Empowering Bladder Cancer Care: A Formal Partnership between IBCG and UroToday in the Era of Expanding Therapies

Ashish M. Kamat | February 01, 2024

“Nothing in life is to be feared; it is only to be understood.” – Marie Curie

As we embark on 2024, we continue to see an explosion of research and clinical trials in bladder cancer. Every FDA approval is the fruit of thousands of hours of dedicated work by investigators, patients, research, and clinical teams. However, regulatory approval is only the first step in linking patients with new therapies. Without effective dissemination of knowledge and guidance, many patients will not receive evidence-based treatments and indeed may not even know their treatment options.

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Ashish Kamat 2Ashish Kamat, MD, MBBS, is a Professor of Urology and Cancer Research and Wayne B. Duddleston Professor of Cancer Research at MD Anderson Cancer Center in Houston, Texas. Dr. Kamat serves as President of International Bladder Cancer Group, (IBCG), and Co-President of International Bladder Cancer Network.
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Written by Zachary Klaassen, MD, MSc, Wellstar MCG Health Georgia Cancer Center Augusta, Georgia, USA
December 12, 2023

Bladder cancer remains the sixth most commonly diagnosed cancer in the United States, with an estimated 82,290 incident cases in 2023.1 Because of the persistent recurrence risk of NMIBC in a highly comorbid population, there has been an FDA-led drive towards developing novel treatment options for these patients. The following article will highlight recent advances in this disease space with a specific focus on the oncolytic adenovirus agent cretostimogene grenadenorepvec, and the registration trial in intermediate risk non-muscle invasive bladder cancer (NMIBC), PIVOT-006. 

 

Written by Rashid K. Sayyid, MD, MSc University of Toronto Toronto, ON and Zachary Klaassen, MD, MSc Medical College of Georgia Augusta, Georgia, USA
October 17, 2023
Bladder cancer remains the sixth most commonly diagnosed cancer in the United states, with an estimate of 82,290 incident cases in 2023.1 At diagnosis, approximately 75% of patients present with non-muscle invasive disease, with significant clinical heterogeneity observed within this disease group.2,3 Patients with initial low-grade Ta disease (i.e., confined to the mucosal lining) represent a unique patient cohort given their favorable long-term oncologic outcomes
Written by Rashid K. Sayyid, MD, MSc University of Toronto Toronto, ON and Zachary Klaassen, MD, MSc Medical College of Georgia Augusta, Georgia, USA
September 5, 2023
Intravesical Bacillus Calmette-Guerin (BCG) remains the current standard-of-care, guideline-recommended treatment of choice in the adjuvant setting for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC) due to its ability to reduce the risk of disease recurrence and, more importantly, disease progression.1-3 Despite adequate BCG treatment up to 50% of patients will develop a BCG-refractory, relapsing, or failure state.
Written by Rashid K. Sayyid, MD, MSc, University of Toronto, Toronto, ON and Zachary Klaassen, MD, MSc, Medical College of Georgia, Augusta, Georgia, USA
August 31, 2023
Intravesical Bacillus Calmette-Guerin (BCG) currently remains the standard-of-care, guideline recommended treatment of choice in the adjuvant setting for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC) due to its ability to reduce the risk of disease recurrence and disease progression. However, despite adequate BCG, up to 50% of patients develop a BCG-refractory, relapsing, or failure state.4 Currently, radical cystectomy remains the gold standard approach in this setting.
Written by Rashid K. Sayyid, MD, MSc, University of Toronto, Toronto, ON & Zachary Klaassen, MD, MSc, Medical College of Georgia, Augusta, Georgia, USA
August 23, 2023
Immune checkpoint inhibitors have emerged as a guideline-recommended first line treatment option for patients with cisplatin-ineligible, metastatic urothelial carcinoma of the bladder and as second line therapy for patients with metastatic disease progressing during, or after, platinum-based combination chemotherapy.1 Pembrolizumab, a Programmed Death-1 (PD-1) inhibitor, has been recently approved by the US Food and Drug Administration for the treatment of patients with Bacillus Calmette Guerin (BCG)
Written by Rashid K. Sayyid, MD, MSc University of Toronto Toronto, ON & Zachary Klaassen, MD, MSc Medical College of Georgia Augusta, Georgia, USA
August 22, 2023
Bacillus Calmette Guerin (BCG) is currently guideline-recommended in the adjuvant setting for patients with intermediate or high-risk non-muscle invasive bladder cancer (NMIBC).1 This is based on the results of numerous randomized clinical trials and meta-analyses demonstrating its ability to reduce the rates of disease recurrence and progression, compared to transurethral resection of bladder tumor (TURBT) alone or other adjuvant therapies.
Written by Zachary Klaassen, MD, MSc, Medical College of Georgia, Augusta, Georgia, USA
June 29, 2021
In 2021 in the United States, there will be approximately 83,730 new cases of bladder cancer (~64,280 men and 19,450 women), and approximately 17,200 deaths from bladder cancer (12,260 men and 4,940 women). On a global scale, in 2017 it was estimated that there were 2.63 million (95% CI 2.57-2.72 million) bladder cancer cases, involving 2.03 million (95% CI 1.96-2.11 million) men and 0.60 million (95% CI 0.58-0.62 million) women. As such, although bladder cancer may be a lethal diagnosis for some, there are also millions of bladder cancer survivors worldwide. 
May 18, 2021
While the role of restaging transurethral resection (reTUR) for high-grade (HG) T1 bladder cancer has well-established diagnostic and therapeutic implications, and guidelines agree on the role of reTUR for HG T1 disease,1-3 this remains an area of discussion for HG Ta tumors. The AUA recommends reTUR for all ‘high-risk’ HG Ta tumors (multifocal, ≥3cm, concomitant carcinoma in situ [CIS], variant histology, lymphovascular invasion [LVI], prostatic urethral involvement);2 while the EAU guidelines reserve reTUR for patients without muscularis propria in the index tumor specimen.1
Written by Yair Lotan, Jonathan L Wright, and Angela B Smith
April 28, 2021
To address the importance of high-value care in the context of affordability and access, Institute for Clinical and Economic Review (ICER) an organization whose mission is to conduct evidence-based reviews of health care interventions, independently reviews evidence, free from financial conflicts of interest, to understand an intervention’s ability to extend or improve life, a fair price based on clinical evidence, and how stakeholders can translate evidence into real-world insurance coverage to improve patient outcomes.
Written by Markus Eckstein, MD, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
February 3, 2021
It is profound that despite years of intensive therapeutic efforts, a staggering 50-60% of patients with muscle-invasive urothelial bladder cancer will have a local or distant disease recurrence within five years with only limited therapeutic options.
Written by Marco Bandini, and Andrea Necchi
August 13, 2020
Over the last few years, the landscape of bladder cancer (BC) management has profoundly changed, thanks to increased knowledge of disease biology and the identification of novel therapeutic approaches and biomarkers.1 No more than 5 years ago, the treatment-decision process for non muscle-invasive BC (NMIBC) or muscle-invasive BC (MIBC) was represented by radical surgery in most cases, with an opportunity for perioperative systemic therapy in a few cases. To date, the diagnostic and therapeutic armamentarium has been exceedingly enlarged for these patients.
Written by Zachary Klaassen, MD, MSc
April 20, 2020

The rapid spread of Coronavirus Disease 2019 (COVID-19), caused by the betacoronavirus SARS-CoV-2, throughout the world has had dramatic effects on healthcare systems with impacts far beyond the patients actually infected with COVID-19. Patients who manifest severe forms of COVID-19 requiring respiratory support typically require this for prolonged durations, 

Written by Vikram M. Narayan, Paul Hegarty, Gianluca Giannarini, Rick Bangs, Stephanie Chisolm, and Ashish M. Kamat
April 2, 2020
The ongoing pandemic involving severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its resulting coronavirus disease 2019 (COVID-19)
Written by Catherine Ryan
March 22, 2020
A newly published systematic review and meta-analysis: Evidence-based Assessment of Current and Emerging Bladder-sparing Therapies for Non–muscle-invasive Bladder Cancer After Bacillus Calmette-Guerin Therapy: A Systematic Review and Meta-analysis 
Written by Noah M. Hahn, MD
July 12, 2019
Recent years have seen an explosive rate of transformative advances in both pre-clinical and clinical urothelial carcinoma research.  With the public dissemination of comprehensive molecular data from The Cancer Genome Atlas (TCGA) urothelial carcinoma cohort,
Written by Ashish Kamat, MD, MBBS
July 12, 2019
For those of us who take care of patients with the sixth most common malignancy in the United States and the seventh most common cause of cancer-related death,it was disheartening that, as recently as 2015, patients with advanced bladder cancer had no effective alternatives to cisplatinum-based chemotherapy, a status quo that had persisted for three decades.2
Written by Justin T. Matulay, MD, and Ashish Kamat, MD, MBBS
April 16, 2019
Bladder cancer is the most common malignancy of the urinary tract and second only to the prostate in the entire genitourinary system. The most updated available global estimate, based on registry data collected through the year 2012,
Written by Roger Li, MD and Ashish Kamat, MD, MBBS
April 16, 2019
In the previous sections, we have covered Epidemiology, Diagnosis, and Pathology of Bladder Cancers. As noted, most patients present at a potentially curative stage non-muscle invasive bladder cancer (NMIBC). Although NMIBC can generally be managed...
Written by Justin T. Matulay, MD and Ashish Kamat, MD, MBBS
April 16, 2019
There are no reliable screening tests available for detecting bladder cancer; hence the diagnosis is usually made based on clinical signs and symptoms. Painless hematuria – microscopic or gross – is the most common presentation...
