatment of mUC patients. METHODS: A total of 72 patients with mUC treated with first-line chemotherapy, from January 2019 to November 2022, at our affiliated institutions, were analyzed. We compared clinical parameters and the prognosis of patients treated with Ave (n = 43) because of progression during first-line chemotherapy, with untreated patients (Ave-untreated; n = 29). Among the Ave-treated group, we classified patients showing a complete or partial response or stable disease in their best response to Ave maintenance therapy as Ave-suitable patients; these were retrospectively analyzed. Potential prognostic factors, including the Geriatric Nutritional Risk Index (GNRI) for determining patients suitable for Ave, were evaluated. RESULTS: The basic clinical parameters of patients when first-line treatment was initiated were not statistically different between the two groups. The Ave-suitable group (median 26.6 months, 95% confidence interval [CI]: 19.4-not reached [NR]) showed significantly longer median OS after first-line treatment than the Ave-untreated group (median 12.0 months, 95% CI: 7.5-NR) with tolerable adverse events. The cut-off values of prognostic factors were set by the receiver operating characteristic curve. Low age and GNRI sustainability were revealed as significant prognostic factors for being Ave-suitable both in univariate and multivariate analysis. CONCLUSION: In mUC, Ave maintenance prolonged OS within tolerable safety profiles. GNRI sustainability may be used as a biomarker to predict being Ave-suitable.

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Neoplasms are among the common causes of small bowel obstruction (SBO). Metastatic disease is the most common cause of neoplastic SBO and is most commonly the result of colon, ovarian, pancreatic, and gastric neoplasms. Metastatic SBO secondary to metastatic urothelial carcinoma is exceedingly rare, with only a few cases described in the literature. It is important for physicians to be aware of urothelial carcinoma as a potential etiology of SBO.

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BACKGROUND: In the EV-301 trial, enfortumab vedotin prolonged survival in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based therapy and programmed cell death 1/programmed death-ligand 1 inhibitor. However, real-world Asian data are limited, and potential prognostic markers are non-existent. We aimed to investigate potential prognostic markers for enfortumab vedotin therapy in Asian patients. METHODS: We retrospectively enrolled 61 Japanese patients treated with enfortumab vedotin therapy at our hospital and affiliated hospitals between January 2019 and September 2023. RESULTS: Enrolled patients (38 men, 23 women; median age 74 [IQR: 68-79] years) had bladder cancer (26 patients) or upper-tract urothelial carcinoma (35 patients). Fifty-four patients reported adverse events (grade >3 in 12). Skin disorders, pruritus, and neuropathy were common adverse effects. The median overall survival was 17.1 months (95% confidence interval: 10.0-not applicable). In multivariate analysis, the C-reactive protein level was an independent marker predicting favorable overall survival with enfortumab vedotin. Patient characteristics did not differ between C-reactive protein-high and -low groups. CONCLUSIONS: Our study provides real-world data showing that enfortumab vedotin prolonged survival in Asian patients similar to the EV-301 trial. Additionally, the C-reactive protein level might be considered a prognostic marker of enfortumab vedotin therapy in such patients.

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In the past decade, the therapeutic arsenal for metastatic bladder cancer has expanded considerably, with the development of immune checkpoint inhibitors (ICIs), antibody-drug conjugates such as enfortumab vedotin, and anti-fibroblast growth factor receptor agents. Clinical trials evaluating ICIs as neoadjuvants, adjuvants, or first- or second-line treatments have produced conflicting results. However, first-line therapeutic strategies have been redefined by the recent publication of results from two clinical trials: CheckMate-901, which demonstrated the superiority of combined treatment with nivolumab and chemotherapy in extending overall survival, and EV-302, which demonstrated that combined treatment with pembrolizumab and enfortumab vedotin reduced the risk of death by 53%. In this review, we discuss the role of ICIs, alone or in combination, in bladder cancer management in the metastatic and adjuvant settings in 2024, considering the latest published trials. The potential role of ICIs as neoadjuvants is also discussed.

