Experience and prognostic analysis with avelumab switch maintenance treatment in metastatic urothelial carcinoma.

INTRODUCTION: Avelumab is approved for metastatic urothelial carcinoma (mUC) maintenance therapy and prolongs overall survival (OS). We explored trends related to avelumab 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 avelumab (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 avelumab maintenance therapy as avelumab (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 receiver operating characteristic curve. Low age and GNRI sustainability revealed as significant prognostic factors for being Ave-suitable both in univariate and multivariate analysis. CONCLUSION: In mUC, avelumab maintenance prolonged OS within tolerable safety profiles. GNRI sustainability may be used as biomarker to predict being Ave-suitable.

C-Reactive Protein Is a Potential Prognostic Marker in Patient with Advanced or Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multi-Center Retrospective Study.

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.

Proton pump inhibitors and potassium competitive acid blockers decrease pembrolizumab efficacy in patients with metastatic urothelial carcinoma.

We elucidated the efficacy of gut microbiome-altering drugs on pembrolizumab efficacy in patients with metastatic urothelial carcinoma (mUC). Clinical data were analyzed retrospectively from 133 patients with mUC who received second-line pembrolizumab therapy between January 2018 and January 2021, following failed platinum-based chemotherapy. We evaluated the effects of gut microbiome-altering drugs (proton pump inhibitors [PPI]/potassium-competitive acid blockers [P-CAB], H2 blockers, antibiotics, non-steroidal anti-inflammatory drugs [NSAIDs], metformin, antipsychotics, steroids, and opioids), taken by patients within 30 days before/after pembrolizumab treatment, on progression-free survival (PFS) and overall survival (OS). Fifty-one patients received PPI/P-CAB (37/14, respectively); H2 blockers, 7; antibiotics, 35; NSAIDs, 22; antipsychotics, 8; metformin, 3; steroids, 11; and opioids, 29. Kaplan-Meier curves revealed PPI or P-CAB users showed shorter PFS than non-PPI-P-CAB users (p = 0.001, p = 0.005, respectively). Multivariate analysis highlighted PPI/P-CAB use as the only independent prognostic factor for disease progression (hazards ratio: 1.71, 95% confidence interval: 1.14-2.07, p = 0.010) but not death (p = 0.177). Proton pump inhibitors/potassium-competitive acid blockers may decrease the efficacy of pembrolizumab therapy for mUC, possibly via gut microbiome modulation.

GNRI Sustainability during One Cycle of First-Line Chemotherapy as a Prognostic Indicator in Patients with Metastatic Urothelial Carcinoma.

INTRODUCTION: This study evaluated the prognostic value of a sustained high Geriatric Nutritional Risk Index (GNRI) during first-line chemotherapy for patients with metastatic urothelial carcinoma (mUC). METHODS: Between January 2018 and February 2022, 123 patients received platinum-based chemotherapy at Nagoya City University Hospital and affiliated institutions. Of these, 118 eligible patients who showed an Eastern Cooperative Oncology Group performance status (ECOG-PS) between 0 and 2 were retrospectively examined. Based on body mass index and serum albumin levels, GNRI was calculated immediately before and after the first primary chemotherapy cycle. Patients were divided into two groups based on GNRI: GNRI sustained ≥92 in sustainable (n = 63) and GNRI <92 in unsustainable (n = 55) groups, respectively. Clinical outcomes were compared. RESULTS: No significant differences were noted between the two groups for age, gender, cycle of first-line treatment, and type of series of sequential treatments after failure of first-line therapy. Median overall survival from the start of first-line chemotherapy was 30.2 months (95% confidence interval [CI]: 20.9-NA) for sustainable and 12.6 months (95% CI: 9.0-21.2) for unsustainable groups, respectively (p < 0.05). Multivariate analysis identified ECOG-PS:2 and fatigue, an adverse event, as independent predictors of unsustainable GNRI transition (95% CI: 1.29-90.6, odds ratio [OR]: 10.8; 95% CI: 1.06-26.9, OR: 5.34, respectively). CONCLUSION: Sustaining a high level of GNRI was an important prognostic indicator in patients with mUC receiving first-line chemotherapy. Appropriate intervention for controlling adverse events, including fatigue, may enhance physical strength during cancer treatment.

A Multicenter, Prospective, Non-randomized Study Evaluating Surgical hand Preparation between Double-Gloving and Single-Gloving for Preventing Postoperative Infection in Robotic and Laparoscopic Minimally Invasive Surgeries.

