Urothelial Bladder Cancer Research Articles

Clinical, Pathological Characteristics and Progression of Urothelial Bladder Cancer in Young Adult Patients. Our Experience and Literature Review.

Bladder cancer is highly prevalent even though its incidence is considerably lower in patients younger than 40 years, thus raising the issue of the influence of age at diagnosis on the natural history of this disease. This study aimed to evaluate the characteristics and progression of young patients with urothelial bladder carcinoma with at least 10 years of follow-up and to compare the results with those of previously reported studies. A retrospective study between 1990 and 2007 was conducted. The medical records and tissue samples of patients with urothelial bladder tumours were reviewed, and patients with a first diagnosis of urothelial carcinoma of the bladder at age 40 years or younger were selected. Their clinical and pathological data and disease-free survival were analysed. This study included 43 patients, with a median follow-up of 152 months (interquartile range (IQR): 96-222) and a mean age at diagnosis of 34 years (SD: 4.6). Thirty-five patients (81.4%) had non-muscle invasive tumours at diagnosis, and 53.5%, 27.9% and 18.6% had tumour grades of G1, G2 and G3, respectively. Fifteen patients (34.9%) experienced recurrence, and eight (18.6%) progressed. At 24 and 60 months, the recurrence-free survival rates were 84.8% (95% confidence interval (CI): 69.2%-92.9%) and 68.9% (95% CI: 51.7%-81%), respectively, and the progression-free survival rates were 94.9% (95% CI: 81%-98.7%) and 92.2% (95% CI: 77.8%-97.4%), respectively. Bladder cancer is an uncommon disease in young patients. In most cases, it consists of non-muscle-invasive tumours, with a low rate of recurrence and progression. The prognosis is based on the tumour's characteristics and not on the patient's age.

Tislelizumab with gemcitabine and cisplatin as a neoadjuvant regimen for muscle-invasive bladder cancer: case series.

The feasibility of combined tislelizumab with gemcitabine and cisplatin as a neoadjuvant regimen for muscle-invasive bladder cancer (MIBC) remains to be investigated. The neoadjuvant treatment not only shrunk tumours significantly but also lowered their stages from T4bN1M0, T3N0M0, and T3bN0M0 to pT1, pT0 and pTis, respectively. The treatment suppressed tumour cell proliferation and promoted luminal-to-basal transition. MIBC is an aggressive bladder cancer with poor prognosis. All three patients with MIBC benefited greatly from the neoadjuvant regimen (tislelizumab + gemcitabine + cisplatin). It appears that the effect of the treatment is independent of the levels of programmed death-ligand 1 nor the subtype of urothelial bladder cancer. Combination of tislelizumab with gemcitabine and cisplatin appeared to be a safe and efficacious neoadjuvant therapy for MIBC.

The role of p27 as a prognostic factor in association with grading and staging of urothelial bladder cancer

The role of p27 as a prognostic factor in association with grading and staging of urothelial bladder cancer

Upper Urinary Tract Urothelial Cancer After Radical Cystectomy for Bladder Cancer: Survival Outcomes After Radical Nephroureterectomy.

Systemic and local recurrences of urothelial bladder cancer (UBC) significantly impair survival after radical cystectomy (RC), but little is known about the impact of the recurrence of urothelial cancer in the upper urinary tract (UTUC). This report describes survival outcomes and their predictors for patients who underwent RC followed by radical nephroureterectomy (RNU) for UTUC. The Surveillance, Epidemiology, and End Results database was queried to identify patients who underwent RC for UBC and subsequent RNU for UTUC. The Kaplan-Meier method and competing-risk Cox regression (CRR) were used for the survival analysis. Overall, 102 patients have undergone RNU within a median of 49 months (interquartile range [IQR], 27-76 months) since RC. Muscle-invasive UTUCs were predominant at RNU (n = 58; 56.7%), but organ-confined bladder tumors were most frequent at RC (n = 42, 41.5%). After RNU, the estimated 5-year overall survival (OS) was 25.9%, the cancer-specific survival (CSS) was 35.6%, the median OS was 23 months (IQR, 11-63 months), and the CSS was 34 months (IQR, 13-132 months). In the multivariable CRR, the factors predictive for CSSafter RNUincluded male gender (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.03-5.42; p < 0.05), muscle-invasive UTUC (HR, 2.20; 95% CI, 1.13-4.28; p < 0.05), and the presence of distant metastasis (HR,11.59; 95% CI, 5.33-25.2; p < 0.001). In conclusion, the patients who underwent RNU for UTUC after RC for UBC experienced poor OS and CSS. The majority of RNUs were performed for locally advanced tumors. The independent risk factors for worse OS and CSS after RNU were UTUC T stage, presence of metastasis, and male gender.