Physician-Scientist Commentaries
Peer-reviewed Abstract Supplemental Commentaries
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
The plasmacytoid variant of bladder cancer (PV-BCa) is an aggressive subtype with a low 5-year survival rate. Mutations that lead to truncation of CDH1 are central to the pathology of PV-BCa and lead to loss of E-cadherin expression, which in turn allows the invasive spread of tumor cells.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
The median age at diagnosis of bladder cancer is 73 and increased age is a major risk factor for progression to invasive disease. However, there is a tendency for elderly patients with non-muscle invasive bladder cancer (NMIBC) to receive less guideline-concordant care. Lobo et al. investigated factors contributing to age disparities in NMIBC care and associated tumor biology features.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Differentiating reactive lymph nodes from lymph node bladder cancer metastasis through imaging is an area of unmet need that affects clinical management. A recent study by Zhou et al. examined the utility of dual time-point 18F-FDG PET/CT imaging to address this problem.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Radiation therapy can be an effective way to eliminate the need for radical surgery in bladder cancer patients. Trimodality therapy (TMT) is a bladder-preserving treatment that consists of maximal transurethral resection of bladder tumor (TURBT) followed by chemoradiation. Identifying biomarkers predicting tumor response to different treatments can enable selecting patients
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Squamous cell carcinoma represents 5% of lower urinary tract tumors in the U.S. Several factors are linked to squamous cell carcinoma of the bladder (BSCC), such as Schistosoma infection, recurrent urinary tract infections (UTIs), bladder calculi, pelvic radiation, antecedent intravesical Bacillus Calmette-Guérin (BCG), and indwelling catheters. Human papillomavirus (HPV) is also known to contribute to SCC
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Sarcomatoid urothelial bladder cancer (SARC) comprises less than 1% of all bladder cancers and is characterized by early metastasis and poor prognosis. SARC is commonly identified alongside conventional urothelial carcinoma (UC), which has led to the hypothesis that they share a common clonal origin.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Robot-assisted RC (RARC) procedures are popular due to faster recovery times. A recent study by Khetrapal et al. performed a systematic review and meta-analysis of randomized controlled trials (RCTs) – of outcomes in patients with bladder cancer who underwent RARC versus open RC (ORC). A total of seventeen studies were included in the analysis, which encompassed eight RCTs and 1,024 patients. 509 patents underwent ORC
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Carcinogenic agents may act by inducing genetic mutations that contribute to bladder cancer development. The most commonly mutated genes in non-muscle invasive bladder cancer (NMIBC) are FGFR3 and PIK3CA, occurring in 65% and 25% of tumors, respectively. The most common mutations in muscle-invasive bladder cancer (MIBC) are in tumor suppressor genes. Rao et al. hypothesized that recurrent mutations
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
In patients with bladder cancer (BC), neoadjuvant chemotherapy after radical cystectomy (RC) has been found to enhance survival and is therefore considered a gold standard for treatment. Li et al. investigated long-term outcomes among BC patients who underwent RC with or without perioperative chemotherapy. A total of 1,700 patients were included in the study, among whom 805 underwent RC without any perioperative chemotherapy (NC)
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Neuroendocrine carcinoma of the urinary tract (NEC-URO) is a rare and aggressive variant of urothelial carcinoma (UC). There has been limited data on the optimal management for NEC-URO. Accordingly, Alhalabi et al. previously conducted a phase 2 study in which patients with NEC-URO received an alternating doublet treatment of chemotherapy with ifosfamide plus doxorubicin (IA) and etoposide plus cisplatin (EP).
Written by Mohamad Abou Chakra, MD,1 Neal D. Shore, MD, FACS,2 Michael A. O'Donnell, MD1
In the US urologic community, there is a dearth of data regarding the treatment regimens currently used for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). According to our survey, the most commonly used treatment for NMIBC cases who failed BCG is intravesical single-agent chemotherapy (more than 50% of respondents), with gemcitabine or mitomycin C accounting for over 70% of these chemotherapy regimens.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
A subset of bladder cancer cases can develop secondary to radiation treatment for prostate cancer. This association has been shown in studies on patients undergoing external beam radiation therapy, but the effect of brachytherapy is unclear. Monda et al. set out to determine the risk of bladder cancer after different prostate cancer treatment modalities.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Nested urothelial carcinoma (NUC) and large nested urothelial carcinoma (LNUC) are aggressive but rare subtypes of urothelial carcinoma that are characterized by nested histological architecture and bland morphology, with the former exhibiting small nests and the latter exhibiting large nests. Aron et al. recently characterized the clinical and molecular features of NUC and LNUC tumors.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Field cancerization is a state in which mutated clones expand in morphologically normal tissues, eventually resulting in multi-focal cancer. In bladder cancer, field cancerization may be partly responsible for high recurrence rates. Strandgaard et al. aimed to determine whether urinary tumor DNA (utDNA) is a valid prognostic and predictive tool for monitoring field cancerization. The cohort consisted of 136 patients with non-muscle invasive bladder cancer (NMIBC) 
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Genetic alterations in fibroblast growth factor receptors (FGFRs) are common in patients with urothelial carcinoma. Erdafitinib, a kinase inhibitor, is the current standard of care for patients with FGFR3 or FGFR2 genetic alterations. Guercio et al. investigated how different genetic alterations affect treatment response and their variation across primary and metastatic sites. The study cohort consisted of 1,421 patients, among whom 27.5% exhibited FGFR2/3 alterations that were predictive of response to erdafitinib.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Incidence and mortality rates of bladder cancer have fluctuated over time in a region-specific manner. A solid understanding of these patterns is crucial for health policy planning and appropriate allocation of resources. To this end, Zhang et al. assimilated data on recent global patterns of bladder cancer. The researchers collected metrics from the GLOBOCAN 2020 database for 185 countries. In 2020, approximately 573,000 people were diagnosed
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Recent studies have highlighted emerging associations between the urinary microbiome and bladder cancer. Bukavina et al. conducted an in-depth survey of differences in the urinary microbiome between patients with bladder cancer and healthy controls using a new urinary microbiome dataset and existing datasets across three other countries. Data were collected from three published studies conducted in China, Croatia, and Hungary
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Intermediate-risk non-muscle invasive bladder cancer is a heterogeneous disease frequently treated with adjuvant intravesical chemotherapy or Bacillus Calmette-Guérin. The global BCG supply shortage has intensified the need for alternative treatment modalities, leading to the identification of sequential intravesical gemcitabine and docetaxel as an effective option for patients with high-risk NMIBC. 
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Patients with clinically node-positive (cN+) bladder cancer have a worse prognosis than patients without node involvement. Nevertheless, most treatments are more established in patients with node-negative bladder cancer. This includes favorable bladder-sparing protocols that consist of transurethral resection of bladder tumor followed by radical dose radiotherapy with a concurrent radiosensitizing agent.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Various studies have demonstrated significant differences in bladder cancer mortality across sex and race. These are partly related to differences in social and environmental factors, in addition to varying degrees of access to healthcare. Unfortunately, patients from diverse ancestries are often underrepresented in genomic cohorts. Nyame et al. investigated the hypothesis that tumor mutational burden (TMB) and other tumor features vary according to patients’ sex and race.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
While intravesical Bacillus Calmette-Guérin has been effective in patients with non-muscle invasive bladder cancer (NMIBC), recurrence rates are high. A recent study by Li et al. described the responses to durvalumab treatment among patients with BCG-unresponsive carcinoma in situ (CIS)-containing NMIBC.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
A major recent focus in cancer research has been the development of a multi-cancer detection test that can facilitate early diagnosis and enhance survival across different cancer types. Accordingly, the Circulating Cell-free Genome Atlas (CCGA) is a large study established to develop and validate blood-based cell-free DNA (cfDNA) tests. In a recent study, Bryce et al. reported the performance of the test in a large cohort of patients with cancer-related symptoms.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Loss of the Y chromosome (LOY) has been correlated with various health conditions, particularly in aging men. Up to 40% of bladder cancer tumors display LOY. However, the impact of LOY on tumor features and response to treatment is unknown. A landmark study by Abdel-Hafiz et al. investigated LOY in human bladder cancers. The investigators first analyzed transcriptomic data from 300 males with muscle-invasive bladder cancer (MIBC) using The Cancer Genome Atlas (TCGA). 