PURPOSE: This study aimed to analyze a feasible and suitable surgical precautionary preparatory technique. The techniques of double-gloving with hygienic hand wash (DH) and single-gloving with surgical hand wash (SS) were compared for their ability to prevent postoperative infection in robotic and laparoscopic minimally invasive surgeries. MATERIALS AND METHODS: A prospective, non-randomized, multicenter study was conducted between January 2016 and June 2020. We divided the robotic and laparoscopic cases into two groups: DH and SS. Data on infectious outcomes were collected. Propensity score matching was performed to control for operative characteristics between the two groups. The primary endpoint was the presence of fever and surgical site infections (SSIs) indicating postoperative infection. RESULTS: Among four medical centers, seven surgeons were allocated to either the DH or the SS group. A total of 221 and 251 patients underwent DH and SS, respectively. Propensity score matching, which included 171 cases from each group, showed that the incidence of fever during hospitalization was significantly lower in the DH group than that in the SS group (11.7% vs. 23.4%, p=0.007). Multivariable analysis revealed that DH was associated with a reduced odds ratio for developing postoperative fever during hospitalization (risk ratio: 0.49, p=0.043). No differences were found in SSI before and after hospitalization between the two groups. CONCLUSION: DH resulted in less postoperative fever and had a comparable effect in preventing SSIs. This procedure could be an alternative to the SS protocol in some minimally invasive surgeries.

Chronological transition in outcome of second-line treatment in patients with metastatic urothelial cancer after pembrolizumab approval: a multicenter retrospective analysis.

BACKGROUND: After first-line chemotherapy failure, metastatic urothelial carcinoma (mUC) patients undergo pembrolizumab (PEM) or gemcitabine and docetaxel (GD) therapy. We retrospectively investigated outcomes of second-line GD or PEM for mUC patients. METHODS: A total of 198 mUC patients from Nagoya City University and affiliated hospitals who received second-line treatment were grouped according to immune check point inhibitor (ICI) availability: Groups A (pre-ICI: n = 104) and B (post-ICI: n = 94). We compared clinical outcomes using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses assessed potential prognostic factors for overall survival (OS). RESULTS: Median OS was significantly longer for Group B [median 13.6 months, 95% confidence interval (CI): 7.6-17.6] than A (7.6 months, 5.3-8.8). By sub-group analysis, patients received no additional treatment (Naïve, n = 70), or PEM or GD (Salvage, n = 24) in Group B, with median OS of Naïve and A groups similar. Compared to the Salvage group, significant differences in OS were observed (median 7.6 months, 95% CI 5.3-8.8; Group A, 7.6 months, 4.7-13.8; Naïve, 25.7 months, 14.0-31.0; p < 0.01). For the Salvage group, OS for sequential treatment of GD-salvage PEM and PEM-salvage GD patients was similar (p = 0.10). Multivariate analysis showed a low neutrophil-to-lymphocyte ratio (NLR) and high geriatric nutritional risk index (GNRI) as significant prognostic factors affecting long OS [95% CI 1.12-3.45, hazard ratio (HR): 1.97; 95% CI 0.24-0.71, 0.41, respectively]. CONCLUSION: Second-line GD or PEM therapy for mUC patients showed equivalent survival benefits. GNRI and NLR are prognostic biomarkers for survival outcome.

Recurrent hemorrhagic shock from hemorrhagic cystitis due to neurogenic bladder.

INTRODUCTION: Hemorrhagic cystitis is characterized by gross hematuria, with hemorrhagic shock a rare complication. However, to our knowledge, its exact frequency has not been reported. CASE PRESENTATION: We report a case of an 86-year-old woman who showed repeated hemorrhagic cystitis with massive bleeding and hemorrhagic shock. The hemorrhagic cystitis was supposedly caused by the administration of aspirin and a neurogenic bladder. A urethral catheter was indwelled and hemorrhagic cystitis subsequently ceased. CONCLUSION: A review of patients with hemorrhagic cystitis at our hospital showed that only 3.3% experienced hemorrhagic shock. This case was even rarer because the patient experienced recurrent hemorrhagic shocks. A neurogenic bladder, which reduces the bladder's ability to function as a uroepithelial barrier against recurrent bacterial infections, caused the condition in this case. This report highlights how hemorrhagic cystitis can sometimes cause hemorrhagic shock.

Modified Glasgow Prognostic Score 2 as a Prognostic Marker in Patients With Metastatic Urothelial Carcinoma.

BACKGROUND/AIM: Predicting the prognosis of metastatic urothelial carcinoma (mUC) patients is needed for clinical decisions. We examined the value of a modified Glasgow prognostic score (mGPS) as a predictive marker for mUC patients. PATIENTS AND METHODS: In a multicenter study, 68 mUC patients received short hydration gemcitabine/cisplatin (shGC) and 74 received pembrolizumab (PEM). Patients were allocated according to mGPS. Progression-free (PFS) and cancer-specific (CSS) survival were examined. RESULTS: Higher mGPS reflected poorer PFS and CSS in shGC (p=0.03, p<0.0001, respectively) and PEM (p=0.02, p<0.001, respectively) patients. PFS for the high mGPS group was longer than that of the low mGPS group in the two cohorts (p <0.0001 for both), with similar CSS results (p<0.0001 and p<0.001, respectively). Multivariate analyses revealed high mGPS was a risk factor for poor CSS in both cohorts (HR=3.55, p<0.001, and HR=2.21, p<0.01, respectively). CONCLUSION: In the mUC patients receiving shGC or PEM, mGPS was a predictive prognostic marker.