Expression of PVRL4, a molecular target for cancer treatment, is transcriptionally regulated by FOS.

PVRL4 (or nectin‑4) is a promising therapeutic target since its upregulated expression is found in a wide range of human cancer types. Enfortumab vedotin, an antibody‑drug conjugate targeting PVRL4, is clinically used for the treatment of urothelial bladder cancer. In addition, rMV‑SLAMblind, a genetically engineered oncolytic measles virus, can infect cancer cells and induce apoptosis through interaction with PVRL4. Although PVRL4 transcript levels are elevated in breast, lung and ovarian cancer, the mechanisms of its upregulation have not yet been uncovered. To clarify the regulatory mechanisms of elevated PVRL4 expression in breast cancer cells, Assay for Transposase‑Accessible Chromatin‑sequencing and chromatin immunoprecipitation‑sequencing (ChIP‑seq) data were used to search for its regulatory regions. Using breast cancer cells, an enhancer region was ultimately identified. Additional analyses, including ChIP and reporter assays, demonstrated that FOS interacted with the PVRL4 enhancer region, and that alterations of the FOS‑binding motifs in the enhancer region decreased reporter activity. Consistent with these data, exogenous expression of FOS enhanced the reporter activity and PVRL4 expression in breast cancer cells. Furthermore, RNA‑seq analysis using breast cancer cells treated with PVRL4 small interfering RNA revealed its possible involvement in the cytokine response and immune system. These data suggested that FOS was involved, at least partly, in the regulation of PVRL4 expression in breast cancer cells, and that elevated PVRL4 expression may regulate the response of cancer cells to cytokines and the immune system.

Identification of SPP1 as a Prognostic Biomarker and Immune Cells Modulator in Urothelial Bladder Cancer: A Bioinformatics Analysis

Secreted phosphoprotein-1 (SPP1) expression is differentially altered in many malignancies and could serve as a potential prognostic biomarker. Recent findings indicated that SPP1 possesses a broader role in bladder cancer (BC) pathogenesis than previously envisioned; however, the underlying mechanisms governing its expression, cellular localization, prognostic value and immune-related role in bladder cancer remain poorly understood. The expression and the prognosis value of SPP1 were assessed using immunohistochemistry (IHC) staining on a tissue microarray. SPP1 expression was correlated with the clinicopathological parameters, and survival analysis was calculated using a Kaplan–Meier plotter. Bioinformatics analysis of TCGA data was queried using UALCAN, CIBERSORT and TIMER datasets to decipher the biological processes enrichment pattern, protein–protein interactions and characterize tumor-infiltrating immune cells, respectively. IHC revealed that SPP1 expression is significantly associated with tumor type, stage, grade and smoking status. The Kaplan–Meier survival curve showed that low SPP1 expression is an unfavorable prognostic indicator in bladder cancer patients (p = 0.02, log-rank). The significant increased expression of the SPP1 level is associated with evident hypomethylation of the gene promoter in cancer compared to normal tissues in the TCGA-bladder dataset. Missense mutation is the most frequent genetic alteration of the SPP1 gene. Protein–protein interactions demonstrated that SPP1 shares the same network with many important genes and is involved in many signaling pathways and biological processes. TIMER reported a significant correlation between SPP1 expression and multiple immune cells infiltration. Furthermore, the expression of SPP1 was found to be positively correlated with a number of immune checkpoint genes such as PD-1 and CTLA4. The current investigation indicates that the SPP1 protein could serve as a prognostic biomarker and merit further investigation to validate its clinical usefulness in patients with bladder cancer.