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Radical cystectomy and Trimodality therapy, which combines transurethral resection of the bladder tumor (TURBT) and concurrent chemoradiation, are effective treatments for muscle-invasive bladder cancer (MIBC). A recent study investigated the outcomes of patients with MIBC who were eligible for both treatment options.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Post-transcriptional RNA modifications that underlie gene regulation have been implicated in severe diseases. The N-acetyltransferase 10 (NAT10), the only known human enzyme that catalyzes the formation of the N4-acetylcytidine (ac4C) mark, contributes to the epithelial-to-mesenchymal (EMT) transition of cancer cells. Xie et al. characterized the role of these epi-transcriptomic processes in
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
The standard treatment for non-muscle invasive bladder cancer (NMIBC) is transurethral resection of the bladder tumor (TURBT) and intravesical Bacillus Calmette-Guérin (BCG) instillations. Patients with high-risk NMIBC have a 50% risk of developing recurrence within five years and a 20% risk of progression. A recent study by de Jong et al. uncovered molecular subtypes associated 
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Bacillus Calmette-Guérin (BCG) is the standard treatment for patients with non-muscle invasive bladder cancer (NMIBC). Tan et al. investigated whether BCG relapsing versus refractory NMIBC outcomes are distinct enough to warrant separation into sub-groups in clinical trials. The investigators analyzed data from 76 patients with NMIBC who were unresponsive to BCG and underwent bladder-sparing treatment.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Plasmacytoid urothelial cancer is associated with poor clinical outcomes, with up to 75% of PUC patients developing lymph node metastases. To better understand these trends, Davaro et al. examined the effect of surgical margin status and lymph node count on oncologic outcomes in patients with PUC who underwent radical cystectomy.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Muscle-invasive bladder cancer tumors can be divided into luminal and non-luminal subtypes. The establishment of the six molecular subtypes represents gene regulatory networks that integrate changes at the level of the genome, the epigenome, and the transcriptome. Moreover, highly active enhancers, known as super-enhancers, play a significant role in cell identity changes and oncogenic transformation.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Sarcomatoid urothelial carcinoma (SUC) is one of the rare variants of bladder cancer. A recent study by Diamantopoulos et al. developed nomograms to predict clinical outcomes for these patients. The authors collected data from 741 SUC patients from the surveillance, epidemiology, and end results program (SEER) database.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Smokers are more than three times more likely to develop bladder cancer than non-smokers. Tobacco smoking is considered the most significant risk factor for bladder cancer due to the resulting DNA damage and mutagenesis. The prevalence of smoking among individuals in the United States has decreased since the 1950s and 1960s
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Micropapillary bladder cancer is a rare variant of urothelial carcinoma. It is typically characterized by an advanced pathological stage at diagnosis and a high risk of metastasis, with a worse prognosis. However, there have been mixed findings regarding its impact on patient survival. Nomograms are statistical modeling tools that
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
A standard of care treatment for patients with muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy. Since this treatment modality is associated with significant toxicity, predicting patient response to treatment can prevent unnecessary adverse events and delays to effective treatment.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Although the gold standard for muscle-invasive bladder cancer treatment is cisplatin-based chemotherapy followed by radical cystectomy, many patients are ineligible for cisplatin. Accordingly, the NABUCCO trial was established to evaluate the response to pre-operative ipilimumab, an anti-CTLA-4 drug, and nivolumab, an anti-PD-1 drug, among patients with advanced (stage III) urothelial carcinoma.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
The presence of tumor DNA in urine has been used to evaluate clinical outcomes in bladder cancer patients. However, the sensitivity for detecting molecular residual disease (MRD) requires optimization. Chauhan et al. tested whether urine cell-free DNA (cfDNA) sequencing could lead to enhanced sensitivity for detecting MRD and predicting patient survival after radical cystectomy.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Approximately 25% of bladder cancer patients harbor a deletion in MTAP, a gene involved in purine synthesis. Importantly, MTAP deletion has been associated with enhanced sensitivity to the anti-metabolite pemetrexed (in patients and in vitro). On the other hand, MTAP-deleted tumors exhibit low responsiveness to immune checkpoint inhibitors.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease with highly varied patient outcomes. There is a significant need for prognostic biomarkers to help guide treatment decisions. Certain features of the tumor microenvironment (TME) have been suggested to modulate response to treatment.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Enfortumab Vedotin (EV) is approved for patients with advanced urothelial cancer following progression after chemotherapy and PD-1 or PD-L1 inhibitor treatment. EV is an anti-nectin-4 antibody conjugated to a chemotherapeutic compound (MMAE). Various toxicities are associated with its use, including blood glucose elevation, neuropathy, and cutaneous toxicity.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Computed tomography (CT) is the most commonly used technique for imaging lymph node metastases, although it has relatively low sensitivity rates. Accordingly, targeted imaging techniques are needed for enhanced detection. Vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and prostate-specific membrane antigen (PSMA)
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
In recent years, immune checkpoint inhibitors, such as anti-PD-L1, have been added to the treatment options for patients with metastatic urothelial carcinoma (mUC) in the first-line, second-line, and maintenance therapy settings. While PD-L1 assessment has been useful as a predictive marker of treatment response
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Brachytherapy is an effective treatment for localized prostate cancer. However, radiation therapy can be associated with subsequent secondary malignancies. Chin et al., therefore, investigated the effect of radiation on clinical parameters among patients with secondary bladder cancer.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Accurate staging of bladder cancer tumors is essential for guiding treatment decisions. The gold standard for diagnosis and staging is currently biopsy following transurethral resection of bladder tumor (TURBT) and cystoscopy. MRI and CT are imaging techniques that can be used for detection and staging, but challenges in determining
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Diagnosis, staging, and accurate treatment decisions for patients with bladder cancer require invasive biopsies that are associated with a high cost and risk of complications. Non-invasive liquid biopsy tests using blood or urine offer many advantages for diagnosis and monitoring. For bladder cancer, this can include the detection of urine exfoliated tumor cells (UETCs).
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Therapeutic blockade of PD-1, a receptor on T cells that inhibits tumor suppressive activity, has been highly effective in treating many different types of cancer. Pembrolizumab is a monoclonal antibody that targets PD-1. This type of treatment is particularly valuable for patients who are ineligible for chemotherapy, including patients with muscle-invasive bladder cancer (MIBC).
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Proteins regulating m6A modification, labeled ‘writers,’ ‘readers,’ and ‘erasers,’ have been shown to interact with lncRNAs during tumor initiation and progression. However, this phenomenon is understudied in bladder cancer. A recent study by Huang et al. applied 
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Transurethral resection of bladder tumor (TURBT) is therapeutic in non-muscle invasive bladder cancer (NMIBC), but the role of repeat TURBT (reTURBT) in MIBC patients remains poorly understood. TURBT with concurrent radiotherapy and chemotherapy can contribute to bladder preservation.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Our knowledge of the role of the gut microbiome has evolved in recent years. However, less is known about the urinary microbiome. Changes in urinary microbiota have been reported in cases of urinary incontinence, pelvic pain, and bladder cancers. However, studies have produced mixed findings on whether bladder cancer
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Intravesical instillation of Bacillus Calmette-Guérin (BCG) is a standard treatment for non-muscle invasive bladder cancer (NMIBC). BCG is thought to act by activating inflammatory processes, local infiltration of immune cells, and stimulating interferon-gamma (IFNγ) secretion from lymphocytes.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Patients with muscle-invasive bladder cancer (MIBC) typically receive cisplatin-based chemotherapy prior to radical cystectomy. However, around half of MIBC patients may be ineligible for cisplatin, therefore necessitating alternative treatment modalities.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
The Urothelial Cancer – Genomic Analysis to Improve Patient Outcomes and Research (UC-GENOME) study was initiated as a collaboration between the Bladder Cancer Advocacy Network (BCAN) and academic institutions to create a clinical database and biospecimen repository that can be used for biomarker discovery.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Talazoparib is a PARP inhibitor used to treat patients with genetic alterations in BRCA1/2 or other genes. PARP inhibitors may exhibit synergy in conjunction with immune checkpoint inhibitors. The JAVELIN PARP Medley trial was initiated to define the safety and efficacy of combination treatment with avelumab
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Patients with advanced urothelial carcinoma have high progression rates following first-line platinum-based chemotherapy. Second-line treatments like immunotherapy have been approved for use in these patients. Importantly, response to treatment can be modulated by fibroblast
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Treatment for patients with intermediate- or high-risk non-muscle invasive bladder cancer (NMIBC) entails transurethral resection of bladder tumor (TURBT) followed by intravesical instillations with Bacillus Calmette-Guérin (BCG). However, many patients do not respond to BCG or experience relapse following the initial treatment.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Quality of life in patients with advanced urothelial cancer is determined mainly by disease symptoms and treatment side effects. Unfortunately, studies evaluating health-related quality of life (HRQoL) among patients with advanced urothelial carcinoma undergoing immunotherapy are lacking.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
The molecular subtyping of muscle-invasive bladder cancer (MIBC) cases in recent years provided a framework for understanding the biology of the disease. There is a knowledge gap regarding whether specific molecular subtypes are driven by genetic alterations that can impact the underlying pathology.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Node-positive bladder cancer is a transitional step in the metastatic cascade between localized and metastatic disease. Wagner et al. examined the radiographical and pathological lymph node status as an independent predictor for survival following neoadjuvant gemcitabine and cisplatin in patients
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
For patients with muscle-invasive bladder cancer (MIBC), the gold standard for treatment is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy. However, the response to neoadjuvant chemotherapy varies significantly, and additional regimens that enhance
Written by Bishoy M Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Molecular subtyping of muscle-invasive bladder cancer (MIBC) tumors has the potential to guide treatment decisions and predict outcomes. However, RNA sequencing is costly and not readily available. Artificial intelligence has made its way into various clinical procedures, and recent studies have validated the use of deep
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Tumor mutation burden (TMB) is a measure of the number of genetic mutations within a tumor. High TMB levels are associated with better patient prognosis and enhanced sensitivity to immune checkpoint inhibitors. Biologically, TMB levels are linked to increased expression of neoantigens on cancer cells, which facilitates their recognition and subsequent elimination
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Non-urothelial variants represent only a small subset of bladder cancer cases and consist of squamous cell carcinoma (SCC), adenocarcinoma, and small cell carcinoma. Interestingly, while SCC only represents 2-5% of global bladder cancer cases, it is estimated to account for up to 75% of bladder cancers in the Middle East and East Africa.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Various technical limitations exist to the tools currently used to diagnose and stage bladder cancer. Some techniques for diagnosis and staging include cystoscopy, ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Multiparametric MRI (mp-MRI) combines T2-weighted images (T2WI)
