Gustave Roussy Immune score as a prognostic biomarker in patients with platinum-refractory metastatic urothelial carcinoma treated with pembrolizumab: YUSHIMA study.

BACKGROUND: This study aimed to investigate the prognostic value of the Gustave Roussy Immune score (GRIm-score) in platinum-refractory metastatic urothelial carcinoma (UC) treated with pembrolizumab. METHODS: This multicenter retrospective study (YUSHIMA study) evaluated 331 patients with metastatic UC treated with pembrolizumab after platinum-based chemotherapy between January 2018 and June 2023 at 13 institutions. We collected pretreatment variables, including the GRIm-score based on serum albumin, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio. The patients were divided into low and high GRIm-score groups. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were determined using the multivariate Cox proportional hazard model. RESULTS: During the median follow-up period of 7.3 months, 278 (84%) patients showed disease progression, and 223 (67%) died from any cause. Multivariate analysis revealed that the high GRIm-score group was an independent and significant adverse prognostic factor of both OS and PFS (hazard ratio, 1.65 and 1.82, respectively; both p < 0.001) along with Eastern Cooperative Oncology Group Performance Status of ≥ 2 (both p < 0.001), presence of visceral metastasis (both p < 0.001), and hemoglobin of < 9.2 g/dL (p = 0.030 and p = 0.038). C-reactive protein of > 42 mg/L was a significant prognostic factor for OS (p = 0.001). CONCLUSION: The GRIm-score is an independent prognostic marker for survival outcomes in patients with platinum-refractory metastatic UC treated with pembrolizumab.

Outcomes and prognostic factors in patients with synchronous and metachronous oligometastatic urothelial carcinoma with visceral metastases.

OBJECTIVES: To evaluate the clinical characteristics of oligometastatic disease (OMD) in metastatic urothelial carcinoma (mUC) with visceral metastases when classified into synchronous and metachronous metastases. METHODS: Of 957 cases of de novo mUC treated between 2008 and 2023, 374 with visceral metastases were analyzed. Cases were classified into OMD with up to three metastatic lesions and polymetastatic disease (PMD), and into synchronous and metachronous metastases. The clinical characteristics and overall survival (OS) for each group were analyzed. RESULTS: Overall, 196 (52.4%) had synchronous metastasis and 178 (47.6%) had metachronous metastasis. Median OS for synchronous metastases was significantly shorter than for metachronous metastases (12.1 months vs. 15.3 months, p = 0.011). Among the synchronous metastases, 48 (24.5%) were OMD and 148 (75.6%) were PMD. There was no significant difference in OS between the OMDs and PMDs (median 14.9 months vs. 11.7 months, p = 0.32), and only decreased albumin level was identified as a significant predictor of poor OS. Among the metachronous metastases, 64 (36.0%) were OMD and 114 (64.0%) were PMD. There was no significant difference in OS between the OMD and PMD (median 21.2 months vs. 15.0 months, p = 0.35), and no significant predictors of poor OS were identified. CONCLUSIONS: For mUC with visceral metastases, the timing of metastasis appearance was associated with prognosis, with synchronous metastases being a poorer prognostic factor compared to metachronous metastases. There was no prognostic difference between OMD and PMD with visceral metastases when classified into synchronous or metachronous metastases.

[Usefulness of Ascitic Fluid Analysis for Diagnosis of Intraperitoneal Bladder Rupture : A Case Report].

An inebriated 58-year-old woman with a history of hysterectomy presented to the emergency department with abdominal pain. The patient received hydration and acetaminophen, which led to symptom resolution. The patient returned with severe abdominal pain, 12 hours later. Computed tomography (CT) revealed a large volume of ascites and bladder wall disruption. Ascitic fluid analysis showed an elevated creatinine (Cre) level of 7.56 mg/dl, and the ascites to serum Cre ratio was 2.96, which indicated urinary ascites secondary to bladder rupture. The patient was diagnosed with intraperitoneal bladder rupture and underwent successful conservative treatment using an indwelling urinary catheter.

Spontaneous bladder rupture due to bladder carcinoma: A case report required emergency radical cystectomy.

We report a case of spontaneous bladder rupture due to bladder carcinoma. A 52-year-old female presented in septic shock, and computed tomography revealed free air in the subphrenic space and a mass in the middle of the pelvis. The exploratory laparotomy helped to confirm a definitive diagnosis: bladder rupture due to bladder carcinoma. She underwent a radical cystectomy and survived. Surgical intervention is recommended to manage carcinomatous bladder rupture. Timely and accurate diagnosis is essential to optimize the patient's outcomes. The possibility of spontaneous bladder rupture should not be overlooked as a differential diagnosis in cases of the acute abdomen.

Impaired p63 expression associates with poor prognosis and uroplakin III expression in invasive urothelial carcinoma of the bladder.

