Patient-derived Organoids in Bladder Cancer: Opportunities and Challenges.

Background And Objective: Bladder cancer (BLCa) remains a prevalent malignancy with high recurrence rates and limited treatment options. In recent years, patient-derived organoids (PDOs) have emerged as a promising platform for studying cancer biology and therapeutic responses in a personalized manner. Using drug screening, PDOs facilitate the identification of novel therapeutic agents and translational treatment strategies.

Histologic subtypes of non-muscle invasive bladder cancer.

The majority of bladder cancers (BCs) are non-muscle invasive BCs (NMIBCs) and show the morphology of a conventional urothelial carcinoma (UC). Aberrant morphology is rare but can be observed. The classification and characterization of histologic subtypes (HS) in UC in BC have mainly been described in muscle invasive bladder cancer (MIBC).

Diagnostic Value of Urine Cytology in Pharmacologically Forced Diuresis for Upper Tract Urothelial Carcinoma Diagnosis and Follow-Up.

We performed a urine cytology analysis of a pharmacologically induced diuresis for the diagnosis of upper tract urothelial carcinoma. To evaluate the diagnostic value of cytology of pharmacologically forced diuresis, an initial cohort of 77 consecutive patients with primary upper tract urothelial carcinoma treated via radical surgery was enrolled. To evaluate pharmacologically forced diuresis cytology as a follow-up procedure, a second cohort of 1250 patients who underwent a radical cystectomy for bladder cancer was selected.

Guidance of adjuvant instillation in intermediate-risk non-muscle invasive bladder cancer by drug screens in patient derived organoids: a single center, open-label, phase II trial.

Background: In intermediate-risk non-muscle invasive bladder cancer (NMIBC) clinical guidelines suggest an adjuvant instillation with a chemotherapeutic agent. However, the agent and regimen are not clearly defined. Worldwide, less than 15% of patients receive this adjuvant chemotherapeutic instillation.

Bladder cancer organoids as a functional system to model different disease stages and therapy response.

Bladder Cancer (BLCa) inter-patient heterogeneity is the primary cause of treatment failure, suggesting that patients could benefit from a more personalized treatment approach. Patient-derived organoids (PDOs) have been successfully used as a functional model for predicting drug response in different cancers. In our study, we establish PDO cultures from different BLCa stages and grades.

Which Patients To Consider for Bladder Preservation After a Complete Response to Neoadjuvant Chemotherapy.

The decision on which patients with muscle-invasive bladder cancer to consider for bladder preservation remains controversial. New promising technologies and biomarkers may allow to precise selection of patients for bladder preservation in the future. Currently, bladder preservation should only be considered in highly selected cases and in the setting of clinical trials.

Bladder preservation after neoadjuvant therapy - 2021 IBCN updates part 1.

The morbidity associated with radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) has fueled investigations into the feasibility of bladder preservation strategies after a favorable clinical response to neoadjuvant therapy (NAT). Identifying optimal candidates for bladder preservation is predicated on our ability to identify tumors with inherent cisplatin sensitivity and accurately stage patients before and after NAT. In the present review, we evaluate the accuracy and limitations of contemporary staging modalities and investigate clinical outcomes in patients with MIBC who were managed with bladder preservation after NAT.

Oncological Outcomes for Patients Harboring Positive Surgical Margins Following Radical Cystectomy for Muscle-Invasive Bladder Cancer: A Retrospective Multicentric Study on Behalf of the YAU Urothelial Group.

Introduction: Adjuvant therapy has no defined role for patients with positive surgical margins (PSMs) following radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). The aim of our study was to describe loco-regional recurrence-free survival (LRFS), metastatic-free survival (MFS), recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) and identify predictors of each endpoint in patients with PSMs following RC for MIBC. Methods: A collaborative retrospective cohort study was conducted on 394 patients with PSMs who underwent RC for MIBC between January 2000 and December 2018 at 10 tertiary referral centers.

25 years International Bladder Cancer Network (IBCN): The past, the present, and the future.

In 1997 an international group of scientists organized a meeting in Barcelona, Spain, to discuss the use of biomarkers in the management of patients with bladder cancer. This meeting was the offspring of an - initially informal - group that finally resulted in the foundation and incorporation of the International Bladder Cancer Network (IBCN) e.V.

Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer.

Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is recommended for patients with muscle-invasive bladder cancer (MIBC). It has been shown that somatic deleterious mutations in ERCC2, gain-of-function mutations in ERBB2, and alterations in ATM, RB1, and FANCC are correlated with pathological response to NAC in MIBC. The objective of this study was to validate these genomic biomarkers in pretreatment transurethral resection material from an independent retrospective cohort of 165 patients with MIBC who subsequently underwent NAC and radical surgery.

Prognostic Role of RNA Expression Molecular Biomarkers in Prostate and Bladder Cancers.

Prostate cancer and bladder cancer are two of the most common urologic cancers. Cancer risk stratification and prediction of prognosis have always been challenging. Following recent advances in genomic and proteomic technologies, several genomic biomarkers have been developed and proposed as a noninvasive and nonexpansive approach that can supplement our current data to improve prediction and accuracy.