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Aim: This study assessed real-world treatment in patients with metastatic urothelial carcinoma (mUC) in Germany. Materials & methods: Patients diagnosed with mUC from 2015 to 2019 were identified in two claims databases: AOK PLUS and GWQ. Results: 3226 patients with mUC were analyzed; 1286 (39.9%) received systemic treatment within 12 months of diagnosis (platinum-based chemotherapy: 64.2%). Factors associated with receiving treatment were: younger age, male sex, less comorbidity and recent diagnosis. In AOK PLUS and GWQ populations, unadjusted median overall survival (interquartile range) from diagnosis in treated patients was 13.7 (6.8-32.9) and 13.8 (7.1-41.7) months, and in untreated patients was 3.0 (1.2-10.8) and 3.6 (1.2-18.8) months, respectively. Conclusion: A significant proportion of patients with mUC in Germany receive no systemic treatment.

What is this article about? This article reports the results from a study in Germany between 2015 and 2019 that investigated how advanced bladder cancer that has spread to other organs was treated and how long people lived after diagnosis. The study looked at systemic therapies, which means treatments that affect the entire body.What were the results? Only 40% of people diagnosed with advanced bladder cancer received systemic treatment within the first 12 months. Of those who did receive systemic treatment, the majority received combination therapy that included a chemotherapy drug containing platinum (64%). Systemic treatment was more likely to be given to people who were younger, less sick, male, or more recently diagnosed. After 12 months, 56% of treated people were still alive, compared with 26% of people without treatment. On average, people who received systemic treatment lived for about 14 months, while people without systemic treatment lived for only 3 to 4 months.What do the results of the study mean? Many people with advanced bladder cancer in Germany do not receive systemic treatment. People who receive treatment are likely to live longer than those who do not receive treatment.

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AIMS: This retrospective claims data study characterized real-world treatment patterns, healthcare resource utilization (HCRU), and costs in patients with metastatic urothelial carcinoma (mUC) in Germany. MATERIALS AND METHODS: Continuously insured adults with incident mUC diagnosis (=index; ICD-10: C65-C68/C77-C79) in 2015-2019 were identified from two German claims databases. Patients who received first-line (1 L) treatment within 12 months of index were divided into three mutually exclusive sub-cohorts: platinum-based chemotherapy (PB-CT), non-PB-CT, and immunotherapy (IO). Patient characteristics were assessed during a 24-month baseline period; treatments, HCRU, and costs (of the health insurance fund) per patient-year (ppy) were described during 12-month follow-up. RESULTS: We identified 3,226 patients with mUC (mean age, 73.8 years; male, 70.8%; mean Elixhauser Comorbidity Index, 17.6); 1,286 (39.9%) received 1 L treatment within 12 months of index. Of these, 825 (64.2%) received PB-CT, 322 (25.0%) non-PB-CT, and 139 (10.8%) IO. On average, treated patients had 5.1 hospitalizations ppy. Most UC-related hospitalizations ppy were observed in the PB-CT cohort (5.8), followed by the non-PB-CT (4.2) and IO (2.3) cohorts. Mean UC-related hospitalization costs ppy were €22,218 in the treated cohort, €24,294 in PB-CT, €19,079 in IO, and €18,530 in non-PB-CT cohorts. Cancer-related prescription costs ppy averaged €6,323 in treated patients, and €25,955 in IO, €4,318 in non-PB-CT, and €4,270 in PB-CT cohorts. LIMITATIONS: We recognized limitations in our study's sample selection due to unavailable mUC disease status data. We addressed this through an upstream feasibility study conducted in consultation with clinical experts to determine a suitable proxy. Proxies were also used to delineate treatment lines, switches, and discontinuations due to data absence. Furthermore, due to data restrictions, collective dataset analysis was not possible, prompting a meta-analysis for pooled results. CONCLUSIONS: The study shows that mUC is associated with significant HCRU and costs across different types of 1 L systemic therapy.

