Bladder Cancer Journal Vol. 5 Issue 1

Systematic Review: Targeting HER2 in Bladder Cancer

HER2 (ErbB2) is a receptor of the Human Epidermal Growth Factor Receptor (HER) family whose role in oncogenesis of numerous malignancies is well described. Drugs targeting HER2 are currently approved in breast and gastroesophageal cancers while pan-HER targeting agents are being evaluated in multiple malignancies. HER2 genomic alterations are commonly described in urothelial cancer and multiple trials have assessed the efficacy of anti-HER2 agents in both muscle-invasive and metastatic urothelial carcinoma. Objective: To review prospective clinical trials of therapeutic agents with HER2– targeting activity in patients with bladder cancer. Methods: A systematic search of PubMed, 

The Outcome of Post-Chemotherapy Retroperitoneal Lymph Node Dissection in Patients with Metastatic Bladder Cancer in the Retroperitoneum

Purpose: While a definitive cure can be achieved by radical cystectomy and pelvic lymph node dissection in select patients with regional lymphadenopathy, the benefit remains uncertain in patients who present with non-regional metastases. We analyzed the survival outcomes of post-chemotherapy retroperitoneal lymph node dissection. Materials and Methods: We reviewed our institutional database and identified 13 patients with radiographically evident or biopsy proven retroperitoneal nodal metastases with a significant response to chemotherapy. These patients underwent consolidative surgery with concomitant or delayed retroperitoneal lymph node dissection. The primary endpoints were progression-free survival and disease-specific survival from the time 

Thermo Reversible Hydrogel Based Delivery of Mitomycin C (UGN-101) for Treatment of Upper Tract Urothelial Carcinoma (UTUC)

Background: There is an unmet need for an effective local treatment of upper tract urothelial carcinoma (UTUC). Drug delivery to the pyelocaliceal system and pursuant efficacy of intracavitary therapy is limited by urine production that washes the drug away, shortening dwell time and direct contact with the urothelium. Successful endoscopic management is often dictated by lesion size, grade, and focality. A thermo-reversible hydrogel formulation of Mitomycin C (UGN-101, formerly MitoGel) was developed and has demonstrated the safety and feasibility of increased time of the drug in the pyelocaliceal system resulting in chemoablation of tumors. Objectives: To examine the 

Assessment of a European Bladder Cancer Predictive Model for Non-Muscle Invasive Bladder Cancer in an Australian Cohort

Background and Objectives: To validate the European Organization for Research and Treatment of Cancer (EORTC) model using an Australian cohort and to identify variables within our cohort that may predict non-muscle invasive bladder cancer (NMIBC) recurrence and progression. Methods: A retrospective chart review of patients undergoing transurethral resection of bladder tumour (TURBT) at a single academic institution between 1995 and 2015 was performed (n  = 366). Only patients with available TURBT pathology having initial Ta or T1 disease were included (n  = 255). EORTC risk groups were calculated for individual patients and compared to actual recurrence rates using a binomial 

Multi-Perspective Tolerance Evaluation of Bacillus Calmette-Guerin with Interferon in the Treatment of Non-Muscle Invasive Bladder Cancer

Background: Bacillus Calmette-Guerin (BCG) toxicities have been reported but with relative agranularity regarding severity and temporal changes during therapy. In its most severe form, BCG intolerance remains poorly understood and exploring ways to optimize toleration of the most effective treatment (BCG) is prudent. Objective: To report the results of both patient- and physician-centered metrics of BCG toxicity as part of the National Phase II BCG/Interferon (IFN) study, as well as the efficacy of low-dose BCG/IFN for previously deemed BCG intolerant patients. Methods: Patients were treated with 6 weekly treatments of BCG (various dosing based on prior 

Recovering from Cystectomy: Patient Perspectives

Background: Bladder cancer patients who undergo cystectomy and urinary diversion face functional and quality-of-life challenges. Little is known about these patients’ experiences during decision-making, surgery, and recovery, or how they vary by treatment setting. Objective: To learn about patients’ experiences with treatment choice, surgical care, and recovery across health settings. Understanding patient experiences is essential to closing care gaps and developing patient-reported measures. Methods: We conducted focus groups with cystectomy patients and family caregivers at a large comprehensive health care system (N = 32 patients) and an NCI-designated comprehensive cancer center (N = 25 patients and 5 caregivers). Using standard 

Immune Checkpoint B7x (B7-H4/B7S1/VTCN1) is Over Expressed in Spontaneous Canine Bladder Cancer: The First Report and its Implications in a Preclinical Model

Background: B7x (B7-H4/B7S1/VTCN1), an inhibitory immune checkpoint molecule is a potential therapeutic target owing to its immunosuppressive effect and well-known expression in cancers. Immune checkpoints in canine bladder cancer are largely undefined. Here, we report the first evaluation on expression of B7x in spontaneous canine invasive bladder cancer, a novel model system for the study of invasive human urothelial carcinoma. Objective: This work aims to study expression of immune checkpoint B7x in spontaneous canine invasive bladder cancer. Methods: RNA-seq analysis was performed to determine B7x expression in tumor versus normal bladder. Gene ontology (GO) study was 

Intravesical Therapy – BCG and Beyond

Non-muscle invasive bladder cancer is marked by frequent recurrences and a risk for progression to life threatening disease. Intravesical Bacillus Calmette–Guérin (BCG), one of the earliest effective immunotherapies for cancer, remains the current standard for treating high-risk non-muscle invasive bladder cancer. Optimal treatment with BCG includes periodic 3 weekly maintenance instillations, often with dose reduction to minimize toxicity. However, despite its efficacy, treatment failure is common. Efforts to provide alternate and potentially more effective therapy for this disease include increased understanding of bladder cancer through molecular profiling, multi-agent intravesical chemotherapy, and novel forms of immunotherapy.

Challenging Cases in Urothelial Cancer

L.R. is a healthy appearing 83 year old woman that presented to a urologist upon referral from her primary care physician with a 6 month history of recurrent urinary tract infections and more recently some right flank discomfort. A CT scan of the abdomen and pelvis revealed moderate right hydronephrosis with a point of obstruction near or at the bladder. The left upper tract was normal. Images of the bladder indicated masses consistent with bladder cancer.

Clinical Trials Corner

An Open Label, Single Arm, Phase II, Multicenter Study of the Safety and Efficacy of CG0070 Oncolytic Vector Regimen in Patients With Non-Muscle Invasive Bladder Carcinoma Who Have Failed BCG Therapy and Refused Cystectomy

Rationale: CG0070 is a replication-competent oncolytic adenovirus that selectively replicates in retinoblastoma (Rb) pathway-defective cells that are often present in bladder cancer. The adenovirus also contains a transgene for granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that can active the immune system. CG0070 works by 2 major mechanisms: 1) induction of tumor lysis by selective replication in Rb-deficient tumor cells and 2) local GM-CSF production that augments immunogenic cell death.