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Bladder cancer is the fourth most common cancer in men, surpassed in incidence only by prostate, lung, and colon cancers. It comprises a large part of the practice of urology. Its incidence increases with age and is four times more common in men than women and twice as high in Caucasian men than African American men. 80% of newly diagnosed individuals are 60 or older. Except for skin cancers, bladder cancers are the most frequently recurring cancer, with up to 70% of patients experiencing a recurrence. When the disease is diagnosed and treated in early stages, the chances of survival are excellent, highlighting the importance of a timely and accurate diagnosis.
The highest prevalence of bladder cancer is in industrialized nations. Tobacco is the leading risk factor for bladder cancer, accounting for half of all cases, and most newly diagnosed bladder cancer patients are smokers or former smokers. About 20% of newly diagnosed bladder cancer patients are current smokers. Even if one stopped smoking years ago, the risk is related to the quantity of tobacco smoked over the years. Bladder cancer is second most common tobacco-related malignancy (#1 is lung cancer). Carcinogens in tobacco (cancer causing chemicals) are absorbed through the lungs into the bloodstream, circulate throughout the body, filter through the kidneys and into the urine and have prolonged contact time with the urinary bladder. There is a long lag time between carcinogen exposure and the development of bladder cancer, often more than twenty years, like the relationship between sun exposure and skin cancer.
The health benefits of smoking cessation are considerable, decreasing the chances of bladder cancer recurrence, progression, and development of other tobacco-related cancers. Smokers diagnosed with bladder cancer have a unique inclination to quit at the time of diagnosis, which seems to be a critical teachable moment, a window of opportunity where a lifestyle change can be leveraged. Continuing to smoke after diagnosis is associated with worse disease outcomes compared to those who quit.
Occupational exposure to other cancer-causing chemicals (carcinogens) are also risk factors for bladder cancer: dyes, rubber, leather, aluminum, paint, and arsenic in drinking water. Occupations at higher risk for bladder cancer because chemical exposure include hairdressers, painters, machinists, printers, and those who work with dyes, textiles, rubber, leather, and petrochemicals.
Bladder cancer typically manifests with blood in the urine, either visible or microscopic (seen only under microscopic magnification). It may also cause irritative lower urinary tract symptoms including urgency, frequency, discomfort with urinating, and urinary leakage.
The evaluation of a patient with blood in the urine includes imaging, cytology, and cystoscopy. Imaging tests are means of visualizing the anatomy of the urinary tract, typically through ultrasound, computerized tomography (CT), or magnetic resonance imaging (MRI). Cytology is a microscopic inspection of a urine sample by a pathologist for the presence of abnormal or cancerous cells that slough off the lining of the bladder, like a Pap smear done to screen for cervical cancer. Cystoscopy is a visual inspection of the lower urinary tract (bladder and urethra) using a tiny, flexible, lighted instrument attached to a camera and monitor.
When a bladder tumor is identified on cystoscopy, attention is directed to the number of tumors present, their size, location within the bladder, and physical appearance. A papillary appearance consists of fronds (finger-like projections floating in the bladder) with narrow attachments to the bladder lining versus a sessile appearance, in which the tumor appears solid and is broadly attached to the bladder lining.
After a bladder tumor is recognized, it needs to be removed and sent for pathological evaluation. This is performed under general or spinal anesthesia via cystoscopy, using an electric loop controlled by the urologist that is used to remove the area of concern as well as cauterize (coagulate using electricity) the underlying and adjacent tissue, both to stop bleeding and further destroy tumor cells. This procedure is called a transurethral resection bladder tumor (TURBT).