Uroplakin II as a single marker for luminal versus basal molecular subtypes in muscle invasive urothelial carcinoma.

Bladder cancer is a heterogeneous disease classified into two broad molecular subtype categories, basal and luminal, with critical treatment and prognostic implications. Recent studies have shown the utility of immunohistochemistry in predicting bladder cancer molecular subtypes, with a two-marker approach using GATA3 and CK5/6 showing over 80% reliability. In the current study, we calculated the accuracy of uroplakin II (UPII), a marker of urothelial differentiation, with different scores (0: <1%, 1+: 1-10%, 2+: 10-50%, 3+: >50%) to predict RNA-based luminal versus basal subtypes in a cohort of muscle-invasive bladder cancer-received neoadjuvant chemotherapy followed by radical cystectomy.

Characteristics of upper urinary tract urothelial carcinoma in the context of bladder cancer: a narrative review.

Urothelial carcinomas (UC) arise from the urothelium that covers the proximal urethra, urinary bladder, and the upper urinary tract. In daily routine and clinical trials UC originating from different locations are often treated and investigated in the same manner. However, differences between the two locations seem to be apparent and may question in handling them as a single oncologic entity.

Predictive models of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer using nuclear morphology and tissue architecture.

Characterizing likelihood of response to neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) is an important yet unmet challenge. In this study, a machine-learning framework is developed using imaging of biopsy pathology specimens to generate models of likelihood of NAC response. Developed using cross-validation (evaluable N = 66) and an independent validation cohort (evaluable N = 56), our models achieve promising results (65%-73% accuracy).

Swiss germ-cell cancer consensus recommendations.

Approximately 420 men are diagnosed with germ-cell cancer (GCC) in Switzerland each year. Recent international guidelines outline management issues, but many aspects remain controversial in an area of highly individualised treatments. Even more than in other tumour types, in GCC the challenge is to choose exactly the correct treatment for an individual patient.

A longitudinal study evaluating interim assessment of neoadjuvant chemotherapy for bladder cancer.

Objectives: To evaluate the usefulness of radiological re-staging after two and four cycles of neoadjuvant chemotherapy (NAC), the impact of re-staging on further patient management, and the correlation between clinical and final pathological tumour stage at radical cystectomy (RC).

Patients And Methods: We conducted a longitudinal, single-centre, cohort study of prospectively collected consecutive patients who underwent NAC and RC for urothelial muscle-invasive bladder cancer between July 2001 and December 2017. Patients underwent repeated computed tomography scans for re-staging after two cycles of NAC and after completion of NAC before RC.

Postoperative Chemotherapy Bladder Instillation After Radical Nephroureterectomy: Results of a European Survey from the Young Academic Urologist Urothelial Cancer Group.

Background: Level 1 evidence supports the administration of single postoperative intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), in order to decrease intravesical recurrence risk.

Objective: The Young Academic Urologist Urothelial Cancer Group aimed to investigate the use of pIVC in daily practice among European colleagues.

Design Setting And Participants: An online survey was shared with European Association of Urology Section of Oncological Urology (ESOU) 2017 participants via e-mail.

Evaluation of carbonic anhydrase IX as a potential therapeutic target in urothelial carcinoma.

Objective: Carbonic anhydrase IX (CA9) is important in the regulation of intra- and extracellular pH in solid tumors, contributing to cell growth and invasion. In urothelial carcinoma (UC), CA9 has been identified as a urinary marker for disease detection, but its biologic role is unknown. To date, differential gene expression patterns of CA9 in various molecular subtypes and potential effects of CA9 inhibition in UC cells are unknown.

Receptor Activator of NF Kappa B (RANK) Expression Indicates Favorable Prognosis in Patients with Muscle-invasive Bladder Cancer.

Background: Receptor activator of NF kappa B (RANK) and its ligand have an essential role in T-cell regulation and the development of bone metastases. The role of RANK expression in muscle-invasive bladder cancer (MIBC) is unknown.

Objective: To assess the relevance of RANK expression in patients with MIBC.

Molecular Characterization of Residual Bladder Cancer after Neoadjuvant Pembrolizumab.

Background: In patients with muscle-invasive urothelial bladder cancer (MIBC), molecular alterations in immunotherapy-resistant tumors found at radical cystectomy (RC) remain largely unstudied.

Objective: To investigate the biology of pembrolizumab-resistant tumors in comparison to an RC cohort treated without any systemic therapy and a cohort of neoadjuvant chemotherapy (NAC)-treated tumors.

Design, Setting, And Participants: Transcriptome-wide expression profiling was performed on 26 RC samples from patients with ypT2-4 disease after pembrolizumab treatment, of which 22 had matched pretherapy samples.

A showcase study on personalized in silico drug response prediction based on the genetic landscape of muscle invasive bladder cancer.

Improved and cheaper molecular diagnostics allow the shift from "one size fits all" therapies to personalised treatments targeting the individual tumor. However, the wealth of potential targets based on comprehensive sequencing remains a yet unsolved challenge that prevents its routine use in clinical practice. Thus, we designed a workflow that selects the most promising treatment targets based on multi-omics sequencing and in silico drug prediction.