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The Latest Research on Advanced Bladder Cancer

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From the Desk of the Editor

Petros Grivas | June 16, 2019

Bladder cancer is common and challenging to treat. A thorough assessment of the molecular biology and immunology background has pinpointed potential biomarkers, “drivers” and promising therapeutic targets. The advent of immune checkpoint inhibitors (ICI) has heralded a new era after approximately two decades of a “stagnant landscape”.  As single agents in patients with advanced urothelial carcinoma, ICI can induce rapid and durable responses, with a very small proportion of patients achieving long term remission. However, most patients do not achieve response, while a proportion may have immune-related adverse events. Therefore, there is an urgent need for additional therapies that raise the bar, improve quality of life, and prolong the life of our patients.

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Petros Grivas, MD

Petros Grivas, MD, Ph.D. is an Associate Professor and the Clinical Director of the Genitourinary Cancers Program at the University of Washington, and an Associate Member of the Clinical Research Division at the Fred Hutchinson Cancer Research Center with expertise in genitourinary cancers such as bladder cancer, prostate cancer, and testis cancer.
Dr. Grivas is dedicated to efficient, personalized and outstanding patient care. He believes in an optimal patient-physician relationship and community outreach. Dr. Petros Grivas was recruited from the Cleveland Clinic where he was leading the bladder/urothelial cancer program and was seeing numerous patients with bladder/urothelial cancer, prostate cancer and testis cancer. Prior to Cleveland Clinic, Dr. Grivas was seeing patients with similar diseases at the University of Michigan, Ann Arbor. He played an important role in clinical trials that led to the FDA approval of new drugs for bladder/urothelial cancer, and he is considered a thought leader and international expert, giving lectures in several countries, educating other oncologists and trainees, leading clinical trials and publishing novel and important research.

Videos
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State-of-the-industry video lectures by leading urology experts
Everyday Urology - Oncology Insights
Publications focusing on urologic cancer treatments through original manuscripts
By Noah Hahn, MD
This is an extraordinary time in urology. After decades of relative stagnation, patients with urothelial carcinoma are receiving approved immuno-oncologic drugs that significantly extend survival and are safer and more tolerable than chemotherapy.  The success of these treatments in metastatic bladder cancer has generated strong interest and promising early results for their use in localized disease.
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By Neal Shore, MD, FACS
Initial Considerations
From BCG to interferon gene therapy, physicians have treated bladder cancer with immunotherapy for decades. Treatment particulars generally depend on whether bladder cancer is non-muscle invasive, muscle-invasive, or metastatic. About 75% of patients have non-muscle invasive bladder cancer (NMIBC),1 which is considered high-risk if it consists of non-invasive papillary carcinoma (TaHG),
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Library Resources
Evidence based monographs by experts to define and guide clinical practice
Written by Janet Baack Kukreja, MD, MPH and Ashish Kamat, MD, MBBS
April 16, 2019
Bladder cancer was one of the top five leading causes of cancer death in 2015.1 Most of these cases are of urothelial histologic origin. For about 35% of patients, bladder cancer is either muscle-invasive or metastatic at disease presentation.
April 16, 2019
BALVERSA is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma that has 