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The recommended treatment for patients with muscle-invasive bladder cancer (MIBC) is neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy. However, many patients do not respond to NAC, and extensive research is therefore being undertaken to identify biomarkers that predict response to treatment.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Bacillus Calmette-Guérin (BCG) has long been considered a standard of care in treating intermediate-risk or high-risk non-muscle invasive bladder cancer (NMIBC). For maintenance, recommendations stipulate a 1-year treatment for intermediate-risk patients and up to 3 years for high-risk patients.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Definitive treatment of muscle-invasive bladder cancer (MIBC) involves cystectomy or radiotherapy. The Bladder Cancer 2001 (BC2001) is a large bladder preservation trial comparing the efficacy of chemoradiotherapy with 5-fluorouracil (5FU) and mitomycin C (MMC) to radiotherapy alone.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Patients with intermediate-risk non-muscle invasive bladder cancer (NMIBC) frequently require adjuvant therapy. The HIVEC-II study is a multi-center randomized controlled trial (RCT) that compared clinical outcomes of intermediate-risk NMIBC patients receiving hyperthermia and mitomycin C versus mitomycin C alone.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Despite initial responses, a significant limitation of immunotherapy is the development of resistance that is thought to be related to immune exhaustion, suppression of T-cell activity, and loss of neoantigens. Previous studies detected high expression of E2F and EZH2 in a subset of patients
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Treatment for high-risk non-muscle invasive bladder cancer (NMIBC) typically includes intravesical administration of bacillus Calmette-Guérin (BCG) as a form of immunotherapy. BCG is thought to activate both innate and adaptive immune responses with anti-tumor effects.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
After transurethral bladder tumor resection (TURBT), recurrence of non-muscle-invasive bladder cancer (NMIBC) is common. Recently, Heer at al. performed an open-label, parallel-group randomized trial conducted in 22 National Health Service hospitals in the United Kingdom.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The administration of bacillus Calmette-Guérin (BCG) as an adjuvant is recommended in the context of high-risk non-muscle invasive bladder cancer (NMIBC) after complete transurethral resection of bladder tumor (TURBT). However, there have been production shortages of BCG.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Combining real-world data and electronic health records for biomarker discovery can inform future clinical trial designs. This is important given that most randomized controlled trials do not always investigate clinical biomarkers along with the tested drug. A recent study by Szabados et al.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
DNA methylation is known to be altered in many cancers, including bladder cancer, and has therefore been a promising alternative for surveillance in patients with non-muscle invasive bladder cancer (NMIBC). The Bladder EpiCheck test has been validated for detecting bladder cancer by
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
There is a well-documented increase in the risk of cancer development after a kidney transplant. For example, Lim et al. recently published a whole-exome sequencing analysis of somatic mutations in patients who underwent kidney transplants and subsequently developed urothelial carcinoma.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
The two most prevailing models of metastatic progression are the linear and parallel models. The linear model predicts genetic and epigenetic alterations and tumor fitness. Once a founder cell gains a metastatic phenotype, the invasion-metastasis cascade begins. On the other hand, the parallel model suggests
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Cisplatin is frequently used in neoadjuvant, adjuvant, and systemic therapy for advanced bladder cancer. A recent study by Fu et al. characterized the effects of cisplatin on cGAS-STING activation in bladder cancer. Cisplatin treatment of the T24 bladder cancer cell lines followed by RNA sequencing showed downstream
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
The immune checkpoint inhibitor (ICI) pembrolizumab is approved for the treatment of solid tumors with a high tumor mutational burden (TMB-high ≥ 10 variants/Mb). However, measurements of TMB as a biomarker for ICI response are mainly based on studies in European populations.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Patients with non-muscle invasive bladder cancer are typically followed up with a combination of cystoscopy and urinary cytology examinations. However, these methods may be insufficient due to inconsistencies and low sensitivity rates, particularly for lower grade lesions or detecting atypical urothelial cells
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Chemotherapy can alter the antitumor immune response, which is a critical target of immune checkpoint inhibitor treatment, van Wilpe et al. aimed to characterize changes in lymphocytes in patients treated with cisplatin-based chemotherapy. The study consisted of 81 muscle-invasive bladder cancer patients who
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Predicting response to adjuvant therapy in patients with bladder cancer has the potential to prevent needless toxicity and optimize efficacy. In recent years, transcriptomic studies of bladder cancer tissues have identified molecular subtypes that exhibit differential responses to different
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Cell-cell communication in the tumor microenvironment is known to drive oncogenesis and is mediated by ligand-receptor interactions. Wang et al., therefore, aimed to investigate a network of ligand-receptor pairs to identify whether different associations could predict
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Immune checkpoint inhibitors are increasingly used to treat patients with advanced urothelial carcinoma. Clinical factors, such as metastasis sites and albumin levels, are associated with prognosis after immune checkpoint inhibitor treatment.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
The optimal pairings of regimens across first- and second-line therapy regimens for patients with advanced urothelial carcinoma are unknown. Miron et al. sought to determine the effects of different combinations of first-line platinum-based chemotherapy and 
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
The use of cisplatin-based neoadjuvant chemotherapy has been shown to improve survival in muscle-invasive bladder cancer patients undergoing radical cystectomy. Benidir et al. aimed to investigate differences in pathologic and survival outcomes
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
The loss of the chromosomal region 9p21.3 is a common genetic event in patients with urothelial cancer and is typically associated with poor clinical outcomes. In addition to CDKN2A, CDKN2B genes, this locus also harbors the metabolic gene MTAP (Methylthioadenosine phosphorylase), which encodes
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Micropapillary bladder cancer is a rare and aggressive variant of bladder cancer. Extensive research has focused on molecular subtyping of bladder cancer as a predictor of prognosis and response to treatment. Luminal tumors have been associated with better patient prognosis
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Up to 30% of bladder cancers harbor genetic alterations in the fibroblast growth factor receptor 3 (FGFR3) gene. The FGFR3 erdafitinib was approved by the FDA in 2019 to treat advanced bladder cancers harboring activating FGFR3 alterations. Nevertheless, the median progression-free survival is 3.7- 5.5 months
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
In recent years, the molecular subtyping of muscle-invasive bladder cancer using gene expression patterns has been a major area of research. This has allowed the categorization of cells into luminal or basal major subtypes and several classification schemes. However, several factors limit the widespread
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
The RANGE trial enrolled platinum-refractory urothelial cancer patients who were randomized to receive either the angiogenesis inhibitor ramucirumab and docetaxel or placebo and docetaxel. A recent study by van der Heijden et al. sought to identify predictive biomarkers for determining response to treatment with ramucirumab.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
The stromal antigen 2 protein is 1231-amino-acid protein cohesin subunit A2 encoded by the STAG2 gene on the X chromosome. This protein plays a critical role in chromatid separation. The deficiency of STAG2 due to truncating somatic mutations has been described as an early event in urothelial carcinogenesis.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Treatment options for bladder cancer are expanding but finite. Identifying novel potential therapeutic agents for patients with bladder cancer is a key research priority. In a recent study, Ertl et al. recently performed a drug screening study to examine the effects of novel and repurposed compounds on bladder cancer cell lines.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Systemic chemotherapy is the mainstay of treatment of metastatic bladder cancer. In a recent study, Fischer-Valuck et al. examined the role of local radiation therapy to the primary tumor in patients with metastatic bladder cancer treated with chemotherapy.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
AT-rich interactive domain-containing protein 1A Arid1a, also known as Baf250a, is the largest subunit of the SWI/SNF or BAF chromatin remodeling ATPase complex. Somatic mutations in ARID1A are common in patients with urothelial bladder carcinomas.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Single-cell RNA sequencing is advancing our understanding of the contributions of different cells in the tumor microenvironment to clinical phenotypes. A recent report by Luo et al. used single-cell RNA-sequencing to characterize the molecular and cellular differences between bladder cancer and Cystitis glandularis (CG)
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Primary bladder malignancy accounts for up to 95% of urothelial carcinomas (UC), and upper tract urothelial carcinoma (UTUC) accounts for the rest of UC cases. Radical cystectomy (RC) is the typical treatment for aggressive UC, while radical nephroureterectomy (RNU) is the treatment of choice for aggressive UTUC.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Smoking is a major modifiable risk factor for bladder cancer. N-acetyltransferase-2 (NAT2) is a gene that encodes an enzyme that detoxifies carcinogens, such as those found in tobacco smoke. To provide insights for personalized prevention of smoking among individuals with vulnerable genotypes
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Risk factors associated with bladder cancer, such as smoking, age, and BMI, can alter metabolic profiles and can be evaluated in patients through metabolomic analysis. Recently, Jacyna et al. collected urine from ten patients (eight men and two women) with non-muscle-invasive bladder cancer at three different time points:
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
The standard-of-care first-line systemic therapy for metastatic urothelial cancer (mUC) remains platinum-based chemotherapy. Post-platinum options included immune checkpoint inhibitors, fibroblast growth factor receptor (FGFR) inhibitors
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
The role of adjuvant therapy in muscle-invasive urothelial carcinoma is unclear, despite the high risk of metastatic recurrence. Adjuvant cisplatin-based chemotherapy is challenging to administer, and some patients are ineligible for or decline neoadjuvant cisplatin-based chemotherapy.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Incorporating neoadjuvant chemotherapy (NAC) into the management of patients with localized muscle-invasive bladder cancer (MIBC) improves survival. However, due to multiple factors, NAC is still not effectively used in real-life settings.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Muscle-invasive bladder cancer (MIBC) is associated with a high risk of developing pelvic recurrence. Although adjuvant external beam radiotherapy (EBRT) decreases the risk of local recurrence, it has been associated with severe toxicity.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
CD19-directed chimeric antigen receptor (CAR) T cells are now used to treat B-cell malignancies. Extending their use to solid tumors requires optimizing the interactions between CAR-T cells and specific cancer cell types. A recent study by Grunewald et al. examined the role of DNA methyltransferases
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Squamous cell carcinoma of the urinary bladder associated with non-schistosomiasis (NSR-SCCUB) is an uncommon tumor subtype distinct from urothelial carcinoma (UC). NSR-SCCUB type is slightly more prevalent in men and is associated with chronic bladder irritation
Written by Niyati Lobo, FRCS (Urol) & Ashish Kamat, MD
Non-muscle invasive bladder cancer (NMIBC) represents a heterogeneous group of patients with varying risks of recurrence and progression. Accurate risk stratification of patients is therefore crucial in establishing treatment recommendations.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Tumor cells frequently rewire their metabolism to satisfy increased demands for cellular building blocks. The relative abundance of pyruvate kinase M1 (PKM1) versus PKM2 mediated by alternative splicing of the Pkm gene has been implicated in the shift between oxidative