Effects of Lactate Transport Inhibition by AZD3965 in Muscle-Invasive Urothelial Bladder Cancer.

The Warburg Effect is characterized by high rates of glucose uptake and lactate production. Monocarboxylate transporters (MCTs) are crucial to avoid cellular acidosis by internal lactate accumulation, being largely overexpressed by cancer cells and associated with cancer aggressiveness. The MCT1-specific inhibitor AZD3965 has shown encouraging results in different cancer models. However, it has not been tested in urothelial bladder cancer (UBC), a neoplasm where rates of recurrence, progression and platinum-based resistance are generally elevated. We used two muscle-invasive UBC cell lines to study AZD3965 activity regarding lactate production, UBC cells' viability and proliferation, cell cycle profile, and migration and invasion properties. An "in vivo" assay with the chick chorioallantoic membrane model was additionally performed, as well as the combination of the compound with cisplatin. AZD3965 demonstrated anticancer activity upon low levels of MCT4, while a general lack of sensitivity was observed under MCT4 high expression. Cell viability, proliferation and migration were reduced, cell cycle was arrested, and tumor growth "in vivo" was inhibited. The compound sensitized these MCT4-low-expressing cells to cisplatin. Thus, AZD3965 seems to display anticancer properties in UBC under a low MCT4-expression setting, but additional studies are necessary to confirm AZD3965 activity in this cancer model.

DNA methylation profiles in urothelial bladder cancer tissues and children with schistosomiasis from Eggua, Ogun State, Nigeria

BackgroundSquamous cell carcinoma has been attributed to chronic schistosomiasis and is the predominant type of bladder cancer in schistosomiasis endemic areas. The aim of this study was to assess early promoter DNA methylation in selected genes implicated in schistosomiasis-associated bladder cancer (SABC).MethodsA total of 159 urine samples were collected from school-aged children in Eggua Community of Ogun State and examined by microscopy for Schistosoma haematobium eggs. From this sample, a subset of 34 (21.1%) urine samples positive for S. haematobium, age and sex-matched with negative urine control samples, and 16 formalin-fixed paraffin-embedded bladder cancer tissues obtained from the University College Hospital were subjected to DNA isolation and bisulphite DNA conversion. Quantitative methylation-specific PCR was used to determine the methylation status of APC, RARβ2, RASSF1A, and TIMP3 in the samples.ResultsHigh degrees of methylation of RARβ2(67.7%), RASSF1A (38.2%), and TIMP3(52.9%) was more common in urogenital schistosomiasis (UGS)-positive urine samples than negative urine (control) samples and in bladder cancer tissues. Promoter DNA methylation in the positive urine samples was 1.4-fold, 13.3-fold, 3.4-fold, and 3.8-fold higher in APC, RARβ2, RASSF1A, and TIMP3, respectively, than in the matched controls. The odds of promoter methylation were likely to increase with age group for APC (OR: 1.615) and TIMP3(OR: 2.000); sex for TIMP3(OR: 2.644); and haematuria for RARβ2(OR: 1.094), RASSF1A (OR: 1.143), and TIMP3(OR: 1.842), although there were no significant associations. Conclusions: Gene promoter DNA methylation in tumour suppressor genes was observed in schistosomiasis cases. Hence, promoter DNA methylation may occur during active schistosomiasis in children. This result may serve as an early non-invasive biomarker to detect and hint at the risk of developing SABC later in life.