PURPOSE: p63 is proposed to play roles in normal development and differentiation of stratified epithelia including urothelium. We recently reported that impaired p63 expression is a common feature of high-grade invasive urothelial carcinomas and associates with reduced beta-catenin. On the basis of these facts, we proposed that impaired p63 expression contributes to biological aggressiveness of urothelial neoplasms. Uroplakin (UP) III expression was also evaluated to investigate a possible association between loss of p63 expression and terminal urothelial differentiation. EXPERIMENTAL DESIGN: Expression of p63, beta-catenin, and UP III was immunohistochemically analyzed in 75 cystectomy specimens of high-grade invasive bladder carcinoma. p63 expression was semiquantified and compared with pathological parameters, expression of beta-catenin and UP III, and cancer-specific survival. RESULTS: Lower p63 expression was significantly associated with higher Tumor-Node-Metastasis (TNM) stage (P = 0.0004), lymph-node metastasis (P = 0.013), and reduced beta-catenin expression (P = 0.003). By univariate analysis, lower p63 expression, along with TNM stage and lymph-node status, were significantly associated with a poor prognosis (P = 0.0005), whereas reduced beta-catenin was not. By multivariate analysis, the prognostic effect of p63 expression was independent of TNM stage and lymph-node status with marginal statistical significance (P = 0.074). UP III expression was restricted to a subset of p63-negative carcinoma cells, including even anaplastic carcinoma cells. CONCLUSIONS: Impaired p63 expression characterizes biological aggressiveness of high-grade invasive urothelial carcinomas. Moreover, loss of p63 expression is a prerequisite for UP III expression. Our data suggest that p63 plays critical roles in tumor progression and biochemical terminal differentiation of urothelial neoplasms.

The impact of preoperative serum C-reactive protein on the prognosis of patients with upper urinary tract urothelial carcinoma treated surgically.

OBJECTIVE: To assess the impact of preoperative C-reactive protein (CRP) levels on the prognosis in patients with upper urinary tract (UUT) urothelial carcinoma (UC) primarily treated surgically, as it is increasingly recognized that a systemic inflammatory response is associated with the prognosis for patients with various malignancies. PATIENTS AND METHODS: The clinical records of 130 patients treated surgically for UUT-UC were reviewed retrospectively. An elevated CRP was defined as >0.5 mg/dL. Actuarial survival curves were calculated by Kaplan-Meier method, with the difference between curves evaluated using the log-rank test. A multivariate analysis was used to identify prognostic factors, with Cox's proportional hazard model. RESULTS: The median (range) follow-up was 47 (3-190) months. The preoperative serum CRP level was elevated in 24 patients (23%). There were significant associations between CRP level and haemoglobin concentrations, pathological T stage, tumour grade, lymph node involvement and lymphovascular invasion. The 5-year disease-specific and recurrence-free survival rates of 24 patients with elevated CRP were significantly worse than those of the 106 with no CRP elevation (both P < 0.001). On multivariate analysis, preoperative CRP level, pathological T stage and lymph node involvement were significant prognostic factors for disease-specific and recurrence-free survival. CONCLUSION: This study indicated that an elevated preoperative CRP level predicts a poor survival in patients with UUT-UC.

Loss of uroplakin III expression is associated with a poor prognosis in patients with urothelial carcinoma of the upper urinary tract.

OBJECTIVE: To investigate the association between the expression of uroplakin III (UPIII) and the prognosis of patients with urothelial carcinoma of the upper urinary tract, as uroplakins are urothelium-specific markers of terminal urothelial differentiation. PATIENTS AND METHODS: Clinicopathological and follow-up data from 71 patients who had undergone radical nephroureterectomy and lymph node dissection or sampling for urothelial carcinoma of the upper urinary tract were reviewed. The expression of UPIII was evaluated immunohistochemically in surgical specimens. Cancer-specific survival was calculated using Kaplan-Meier plots. Prognostic values of clinicopathological variables including UPIII expression status, tumour stage and grade were evaluated by univariate analyses, followed by multivariate analysis using the Cox proportional-hazard model. RESULTS: In all specimens there was intense UPIII immunoreactivity of umbrella cells of normal urothelium. In tumour samples, UPIII expression was positive in 75% of < or = pT1 tumours and 40% of > or = pT2 (P = 0.02), and in 65% of grade 1-2 tumours and 33% of grade 3 (P = 0.009). Of the 71 patients, 21 died from the disease during the median follow-up of 61 months. The cancer-specific survival of patients with negative UPIII expression was significantly worse than that of those with positive UPIII expression (5-year cancer-specific survival, 100% vs 46%, P < 0.001). Neither patient age at diagnosis, histological grade, sex, or multiplicity of the tumour had significant prognostic value. Multivariate analysis revealed that UPIII expression was the most powerful prognostic indicator (P < 0.001) followed by tumour stage (P = 0.04) and lymph node metastasis (P = 0.05). CONCLUSION: The present data suggest that UPIII expression is a powerful prognostic factor in patients with upper urinary tract urothelial carcinoma.