Prostate Cancer

No One Answer for Testing or Treatment


Publication No. (FDA) 00-1297

September-October 1998 FDA Consumer.
With revisions made in May 2000

by John Henkel

Russ Ingram didn't sense pending calamity when he reported for a company physical seven years ago. After all, he was in good shape and, at 39, still very much a robust young man with no signs of health problems.

During part of the exam, however, the doctor noticed that Ingram's prostate was enlarged. While this can indicate a tumor, often it signals a common benign prostate condition, usually in men much older than Ingram. But a visit to a urologist produced the grim news that his condition was not benign. He had prostate cancer.

"I was devastated," says Ingram. "Due to my age, I didn't think there was anything to worry about. It caught me totally off guard. I didn't even know where the prostate was."

To be sure, Ingram's case is not typical. His age at diagnosis placed him well outside the primary risk group for prostate cancer. Statistically, at least 80 percent of prostate cancers occur in men over 65. In fact, men in their 30s are not usually tested for prostate cancer in a physical and Ingram says it was just "a fluke" that the doctor discovered the enlarged prostate.

While the disease can strike any man, younger men at increased risk include African Americans, who have double the risk and death rate of white men and often are stricken before age 50. Men with a family link to prostate cancer through brothers or fathers also are at a greater risk of getting the disease before 50.

The American Cancer Society estimates that in the year 2000, nearly 180,400 American men will be diagnosed with prostate cancer and 31,900 will die from the disease. (In comparison, 1998 estimates for lung cancer in men are 171,500 cases and 160,100 deaths; for colorectal cancer, the estimates are 131,600 cases and 56,000 deaths.)

Despite the bleak numbers, 89 percent of men diagnosed with the disease will survive at least five years and 63 percent will survive at least 10 years, the society says. These rates are partly due to improved screening tests and diagnostics the Food and Drug Administration has approved that discover cancer in early stages. Also, prostate cancer is very slow-growing in some men, who may die of some other cause before the disease takes its toll.

Detecting Prostate Cancer

The prostate is a male sex gland, about the size of a walnut. It produces a thick fluid that helps propel sperm through the urethra and out of the penis during sex. Because the prostate is just below the bladder and directly in front of the rectum, a doctor can check the size and condition of the gland by inserting a rubber-gloved finger into the rectum. This digital rectal exam (DRE) has for years been the gold standard for detecting prostate cancer as well as the noncancerous disorder benign prostatic hyperplasia (see "Noncancerous Prostate Disorder").