Clinical and Biological Differences between Upper Tract Carcinoma and Bladder Urothelial Cancer, Including Implications for Clinical Practice

Upper tract urothelial carcinoma (UTUC) is a rare disease included, along with the much more frequent urothelial bladder cancer (BUC), in the family of urothelial carcinomas (UCs). However, while UTUCs and BUCs share several features, their epidemiological, clinical, pathological, and biological differences must be considered to establish an optimal therapeutic strategy. This review examines the clinical differences between UTUC and BUC, as well as the main results obtained by molecular screening of the two diseases. The findings of clinical trials, performed in peri-operative and metastatic settings and assessing systemic treatments in UC, are summarised. A comparison of the data obtained for UTUC and BUC suggests improved therapeutic approaches, both in regards to routine practice and future drug development.

Impact of consensus molecular subtypes on survival with and without adjuvant chemotherapy in muscle-invasive urothelial bladder cancer

AimsAdjuvant chemotherapy after radical cystectomy can reduce the risk of recurrence and death in advanced muscle-invasive urothelial bladder cancer (MIBC). Molecular subtypes have been shown to be associated with survival....

Prognostic value of preoperative De Ritis ratio on oncological outcomes in patients with muscle-invasive bladder cancer.

We aimed to assess the prognostic value of De Ritis ratio on oncological outcomes in patients suffering from urothelial bladder cancer and undergoing radical cystectomy (RC). Analytical cohort comprised a single-center series of 367 patients treated between January 2015 and December 2018. Patients were classified into two groups based on De Ritis ratio (<1.3 [normal] vs. ≥1.3 [high]). Along with the Kaplan-Meier survival probability, cox proportional hazard regression models were used. A total of 299 patients were included, 60.5% of them having a De Ritis ratio of <1.3% and 39.5% with a De Ritis ratio of ≥1.3. Preoperative increased De Ritis ratio was associated with age (p = 0.001), gender (p = 0.044), cancer-related death (p = 0.001), overall death (p = 0.001), and tumor stage (p = 0.001). Multivariate analysis implied that preoperative De Ritis ratio was a significant independent prognosticator of overall survival (HR 0.461; 95% CI 0.335-0.633; p < 0.001) and CSS (HR 0.454; 95% CI 0.330-0.623; p < 0.001). Only tumor stage (HR 1.953; 95% CI 1. 106-3.448; p = 0.021) was independently associated with recurrence-free survival (RFS). De Ritis ratio was not independently associated with RFS in multivariate analyses. During the follow up, a total of 198 (66.2%) patients died, including 173 (57.9%) from BC, 5-year CSS was 45.8%. De Ritis ratio is an independent prognostic factor of cancer specific and overall survival in patients treated with RC for urothelial BC. RC patients may benefit from the use of the De Ritis ratio as a valid predictive biomarker.

Enfortumab vedotin as a salvage option as 5th line therapy for metastatic urothelial bladder cancer

Abstract A 67-year-old female patient with a muscle-invasive, non-metastatic urothelial bladder cancer (UC) (pT2 G3 cN0 cM0) developed metachronous metastases within 6 months after radical cystectomy with ileal conduit urinary diversion. After a good primary response to platinum-based chemotherapy, treatment was switched to the immune checkpoint inhibitor (ICI) pembrolizumab due to progressive disease. Subsequently the patient underwent selective internal radiotherapy (SIRT) of the liver and received vinflunine as well as a re-challenge with pembrolizumab. Two years after the initial diagnosis, rapid disease progression ultimately led to a switch to 5th line therapy with enfortumab vedotin (EV), which had only been approved in the United States at that time. The antibody-drug conjugate was well tolerated by the patient after dose reduction to 1.0 mg/ kg body weight. Simultaneous irradiation of newly occurring precardiac, hepatic and cerebral metastases were necessary. After 10 months of therapy with EV, tumour regression was observed accompanied with good symptom control. The presented case illustrates the efficacy and tolerability of EV in a heavily pre-treated patient with metastatic UC (mUC).

