Advanced & Metastatic Bladder Cancer (mUC)

Neoadjuvant TAR-200 Plus Cetrelimab versus Cetrelimab Monotherapy in Cisplatin-Ineligible Patients with MIBC - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

The treatment of muscle-invasive bladder cancer (MIBC) in patients who cannot receive or decline standard cisplatin-based neoadjuvant chemotherapy is particularly challenging. To address this clinical need, a recent interim analysis of the SunRISe-4 trial evaluated the efficacy and safety of combining TAR-200

Surgical Consolidation in Advanced Urothelial Carcinoma After Enfortumab Vedotin and Immune Checkpoint Inhibitor - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Advanced urothelial carcinoma has historically shown poor response to cisplatin-based chemotherapy, with few patients achieving durable responses suitable for surgical consolidation. The EV-302 trial demonstrated unprecedented median overall survival with enfortumab vedotin and pembrolizumab compared to

ERBB2 Alterations in Circulating Tumor DNA in Patients with Metastatic Urothelial Cancer - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

HER2-targeted therapies are becoming more relevant in patients with metastatic urothelial cancer (mUC), yet optimal biomarker strategies remain unclear. A recent study examined ERBB2 alterations in circulating tumor DNA (ctDNA) and their correlation with tissue-based HER2 assessment to inform precision therapy approaches.

Immunohistochemistry-based Subtyping of Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Molecular subtyping of urothelial carcinoma (UC) based on RNA expression profiling provides additional prognostic insights beyond traditional staging and grading systems. A recent study developed an immunohistochemistry (IHC)-based alternative using four accessible antibodies to stratify UC patients in resource-constrained settings.

Treatment Outcomes after Progression on Enfortumab Vedotin in Patients with Advanced Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Advanced urothelial carcinoma (UC) patients who experience disease progression after enfortumab vedotin (EV) treatment have limited treatment options. No established treatment strategies exist for this population. A recent retrospective study by Furubayashi et al. evaluated clinical outcomes of post-EV treatments compared with best supportive care (BSC) in patients with advanced UC

Long-term Patient-reported Outcomes in Patients Receiving Avelumab Maintenance - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Advanced urothelial carcinoma (UC) significantly impacts patients' quality of life due to cancer-related symptoms, treatment toxicity, and effects on mental health. A new analysis of the JAVELIN Bladder 100 trial by Grivas et al. examined long-term patient-reported outcomes (PROs)

Personalized Neoantigen Vaccines and immunotherapy for Urothelial Cancer - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Most patients with urothelial cancer (UC) patients do not benefit from single agent immune checkpoint inhibitors (ICIs). A recent phase 1 trial by Saxena et al. evaluated the combination of atezolizumab (anti-PD-L1) with PGV001, a novel personalized neoantigen vaccine, in patients with urothelial cancer to stimulate antitumor immunity.

Spatial Heterogeneity in Expression of Targets of Antibody-Drug Conjugates in Bladder Cancer - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Antibody-drug conjugates (ADCs) targeting HER2, NECTIN4, and TROP-2 have emerged as effective therapeutic options for patients with muscle-invasive bladder cancer (MIBC). A recent study by Dernbach et al. examined the heterogeneity of these ADC targets in MIBC primary tumors and metastases, analyzing their correlation with molecular subtypes and clinical outcomes.

HER2, NECTIN4, and TROP-2 Expression Heterogeneity in Bladder Cancer - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Muscle-invasive bladder cancer (MIBC) presents significant treatment challenges, with antibody-drug conjugates (ADCs) targeting HER2, NECTIN4, and TROP-2 emerging as promising therapeutic options. This study examined the spatial heterogeneity of these ADC targets in MIBC primary tumors and metastases, analyzing their correlation with molecular subtypes and clinical outcomes.

Molecular Subtypes in Urothelial Carcinoma as Predictors of Response to Immunotherapy - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Despite progress with immune checkpoint inhibitors in urothelial carcinoma (UC), many patients fail to respond. A new study by Hamidi et al. in Cancer Cell characterized the molecular determinants of response and resistance to PD-L1 blockade by analyzing 2,803 UC patients from four randomized clinical trials evaluating atezolizumab.