  • susceptible FGFR3 or FGFR2 genetic alterations and
  • progressed during or following at least one line of prior platinum-containing chemotherapy including within 12 months of neoadjuvant 
Expert Commentary
Evidence based monographs by experts to define and guide clinical practice
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
Intravesical recurrence (IVR) rates remain high in urothelial carcinoma of the upper urinary tract (UTUC) patients following radical nephroureterectomy
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Lynch syndrome (LS), caused by a mutation in the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2). LS increases the individual’s risk of getting upper urinary tract urothelial carcinoma (UTUC).
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
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.
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
The optimal treatment for cisplatin-ineligible patients with metastatic urothelial cancer is unknown.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Patients who achieved a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have a better prognosis compared to patients with pathologic residual disease (pRD).
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
The optimal treatment for patients with metastatic urothelial carcinoma (mUC) patients who are unfit to receive the standard cisplatin-based chemotherapy is uncertain.
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.
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
A shortage of the Bacillus Calmette-Guérin (BCG) Connaught strain occurred between 2013-2016. 
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.
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
Neoadjuvant chemotherapy followed by radical cystectomy (RC) with lymph node dissection is the standard of care in patients with muscle-invasive urothelial bladder carcinoma (MIBC).
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Although urothelial carcinomas of the bladder and upper tract urothelial carcinoma (UTUC) can have similar histology, they significantly differ in prevalence and risk factors.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Upper tract urothelial carcinoma (UTUC) is a distinct clinical entity with poor clinical outcomes.
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.
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
Patients with muscle-invasive bladder cancer  (MIBC) who are treated with neoadjuvant chemotherapy (NAC) before cystectomy have a survival advantage.
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
Downstaging of muscle-invasive bladder cancer (MIBC) following neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) has been correlated with higher survival rates.  
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
Lynch Syndrome (LS) is a common hereditary cancer syndrome that is characterized by mutations in the mismatch repair (MMR) genes.
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 Zhamshid Okhunov, MD
Department of Urology, University of California, Irvine Urology
Though nephrectomy is the gold standard treatment for renal cell carcinoma, 20%-40% of patients have a recurrence and 20-30% of patients present with metastatic disease1.
Written by Zhamshid Okhunov, MD
Department of Urology, University of California, Irvine Urology
As men get older, starting at the age of 30 years, their testosterone levels decrease by an average of 3.1 to 3.5ng/dL per year.
Written by Zhamshid Okhunov, MD
Department of Urology, University of California, Irvine Urology
Partial nephrectomies are the standard of care with treatment of T1a or T1b tumors due to their better functional outcomes and decrease cardiovascular morbidity.
Written by Zhamshid Okhunov, MD
Department of Urology, University of California, Irvine Urology
Laparoscopic renal surgery (LRS) has long been recognized for its improvements over open renal surgery for patient quality of life.
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
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.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Neoadjuvant chemotherapy is a standard of care for patients with urothelial muscle-invasive bladder cancer.
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
Circulating tumor cells (CTCs) are cancer cells shed from the tumor that enter the circulation.
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
Upper tract urothelial carcinoma is less common than bladder urothelial carcinoma. The biological characteristics of this form of the disease is not completely understood.
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.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) neoadjuvant chemotherapy is a standard of care for muscle-invasive urothelial bladder cancer.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Neoadjuvant chemotherapy is a standard of care for muscle-invasive bladder cancer (MIBC).
Conference Coverage
Recent data from conferences worldwide
Presented by Enrique Grande, MD
Barcelona, Spain (UroToday.com) First-line metastatic urothelial carcinoma treatment includes cisplatin or carboplatin-based chemotherapy or checkpoint inhibitors, depending on patient eligibility and PD-L1 status.
Presented by Scott T. Tagawa, MD, MS
Barcelona, Spain (UroToday.com) Platinum-based chemotherapy has been the standard first-line therapy for patients with metastatic urothelial cancer (mUC). Historically, response to standard of care second-line chemotherapy regimens is < 15%.
Presented by Christopher J. Hoimes, DO
Barcelona, Spain (UroToday.com) Platinum-based chemotherapy remains the standard of care for patients with locally advanced or metastatic urothelial carcinoma. Despite the use of first-line PD-1/PD-1L inhibitors, 71–76% of patients who are cisplatin-ineligible do not respond to treatment.
Presented by Daniel Peter Petrylak, MD
Chicago, IL (UroToday.com) After cisplatin-based chemotherapy and immune checkpoint inhibitors, there exist a paucity of effective therapies for patients with metastatic urothelial carcinoma (mUC). Enfortumab vedotin (EV) is an antibody-drug 
Presented by Arlene O. Siefker-Radtke, MD
Chicago, IL (UroToday.com) FGF receptor 3 (FGFR3) alterations are frequently encountered in urothelial carcinoma, both in non-muscle invasive and muscle-invasive disease.1 For patients with muscle-invasive disease, FGFR3 mutations have been observed in 2% of primary tumors and 9% of metastases.2
Presented by Bradley Alexander McGregor, MD
Chicago, IL (UroToday.com) Combination ipilimumab/nivolumab (ipi/nivo) has seen success in melanoma, MSI high colorectal cancer, and renal cell carcinoma (RCC).1 In urothelial carcinoma, CheckMate 032 evaluated the efficacy of ipi/nivo in an open-label, multicenter, phase I/II
Presented by Xinan Sheng, MD
Antibody-drug conjugates (ADCs) have made significant progress in several tumor types over the past few years, including brentuximab vedotin for Hodgkin lymphoma, TDM1 for breast cancer, and inotuzumab ozogamicin for non-Hodgkin lymphoma.1 Linking a targeted monoclonal 

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