Evaluating residual tumor after neoadjuvant chemotherapy for muscle-invasive urothelial bladder cancer: diagnostic performance and outcomes using biparametric vs. multiparametric MRI

BackgroundNeoadjuvant chemotherapy (NAC) before radical cystectomy is standard of care in patients with muscle-invasive bladder cancer (MIBC). Response assessment after NAC is important but suboptimal using CT. We assessed MRI without vs. with intravenous contrast (biparametric [BP] vs. multiparametric [MP]) for identifying residual disease on cystectomy and explored its prognostic role.MethodsConsecutive MIBC patients that underwent NAC, MRI, and cystectomy between January 2000–November 2022 were identified. Two radiologists reviewed BP-MRI (T2 + DWI) and MP-MRI (T2 + DWI + DCE) for residual tumor. Diagnostic performances were compared using receiver operating characteristic curve analysis. Kaplan-Meier curves and Cox proportional-hazards models were used to evaluate association with disease-free survival (DFS).Results61 patients (36 men and 25 women; median age 65 years, interquartile range 59–72) were included. After NAC, no residual disease was detected on pathology in 19 (31.1%) patients. BP-MRI was more accurate than MP-MRI for detecting residual disease after NAC: area under the curve = 0.75 (95% confidence interval (CI), 0.62–0.85) vs. 0.58 (95% CI, 0.45–0.70; p = 0.043). Sensitivity were identical (65.1%; 95% CI, 49.1–79.0) but specificity was higher in BP-MRI compared with MP-MRI for determining residual disease: 77.8% (95% CI, 52.4–93.6) vs. 38.9% (95% CI, 17.3–64.3), respectively. Positive BP-MRI and residual disease on pathology were both associated with worse DFS: hazard ratio (HR) = 4.01 (95% CI, 1.70–9.46; p = 0.002) and HR = 5.13 (95% CI, 2.66–17.13; p = 0.008), respectively. Concordance between MRI and pathology results was significantly associated with DFS. Concordant positive (MRI+/pathology+) patients showed worse DFS than concordant negative (MRI-/pathology-) patients (HR = 8.75, 95% CI, 2.02–37.82; p = 0.004) and compared to the discordant group (MRI+/pathology- or MRI-/pathology+) with HR = 3.48 (95% CI, 1.39–8.71; p = 0.014).ConclusionBP-MRI was more accurate than MP-MRI for identifying residual disease after NAC. A negative BP-MRI was associated with better outcomes, providing complementary information to pathological assessment of cystectomy specimens.

Epigenetic alterations in urothelial bladder cancer associated with disease outcomes.

Bladder cancer (BLCA) is a molecular heterogeneous disease with known genetic distinctive signatures. However, DNA methylation is highly prevalent across a wide range of tumors, suggesting its potential in oncogenesis. Here, we aimed to interrogate the role of nine epigenetic alterations as diagnostic and prognostic markers in BLCA. DNA methylation, gene expression, and clinicopathological information were retrieved from The Cancer Genome Atlas data portal. Methylation values and gene expression were assessed to determine their association with normal and malignant tissue. Additionally, we studied the association between methylation values and clinicopathological variables. For the prognostic model, Kaplan-Meier Survival curves were generated. Lastly, univariate and multivariate analysis were performed to evaluate the simultaneous impact of methylation and clinicopathological variables on the risk of tumor progression and survival. Nine CpG sites' methylation -values involved in our study demonstrated different methylation signatures between normal and malignant urothelium. Hypermethylated CpGs were overrepresented in tumor tissue (p < 0.0001). Opposingly, 4 CpG sites showed lower methylation values in tumor samples (p < 0.0001). Cg12743248high and cg17192862low are risk factors for progression-free survival, whereas cg12374721high (HR:3.003 (1.283-7.030)) also demonstrated to be the most valuable independent risk factor for disease progression and a risk factor for overall survival. We have identified that methylated cg12374721 shows promise as a diagnostic and independent prognostic marker in BLCA progression.

MRNA expression of CRF family members in urothelial bladder cancer.