Combining Immune Checkpoint Inhibition with Human Recombinant IL-7 (CYT107) in Advanced Urothelial Cancer - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Single-agent immunotherapy in advanced urothelial cancer achieves response rates of only 20-25%. A recent phase II study by Sweis et al. in Clinical Cancer Research investigated whether adding the lymphocyte growth factor CYT107 (recombinant IL-7) to atezolizumab could enhance anti-tumor immune responses and improve efficacy.

Efficacy and Safety of an Avelumab and Chemotherapy Combination Treatment Regimen in Cisplatin Ineligible Patients with Metastatic Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

The standard of care for metastatic urothelial carcinoma (mUC) has been cisplatin-based chemotherapy, although approximately 50% of patients are not eligible to receive it. The recent development of immune checkpoint inhibitors (ICIs) has enhanced treatment options in the first- and second-line settings.

Efficacy and Safety of Sacituzumab Govitecan in Cisplatin-Ineligible Patients with Metastatic Urothelial Cancer After Immunotherapy - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

May patients with metastatic urothelial cancer are ineligible to cisplatin due to kidney dysfunction and other comorbidities. Recently, various antibody drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) have been approved for mUC treatment, with varying response rates and efficacies. Sacituzumab govitecan (SG) is an ADC consisting of an anti-Trop-2 antibody coupled to cytotoxic SN-38.

Treatment Preferences and Tradeoffs Among Patients with Locally Advanced or Metastatic Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

With the expanding therapeutic options for patients with locally advanced or metastatic urothelial carcinoma (mUC), selecting the most appropriate option for each patient has become increasingly complex. A more patient-centered approach based on collaboration and shared decision-making is emphasized in the literature and guidelines.

Population Estimates of Ovarian Cancer Risk in a Cohort of Patients with Bladder Cancer - Beyond the Abstract

Written by Sneha Parekh, MD, Laura Davis, MD, & Laura Bukavina, MD, MPH, MSc

The rationale for incorporating bilateral oophorectomy during cystectomy in females diagnosed with bladder cancer (BC) is rooted in the historical prominence of radical cystectomy (RC) as the primary treatment for muscle-invasive BC and non–muscle-invasive BC (NMIBC) with a high risk of progression or resistance to intravesical therapy.1

Efficacy of Gemcitabine and Docetaxel for Treatment of Micropapillary Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Optimal treatment regimens for histologic variants of non-muscle invasive bladder cancer (NMIBC) are not well established. Accordingly, patients with variant cases exhibit worse clinical outcomes. Micropapillary urothelial carcinoma (MPUC) is the most common variant of urothelial carcinoma.

Digital Spatial Profiling in Muscle-Invasive Bladder Cancer - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Bulk molecular analysis of bladder cancer (BC) does not capture critical spatial information that could be important for understanding disease pathology. Interest in spatial biology has surged in recent years, resulting in the development of various new techniques, such as whole transcriptome digital spatial profiling (DSP).

Efficacy of FGFR Inhibitor Derazantinib in Metastatic Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

There have been significant advancements in treatment options for patients with metastatic urothelial carcinoma (mUC) in recent years, including immune checkpoint inhibitors (ICIs), antibody-drug conjugates, and fibroblast growth factor receptor (FGFR) inhibitors.

Efficacy of Neoadjuvant Chemotherapy in Patients with MIBC Undergoing Radiation - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is a standard of care in patients with muscle-invasive bladder cancer (MIBC). However, the role of NAC remains controversial for patients undergoing bladder preservation with radiation therapy (RT). Kool et al. recently investigated the effect of NAC on survival outcomes in MIBC patients treated with curative RT.

Evaluating Antibody-Drug Conjugates Combination with Radiation Therapy in Bladder Cancer - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

The antibody-drug conjugates (ADCs) enfortumab vedotin (EV) and sacituzumab govitecan (SG) are approved for metastatic bladder cancer treatment. However, little is known about their efficacy in earlier stages and whether they can be combined with radiation for bladder preservation approaches.

Predictive Biomarkers in Sarcomatoid and Rhabdoid Bladder Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Antibody-drug conjugates (ADCs) have revolutionized the treatment metastatic urothelial carcinoma. These include sacituzumab govitecan targeting TROP-2 and enfortumab vedotin targeting NECTIN-4. The conventional urothelial cancers express TROP-2 and NECTIN-4, the protein targets of these ADCs.

