Bladder Cancer: What You Should Know

September 27, 2021

Bladder cancer comprises a large part of the practice of urology. The incidence of bladder cancer 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 years of age or older. Excepting 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.

Causes of Bladder Cancer 

The highest prevalence of bladder cancer is in industrialized nations. Tobacco is the greatest risk factor for bladder cancer, accounting for half of all cases. Even if one stopped smoking years ago, the risk is related to the quantity of tobacco smoked over the years. Occupational exposure to cancer-causing chemicals (carcinogens) is another risk factor: dye, 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.

­The Relationship Between Tobacco and Bladder Cancer

Bladder cancer is second most common tobacco-related malignancy (#1 is lung cancer). Tobacco is the leading risk factor for bladder cancer and most newly diagnosed bladder cancer patients are smokers or former smokers. About 20% of newly diagnosed bladder cancer patients are current smokers. Carcinogens in tobacco (cancer causing chemicals) are absorbed through the lungs into the bloodstream, circulate throughout the body, filter through the kidneys into the urine and have prolonged contact time with the urinary bladder as urine is stored in the bladder. There is a long lag time between carcinogen exposure and the development of bladder cancer, often more than twenty years, similar to the relationship between sun exposure and skin cancer.

The health benefits of smoking cessation are considerable, decreasing chances of bladder cancer recurrence, progression and development of another tobacco-related cancer. Those smokers diagnosed with bladder cancer have a unique propensity 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.

Diagnosing Bladder Cancer

Bladder cancer typically presents 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 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, similar to 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.

The Stages of Bladder Cancer

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 a narrow attachment to the bladder lining versus a sessile appearance, in which the tumor appears solid and is widely attached to the bladder lining.

Once 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 that is used to remove the area of concern as well as cauterize (use electricity to coagulate tissue) the underlying and adjacent tissue, both to stop bleeding and further destroy tumor cells.

The biopsied tissue is examined by a pathologist, who provides information regarding malignancy vs. benignity, tumor type, depth, and grade. The vast majority of 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 largely 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) fashion versus high-grade cancers that can 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 and the worst prognosis is for multi-focal (originating from many different areas of the bladder), large, invasive (deep), sessile, high-grade tumors.

The biopsy information enables staging of the bladder cancer, a means of classifying the cancer, as follows:

  • Ta: Superficial cancer is found only in polyps (papillary) on the surface of the inner lining of the bladder.
  • Tis: Carcinoma-in-situ. Tumor is found only in flat lesions on the surface of the inner lining of the bladder.
  • T1: Tumor is found in the connective tissue below the lining of the bladder but has not spread to the bladder muscle.
  • T2: Tumor has spread to the muscle layer deep to the lining of the bladder.
  • T3a: Tumor has spread through the muscular wall of the bladder into the fatty tissue layer as identified under microscopic examination.
  • T3b: Tumor has spread through the muscular wall of the bladder into the fatty tissue layer and is capable of being identified without a microscope.
  • T4: Tumor 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.


Stages of Bladder Cancer

The majority of 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.

Treating Bladder Cancer

Superficial cancers are managed with regular “surveillance” 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 by bladder instillation.

Muscle-invasive cancers most often need to be treated with a surgical procedure involving either partial or complete removal of the urinary bladder. In the circumstance that the entire bladder needs to be removed, the ureters (tubes that conduct the urine from the kidneys to the bladder) need to be diverted to a piece of intestine that is either attached to the skin to a collection bag (ileal conduit) or attached to the urethra (neo-bladder or “reconstructed” bladder). 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).

Bladder cancer often behaves as two separate types of diseases: one that typically presents as multiple, superficial papillary tumors, which tend to reoccur, but are not lethal (similar to many skin cancers), versus another more deadly form characterized by high-grade, non-papillary, muscle-invasive tumors that have a tendency to metastasize. Fortunately, the vast majority of bladder cancers are the superficial type.

Written by Dr. Andrew Siegel


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