The corticotropin-releasing factor (CRF) gene family includes the three urocortins (UCN1, 2 and 3) and the two receptors (CRFR1 and 2), which play a significant role in the physiology of various organs. The expression of the CRF family of genes and its receptors are shown to participate in the pathogenesis of inflammation and even tumorigenesis. However, data regarding the human urinary tract, especially the bladder, are scarce. To the best of our knowledge, no studies are currently available on the CRF system and bladder cancer. The primary goal of the present study was to investigate the mRNA expression of the CRF family members in bladder cancer. The secondary aim was to analyze the differences with the expression of the same mRNAs in normal bladders. From August 2018 to July 2021, 43 recruited patients were divided into three groups. Group A included healthy patients, group B included patients with bladder cancer and group C included patients with a history of cancer from whom samples were taken from the normal bladder mucosa. Detection of mRNA of the CRF family of genes was performed using reverse transcription-quantitative PCR. The mRNA of the three urocortins, CRF and the two receptors were predominantly expressed in all three groups of patients. Statistical analysis using the Kruskal-Wallis test showed that UCN1 was downregulated in patients with bladder cancer and those with possible cancer compared with the healthy group (mean rank group A=24.3 vs. mean rank group B=12.58; P=0.006) and (mean rank group A=24.3 vs. mean rank group C=8.88; P=0.001). The present experiments showed that mRNA of the CRF family of genes was amplified in normal and cancer bladder tissues. Downregulation of the UCN1 gene may be associated with bladder cancer, contributing to the prognosis, diagnosis or therapy of urothelial malignancies.

Pelvic lymphadenectomy: Evaluating nodal stage migration and will rogers effect in bladder cancer

IntroductionPelvic lymphadenectomy (PLND) alongside radical cystectomy (RC), provides crucial diagnostic and therapeutic value in patients with bladder cancer. With the advent of neoadjuvant chemotherapy and prospective data supporting standard PLND, controversy remains regarding the optimal PLND extent and patient selection. Nearly 40% of patients may not receive adequate PLND, even though 25% of patients have positive lymph nodes (LN) at time of RC. We hypothesized that PLND still remains an important facet of bladder cancer treatment. To clarify the prognostic importance of nodal yield, we performed a retrospective investigation of a heterogenous population (pTanyNx/0M0) of patients undergoing RC. MethodsFrom the Surveillance, Epidemiology, and End Results (SEER) program, we identified pTanyNx/0M0 bladder cancer patients undergoing RC from 2004 to 2015. Kaplan Meier curves and Cox proportional hazards models assessed cancer-specific survival. Patients were analyzed with PLND performed as the primary covariate. Survival analysis then stratified patients undergoing PLND by LN yield, both as a continuous and categorial variable (≤10, 11–20, 21–30, and >30), and T stage. ResultsThe final cohort included pTanyNx/0M0 patients with urothelial bladder cancer (n = 12,096); median follow up was 39 (IQR: 17–77) months. PLND was performed in 81.45% of patients with a median LN yield of 14 (IQR: 7–23). Most commonly, patients had T2 disease (44.68%). After controlling for age and T stage, patients receiving PLND had improved CSS (HR = 0.56, [95% CI: 0.51–0.62]) compared to those that did not receive PLND. When grouping patients by LN yield, survival improved in a “dose dependent” manner (>30 LN: HR = 0.76, [95% CI: 0.66–0.87]). We noted similar results when stratifying patients into non–muscle-invasive (NMIBC) and muscle-invasive bladder cancer (MIBC). ConclusionsIn a large contemporary series of pTanyNx/0M0 bladder cancer patients, we found a significant oncologic benefit to PLND. Higher LN yield correlated to improved CSS in non–muscle-invasive and muscle-invasive disease. Our data support the possibility of occult micrometastasis even in non–muscle-invasive disease. Additionally, in light of recent advances in adjuvant immunotherapy, our results emphasize the importance of adequate nodal yield for accurate staging and optimal treatment.

