The identification of mutations in FGFR3 in bladder tumors in 1999 led to major interest in this receptor and during the subsequent 20 years much has been learned about the mutational profiles found in bladder cancer, the phenotypes associated with these and the potential of this mutated protein as a target for therapy. Based on mutational and expression data, it is estimated that >80% of non-muscle-invasive bladder cancers (NMIBC) and ∼40% of muscle-invasive bladder cancers (MIBC) have upregulated FGFR3 signaling, and these frequencies are likely to be even higher if alternative splicing of the receptor, expression of ligands and
From 2016 through the present day, we have witnessed extraordinarily rapid advances and regulatory approvals of immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway, which has significantly improved survival among patients with advanced and metastatic urothelial carcinoma (mUC). Although these agents usually are well tolerated, their unique mechanism of action may enhance cytotoxic T-cell mediated immunity, evoking unique side effects that differ from conventional chemotherapy or molecularly targeted agents. The most common immune-related adverse events (irAEs) are dermatitis, colitis, pneumonitis, thyroid dysfunction, and transaminitis, but any organ system permeated by the lymphatic vasculature can be affected; also, neuropathies and arthralgias may
Etiology of Treatment Delays in Patients Receiving Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer
BACKGROUND: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) improves overall survival in muscle-invasive bladder cancer (MIBC), but successful completion rates of NAC are low. A retrospective analysis was undertaken to determine the etiology of deviations of NAC administration for MIBC. METHODS: We performed a retrospective review of MIBC patients in an institutional database who received NAC followed by RC from 2008 to 2016. Patients were characterized as having completed NAC without deviation (“No Deviation”) or with deviation (“Deviation”). Factors associated with “Deviation” were assessed with logistic regression models.
RESULTS: 172 MIBC patients received NAC followed
BACKGROUND: Bladder cancer (BC) is a common genitourinary malignancy with over 80,000 new cases diagnosed annually and over 17,000 associated deaths. OBJECTIVE: We review 25 years of BC incidence (1993-2017) within the state of Pennsylvania to better define the incidence, geographic distribution, and trends over time. METHODS: The Pennsylvania Cancer Registry was reviewed for statewide and component county age-adjusted BC incidence rates and stage distribution. Chloropleth maps plotting statewide and county-specific incidence rates across time were created using the GeoDa statistical package.
RESULTS: 93,476 cases of BC were recorded in Pennsylvania from 1993 to 2017. Age-adjusted
Outcomes of Trimodal Therapy for cT2-3 Urothelial Carcinoma in a Racially Diverse Population: A Single Institution Experience in the Bronx
BACKGROUND: Radical cystectomy (RC) is the historical “gold standard” treatment for cT2-3 urothelial carcinoma (UC). However, recent evidence supports comparable outcomes of bladder preserving trimodal therapy (TMT) to RC in select patients.
OBJECTIVE: To assess the oncologic outcomes of our institutional TMT experience. METHODS: We retrospectively identified all patients that received radiation therapy (RT) for cT2-3 UC from 2012 to 2018. Clinicopathologic data were then extracted from the patients’ medical records. We included patients who underwent RT with or without concurrent chemotherapy for curative intent after diagnostic TURBT, with or without re-staging TURBT. Patient clinical (age,
BACKGROUND: Nearly 70% of all new cases of bladder cancer are non-muscle invasive disease, the treatment for which includes transurethral resection followed by intravesical therapy. Unfortunately, recurrence rates approach 50% in part due to poor intravesical drug delivery. Hyperthermia is frequently used as an adjunct to intravesical chemotherapy to improve drug delivery and response to treatment.
OBJECTIVE: To assess the solubility profile of intravesical chemotherapies under varying conditions of pH and temperature.