In 1985, FDA approved the first test for monitoring blood levels of a substance called prostate specific antigen (PSA), which, when elevated, can indicate cancer presence. Several companies now have approved PSA tests, which, experts say, have revolutionized the screening and monitoring of patients.
PSA is an ideal marker for prostate cancer because it is basically restricted to prostate cells. A healthy prostate will produce a stable amount--typically below 4 nanograms per milliliter, or a PSA reading of "4" or less--whereas cancer cells produce escalating amounts that correspond with the severity of the cancer. A level between 4 and 10 may raise a doctor's suspicion that a patient has prostate cancer, while amounts above 50 may show that the tumor has spread elsewhere in the body.
Most PSA tests measure "total PSA," or the amount that is bound to blood proteins. In 1998, FDA approved the Tandem R test, which measures not only total PSA but another component called "free PSA," which floats unbound in the blood. Comparing the two helps doctors rule out cancer in men whose PSA is mildly elevated from other causes. A 1995 study in the Journal of the American Medical Association showed that the free PSA test can reduce unnecessary prostate biopsies by 20 percent in patients with a PSA between 4 and 10.
The availability of increasingly sensitive testing devices has created a debate over when men should be tested for prostate cancer, how often, and whether men under 50 with no symptoms should be routinely screened. Opponents say mass screening would be expensive, and the verdict is still out on whether early detection can curb the disease's mortality rate. But proponents say early detection is the closest thing currently to a cure and that it can save lives. The American Cancer Society and the American Urological Association recommend annual PSA tests--along with the digital exam--for all men over 50 and for high-risk men over 40.
The PSA test, though a powerful tool, "is not perfect," says Jean Fourcroy, M.D., a urologist and medical officer in FDA's Center for Devices and Radiological Health. Besides being thrown off by noncancerous conditions, the tests can vary between manufacturers. "Patients and physicians should use the same brand of PSA test throughout monitoring because of these possible variations," Fourcroy says.
When PSA or digital tests indicate a strong likelihood that cancer is present, doctors usually order a transrectal ultrasound (TRUS), a probe inserted into the rectum that uses sound waves to "map" the prostate and show any suspicious areas. Doctors then may take biopsies of various sectors of the prostate using tiny hollow needles inserted through the rectum. Biopsies are the only definitive way to determine if prostate cancer is present.
If the biopsy indicates cancer, the doctor then "stages" the tumor based on which biopsy specimens contain cancer, the extent of cancer, and the location of cancer in the specimens. Staging also depends on the extent and location of cancer outside the confines of the prostate.
Another important measure, the Gleason score, gauges the probable aggressiveness of the tumor based on the cellular differences of the cancer. Tumor cells that look similar to normal cells tend to be less aggressive, while those distributed randomly with uneven edges are likely to spread rapidly. Two numbers, each from 1 to 5, are assigned. The higher the numbers when the two are added, the more aggressive the tumor is likely to be.
Doctors also examine the ploidy, or number of sets of chromosomes in a cancer cell. Diploid cells, for example, have a complete set of normally paired chromosomes, and tend to grow slowly and respond well to therapy.
Recently, some doctors have begun using Partin Tables, a scoring method developed at Johns Hopkins University that uses PSA, Gleason number, and staging to predict if the disease is confined or has spread to other sites. Doctors also can determine cancer spread with imaging techniques such as bone scans and computerized tomography (CT) scans.
Treating the Disease

Armed with diagnostic data, patients and their doctors must then decide on a treatment course. It is at this point that patients must be well educated, says FDA's Fourcroy. "The decisions made [on treatment] are so crucial and will have such an effect on quality of life, men must weigh them very carefully," she says. "And they must also remember to include their partners in the decisions because they will be affected by the course of action too."

One possible treatment is actually no treatment at all. Doctors call it watchful waiting, and it is best suited for men with a 10-year life expectancy or less who have a low Gleason number and whose tumor has not spread beyond the prostate. The idea is that in these men the cancer is growing so slowly, they likely won't die from it. More radical treatments such as surgery might be more dangerous than simply waiting. Marty Feins, 77, opted for watchful waiting in 1993 when diagnosed with prostate cancer, and he's "going great," he says. Though the Las Vegas man was deemed a good candidate for radiation treatment, he says he did a lot of research and decided his was a prudent course. His PSA level is elevated but is not rising rapidly. "Right now I'm holding steady," he says. "In fact, if I hadn't had a biopsy, I wouldn't even know I have [cancer]."
Californian Jerry Coleman, 61, diagnosed in 1995, opted for a surgical treatment called radical prostatectomy (RP), in which the prostate is completely removed. If performed when cancer is confined to the gland, RP is tantamount to a cure since in theory it removes all the cancer. Coleman says he chose RP because he was unsure of the track record of other treatments. "I felt comfortable that this was the appropriate attack considering my health, age, and the stage of my disease," he says.
Besides being a serious operation that requires weeks of recuperation, RP can have lingering side effects, including impotence and incontinence. Until the early 1990s, virtually all RP patients were saddled with these effects. But "nerve sparing" techniques developed at Johns Hopkins University have preserved urinary and erectile functions in increasing numbers of RP patients. The CaverMap, a device cleared by FDA in 1998, aids surgeons in locating nerve bundles to help avoid severing nerves related to continence and erections when removing the prostate.
Radiation is a treatment option that may be less traumatic than RP and appears to have similar results when used in early-stage patients. Radiation also produces side effects, including impotence, in about half of patients. It can be applied through an external beam that directs the dose to the prostate from outside the body. FDA also has cleared low-dose radioactive "seeds," each about the size of a grain of rice, that are implanted within the prostate to kill cancer cells locally. Called brachytherapy, the seeding technique is sometimes combined with external-beam radiation for a "one-two punch." Studies done at the Georgia Center for Prostate Cancer Research and Treatment show that 68 percent of men treated with both radiation methods applied simultaneously are cancer free 10 years after treatment. Intel Corporation chairman Andy Grove, who was Time magazine's 1997 "Man of the Year," underwent the combined radiation therapy in 1995. According to company spokesman Howard High, Grove, 62, is "in excellent condition" now.
Cryotherapy, in which prostate tumors are killed by freezing, shows encouraging early results. But some medical professionals consider it experimental with not enough long-term data yet to determine its effectiveness.
Hormonal therapy is often used in all phases of prostate cancer treatment to help block production or action of the male hormones that have been shown to fuel prostate cancer. Among widely used approved hormone blockers, often used in combination, are Lupron (leuprolide acetate), Casodex (bicalutamide), Eulexin (flutamide), Nilandron (nilutamide), Zoladex (goserelin acetate implant), and Viadur (leuprolide acetate). Because the testicles produce male hormones, some men also undergo testicle removal to cut off the hormone supply. Advanced prostate cancer patients are usually treated with any number of chemotherapeutic drugs such as Novantrone (mitoxantrone), which do not cure the disease but often do ease pain and other symptoms.
Looking Ahead