QUANTITATIVE IMMUNOFLUORESCENCE EVALUATION OF PD-L1 EXPRESSION IN NON-MUSCLE-INVASIVE AND MUSCLE-INVASIVE UROTHELIAL BLADDER CANCER

The expression of PD-L1 protein was quanti ed in 56 samples of urothelial bladder cancer (BC). PD-L1 expression was detected in all BC samples, while in non-muscle-invasive bladder cancer (NMIBC) the median value is 1,5 times higher than in muscle-invasive bladder cancer (MIBC) (p = 0,001). High PD-L1 expression level (≥30%) was observed in 20% of MIBC samples and among NMIBC tumors - in 68% of cases, that is 3,4 times more often (p = 0,0004). The last fact justi es the prospect of starting therapy with immune checkpoint inhibitors already at the onset of the disease - at NMIBC.

Patient-derived organoids identify tailored therapeutic options and determinants of plasticity in sarcomatoid urothelial bladder cancer

Sarcomatoid Urothelial Bladder Cancer (SARC) is a rare and aggressive histological subtype of bladder cancer for which therapeutic options are limited and experimental models are lacking. Here, we report the establishment of a long-term 3D organoid-like model derived from a SARC patient (SarBC-01). SarBC-01 emulates aggressive morphological, phenotypical, and transcriptional features of SARC and harbors somatic mutations in genes frequently altered in sarcomatoid tumors such as TP53 (p53) and RB1 (pRB). High-throughput drug screening, using a library comprising 1567 compounds in SarBC-01 and conventional urothelial carcinoma (UroCa) organoids, identified drug candidates active against SARC cells exclusively, or UroCa cells exclusively, or both. Among those, standard-of-care chemotherapeutic drugs inhibited both SARC and UroCa cells, while a subset of targeted drugs was specifically effective in SARC cells, including agents targeting the Glucocorticoid Receptor (GR) pathway. In two independent patient cohorts and in organoid models, GR and its encoding gene NR3C1 were found to be significantly more expressed in SARC as compared to UroCa, suggesting that high GR expression is a hallmark of SARC tumors. Further, glucocorticoid treatment impaired the mesenchymal morphology, abrogated the invasive ability of SARC cells, and led to transcriptomic changes associated with reversion of epithelial-to-mesenchymal transition, at single-cell level. Altogether, our study highlights the power of organoids for precision oncology and for providing key insights into factors driving rare tumor entities.

Sex Does Not Affect Survival: A Propensity Score-Matched Comparison in a Homogenous Contemporary Radical Cystectomy Cohort

ObjectivesTo determine whether biological sex affects oncological outcome after extended pelvic lymph node dissection, radical cystectomy, and urinary diversion for muscle-invasive bladder cancer, and to identify risk factors impacting outcome. Patients and MethodsWe performed a single-center, retrospective observational cohort study with prospective data collection with a propensity score matched population. A total of 1165 consecutive patients from 2000 to 2020, (317 women and 848 men) scheduled for open extended pelvic lymph node dissection, radical cystectomy, and urinary diversion for urothelial bladder cancer were included in the final analysis. Overall Survival (OS), Cancer-Specific-Survival (CSS), and Recurrence-Free-survival (RFS) were assessed with multivariable weighted Cox regression analysis as well as with propensity score matched Cox-Regression. ResultsNo significant difference was found between sexes regarding OS (HR 1.18, [0.93-1.49], P = .16), CSS (HR 0.87, [0.64-1.18], P = .38), or RFS (HR 0.80, [0.59-1.07], P = .13). These results were confirmed after propensity score matching: female sex was not associated with inferior OS (HR 1.20, [0.91-1.60], P = .19), CSS (HR 1.01, [0.75-1.35], P = .97) or RFS (HR 0.98, [0.75-1.27], P = .86). ConclusionsWe did not find a significant difference in cancer-related outcomes or overall survival after extended pelvic lymph node dissection, open radical cystectomy, and urinary diversion for urothelial cancer between males and females even after adjustment with propensity matching score for multiple factors including oncological parameters, smoking status, and renal function.

P199 - Utilization of Tropomyosin isoform expression pattern in development of a urine-based assay for detection of urothelial bladder cancer

P199 - Utilization of Tropomyosin isoform expression pattern in development of a urine-based assay for detection of urothelial bladder cancer