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OBJECTIVES: Evaluate real-world epidemiologic trends and treatment patterns in newly diagnosed patients with locally advanced or metastatic urothelial carcinoma (la/mUC) in Japan. METHODS: This retrospective analysis included adults with newly diagnosed la/mUC in Japan (January 2015-December 2019) from a nationwide-linked electronic medical record Diagnostic Procedure Combination claims dataset. Outcomes included epidemiologic trends (incidence and prevalence), baseline demographics, clinical characteristics, and treatment patterns in newly diagnosed patients with la/mUC before (2015-2017) and after (2018-2019) approval of pembrolizumab in Japan. RESULTS: Of 975 patients included, 76.4% were men; 71.6% were aged 70 years or older. Most cases (70.5%) were of the bladder. Between 2015 and 2019, the annual age-adjusted incidence increased from 6.8 to 12.4 per 100 000; the annual age-adjusted period prevalence increased from 13.0 to 25.2 per 100 000; and 307 (31.5%) and 668 (68.5%) patients were diagnosed from 2015 to 2017 and 2018 to 2019, respectively. Overall, 731 (75%) patients received systemic anticancer therapy; all received 1 line and 50.2% received 2 lines of therapy; 78.3% of patients received gemcitabine plus platinum-based therapy and 2.2% received pembrolizumab as first-line treatment. First-line treatment rates increased from 69.4% to 77.5% after pembrolizumab approval. Of 367 patients who received second-line treatment, 22.3% received gemcitabine plus platinum-based therapy; 14.7% received pembrolizumab. CONCLUSIONS: In the Japanese regions considered, incidence and prevalence of newly diagnosed la/mUC increased over time and first-line treatment with pembrolizumab increased after approval.

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INTRODUCTION: Despite the prospective randomized controlled JAVELIN Bladder 100 trial, no real-world evidence exists regarding tumor characteristics, adverse events (AEs), and survival of avelumab maintenance (AVM)-treated patients with partial/complete response or stable disease after previous platinum-based chemotherapy for advanced/metastatic urothelial carcinoma (mUC). METHODS: We relied on our institutional database to identify mUC patients who received AVM between January, 2021 and December, 2023. The main outcomes consisted of overall survival (OS) and progression-free survival (PFS) and were computed by Kaplan-Meier estimates. Stratification was performed according to programmed death ligand 1 (PD-L1) status. RESULTS: Overall, 24 AVM patients were identified at a median age of 71 (interquartile range [IQR]: 67-76) years, of which 67% were males. Of these, 63%, 21%, and 17% received AVM therapy for bladder cancer and upper tract urothelial carcinoma or both, respectively. PD-L1 status was positive in 45% of patients. During AVM treatment, AEs were observed in 33% of patients; however, they were limited to ≤2 grade AEs. At a median follow-up of eight (IQR 4-20) months, 71% of patients had progressed under AVM with median PFS of 6.2 months (confidence interval [CI]: 3.2-18.2). Median OS was 13.4 (CI: 6.9 - not reached [NR]) months. One-year OS after AVM was 52%. In PD-L1-positive patients, median PFS and OS were 6.4 (CI: 2.7 - NR) months and 13.4 (CI: 7.7 months - NR), respectively. CONCLUSION: AVM is associated with moderate AE rates. Despite similarities in baseline characteristics compared to trial-selected JAVELIN Bladder 100 mUC patients, AVM resulted in longer/similar PFS but significantly shorter OS in real-world setting.

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BACKGROUND: Combinations of immune checkpoint inhibitors (ICI) with platinum-based chemotherapy (PlatinumCT) or with another ICI in the first-line setting for patients with metastatic urothelial carcinoma (mUC) have mixed results. METHODS: Records were searched electronically from January 2019 to January 2024. A meta-analysis was performed to evaluate OS, progression-free survival (PFS), and overall response rate (ORR). RESULTS: Immune-based combinations were associated with an OS (HR: 0.75; 95% CI: 0.61-0.92; p < 0.001; I2= 84.1%) and PFS benefit in the intention-to-treat population (HR: 0.67; 95%CI: 0.51-0.89; p < 0.001; I2 = 89.7%). There was no ORR improvement with immune-based combinations (HR: 1.36; 95% CI:0.84-2.20; p < 0.001; I2 = 92.6%). CONCLUSION: This systematic review and study-level meta-analysis demonstrated that the immune-based combinations in first-line treatment for patients with mUC are associated with survival benefit.

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