eMedicine Specialties > Urology > Cancer, Bladder, Penis, and Urethra

Bladder Cancer

Author: Gary David Steinberg, MD, FACS, Professor and Vice Chairman of Urology, Director of Urologic Oncology, Section of Urology, Department of Surgery, The University of Chicago Cancer Research Center
Coauthor(s): Mark H Katz, MD, Fellow in Urologic Oncology and Minimally Invasive Surgery, University of Chicago Medical Center; Kush Sachdeva, MD, Southern Oncology and Hematology Associates, South Jersey Healthcare, Fox Chase Cancer Center Partner; Brendan Curti, MD, Director, Genitourinary Oncology Research, Robert W Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Cancer Center; Bagi RP Jana, MD, Assistant Professor, University of Central Florida College of Medicine; Attending Physician, Department of Medicine, Florida Hospital Cancer Institute, Orlando
Contributor Information and Disclosures

Updated: Jul 27, 2009

Introduction

Background

Bladder cancer is a common urologic cancer. The most common type of bladder cancer in the United States is urothelial carcinoma, formerly known as transitional cell carcinoma (TCC). The urothelium in the entire urinary tract may be involved, including the renal pelvis, ureter, bladder, and urethra.

The clinical course of bladder cancer carries a broad spectrum of aggressiveness and risk. Low-grade, superficial bladder cancers have minimal risk of progression to death; however, high-grade muscle-invasive cancers are often lethal.

Pathophysiology

Almost all bladder cancers are epithelial in origin. The urothelium consists of a 3- to 7-cell mucosal layer within the muscular bladder. Of these urothelial tumors, more than 90% are transitional cell carcinomas. However, up to 5% of bladder cancers are squamous cell in origin, and 2% are adenocarcinomas. Nonurothelial primary bladder tumors are extremely rare and may include small cell carcinoma, carcinosarcoma, primary lymphoma, and sarcoma.

Bladder cancer is often described as a polyclonal field change defect with frequent recurrences due to a heightened potential for malignant transformation. However, bladder cancer has also been described as a problem with implantation and migration from a previously affected site.

The World Health Organization classifies bladder cancers as low grade (grade 1 and 2) or high grade (grade 3). Tumors are also classified by growth patterns: papillary (70%), sessile or mixed (20%), and nodular (10%). Carcinoma in situ (CIS) is a flat, noninvasive, high-grade urothelial carcinoma. The most significant prognostic factors for bladder cancer are grade, depth of invasion, and the presence of CIS.

Upon presentation, 55-60% of patients have low-grade superficial disease, which is usually treated conservatively with transurethral resection and periodic cystoscopy. Forty to forty-five percent of patients have high-grade disease, of which 50% is muscle invasive and is typically treated with radical cystectomy.

Less than 5% of bladder cancers in the United States are squamous cell carcinomas (SCCs). However, worldwide, SCC is the most common form, accounting for 75% of bladder cancer in underdeveloped nations. In the United States, SCC is associated with persistent inflammation from long-term indwelling Foley catheters and bladder stones. In underdeveloped nations, SCC is associated with bladder infection by Schistosoma haematobium.

Adenocarcinomas account for less than 2% of primary bladder tumors. These tumors are observed most commonly in exstrophic bladders and respond poorly to radiation and chemotherapy. Radical cystectomy is the treatment of choice.

Small cell carcinomas are aggressive tumors associated with a poor prognosis and are thought to arise from neuroendocrine stem cells.

Carcinosarcomas are highly malignant tumors that contain both mesenchymal and epithelial elements.

Primary bladder lymphomas arise in the submucosa of the bladder and are treated with radiation therapy.

Leiomyosarcoma is the most common sarcoma of the bladder.

Rhabdomyosarcomas most commonly occur in children and carry a poor prognosis.

Frequency

United States

Bladder cancer is the fourth most common cancer in men in the United States, after prostate, lung, and colorectal cancer. Bladder cancer is the 10th most common cancer in women. From 1985-2000, the number of patients diagnosed annually with bladder cancer increased by 33%. An annual cohort of 300,000-400,000 patients with bladder cancer is reported in the United States. The recurrence rate for superficial transitional cell cancer of the bladder is high, and as many as 80% of patients have at least one recurrence.

International

In developed countries, 90% of bladder cancers are TCC. In developing countries, 75% of bladder cancers are SCCs, and most of these cancers are secondary to S haematobium infection.

Mortality/Morbidity

In 2009, an estimated 70,980 new patients will be diagnosed with bladder cancer in the United States, and 14,330 of those patients will die of the disease.1

Race

Bladder cancer is more common in whites than in blacks; however, blacks have a worse prognosis than whites.

Sex

The male-to-female ratio is 3:1. Women generally have a worse prognosis than men.

Age

The median age at diagnosis is 68 years, and the incidence increases with age.

Clinical

History

  • Approximately 80-90% of patients with bladder cancer present with painless gross hematuria, which is the classic presentation. Consider all patients with gross hematuria to have bladder cancer until proven otherwise. Suspect bladder cancer if any patient presents with unexplained microscopic hematuria.
  • Twenty to thirty percent of patients with bladder cancer experience irritative bladder symptoms such as dysuria, urgency, or frequency of urination that are related to more advanced muscle-invasive disease or CIS.
  • Patients with advanced disease can present with pelvic or bony pain, lower-extremity edema from iliac vessel compression, or flank pain from ureteral obstruction.

Physical

  • Superficial bladder cancer is rarely found during a physical examination.
  • Occasionally, an abdominal or pelvic mass may be palpable.
  • Examine for lymphadenopathy.