Antibody-Drug Conjugate Combination Therapy in Patients with Metastatic Urothelial Cancer - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

The standard treatment for metastatic urothelial carcinoma (mUC) is platinum-based chemotherapy followed by immunotherapy. Recently, two antibody-drug conjugates (ADCs), enfortumab vedotin (EV) and sacituzumab govitecan (SG) have been approved for mUC.

Characterization of Targets for Antibody-Drug Conjugates in Advanced Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Patients with advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitors have exhibited low objective response rates (ORR) of 20-30%. ORR can reach around 40% among patients with FGFR2/3 alterations who receive FGFR inhibitors. Two antibody-drug conjugates (ADCs), sacituzumab govitecan (SG) and enfortumab vedotin (EV) were recently approved for refractory aUC.

Clinical and Molecular Features of Nested and Large Nested Urothelial Carcinoma - Expert Commentary

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.

Survival Outcomes and Parameters of Switch Maintenance - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Platinum-based chemotherapy is the standard of care for first-line treatment in patients with advanced urothelial carcinoma. Switch maintenance therapy with a drug with a different mode of action and better tolerability can enhance the clinical benefit of first-line chemotherapy. This was confirmed in the phase 3 JAVELIN Bladder 100 trial, in which improved survival was observed in patients with advanced urothelial carcinoma

FGFR Genomic Alterations and Response to Erdafitinib - Expert Commentary

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.

Enfortumab Vedotin Versus Chemotherapy for Advanced Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Patients with advanced urothelial carcinoma still have low 5-year survival rates. Most patients experience disease progression after treatment with chemotherapy or PD-1 inhibitors. Enfortumab vedotin is an antibody-drug conjugate that targets Nectin-4, a protein highly expressed in UC. A recent study by Rosenberg et al. reports long-term outcomes from EV-301, an open-label phase III trial for EV versus chemotherapy in previously treated patients with advanced UC.

Racial and Sex Differences in Tumor Genomics in Urothelial Carcinoma - Expert Commentary

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.

Efficacy of Maintenance Avelumab After Chemotherapy in Advanced Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

The standard of care first-line treatment for advanced urothelial carcinoma is platinum-based chemotherapy, followed by avelumab (anti-PD-L1), for maintenance treatment in patients without progression. The JAVELIN trial confirmed that maintenance avelumab was associated with significantly prolonged overall survival and progression-free survival.

Screening for Multiple Cancers, Including Urothelial Cancer, Using a Cell-Free DNA-Based Blood Test - Expert Commentary

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.

The Importance of Surgical Margin and Extent of Lymphadenectomy on Clinical Outcomes in Patients with Plasmacytoid Urothelial Carcinoma - Expert Commentary

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.

Clinical Features of Patients with Muscle-Invasive Urothelial Carcinoma Undergoing Radical Resection - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Radical surgery and neoadjuvant or adjuvant chemotherapy are potentially curative for patients with muscle-invasive bladder cancer and upper tract urothelial carcinoma. Roupret et al. conducted the retrospective MINOTAUR study to analyze real-world data on the epidemiology, management, and survival of patients with muscle-invasive urothelial carcinomas

Effect of Genomic Subtypes of Urothelial Carcinoma on Response to Immune Checkpoint Inhibitors - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

While immune checkpoint inhibitors (ICI) have revolutionized treatment for bladder cancer patients, studies have shown that not all patients achieve a response. To identify potential genetic predictors of ICI treatment response, Sarfaty et al. investigated the link between specific subtypes based on genomic alterations in ICI-treated patients with advanced urothelial carcinoma and survival outcomes.

The Efficacy of First-Line Carboplatin in Metastatic Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

The choice of first-line treatment is particularly crucial for patients with advanced or metastatic urothelial carcinoma (AMUC), as only 15-20% of patients receive second-line treatment due to poor survival. Mori et al. recently re-evaluated the efficacy of carboplatin as a first-line treatment in patients with AMUC by conducting a meta-analysis.

Carboplatin versus Cisplatin Based Chemotherapy for Lymph Node Positive Bladder Cancer - Expert Commentary

Written by Bishoy M. Faltas

Englander Institute for Precision Medicine, Weill Cornell Medicine

Up to a third of patients with muscle-invasive bladder cancer present with clinically lymph node-positive disease, associated with poor prognosis. Eligible patients can be treated with cisplatin-based induction chemotherapy followed by radical cystectomy if they exhibit a clinical response.