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Non-muscle invasive bladder cancer (NMIBC) has one of the highest local recurrence rates of any malignancy. The current standards of care for NMIBC surveillance are white light cystoscopy and urine cytology.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
An effective anti-tumor immune response requires presentation of neoantigens in the context of class I major histocompatibility complex (MHC) molecules and the cytotoxic T lymphocytes. Several computational tools are available
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Potentially actionable genomic alterations are common in advanced urothelial cancers (aUC). However, it is unclear if personalized treatment strategies based on each patient’s genomic profile will be effective in the clinic.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm in muscle-invasive bladder cancer (MIBC). However, not all patients have consistent responses to these agents, and predictive biomarkers are still needed.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Immune checkpoint inhibitors, FGFR3 inhibitors, and antibody drug-conjugates are recent additions to the armamentarium of agents used to treat advanced urothelial cancer (UC). However, cisplatin-based therapy remains a standard front-line treatment
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
RAF kinases are critical proteins in the MAPK cascade, essential for cancer cell processes such as proliferation and migration. RAF1 functions as an obligate homodimer or heterodimer with BRAF. The role of RAF1 amplifications as drivers or therapeutic targets in bladder cancer is unclear.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Cisplatin-based chemotherapy is the standard-of-care neoadjuvant treatment for patients with muscle-invasive bladder cancer (MIBC). Taxanes were evaluated previously combined with cisplatin in the neoadjuvant setting. However, it is unclear if cabazitaxel, a novel taxane, synergizes with cisplatin.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Neoadjuvant cisplatin-based chemotherapy in patients with muscle-invasive bladder cancer (MIBC) before radical cystectomy improves overall survival. Commonly used neoadjuvant chemotherapy regimens include the combination of dose-dense methotrexate
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Platinum-based chemotherapy is the cornerstone of initial treatment for most patients with advanced urothelial cancer (UC). EGFR is a promising target given its high expression levels in UC and the availability of anti-EGFRs inhibitors.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Platinum-based chemotherapy remains the cornerstone for the first-line treatment of platinum-eligible patients with advanced urothelial cancer. Chemotherapy combinations with other agents did not improve survival in the front-line setting.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Treatment options for patients with urothelial cancer (UC) after first-line chemotherapy are limited. It is unclear if targeting DNA damage repair using Poly (ADP-ribose) polymerase (PARP) inhibitors will result in meaningful single-agent activity in this patient population.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Patients who received prior pelvic radiation (XRT) for prostate cancer are at higher risk of developing secondary bladder cancers (SBCs). It was thought that radiation-induced SBCs would lead to a more aggressive phenotype and worse clinical outcomes than primary bladder cancers.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Immune checkpoint blockade (ICB) is associated with durable responses in a select group of patients with advanced cancer achieving. However, attempts to define biomarkers to identify this subgroup of exceptional responders have been elusive. Pan-tumor predictive biomarkers to PD-L1 blockade are lacking.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Non-muscle-invasive bladder cancers (NMIBC) represent a heterogeneous group of tumors with variable clinical outcomes. Multiple risk features are incorporated in predicting the risk of recurrence and progression to muscle-invasive bladder cancer (MIBC).
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Early-phase clinical trials are a treatment option for patients with metastatic bladder cancer (mBC). However, Patients enrolled in these trials have already been exposed to toxicity from prior therapies and developed a poor performance status making it challenging to identify patients who are likely to benefit.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Radiation therapy is commonly used for the definitive and palliative treatment of pelvic malignancies. Secondary pelvic cancers have been reported after radiation therapy, including radiation-associated muscle-invasive bladder cancer (RA-MIBC).
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
A subset of patients with advanced urothelial cancer (aUC) achieves durable responses to immune checkpoint blockade (ICB), but the development of reliable biomarkers to identify these patients has proven challenging.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Radiation therapy is a cornerstone of bladder-sparing treatment regimens for patients with muscle-invasive bladder cancer (MIBC). However, a significant number of MIBCs are radioresistant. Components of tumor immune microenvironment (TIME)
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Imaging-based biomarker research is gaining momentum in oncology due to its non-invasive nature and the potential for monitoring tumor dynamics during treatment. The currently available biomarkers for immune checkpoint inhibitors (ICIs), such as programmed cell death ligand 1 (PD-L1) expression
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Two key methods to preserve tumor tissues in biobanks are broadly adopted: formalin-fixation and paraffin-embedding (FFPE) and optimal cutting-temperature compound (OCT)- embedding and subsequent freezing, of the tissue specimens. Multiple proteins can be quantified simultaneously from the same sample using mass spectrometry (MS).
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Non-muscle invasive bladder cancers (NMIBC) constitute the majority of bladder cancer diagnoses. NMIBCs are stratified based on the risk of progression to muscle-invasive disease into low, intermediate, and high-risk groups.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Primary adenocarcinoma of the bladder is a rare tumor. It is common in the sixth and seventh decades of life and usually has aggressive behavior. Advanced presentation with or without lymph node metastases is common at the time of diagnosis.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Non-urothelial histologic variants of bladder cancer (non-UC), including adenocarcinoma, squamous cell carcinoma (SCC), and neuroendocrine (NE) tumors, are rare, aggressive cancers. The genomic landscape of these tumors is heterogeneous, making a tailored therapy approach challenging.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Copy number variations (CNV) are key molecular events in the development of bladder cancer and have a prognostic value. Several studies characterized the CNVs in the genomic DNA from primary bladder tumors. However, little is known about how the CNV profiles of primary tumors compare to serum and lymph node (LN) metastasis.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The molecular classification of muscle-invasive urothelial cancer (UC) using RNA sequencing (RNAseq) data has confirmed the existence of distinct intrinsic subtypes that vary in their prognosis and response to therapy. The molecular classifier BASE47 (Bladder cancer Analysis of Subtype by gene Expression) uses RNAseq
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Pembrolizumab is approved to treat patients with BCG unresponsive, high-risk, non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy based on the results of the KEYNOTE-057 trial.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Gene expression profiling has successfully classified muscle-invasive bladder cancer (MIBC) tumors into distinct categories that differ in their genetic characteristics and tumor mutation burden (TMB). In addition to cancer-cell autonomous factors,
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Small cell carcinoma of the bladder (SCCB) is a rare, aggressive non-urothelial histologic variant of bladder cancer. Large-scale clinical data evaluating the various management approaches and outcomes are limited.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Recent trials investigated the efficacy of immune checkpoint inhibitors (ICIs) in the neoadjuvant setting for cisplatin-ineligible patients. A recent single-arm trial of atezolizumab (two cycles) in cisplatin-ineligible patients showed a pathologic complete response (pCR) rate of 31%.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
A few bladder-sparing treatment options are available for BCG-unresponsive patients, including valrubicin and the recently FDA-approved pembrolizumab. However, additional treatment options that achieve a durable response are needed.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The COVID-19 pandemic has led to significant changes in the healthcare system. Although it is expected that the diagnosis of cancer care may be delayed, the exact impact on the referral pattern of patients with urologic malignancies is unknown.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Bladder cancers (BC) are among tumor types with a high mutation load. Somatic mutations can encode mutant peptides that can be recognized by T-cells as neoantigens triggering an anti-tumor immune response. T cells can identify mutant epitopes when presented by human
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Rhabdomyosarcoma (RMS) is a soft tissue tumor that commonly occurs in childhood and adolescence. It is less prevalent in adulthood, accounting for 2%–5% of adult soft tissue tumors. RMS has a higher propensity to occur in genitourinary organs in adults than in pediatric patients.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Cisplatin-based chemotherapy is the preferred first-line for patients with metastatic urothelial cancer if they are cisplatin eligible. However, a significant proportion of these patients already receive cisplatin-based chemotherapy in the perioperative setting
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Understanding the biological characteristics that determine clinical outcomes of T1 bladder cancers can guide clinicians in making optimal therapeutic decisions. A recent study published by Robertson et al. in European Urology subcategorized the T1
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The link between the urinary microbiome and bladder carcinogenesis is not well understood. A recent study published by Chipollini et al. in Urologic Oncology profiled the microbial communities in the urine of bladder cancer patients and non-cancer participants.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Bladder cancer affects 550,000 new cases every year. Understanding the gender-specific incidence and mortality patterns and trends of bladder cancer is critical for reducing the global impact of this disease.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Urothelial carcinoma (UC) is the most common histology of bladder cancer. Histological variants (HV) of bladder cancer are less common but frequently more aggressive. A recent paper published by Takemoto et al.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Understanding the concordance rates for different biomarkers assays is critical for assessing their performance. A new study published by Brown et al. in Clinical Genitourinary Cancer evaluated
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Squamous cell carcinoma (SCC) is the second most common histologic variant of bladder cancer. These tumors have pure squamous histology in the absence of any in situ urothelial
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Treatment of patients with non-muscle invasive bladder cancer (NMIBC) who are unable to receive intravesical with Bacillus Calmette Guerin (BCG) remains a challenge.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
There is a need for an accurate tool that predicts the recurrence and progression of non-muscle-invasive bladder cancer (NMIBC). A recent study published by Hayashi et al.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Micropapillary urothelial carcinoma (MPUC) is a rare and aggressive histological variant of urinary bladder cancer. A recent study published by Jin et al. in Cancer Medicine investigated
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The luminal-basal continuum of intrinsic messenger RNA (mRNA) expression-based subtypes is an important framework for understanding the biology of urothelial cancer. Differentiating between the two main molecular subtypes of bladder cancer
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
There is a need for accurate nomograms for predicting oncological outcomes in intermediate-risk non–muscle-invasive bladder cancer (NMIBC) patients. Such accurate tools can be used to guide decision
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Treating patients who received immune checkpoint inhibition (ICI) and experienced treatment-related toxicities, remains complicated due to the high risk of Immune-relate adverse events (
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Some histologic variants of urothelial cancer (UC) are associated with an aggressive clinical course. Understanding whether these variants respond differently to immune checkpoint inhibitors
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
An important study published by Sweis et al. in Cancer Immunology Research investigated the molecular mechanisms that contribute to the lack of immunotherapy efficacy in non-T cell-inflamed bladder cancer.