Causes

Up to 80% of bladder cancer cases are associated with environmental exposure, which suggests that bladder cancer is potentially preventable. Smoking is the most commonly associated risk factor and accounts for approximately 50% of all bladder cancers. Nitrosamine, 2-naphthylamine, and 4-aminobiphenyl are possible carcinogenic agents found in cigarette smoke. Bladder cancer is also associated with industrial exposure to aromatic amines in dyes, paints, solvents, leather dust, inks, combustion products, rubber, and textiles. Therefore, higher-risk occupations associated with bladder cancer include painting, driving trucks, and working with metal.

Several medical risk factors are associated with bladder cancer. Patients with prior exposure to radiation treatment of the pelvis have an increased risk of bladder cancer. Chemotherapy with cyclophosphamide increases the risk of bladder cancer via exposure to acrolein, a urinary metabolite of cyclophosphamide. Patients with spinal cord injuries who have long-term indwelling catheters have a 16- to 20-fold increased risk of developing SCC of the bladder.

Coffee consumption does not increase the risk of developing bladder cancer. Early studies of rodents and a minority of human studies suggested a weak connection between artificial sweeteners (eg, saccharin, cyclamate) and bladder cancer; however, most recent studies show no significant correlation.

Although no convincing evidence exists for a hereditary factor in the development of bladder cancer, familial clusters of bladder cancer have been reported. Several genetic mutations have been identified in bladder cancer. Mutations of the tumor suppressor gene for p53, found on chromosome 17, are associated with high-grade bladder cancer and CIS. Mutations of the tumor suppressor gene for p15 and p16, found on chromosome 9, are associated with low-grade and superficial tumors. Retinoblastoma (Rb) tumor suppressor gene mutations are also noted. Bladder cancer is associated with increased expression of the epidermal growth factor gene and the erb- b2 oncogene, and mutations of the oncogenes p21 ras, c-myc, and c-jun.

More on Bladder Cancer

Overview: Bladder Cancer
Differential Diagnoses & Workup: Bladder Cancer
Treatment & Medication: Bladder Cancer
Follow-up: Bladder Cancer
Multimedia: Bladder Cancer
References
Further Reading
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Keywords

urothelial cancer, urothelial carcinoma, bladder cancer, transitional cell cancer, transitional cell carcinoma, TCC, bladder tumor, leiomyosarcoma, rhabdomyosarcoma, hematuria, urothelial tumors, carcinoma in situ, CIS, squamous cell carcinoma, SCC, urothelial carcinoma, indwelling Foley catheter, bladder stones, Schistosoma haematobium, S haematobium, primary bladder lymphoma, smoking, aromatic amines, radiation treatment of the pelvis, nitrosamine, 2-naphthylamine, 4-aminobiphenyl, chemotherapy with cyclophosphamide, acrolein, muscle-invasive bladder cancer, urinary tract infection, superficial transitional cell carcinoma, superficial TCC

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Contributor Information and Disclosures

Author

Gary David Steinberg, MD, FACS, Professor and Vice Chairman of Urology, Director of Urologic Oncology, Section of Urology, Department of Surgery, The University of Chicago Cancer Research Center
Gary David Steinberg, MD, FACS is a member of the following medical societies: American Association for Cancer Research, American College of Surgeons, American Urological Association, Société Internationale d'Urologie (International Society of Urology), Society of Laparoendoscopic Surgeons, and Society of Urologic Oncology
Disclosure: Spectrum Pharmaceuticals Consulting fee Consulting; Abbott Molecular Consulting fee Speaking and teaching; Endo Pharmaceuticals Consulting fee Consulting; Bioniche Consulting fee Consulting

Coauthor(s)

Mark H Katz, MD, Fellow in Urologic Oncology and Minimally Invasive Surgery, University of Chicago Medical Center
Mark H Katz, MD is a member of the following medical societies: Alpha Omega Alpha, American Urological Association, Endourological Society, and Society of Urologic Oncology
Disclosure: Nothing to disclose.

Kush Sachdeva, MD, Southern Oncology and Hematology Associates, South Jersey Healthcare, Fox Chase Cancer Center Partner
Disclosure: Nothing to disclose.

Brendan Curti, MD, Director, Genitourinary Oncology Research, Robert W Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Cancer Center
Brendan Curti, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, Oregon Medical Association, and Society for Biological Therapy
Disclosure: Nothing to disclose.

Bagi RP Jana, MD, Assistant Professor, University of Central Florida College of Medicine; Attending Physician, Department of Medicine, Florida Hospital Cancer Institute, Orlando
Bagi RP Jana, MD is a member of the following medical societies: American Medical Association and American Society of Clinical Oncology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Dan Theodorescu, MD, PhD, Paul Mellon Professor of Urologic Oncology, Department of Urology, University of Virginia Health Sciences Center
Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology
Disclosure: Nothing to disclose.

CME Editor

J Stuart Wolf Jr, MD, FACS, David A Bloom Professor of Urology, Director of Division of Minimally Invasive Urology, Department of Urology, University of Michigan
J Stuart Wolf Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, Society of University Urologists, and Society of Urologic Oncology
Disclosure: Terumo Corporation Consulting fee Consulting; Gyrus-ACMI Honoraria Speaking and teaching

Chief Editor

Bradley Fields Schwartz, DO, FACS, Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine
Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Association of Military Osteopathic Physicians and Surgeons, Endourological Society, Society of Laparoendoscopic Surgeons, and Society of University Urologists
Disclosure: Nothing to disclose.

 
 
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