Predicting Clinical Outcomes for Patients with Sarcomatoid Urothelial Carcinoma - Expert Commentary

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.

Ipilimumab and Nivolumab Treatment in Patients With Stage III Urothelial Cancer - Expert Commentary

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.

Cutaneous Toxicity and Response to Enfortumab Vedotin in Urothelial Cancer Patients - Expert Commentary

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.

Understanding Primary-Metastatic Immune Phenotype Discordance on Urothelial Cancer Response to Immune Checkpoint Inhibition - Expert Commentary

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

Integrated DNA and RNA Sequencing of Advanced Urothelial Cancers - Expert Commentary

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.

Avelumab and Talazoparib Treatment in Patients with Advanced Urothelial Cancer - Expert Commentary

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

Safety and Efficacy of Rogaratinib Versus Chemotherapy in Advanced Bladder Cancer - Expert Commentary

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

Linear Versus Parallel Metastatic Progression of Urological Cancers - Expert Commentary

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

The Association Between the Site of Metastasis and Clinical Outcomes in Patients with Advanced Urothelial Carcinoma - Expert Commentary

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.

Outcomes of First-line Chemotherapy and Second-line Immune Checkpoint Inhibitor in Patients with Advanced Urothelial Carcinoma - Expert Commentary

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

Predictive Biomarkers for Ramucirumab Response in Patients with Urothelial Cancer - Expert Commentary

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.

Interactions Between Smoking and Single Nucleotide Polymorphisms Influence Urothelial Cancer Risk - Expert Commentary

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

Early-Line Infigratinib for Patients with FGFR3-Altered Metastatic Urothelial Carcinoma - Expert Commentary

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

Updated European Association of Urology (EAU) Prognostic Factor Risk Groups Overestimate the Risk of Progression in Patients with Non-muscle-invasive Bladder Cancer Treated with Bacillus Calmette-Guérin - Beyond the Abstract

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.

Computational Prediction of Neoantigens in Patients with Urothelial Cancer - Expert Commentary

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

Immune Checkpoint Blockade and Targeted Agent Combos in Advanced Urothelial Cancer - Expert Commentary

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.

Results of Bevacizumab-Chemotherapy Combinations for Patients with Advanced Urothelial Cancer - Expert Commentary

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

Efficacy of Adding Panitumumab to Dose-Dense MVAC Chemotherapy in Patients with Advanced Urothelial Cancer - Expert Commentary

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.

Selective ATR Inhibitor Combined with Chemotherapy in Patients with Urothelial Cancer - Expert Commentary

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.

PARP Inhibition in Patients with Advanced Urothelial Cancer - Expert Commentary

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.

Impact of Molecular Profiling Offered to Patients with Metastatic Bladder Cancer in Early-Phase Clinical Trials - Expert Commentary

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.

TERT Promoter Mutations Predict Benefit From Immunotherapy in Patients With Urothelial Cancer - Expert Commentary

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.

Predicting Response to Immunotherapy in Patients with Metastatic Urothelial Cancer Using Radiomics - Expert Commentary

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

Telomerase Reverse Transcriptase (TERT) Promoter Mutations in Primary Adenocarcinoma of Bladder and Urothelial Carcinoma with Glandular Differentiation - Expert Commentary

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.

Dual Immune Checkpoint Blockade in Metastatic Non-Urothelial Cancer of the Urinary Tract - Expert Commentary

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.

Chemotherapy Options for Metastatic Urothelial Cancer Patients Who Already Received Cisplatin for Localized Disease - Expert Commentary

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

ARID1A Mutation plus CXCL13 Expression Act as Combinatorial Biomarkers to Predict Responses to Immune Checkpoint Therapy in Metastatic Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas, MD

Englander Institute for Precision Medicine, Weill Cornell Medicine

The introduction of immune checkpoint inhibitors (ICIs) has improved the outcomes for a subset of metastatic urothelial carcinoma (mUCC) patients. There is a need for a predictive tool to identify

PD-L1 Assay Concordance in Metastatic Renal Cell Carcinoma and Metastatic Urothelial Carcinoma - Expert Commentary

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

Clinicopathological Characteristics and Survival Outcomes in Micropapillary Urothelial Carcinoma of the Bladder — Expert Commentary

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

The Basal to Luminal Transition Classifier for Urothelial Cancer Subtypes - Expert Commentary

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

The Response of Urothelial Cancer Variants to PD-1/PD-L1 Blockade - Expert Commentary

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

Mismatch Repair Deficiency in Urothelial Carcinoma of the Bladder - Expert Commentary

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).