Written by Bishoy M. Falas, MD
Englander Institute for Precision Medicine
Early identification of bladder cancer (BC) is critical for improving clinical outcomes. Developing urine-based molecular biomarkers is an area of active research.
Written by Bishoy Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Mutations in mismatch repair (MMR) genes result in changes in the expression of MMR proteins that can be detected by immunohistochemistry and high microsatellite instability (MSI).
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The effect of restaging transurethral resection (Re-TUR) timing after initial transurethral resection of bladder tumor (TURBT) on survival rates is not well studied.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Urothelial carcinoma variants are rare and some are associated with poor clinical outcomes. The small-cell variant comprises less than 1% of all bladder cancers. These cancers are more aggressive
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
There is a need for a non-invasive for early detection of bladder cancer (BC). Telomerase reverse transcriptase (TERT) promoter mutations are common in bladder cancer patients. A recent study by Hosen
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Radical cystectomy continues to be the mainstay curative modality for bladder cancer patients. Understanding the long-term clinical outcomes of robotic and open radical cystectomy is critical for decision making.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The micropapillary and plasmacytoid variants are rare and aggressive urothelial carcinoma (UC) subtypes. The morphological features of these variants in urine cytology are not well described. A recent
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Effective intravesical postoperative chemotherapy can reduce the risk of bladder cancer recurrence. A recent study by Fukuokaya et al. published in Clinical Genitourinary Cancer examined
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The relationship between the baseline quality of life (QOL) and clinical outcomes for urothelial cancer (UC) patients is not well defined. A recent study published by Suppanuntaroek et al.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The optimal management of non-muscle invasive bladder cancer (NMIBC), some histologic variants, including squamous and glandular, is challenging. A recent article published by Suh et al. in Scientific Reports compared Bacillus Calmette-Guérin
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Understanding the demographic factors which affect clinical outcomes following radical cystectomy (RC) is critical for improving oncologic outcomes for all patients. A recent study published in European Urology Oncology examined intraoperative
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Sarcomatoid urothelial bladder cancer (SARC) is an aggressive histological variant of bladder cancer. It is associated with early distant metastasis and poor survival rates. Understanding the molecular characteristics of SARC
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Non-muscle invasive bladder cancer (NMIBC) has a high recurrence rate. Understanding the risk factors for recurrence is essential. The Urokinase Plasminogen Activator (uPA)
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The American Urological Association (AUA) recommends that non-muscle invasive bladder cancer (NMIBC) patients with persistent or recurrent Ta or CIS should receive a second induction course of Bacillus Calmette-Guerin
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Treatment options available for intermediate or high-risk non-muscle invasive bladder cancer include intravesical Bacillus Calmette-Guerin (BCG) and radical cystectomy.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Point mutations in telomerase reverse transcriptase (TERT) promotor are reported in invasive and noninvasive, primary and recurrent urothelial bladder cancer (UBC). A deeper understanding of the clinical correlates
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The relationship between the expression of GATA3, cytokeratin (CK) 20, CK 5/6, and p53 and survival in patients with muscle-invasive bladder cancer (MIBC) is not well characterized.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Several randomized clinical trials (RCTs) have incorporated patient-reported outcomes (PRO) to evaluate the effectiveness of new treatment modalities. Adhering to systematic and consistent
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Urine cytology plays an essential role in detecting patients who are at high risk for disease recurrence following non-muscle invasive bladder cancer (NMIBC) treatment. A recent study Gupta
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Urine cytology plays a critical role as a noninvasive tool in bladder cancer detection and surveillance. However, a substantial fraction of cytology tests is classified as atypical or indeterminate. A need for a minimally-invasive
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Radiotherapy has the potential to sensitize tumors to immune checkpoint blockade. A recent article published by Sundahl et al. in European Urology assessed
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Enfortumab Vedotin (EV) is a novel antibody-drug conjugate targeting Nectin-4, which is overexpressed in urothelial cancer. A recent study published by Takahashi et al. in Investigational New Drugs
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Bacillus Calmette-Guerin shortage is a critical access issue for patients with non-muscle-invasive bladder cancer (NMIBC). Defining the efficacy of alternative intravesical treatments is an active area of investigation.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Understanding differences in bladder cancer outcomes between men and women can help physicians tailor optimal treatment and follow-up strategies. A recent paper published by Richters et al. in Urologic Oncology: Seminars and Original Investigations studied
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Patients with muscle-invasive and high-risk non-muscle invasive urothelial carcinoma of bladder who undergo radical cystectomy (RC) and lymphadenectomy are closely monitored for recurrence. The risk of disease recurrence is highest during the first 
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The oncogene addiction model occurs when cancer cells become dependent on one mutated oncogene or pathway for the maintenance of a malignant phenotype. Withdrawal of the oncogenic signal
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Carcinoma in situ (CIS) is a distinct pathological entity. The significance of histological variants associated with CIS is not well-understood. A recent paper published by Sangoi et al. in The American Journal of Surgical Pathology
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Non-muscle invasive bladder cancers (NMIBC) represent the majority of new bladder cancer diagnoses. A high recurrence rate characterizes the natural history of the disease. Understanding the risk factors for recurrence
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The use of circulating tumor DNA (ctDNA) as an early detection tool is a promising development. However, the clinical utility of ctDNA in urothelial bladder cancer is not fully understood.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
There is a broad spectrum of bladder cancer responsiveness to treatment in the clinic. The development of practical methods to provide accurate, individualized drug sensitivity information
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Detecting muscle-invasion is a critical step that dictates treatment recommendations. A definitive assessment of muscularis propria (MP) invasion cannot be made in a small number of transurethral resections of bladder tumor
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
High-resolution micro-ultrasound is a promising technology in the staging of prostate cancer but has not been well studied in bladder cancer patients. A recent paper published by Saita et al. European Urology evaluated the
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Defining the genomic landscapes that characterize the different disease states of urothelial carcinoma is an important area of investigation. A recent study by Nassar et al. recently published in Clinical Cancer
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
There is not enough data on the prognostic value of sarcopenia and nutritional indices in bladder cancer patients who receive definitive radiotherapy. A recent paper by Stangl-Kremser et al. in Urologic Oncology studied
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
A recent study published by Guo et al. in BMC Systems Biology investigated the relationship between AURKA expression, clinicopathologic characteristics and overall survival in patients with bladder cancer using sequential gene expression profiling.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Micropapillary (MP) is a histological variant of bladder cancer. As with most other histological variants of bladder cancer, the available data is derived from small case series and treatment is based on expert opinion.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Bladder cancer is a ‘field’ disease in which early-events occurring in morphologically-normal urothelium eventually give rise to urothelial carcinoma.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Chromosomal damage, breakage, loss, and rearrangement are early events in cancer initiations.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Frequent long-term monitoring is required for non-muscle-invasive bladder cancer (NMIBC) patients due to the high rate of recurrence.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Bladder cancer takes an enormous physical, emotional and economic toll on patients.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Primary carcinoma in situ (P-CIS) of the bladder is rare. Adjuvant intravesical Bacillus Calmette-Guérin (BCG) immunotherapy has been reported to be effective in reducing recurrence rates in CIS and P-CIS patients 
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Although hematuria is the most common symptoms of bladder cancer (BC), it can be caused by many non-malignant conditions.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Radical cystectomy (RC) is currently the gold standard operative treatment for localized (T2-T4a) muscle-invasive bladder cancer (MIBC) or recurrent high-risk non-MIBC.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
To achieve progress against Urinary bladder cancer (UBC), studies are needed to understand to understand the racial differences in the incidence, presentation, outcomes, and biology of UBC.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Due to the very high risk of recurrence, bladder cancer patients require periodic screening and monitoring.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Non-muscle-invasive bladder cancer (NMIBC) has a high recurrence rate. Although the BCG therapy is recommended as an immune targeting treatment in high-risk NMIBC tumors, 
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Currently, intermediate or high-risk non-muscle-invasive bladder cancer patients (NMIBC) require intensive follow-up.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Neoadjuvant chemotherapy is a standard of care for patients with cisplatin-eligible muscle-invasive urothelial carcinoma.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Bladder preservation therapy is a definitive treatment option for clinically localized bladder cancer.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Clinically-localized bladder cancer is amenable to local treatments because of its accessibility.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Patients with advanced platinum-resistant urothelial carcinoma have limited therapeutic options.
