Overview of Bladder Cancer
Bladder cancer is the most common tumor of the urinary system and the fifth most common cancer in North America. It is estimated that 75,000 new cases of bladder cancer will be diagnosed in 2008, and that 16,000 individuals will die from it. The World Health Organization (WHO) estimates that there are 330,000 new cases annually worldwide. Bladder cancer prevalence is steadily increasing and its projected rise is 28% by 2010 for both men and women.
The diagnosis of bladder cancer currently relies on identifying malignant cells by urine cytology, with or without adjunct tests, and also by visualizing the tumor by cystoscopic examination and tissue biopsy. Despite its low sensitivity (35% to 40%)[1] in the detection of urothelial carcinoma (UC) of all grades and stages (17% in grade 1, 61% in grade 2 and 90% in grade 3)[1], urine cytology remains the most commonly used non-invasive test.
Risk factors
The greatest risk factor for bladder cancer is cigarette smoking (60%)[2]. However, occupational exposure to industrial chemicals such as aluminium, dye, rubber, coal tar pitch, paint and leather is also a risk factor.
Clinical presentation
Most frequently (in 85%[1] of patients), bladder cancer is suspected based upon gross or microscopic hematuria (blood in the urine). A small percentage of patients complain of frequent urination, urgency or dysuria. Advanced bladder cancer may present symptoms of bladder neck or ureter obstruction, or pain associated with metastases.
Patient diagnosis
A patient presenting with hematuria will usually have a urine cytology test performed. Urinary cytology is helpful when positive but up to 55-60% of patients with early stage bladder cancer may have negative urine cytology results. If abnormal or suspicious cytology results are observed, then the urologist performs a cystoscopy. Visible tumors are resected transurethrally and tissue is submitted for pathological exam. The increased sensitivity of the ImmunoCyt™/uCyt+™ test with urine cytology may increase the early detection rate of bladder cancer recurrence.
Monitoring of patient after diagnosis of bladder cancer tumor [3]
| First 2 years | 1 cystoscopy every 3 months |
|---|---|
| Years 3-4 | 1 cystoscopy every 6 months |
| ≥ 5 years | 1 cystoscopy every 12 months |
(NOTE: Urologists may use the increased sensitivity of ImmunoCyt™ / uCyt™ combined with urinary cytology to replace a number of monitoring cystoscopies.) [4][5]
Bladder cancer staging
The most common bladder cancers begin in the cells lining the bladder. This type of cancer is called transitional cell carcinoma and occurs in over 90% of bladder cancers. Cancer that is confined to the lining of the bladder is called superficial bladder cancer. After treatment, superficial bladder cancer can recur and most often it recurs as another superficial cancer.
In some cases the recurrence begins in the transitional cells and spreads through the lining of the bladder and invades the muscular wall of the bladder. This is known as invasive bladder cancer. Invasive cancer may grow through the bladder wall and spread to nearby organs, or metastasize at distance in the lymph nodes, or the liver, lung or bones. This new tumor is called metastatic bladder cancer.
The stage or local extent of the disease is related to the depth of penetration of the tumor into the bladder wall and is an important predictive feature of the cancer. Most occidental urologists use the TNM (Tumor Node Metastasis) classification system.
TNM Staging Definitions
| Ta | Refers to a papillary (solid) tumor that is limited to the mucosa |
|---|---|
| T1 | Refers to papillary tumors invading submucosa but not muscle |
| Tis | Are carcinoma in situ within the mucosa and are high grade |
| T2 | Muscle invasive cancer |
| T3 | Cancer invading through the wall of the perivesical fat |
| T4 | Invasion of prostate or other adjacent organs |
| N+ | Metastasis to regional lymph nodes |
| M+ | Distance metastasis (liver, lung, bones) |
About 90% of bladder cancers in the United States occur as pure transitional cell carcinoma. The remaining 10% are divided between squamous cell carcinomas, adenocarcinomas and sarcomas.
Bladder cancer grade
Grade defines the disease’s aggressiveness and is determined by the cells’ appearance under the microscope (differentiation: how the cells resemble healthy tissue the same type), and the make-up of their nucleus. This analysis is performed on cells from biopsy specimens.
Bladder cancer treatment options
At first diagnosis, about 80% of tumors, are stage Ta or T1 papillary tumors and are treated adequately by transurethral resection. Recurrence will be observed in 60% of these cases. For the remaining 20% with stage T2 or higher muscle-invasive cancers, treatment is usually radical cystectomy (full removal of the bladder). Monitoring with ImmunoCyt™/uCyt+™ therefore is useful for 80% of patients with initial papillary non-muscle invasive cancers (Ta and T1).
A urologist will generally treat most Ta and T1 tumors (a.k.a. low-stage, low-grade tumors). For each new case that is diagnosed and treated, there will be an average of three recurrences. It is therefore estimated that out of 100 consecutive tumors treated by a urologist, 71% will be Ta stage, 20% will be T1 and less than 10% will be muscle-invasive.
Treatment consists of tumor resection and, when required, intravesical treatment such as immunotherapy or chemotherapy.
The high percentage of low stage, low grade patients being treated, stresses the need for a sensitive test to detect these tumors.
[1] Current bladder tumor tests: does their projected utility fulfil clinical necessity? V.B. Lokeshwar and M.S. Soloway. Journal of Urology, 2001
[2] Current Medical Diagnosis & Treatment. L.M. Tierney, Jr, S.J. McPhee, M.A. Papadakis. Lange Medical Books/McGraw-Hill, 2005.
[3] ImmunoCyt test improves the diagnostic accuracy of urinary cytology: results of a French multicenters study. C Pfister, D. Chautard, M. Devonec, P. Perrin, D. Chopin, P. Rischmann, O. Bouchot, D. Beurton, C. Coulange, J.J. Rambeaud. Journal of Urology, 2003
[4] Monitoring Superficial Bladder Cancer (BC) with the ImmunoCyt Fluorescent Cytology Test. Edward Messing, Howard Korman, Brian Stork, Edward Barker, Jeanne Underhill, Lisat Teot, David Botswick. Journal of Urology, October 2005
[5] The uCyt+ Test: an alternative to cytoscopy for a less invasive follow-up of patients with low risk of urothelial carcinomas. M. Lodde, C. Mian, E. Comploj, S Palermo, El. Longhi, M. Marberger, A. Pycha. Urology, May 2006