Cytological Features of Micropapillary and Plasmacytoid Variants of Urothelial Carcinoma - Expert Commentary

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

Does Pre-Treatment Quality of Life Impact the Prognosis of Patients with Urothelial Carcinoma? - Expert Commentary

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.

A Randomized Phase II Trial of Vinflunine and Gemcitabine Versus Carboplatin and Gemcitabine in Cisplatin-Ineligible Patients with Advanced Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas, MD

Englander Institute for Precision Medicine, Weill Cornell Medicine

A significant number of patients with locally advanced and metastatic urothelial cancer (aUC) are not eligible for cisplatin-based chemotherapy.

Randomized Phase 1 Trial of Pembrolizumab with Sequential Versus Concomitant Stereotactic Body Radiotherapy in Metastatic Urothelial Carcinoma - Expert Commentary

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

A Phase I Study of Enfortumab Vedotin in Japanese Patients with Locally Advanced or Metastatic Urothelial Carcinoma - Expert Commentary

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

Gemcitabine-Eribulin in Cisplatin-Ineligible Patients with Metastatic Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas, MD

Englander Institute for Precision Medicine, Weill Cornell Medicine

The optimal treatment for cisplatin-ineligible patients with metastatic urothelial cancer is unknown.

The Efficacy of Immunotherapy and Carboplatin-Based Chemotherapy in Cisplatin-Ineligible Metastatic Urothelial Cancer Patients - Expert Commentary

Written by Bishoy M. Faltas, MD

Englander Institute for Precision Medicine, Weill Cornell Medicine

The optimal treatment for patients with metastatic urothelial carcinoma (mUC) patients who are unfit to receive the standard cisplatin-based chemotherapy is uncertain.

APOBEC Mutagenesis is Associated with FGFR3 S249C Mutations in Bladder Cancer - Expert Commentary

Written by Bishoy M. Faltas, MD

Englander Institute for Precision Medicine, Weill Cornell Medicine

FGFR3 mutations are common in urothelial carcinoma. The APOBEC mutational process is the dominant mutational mechanism in bladder cancer.

Urothelial Carcinoma with Uncertain Muscularis Propria Invasion - Expert Commentary

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

Trends of Perioperative Chemotherapy for Muscle-Invasive Bladder Cancer - Expert Commentary

Written by Bishoy M. Faltas, MD

Englander Institute for Precision Medicine, Weill Cornell Medicine

Perioperative chemotherapy is frequently underutilized. Understanding the trends in the utilization of neoadjuvant or adjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer (MIBC) undergoing cystectomy is critical.

Molecular Alterations in Urothelial Carcinoma Using CLIA-certified Genomic Testing - Expert Commentary

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

Clinical Outcomes in Patients with Micropapillary Urothelial Carcinoma of the Bladder - Expert Commentary

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.

Response to Platinum Reintroduction After Immune Checkpoint Inhibitors for Metastatic Urothelial Carcinoma - Expert Commentary

Written by Bishoy M. Faltas, MD

Englander Institute for Precision Medicine, Weill Cornell Medicine

Immune checkpoints inhibitors (ICIs) are approved as a second line of treatment for metastatic urothelial carcinoma (mUC) patients with progression on cisplatin-based chemotherapy.

Avelumab, an Anti–Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study - Expert Commentary

Written by Bishoy M. Faltas, MD

Englander Institute for Precision Medicine, Weill Cornell Medicine

Platinum-resistant urothelial carcinoma is a lethal disease. After a long period of therapeutic stagnation, the last two years have witnessed an explosion in the development of new second-line therapies.

Multi-Receptor Tyrosine Kinase Inhibitor Pazopanib versus Weekly Paclitaxel in Relapsed or Progressive Urothelial Cancer - Expert Commentary

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.

Centers of Excellence

Advanced & Metastatic Bladder Cancer (mUC)

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