The biopsied tissue is examined by a pathologist, who provides information regarding malignancy versus benignity, tumor type, depth, and grade. Most bladder tumors are urothelial cancers, referring to the cells that line the bladder. A minority of bladder tumors are squamous cell cancers or adenocarcinomas. Depth refers to the degree that the cancer is growing into the bladder wall. Bladder cancers are broadly categorized into superficial and deep. Superficial tumors are confined to the bladder lining and superficial layers and do not penetrate the muscle layer of the bladder, whereas deep tumors have “roots” that penetrate the muscular wall of the bladder. Tumor grade refers to how much the microscopic appearance of the cancer deviates from the microscopic appearance of healthy bladder cells. Low-grade cancers are similar in cellular appearance to normal bladder cells and generally behave in an indolent (slow growing) fashion versus high-grade cancers that often behave aggressively. Other factors of prognostic importance are the number of tumors present, the size of the tumors, and their physical characteristics.
In general, the best prognosis is for a solitary, small, superficial, low-grade papillary tumor with the prognosis for multi-focal (originating from many different areas of the bladder), large, invasive (deep), sessile, high-grade tumors tending to be less favorable and thus demanding more aggressive treatment.
The biopsy information enables staging of the bladder cancer, a means of classifying the cancer, as follows:
- Ta: Superficial cancer found only in polyps (papillary) on the surface of the inner lining of the bladder.
- Tis: Carcinoma-in-situ. High grade cancer is found only in flat lesions on the surface of the inner lining of the bladder.
- T1: Cancer is found in the connective tissue deep to the lining of the bladder but has not spread to the bladder muscle.
- T2: Cancer identified within the muscle layer of the bladder.
- T3a: Cancer has penetrated through the muscular wall of the bladder into the fatty tissue layer (identified via microscopic exam only).
- T3b: Cancer has penetrated through the muscular wall of the bladder into the fatty tissue layer (identified without a microscope).
- T4: Cancer has spread to the prostate in men and to the uterus or vagina in women, or to the pelvic or abdominal wall in either gender.
Most patients with newly diagnosed bladder cancer have superficial cancer that involves the inner layers of the bladder wall; 20% have invasive disease that involves the deeper layers of the bladder wall; and 5% present with metastatic disease, defined as spread beyond the confines of the bladder.
Following TURBT, superficial cancers are managed with a regular “surveillance” protocol due to the high predilection for recurrence. Surveillance includes cystoscopy, urinary cytology, and upper urinary tract imaging on a scheduled basis.
Under certain circumstances, it is beneficial to use a medication that is instilled in the bladder to help prevent recurrences. This is especially the case when many tumors are present, in the presence of a high-grade tumor, or cancers that have recurred. It is particularly useful for carcinoma-in-situ (CIS), a variant of bladder cancer that is superficial, flat, yet high-grade. The medication of choice is often tuberculosis vaccine—BCG (bacillus Calmette Guerin), which is a live, attenuated (weakened) form of tuberculosis bacteria. There are also several chemotherapy alternatives to BCG that are used via bladder instillation.
Muscle-invasive cancers most often need to be treated with a surgical procedure involving either partial (partial cystectomy) or complete removal of the urinary bladder (cystectomy). In the circumstance that the entire bladder needs to be removed, the ureters (tubes that conduct the urine from the kidneys to the bladder) are diverted to a piece of intestine that is either attached to the skin and drained via a collection bag (ileal conduit) or, alternatively, attached to the urethra (neo-bladder, a.k.a. “reconstructed” bladder). Since muscle-invasive bladder cancer is thought of as a systemic disease because of the high potential for metastases, the standard of care prior to cystectomy is a short course of chemotherapy (neoadjuvant chemotherapy). At times, in lieu of surgery, chemo-radiation can be utilized (a combination of radiation therapy provided by the radiation oncologist and chemotherapy provided by the medical oncologist). This is typically used is the patient is not a surgical candidate or refuses surgical intervention.
Bladder cancer often behaves as two distinct and separate types of diseases: one that typically presents with multiple, superficial papillary tumors that tend to reoccur but are not lethal (like many skin cancers), versus a more serious form characterized by high-grade, non-papillary, sessile, muscle-invasive tumors that may metastasize. Fortunately, most bladder cancers are the superficial type.