First Report of Oncological Outcome and Prognostic Analysis in a First-Line Setting of Short Hydration Gemcitabine and Cisplatin Chemotherapy for Patients with Metastatic Urothelial Carcinoma.

OBJECTIVES: The aim of the study was to examine the effectiveness of a modified-short hydration gemcitabine and cisplatin (m-shGC) regimen for patients with metastatic urothelial carcinoma (mUC) and to assess the efficacy of a geriatric nutritional risk index (GNRI) with regard to prognosis. PATIENTS AND METHODS: From January 2016 to July 2020, 68 patients with mUC underwent first-line m-shGC therapy with 70 mg/m2 cisplatin and 1,000 mg/m2 gemcitabine (days 1, 8, and 15), with 2,050 mL fluid replaced on the first day of each 28-day cycle. Prior to the start of treatment, the serum neutrophil-to-lymphocyte ratio (NLR), and levels of albumin and C-reactive protein (CRP) in serum, as well as body heights and weights were measured. Patients were grouped according to GNRI <92 (low) or ≥92 (high). The analysis of data was done retrospectively. RESULTS: Median follow-up was found to be 12.9 (range 1.7-50.2) months and the objective response rate (ORR) was 54.4% after m-shGC treatment. The ORR was significantly different when high and low-GNRI groups were compared (ORR: 28.0 vs. 69.8% in low- vs. high-GNRI groups). Median overall survival (OS) was calculated as 8.6 (95% confidence interval [CI]: 5.4-21.3) and 34.5 (95% CI: 20.5-NA) months for low- and high-GNRI groups, respectively (p < 0.0001). Unlike for NLR and CRP, univariate and multivariate analyses revealed that low GNRI and visceral metastases were significant prognostic factors for short OS. CONCLUSIONS: First-line m-shGC showed a survival benefit for mUC, with GNRI a useful prognostic biomarker.

UroVysion fluorescence in situ hybridization in urothelial carcinoma: a narrative review and future perspectives.

The number of patients with urothelial carcinoma (UC) is high, with a corresponding demand for detecting UC easily and non-invasively. Cystoscopy and urine cytology, with widely known diagnostic accuracies, are the gold standards for identifying UC originating from the bladder. However, cystoscopy or other tests, such as ureteroscopy or retrograde pyelography, are uncomfortable for patients. Tests for urinary biomarkers are expected to satisfy the demand for less invasive tests that will benefit patients with anxiety for invasive tests such as cystoscopy or ureteroscopy. Although several urinary biomarkers have been reported to support the diagnosis or follow-up of UC, their use in the clinic is uncommon. The UroVysion test examines urinary biomarkers using a multitarget, multicolor fluorescence in situ hybridization (FISH) assay. The test uses exfoliated cells found in urine and is a mixture of centromeric fluorescent denatured chromosome enumeration probes for chromosomes 3, 7, and 17 (labelled stratum red, spectrum green and spectrum aqua, respectively), and a locus-specific identifier probe for 9p21 (spectrum gold). It is used for the initial diagnosis of patients with hematuria or the monitoring of patients previously diagnosed with bladder cancer. Almost 20 years have passed since UroVysion was approved by the U.S. Food and Drug Administration, and so this is a well-established test. However, room exists for further research, with numerous reports on this test having been recently published. In order to update our knowledge, we herein present a brief overview of UroVysion and its features that follows the latest findings as they relate to UC.

Rare case of immunoglobulin G4-related disease arising in gonadal glands with long-term remission without steroid treatment: Discussion and literature review.

INTRODUCTION: Immunoglobulin G4-related disease embraces a wide range of extra-pancreatic manifestations. However, localized pathogenesis in gonadal glands, including testes or seminal vesicles, is rare. The clinical course and therapeutic strategy for this disease have not been clearly characterized. CASE PRESENTATION: A 61-year-old Asian male had a left orchiectomy and right seminal vesicle biopsy because of a mass in the left testis and right seminal vesicle. Histological findings showed an infiltration of immunoglobulin G4-positive plasma cells in the respective tissues and met immunoglobulin G4-related disease diagnostic criteria. No recurrence and exacerbation have been observed after 12 years' follow-up without any clinical intervention. To date, immunoglobulin G4-related disease in gonadal tissue is rare. This is the first case with mass-forming lesions in both the testis and seminal vesicle. CONCLUSION: Based on the clinical course of our case and the literature, for patients with accurately diagnosed inactive gonadal immunoglobulin G4-related disease, watchful waiting is a feasible clinical treatment option.