Conference Coverage
Conference Highlights Written by Physician-Scientist
Presented by Andrea Necchi, MD, Peter Black, MD, Jørgen Bjerggaard Jensen, MD, DMSc
The 2024 European Association of Urology (EAU) annual congress held in Paris, France between April 5th and 8th was host to a plenary session addressing imaging-related controversies for the staging of genitourinary cancers. Professors Andrea Necchi, Peter Black, and Jørgen Bjerggaard participated in a rapid-fire debate discussing whether we can use circulating tumor DNA (ctDNA) and/or urine tumor DNA (utDNA) in patients with muscle-invasive bladder cancer (MIBC) following radical cystectomy to guide treatment decision on adjuvant therapy.
Presented by Paolo Gontero, MD, Benjamin Pradere, MD, MSc, Ashish M. Kamat, MD, MBBS
The 2024 European Association of Urology (EAU) annual congress held in Paris, France was host to a plenary session addressing imaging-related controversies for the staging of genitourinary cancers. Professors Paolo Gontero, Benjamin Pradere, and Ashish Kamat participated in a rapid-fire debate discussing the optimal management of a healthy patient with T1HG micropapillary non-muscle invasive bladder cancer (NMIBC).
Presented by Marek Babjuk, MD, PhD, Kenneth Chen, MBBS, MCI, MRCS (Edin), FRCS (Glasg), FAMS, Philippe E. Spiess, MD
The 2024 European Association of Urology (EAU) annual congress held in Paris, France between April 5th and 8th was host to a plenary session addressing imaging-related controversies for the staging of genitourinary cancers. Drs. Babjuk, Chen, and Speiss participated in a rapid-fire debate discussing how to manage a patient with frequent recurrences of low-grade papillary tumors in the bladder, despite intravesical chemotherapy and BCG therapy.
Presented by Joan Palou MD, PhD, Eva Comperat, MD, PhD, Tahlita Zuiverloon, MD, PhD
The 2024 European Association of Urology (EAU) annual congress held in Paris, France between April 5th and 8th was host to a plenary session addressing imaging-related controversies for the staging of genitourinary cancers. Drs. Joan Palou, Eva Comperat, and Tahlita Zuiverloon participated in a rapid-fire debate that addressed whether there was a role for urinary markers, other than cytology, for the surveillance of patients in the era of modern cystoscopy.
Presented by Valeria Panebianco, MD
The 2024 European Association of Urology (EAU) annual congress held in Paris, France between April 5th and 8th was host to a plenary session addressing imaging-related controversies for the staging of genitourinary cancers. Professor Valeria Panebianco discussed the Vesical Imaging-Reporting and Data System (VI-RADS) and its potential to replace/complement transurethral resection of bladder tumor (TURBT) for diagnosing bladder cancer.
Presented by Joshua J Meeks, MD, PhD
The 2024 GU ASCO annual meeting featured a session on the shortage of drugs for urothelial carcinoma and a presentation by Dr. Josh Meeks discussing what is on the horizon to replace BCG.  Dr. Meeks then discussed the BCG shortage timeline and production challenges. This started in 2012 with the FDA temporarily stopping the Sanofi Pasteur factory due to manufacturing and sterility issues. 
Presented by Andrea Necchi, MD
During the 2023 ESMO annual meeting, Dr. Andrea Necchi presented the study framework for SunRISe-3, a phase 3 randomized trial of TAR-200 plus cetrelimab or TAR-200 monotherapy versus intravesical BCG in patients with BCG-naïve, high-risk, non-muscle invasive bladder cancer (NMIBC).
Presented by Massimo Lazzeri, MD
The 2023 GU ASCO annual meeting included a trials in progress session for bladder cancer, featuring a presentation by Dr. Massimo Lazzeri discussing the trial design of a randomized phase III clinical trial of neoadjuvant intravesical mitomycin C treatment in patients with primary treatment naïve non-muscle invasive bladder cancer (NMIBC).
Presented by Christine E. Lentowski, MS, MBS
The 2022 Society of Urologic Oncology annual meeting featured a session on bladder cancer, including a presentation by Christine Lentowski discussing the trial design of a phase 3 single-arm study of UGN-102 as primary chemoablative therapy in patients with low grade intermediate risk non-muscle invasive bladder cancer.
Presented by Yair Lotan, MD
A series of talks were given on the regulations surrounding clinical and genomic data sharing in an attempt to establish a tissue biobank shepherded by the IBCN. This was capped off by Dr. Lotan’s discussion of the concept of the IBCN biobank.
Presented by Seth Paul Lerner, MD, FACS
A series of talks were given on the regulations surrounding clinical and genomic data sharing in an attempt to establish a tissue biobank shepherded by the IBCN. Dr. Lerner was tasked with providing some lessons learned from a very successful TCGA effort. The Cancer Genome Atlas (TCGA) project was a joint effort between the National Cancer Institute and National Human Genome Research Institute that characterized over 20,000 primary cancer and matched normal samples in 33 cancer types.
Presented by Zesheng An, MD, PhD, MS
Dr. Zesheng An presented results from the TRUCE-02 study (NCT04730232) testing the combination of chemotherapy (nab-paclitaxel) with the anti-PD-1 antibody tislelizumab in HR-NMIBC.
Presented by Karim Chamie, MD
It has been hypothesized that the IL-15 superagonist N-803 could boost the immune response to BCG, thus augmenting patient responses to BCG therapy and limit the need for cystectomy in this disease context. Dr. Chamie presented results from the QUILT 3032 phase 2/3 study using the IL-15 superagonist N-803 in combination with BCG in previously BCG-unresponsive bladder cancer.
Presented by Karandeep Guleria, MD, MS
The 2022 American Urological Association (AUA) Annual Meeting included a session on non-invasive bladder cancer and a presentation by Dr. Karandeep Guleria discussing a randomized study assessing intravesical chemohyperthermia with Mitomycin C versus intravesical BCG for intermediate and high risk non-muscle invasive bladder cancer (NMIBC).
Presented by Michael A. O’Donnell, MD
The 2022 American Urological Association (AUA) Annual Meeting included a session on the epidemiology and evaluation of bladder cancer and a presentation by Dr. Michael O’Donnell discussing long-term follow-up of intravesical gemcitabine and docetaxel as rescue therapy for non-muscle invasive bladder cancer (NMIBC). 
The 2022 American Urological Association (AUA) Annual Meeting included a plenary session and a debate regarding cystectomy, systemic immunotherapy, or intravesical chemotherapy for patients with BCG refractory non-muscle invasive bladder cancer (NMIBC) moderated by Dr. Tracy Downs and panelists Dr. Seth Lerner and Dr. James McKiernan.
Presented by Karim Chamie, MD
In a podium presentation at the 2022 American Urologic Association Annual Meeting held in New Orleans and virtually, Dr. Chamie presented the results of N-803 in combination with BCG in patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC).
Presented by Hiroko Miyagi, MD
The 2022 Southeastern Section of the AUA’s annual meeting included a bladder cancer session and Dr. Hiroko Miyagi discussing preliminary results of a single arm phase II trial of intraoperative intravesical mitomycin C during nephroureterectomy for urothelial carcinoma.
Presented by Angela B. Smith, MD, MS
The 2022 Southeastern Section of the AUA’s annual meeting included a bladder cancer session and Dr. Angela Smith discussing results of OPTIMA II, a phase 2b, open-label, single arm trial assessing primary chemoablation of low-grade intermediate risk non-muscle invasive bladder cancer (NMIBC) using UGN-102. 
Presented by Bishoy Morris Faltas, MD
In this presentation, Dr. Bishoy Faltas offered his perspective on how to navigate sequencing results from patients in the clinic. He first laid out several concepts that are important to understand about genomic sequencing tests.
Presented by Sam S. Chang, MD, MBA
(UroToday.com) The 2022 GU ASCO Annual meeting included a presentation by Dr. Sam Chang and colleagues reporting results of a phase 3 trial assessing IL-15RαFc superagonist N-803 (Anktiva) and BCG for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC).
Presented by Jason Efstathiou, MD, DPhil
The 2021 ASTRO Annual Meeting included a presentation by Dr. Jason Efstathiou discussing results of the NRG Oncology/RTOG 0926 trial. This trial assessed selective bladder preserving treatment by radiation therapy concurrent with radiosensitizing chemotherapy following a thorough restaging TURBT.
Presented by James McKiernan, MD
The 2021 AUA annual meeting included a guideline amendment update for non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) provided by Dr. James McKiernan.
Presented by Michiel S. Van Der Heijden, PhD, Seth Lerner, MD, FACS, and Thomas Powles, MD, MBBS, MRCP
In this rapid-fire debate, the focus is on the management of retroperitoneal lymphadenopathy that has a partial response to platinum-based chemotherapy. Dr. Seth Lerner argues for surgical consolidation, while Dr. Thomas Powles argues for systemic therapy.
Presented by Joan Palou, MD, and J. Alfred Witjes, MD, Ph.D
In this rapid fire debate, the focus is on the management of HG T1 bladder cancer with concurrent CIS. Dr. Palou argues for intravesical therapy while Dr. Witjes argues for upfront radical cystectomy.
