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Harvard Commentaries
Harvard Commentaries
Reviewed by the Faculty of Harvard Medical School

Man to Man Man to Man

Bladder Cancer -- Men at Risk

September 12, 2013

By Harvey B. Simon M.D.

Harvard Medical School

Over 69,000 Americans will be diagnosed with bladder cancer this year. The disease disproportionately targets men.

  • Three-quarters of all people affected are men.
  • Seven out of 10 people who die from bladder cancer are men.

But there's good news, too. Early diagnosis can nip the disease in the bud. And new treatments are improving the outlook for patients with advanced disease. Best of all, bladder cancer is largely preventable.

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What Causes Bladder Cancer?

All cancers are caused by a combination of genetic and environmental factors. In the case of bladder cancer, scientists are just discovering genes that increase risk, but they already know that external factors are responsible for many cases.

Cigarette smoking

Cigarette smoking is the most important cause of the disease. It accounts for almost half of the bladder cancer deaths in men. Many of the toxins that enter the body when inhaling are absorbed into the bloodstream. Then they areexcreted by the kidneys into the urine. Because urine sits in the bladder for hours before it is expelled, the bladder lining is in prolonged contact with carcinogens (cancer-causing substances).

Workplace toxins

Various industrial toxins can also injure the cells that line the bladder, eventually producing cancer. In the past, workers in the rubber, paint, cable, electric and textile industries were at substantial risk. But safety regulations have greatly improved matters in today's workplaces.

Other causes

Other relatively uncommon causes include:

  • Prolonged therapy with cyclophosphamide (Cytoxan) and overuse of the pain killer phenacitin
  • Radiation therapy for prostate cancer, which appears to increase risk for bladder cancer years later
  • Dietary factors (See "Prevention" below.)

Although extremely high doses of artificial sweeteners may cause bladder cancer in animals, there is no evidence that they do so in humans.

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The most common symptom of bladder cancer is blood in the urine that is visible to the naked eye(gross hematuria). Another finding that often leads to the diagnosis is microscopic hematuria, red blood cells in the urine that are only detected during laboratory analysis of a urine specimen. In either case, the bleeding can be consistent or intermittent. And although urinary bleeding should always raise the possibility of bladder cancer, other conditions are often to blame.

In most cases, the urinary bleeding is painless. In some men, though, the disease is linked to urinary discomfort, urgency or frequency. And in the uncommon cases of widespread disease, the first symptoms of bladder cancer can be belly, back, bone pain or weight loss.

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Two-Step Diagnosis

To diagnose bladder cancer the doctor has to:

  1. Rule out other common causes of urinary bleeding
  2. Identify the bladder tumor

Step #1 often involves:

  • A urine culture to rule out bladder or kidney infections
  • A digital rectal exam, usually with a prostate-specific antigen (PSA) test to check for benign prostate hyperplasia and prostate cancer
  • Imaging studies, such as a spiral CT scan, which can detect kidney stones, kidney cancer and even larger bladder cancers

Step #2 often involves an office procedure called cystoscopy. After administering a local anesthetic, the urologist inserts a thin, flexible fiber-optic tube (cystoscope) through the urethra into the bladder. The doctor can visualize and photograph the bladder, and insert tiny instruments through the scope to take biopsies of the bladder wall. This is the most important step of all.

Cystoscopy is the gold standard for the diagnosis of bladder cancer, but it is invasive. As a result, researchers are developing tests to diagnose bladder cancer by checking urine samples. The oldest test is urine cytology, the microscopic evaluation of cells in voided urine. Newer tests depend on finding tumor markers — abnormal genes or their protein products — in the urine. Several tests are available, but none are highly reliable.

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How it's Treated

The treatment of bladder cancer depends how advanced the disease is and how aggressive the tumor cells appear.

Most cases are diagnosed early, before the tumor has invaded the bladder muscle. The treatment for these early-stage (“superficial”) cancers is surgery to remove the tumor. This can be done with a procedure called transurethral resection of the bladder (TURBT). It allows the urologist to work on the inside of the bladder through a cystoscope. In some cases, the urologist will give a chemotherapy drug immediately after the TURBT.

If a superficial bladder cancer has characteristics that suggest it is likely to come back, more treatment is needed. Usually this involves immunotherapy. Bacillus Calmette-Guerin (BCG) bacteria, which were developed over 80 years ago as a vaccine against tuberculosis, are injected into the bladder, where they boost the body's own tumor-fighting immune cells. An alternative is intravesicular (within the bladder) chemotherapy. In either case, a typical program involves weekly treatments for six to eight weeks followed by intermittent maintenance treatments for up to two years.

Superficial bladder cancers that do not respond to local therapy require more aggressive treatment. The same is true of invasive tumors that have penetrated the muscular layers of the bladder wall. The standard treatment for these tumors is radical cystectomy, surgical removal of the entire bladder and nearby lymph nodes. (In men, the prostate and seminal vesicles are also removed, which usually causes erectile dysfunction.) Some patients benefit from supplementary chemotherapy.

Until recently, patients with radical cystectomies required an ileostomy to collect urine in a plastic bag worn on the abdominal wall. Although most patients adjusted remarkably well, new surgical techniques can make life easier after radical cystectomy. Some patients may also get good results with limited surgical removal of the tumor, followed by a combination of radiation and chemotherapy. An experienced medical center is the key to successful bladder-sparing therapies.

Chemotherapy and radiation can help control widespread bladder cancer. But bladder cancer that has spread throughout the body — metastasized — is rarely curable.

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The first step, of course, is to quit smoking. It will also reduce a smoker’s risk of heart attacks, lung cancer and many other major diseases. But in the case of bladder cancer, the benefit accrues slowly, taking 10 years or more; ex-smokers should remain extra vigilant about warning symptoms during this time.

The second step is to review your work history for possible exposures to cancer-causing chemicals. Benzene and various arylamines are high on the list. And since bladder cancer develops slowly — usually at least 25 years after exposure — continued vigilance is appropriate long after the exposure itself.

The third step is to improve your diet. A high intake of fruits and vegetables appears to reduce the risk of bladder cancer. A high fat diet seems to increase risk.

The final protective measure is to drink more fluids. A high urine volume will dilute toxins in the urine and increase bladder emptying, both of which should protect the vulnerable bladder cells from carcinogens.

A Harvard study of 47,909 men showed that dilution may be a solution to the bladder cancer problem. Men who drank the most were only half as likely to develop bladder cancer as the men who drank the least. Although water was particularly beneficial, all types of beverages contributed to protection, including alcoholic and caffeinated beverages.

All in all, men can decrease their risk of bladder cancer by 7% for each additional 8 ounces of fluid they drink each day. In a sense, the bladder is like so many other parts of the body: The more it's used, the healthier it stays.

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Harvey B. Simon, M.D. is an Associate Professor of Medicine at Harvard Medical School and a member of the Health Sciences Technology Faculty at Massachusetts Institute of Technology. He is the founding editor of the Harvard Men's Health Watch newsletter and author of six consumer health books, including The Harvard Medical School Guide to Men's Health (Simon and Schuster, 2002) and The No Sweat Exercise Plan, Lose Weight, Get Healthy and Live Longer (McGraw-Hill, 2006). Dr. Simon practices at the Massachusetts General Hospital; he received the London Prize for Excellence in Teaching from Harvard and MIT.

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