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Evolving Paradigms In Bladder Cancer: Introduction

Published Online: Feb 17,2016
Bladder cancer is the fifth most common cancer in the United States and is three times more prevalent in men than in women, accounting for 7% of expected new cancer cases in males in 2016.1,2

Though many bladder cancers are nonmuscle invasive and successfully treated with local resection and/or adjuvant intravesical therapy,3 the number of deaths from bladder cancer in 2016 is projected to be over 16,000, a number that has remained relatively unchanged since the 1970s.1,2 These deaths are largely due to the high rate of disease relapse in bladder cancer patients, who require additional procedures in order to manage their disease. Between 50% and 70% of patients with superficial bladder cancer will experience recurrence, and 10% to 15% of those patients will progress to muscle-invasive disease.4 The anatomical structure of the bladder is shown in FIGURE 1.

Following a period of stagnation in the development of new therapies for advanced bladder cancer, novel targeted and immunotherapeutic agents have demonstrated promising outcomes in clinical trials and their clinical investigation and the development of molecular profiling approaches is an area of active investigation and intense interest.5 In this article, we provide a general overview of bladder cancer as a disease, highlighting current therapeutic strategies, as well as potential new avenues for advancing bladder cancer therapy.

Bladder cancer can arise from any part of the bladder wall (FIGURE 2). The most common type of bladder cancer is transitional cell carcinoma (TCC), which accounts for 90% of all bladder cancers. TCC arises from the transitional epithelium, comprised of cells in the inner lining of the bladder that expand and contract, and TCC is usually caused by exposure to environmental carcinogens that pass through the urinary tract. Other types of bladder cancer include squamous cell carcinoma (1%-2%), adenocarcinoma (1%), sarcoma (<1%), and small cell (<1%).6

Risk Factors and Symptoms

The biggest risk factor for bladder cancer is smoking, which accounts for about half of TCC cases and triples the risk of developing bladder cancer.7,8 Exposure to other carcinogens in the workplace or ingestion of arsenic is also associated with a higher risk for bladder cancer, as is age >55 years, male sex, and white race. Chronic bladder infections and a family or personal history of bladder cancer predisposes individuals to the development of bladder cancer. Individuals with mutations in the genes encoding GNT, NAT, Rb1, and PTEN, or those who have Lynch syndrome are also at a higher risk for bladder cancer (TABLE 1).9,10

Patients with bladder cancer typically present with symptoms such as gross/macroscopic hematuria or microscopic hematuria, a frequent urge to urinate (sometimes without needing to do so), painful urination, and/or lower back pain. Those patients with advanced disease may experience pelvic/bony pain, lower extremity edema, and/or flank pain. Rarely, a palpable mass may also be detected.11 Diagnostic tests are performed by a urologist before patient referral to a urological surgeon or a medical oncologist. FIGURE 3 illustrates percent of deaths from bladder cancer by age.1 Survival differs between races and is lower in blacks than in whites, Hispanics, and Asian Pacific Islanders.12

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Evolving Paradigms In Bladder Cancer: Introduction
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