Presented by Peter Black, MD, and Hugh Mostafid, FRCS (Urol), FEBU, and Jens Bedke, MD
In this rapid-fire debate, Dr. Peter Black reintroduces the classic debate of ileal conduit or content diversion in an unselected patients with normal kidney function. Dr. Hugh Mostafid of the United Kingdom argues for ileal conduit, while Dr. Jens Bedke of Germany argues for continent diversion.
Presented by Anne K. Schuckman, MD
The optimizing personalized management of non-muscle-invasive bladder cancer session at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) included a presentation from Dr. Anne Schuckman discussing which patients with high-risk non-muscle-invasive bladder cancer may benefit from radical cystectomy.
Presented by Sima Porten, MD, MPH
The plenary session of the last day of the 2020 Annual Meeting of the Society of Urologic Oncology (SUO) began with a panel discussion stepping through the case of a patient with non-muscle invasive bladder cancer. Dr. Sima Porten, the moderator, introduced the case: a 60-year-old otherwise healthy male
Presented by Max Kates, MD

There have been several recent single-arm trials in the Bacillus Calmette-Guerin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) setting. The first question that arises is whether these single-arm trials are enough or do we need to randomize patients for our future trials.

Presented by Ashish M. Kamat, MD, MBBS
The Society of Urologic Oncology (SUO) 2020 virtual meeting featured a session examining the new and emerging agents in bladder cancer chaired by Dr. Neal Shore, which included a presentation by Dr. Ashish Kamat discussing the evolving role of checkpoint inhibition in nonmuscle-invasive bladder cancer (NMIBC).
Presented by Peter Black, MD, FACS, FRCSC
In an oral presentation in the Refining the Treatment of Bladder Cancer session at the 12th European Multidisciplinary Congress on Urological Cancers (EMUC), Dr. Peter Black examined the question of whether molecular subtyping of bladder cancer is useful.
Presented by J. Alfred Witjes, MD, PhD
J. Alfred Witjes, MD, PhD, began his talk explaining that he believes cystoscopy is still needed in the primary diagnosis of bladder tumors. Cystoscopy gives important information regarding multiplicity, size, stage, the grade of bladder tumors, and OR planning.
Presented by Peter Black, MD, FACS, FRCSC
Peter Black, MD, FACS, FRCSC, gave a nice overview of the current and future treatment options for non- muscle-invasive bladder cancer (NMIBC) patients. To date, there are generally three different options for intravesical treatment: Single-dose chemotherapy, BCG or chemotherapy induction therapy and maintenance, and device-assisted.
Presented by Anne Schuckman, MD
At the American Urological Association (AUA) 2020 Virtual annual meeting, Dr. Anne Schuckman discussed blue light cystoscopy for bladder cancer and several of her tips and tricks. Dr. Schuckman notes that there are over 75,000 new bladder cancer diagnoses per year, leading to more than 15,000 deaths. The prevalence of bladder cancer is >550,000 cases, making it the highest per capita treatment cost due to recurrent disease and multiple recurrences.
Presented by Thomas Powles, MBBS, MRCP, MD
Advanced urothelial carcinoma resulted in over 200,000 deaths across the world in 2018. Though the majority of patients eligible for such therapy respond to platinum-based chemotherapy, disease progression occurs relatively quickly and half or less of patients receive second line treatment.
Presented by Arjun V. Balar, MD
Patients with nonmuscle-invasive bladder cancer are at high risk of recurrence and progression. In particular, patients with high-grade disease and those with carcinoma in situ are at notably elevated risk.
Presented by Stephen A. Boorjian, MD
San Francisco, California (UroToday.com) For patients with BCG unresponsive non-muscle invasive bladder cancer, the standard of care for patients who are operative candidates is radical cystectomy. However, not all patients may be cystectomy candidates, often for a multitude of reasons, including coexisting comorbidities as well as personal considerations and quality of life.1
Presented by Timothy Clinton, MD
Washington, DC (UroToday.com)  On the final day of the Society of Urologic Oncology Meeting (SUO 2019), the six best abstracts submitted were selected for presentation.
Presented by Colin Dinney, MD
Washington, DC (UroToday.com) During the bladder cancer session at the Society of Urologic Oncology Meeting on Thursday, December 5th, Dr. Colin Dinney presented the results of a phase III clinical trial for Adstiladrin® (rAd-INFa/syn3) in BCG unresponsive non-muscle invasive bladder cancer.
Presented by Rodolfo Hurle, MD
Athens, Greece (Urotoday.com) Oncofid-P-B is a conjugate of paclitaxel and Hyaluronic acid (HA) for the treatment of non-muscle-invasive bladder cancer (NMIBC) by intravesical instillation.
Presented by Badrinath Konety, MD, MBA
Athens, Greece (Urotoday.com) Dr. Badrinath Konety presented on intravesical therapy for non-muscle invasive bladder cancer (NMIBC). The current risk-based therapy entails:
Presented by Charles C. Guo, MD
Aarhus, Denmark (UroToday.com) Dr. Charles Guo from the University of Texas MD Anderson Cancer Center presented data investigating immunohistochemical markers
Presented by Madhuri Koti, DVM, MVSc, PhD
Aarhus, Denmark (UroToday.com) Dr. Madhuri Koti of Queen’s University in Kingston, Canada presented data investigating the synergistic potential of Bacillus Calmette-Guerin (BCG)
Presented by Enrique Grande, MD
Barcelona, Spain (UroToday.com) Cisplatin based chemotherapy has been the standard of care first line therapy for metastatic urothelial carcinoma (mUC) for several decades.
Presented by Christopher J. Hoimes, DO
Barcelona, Spain (UroToday.com)  Enfortumab vedotin is an antibody-drug conjugate comprised of the nectin-4 antibody enfortumab coupled to the microtubule
Presented by Thomas Powles, MBBS
Barcelona, Spain (UroToday.com) Durvalumab is a PD-L1 inhibitor with efficacy in platinum-refractory advanced urothelial cancer and approved by the FDA
Presented by Axel S. Merseburger, MD
Barcelona, Spain (UroToday.com) Dr. Axel Merseburger presented the preliminary results of the Safety of Atezolizumab in locally advanced or metastatic UrotheliaL and non-urothelial carcinoma of the urinary tract (SAUL) study at the EAU 2019 Breaking News Session.
Presented by Ricardo Leão, MD
Barcelona, Spain (UroToday.com) Up to 3/4 of non-muscle invasive bladder cancer (NMIBC) patients will endure recurrence during their lifetime. Disease follow up is invasive, costly and long and consists of cystoscopy, cytology, and imaging. The most prevalent non-invasive approach for the diagnosis of recurrence remains urinary cytology,
Presented by Yair Lotan, MD
Barcelona, Spain (UroToday.com) At the urogenital cancer treatment session, Dr. Yair Lotan discussed the impact of blue light flexible cystoscopy and utilization in the clinic setting. Dr. Lotan notes that there are several unmet medical needs with regards to non-muscle invasive bladder cancer (NMIBC). First, it is associated with a high risk of recurrence, with up to 61% of patients recurring in the first year, and up to 78% within 5 years.
Presented by Arlene O. Siefker-Radtke, MD
San Francisco, CA (UroToday.com) Immune checkpoint inhibitors are approved both in the first line and second line for patients with metastatic urothelial carcinoma. In the first line, KEYNOTE 052 showed that pembrolizumab as significant anti-tumor activity for cisplatin ineligible patients with UC1, for a 38% objective response rate for patients with a combined positive score of 10% or more (PD-L1 positive).
Presented by Scott T. Tagawa, MD, MS
San Francisco, CA (UroToday.com) Sacituzumab govitecan (SG) is a humanized antibody-drug conjugate, made from anti-Trop-2 monoclonal antibody linked with SN-38, the active metabolite of irinotecan.Trop-2 is transmembrane glycoprotein encoded by the Tacstd2 gene, and is differentially expressed in a wide range of tumor types, including gastric, pancreatic, triple-negative breast, colonic, prostate, and lung cancer.2
Presented by Yair Lotan, MD
San Francisco, CA (UroToday.com) Dr. Yair Lotan presented on Genomic Insights and Biomarkers for Treatment Selection in Muscle-Invasive and Non-Muscle-Invasive Bladder Cancer. He discussed the role of markers in bladder cancer and how they add independent information that can impact patient care.
Presented by Ananya Choudhury, MA, Ph.D., MRCP, FRCR
San Francisco, CA (UroToday.com) In this case panel discussion, 3 patient cases were reviewed highlighting important points in the management of bladder cancer. The text below includes a summary of each case presented and key points made by the panelists. The cases detail patients with small cell bladder cancer, upper tract urothelial carcinoma and recurrent NMIBC, respectively. 
Presented by Robert A. Huddart
Toronto, Ontario (UroToday.com) In this discussion, the topic of bladder preservation was presented by Dr. Huddart from the Royal Marsden NHS Foundation Trust in the United Kingdom. Muscle invasive bladder cancer, after diagnosis using TURBT, is usually treated with radical cystectomy with the option of neoadjuvant chemotherapy before surgery.
Presented by Joaquim Bellmunt, MD
Toronto, Ontario (UroToday.com) In this discussion, Dr. Bellmunt presented the standard of care in second-line management of advanced bladder cancer and gave an update on targeted therapies. He also discussed some of the phase 2 and phase 3 trials with PD-1/PD-L1 inhibitors, and associated biomarkers.
Presented by Jeff Holzbeierlein, MD, FACS
San Francisco, CA (UroToday.com)  Dr. Holzbeierlein began his discussion on the new muscle-invasive bladder cancer (MIBC) guidelines,a collaborative multi-disciplinary effort led by Dr. Sam Chang that involved input from all the major organizations, including AUA, ASCO, ASTRO, and patient advocates.