METHODS: Using microplate laser nephelometry we measured the solubility of three intravesical chemotherapy agents (mitomycin C, gemcitabine, and cisplatin) at varying physical conditions. Drugs
Synthesis, Characterization, and Biological Activity of Anthraquinone-Substituted Imidazolium Salts for the Treatment of Bladder Cancer
BACKGROUND: Bladder cancer is one of the most common types of cancer diagnosed each year, and more than half of patients have non-muscle invasive bladder cancer (NMIBC). The standard of care for patients with high-grade NMIBC is Bacillus Calmette-Guerin (BCG). Unfortunately, multiple BCG shortages have limited access to this treatment. Available alternatives using intravesical administration of chemotherapy have some efficacy, but lack prospective validation and long-term outcomes. Development of novel intravesical therapies may provide more active alternatives to BCG for patients with high-grade NMIBC.
OBJECTIVE: To develop an optimal imidazolium salt for the intravesical treatment of NMIBC and
5α-Reductase Inhibitors Do Not Prevent the Development and Progression of Urothelial Cancer: In Vitro Evidence
BACKGROUND: Androgen receptor (AR) activation has been implicated in the pathogenesis of urothelial cancer. However, it remains controversial whether 5α-reductase inhibitors (5α-RIs), which are known for blocking the conversion of testosterone to the more potent androgen dihydrotestosterone and often prescribed for the treatment of, for instance, benign prostatic hyperplasia, contribute to preventing the development of bladder cancer.
OBJECTIVE: To determine the role of 5α-RI therapy in urothelial tumorigenesis and tumor progression, using cell line models. METHODS: In a human non-neoplastic urothelial SVHUC subline stably expressing a full-length wild-type human AR (SVHUC-AR) with carcinogen/MCA challenge and human
Deciding When to Omit Repeat Transurethral Resection of Superficial Bladder Cancer: Do Photodynamic Diagnostics help?
BACKGROUND: Repeat transurethral resection of bladder tumor is recommended when certain risk constellations are present on initial resection. Current evidence is conflicting, leading to dissenting recommendations in multinational guidelines around the world. Photodynamic diagnostics (PDD) is a tool which has been shown to increase diagnostic accuracy, but evidence is still lacking if this may permit omission of repeat resections in certain cases.
OBJECTIVE: To evaluate whether the use of photodynamic diagnostics has an impact on resection quality and residual tumor rate, and to explore which parameters may have an impact on the necessity of repeat transurethral resections.
BACKGROUND: Bladder cancer (BC) poses an enormous burden on health care systems. Latinos in Texas (TX) were underrepresented in previous studies on racial/ethnic disparity of BC in the US.
OBJECTIVE: To examine whether BC incidence and survival rates differ among Latinos compared to non-Latino whites (NLW) in South TX, TX, and the US SEER.
METHODS: Data was collected from the US SEER Program and the Texas Cancer Registry. Annual age-specific and age-adjusted BC incidence rates and annual 5-year relative survival were calculated.
RESULTS: South TX and TX had significantly lower BC incidence rates than
Identification of Sex Differences in Tumor-Specific T Cell Infiltration in Bladder Tumor-Bearing Mice Treated with BCG Immunotherapy
BACKGROUND: Bladder cancer is the fourth most common cancer for men. However, women are often diagnosed with later stage disease and have poorer outcomes. Whether immune-based sex differences contribute to this discrepancy is unclear. In addition, models to investigate tumor-specific immunity in bladder cancer, in the context of tumor development or response to therapy, are lacking.
OBJECTIVE: To address this specific unmet need, we incorporated a commonly used model antigen, ovalbumin, into two well-established models of bladder cancer; the orthotopic MB49 cell line model and the carcinogenic BBN bladder cancer model.
METHOD: We tested the utility
Adjuvant Treatment of Residual Disease Following Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle Invasive Bladder Cancer
BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) has shown overall survival benefit for patients with muscle invasive bladder cancer (MIBC). In contrast, there is limited data for adjuvant treatment options in patients with residual muscle invasive disease after NAC followed by radical cystectomy (RC).
OBJECTIVE: This systematic review aims to give an overview of studies examining adjuvant treatment options for patients with residual MIBC at RC despite NAC.
METHODS: We systematically searched the PubMed database and Clinicaltrials.gov (end point August 2019) for publications and registered trials combining NAC, RC, and adjuvant treatment options.
RESULTS: After removal