Incidences of prostate cancer have dipped slightly in the last five years, says the American Cancer Society. But as FDA's Fourcroy says, there's no "magic bullet" right now that will significantly reduce prostate cancer cases or deaths. As for the future, some strong possibilities exist.

  • Over a hundred drugs and vaccines for treating prostate cancer are currently in clinical trials. Proposed drugs that may choke off the blood supply to prostate tumors, along with vaccines that rev up the immune system to attack prostate tumors, appear possible.


  • Treatments based on the hormone IGF-1, which can be a marker for increased prostate cancer risk, are feasible, researchers from McGill and Harvard Universities report.


  • Studies examining the relationship between diet and prostate cancer have identified a high-fat diet as a risk factor for the disease. Other diet research has shown a possible inhibitory effect for prostate cancer when foods such as soy products and cooked tomatoes are added to the diet.


  • A study sponsored in part by the National Cancer Institute showed that vitamin E may reduce prostate cancer risk by 30 percent, but NCI stopped short of recommending supplements.


  • NCI is studying 18,000 men over seven years to determine if the drug Proscar (finasteride) can prevent prostate cancer.



Meanwhile, patients are benefiting from prostate cancer's increasing visibility. "It's finally coming out of the closet," says Howard Waage, 51, a California prostate cancer patient. "It's crucial for us men to be on top of our health, and that's easier to do now than ever."

John Henkel is a member of the U.S. Food and Drug Administration's Website Management Staff.

Out in the Open

Until this decade, not much support or information was available for prostate cancer patients. Then, in the early 1990s, public figures began talking openly about the disease, books and articles appeared, and hundreds of support groups sprang up nationwide. Numerous celebrity deaths from prostate cancer--among them actor Telly Savalas, musician Frank Zappa, and Nobel Prize winner Linus Pauling--were clustered a few months apart. Other personalities, including former Sen. Bob Dole, golfer Arnold Palmer, and retired Gen. H. Norman Schwarzkopf, went public with their experiences. Men started getting the message that the disease can strike any man and that it is possible to survive prostate cancer if it is discovered early enough.

Along with the abundance now of printed prostate materials, the burgeoning popularity of the Internet has helped spawn a new breed of prostate cancer patient, a well-informed man who is in charge of his destiny. Huge amounts of reliable material from organizations such as the American Cancer Society, the National Cancer Institute, and various university hospitals are available online.

Patients also are using the Internet to connect with fellow patients through electronic mailing lists. This allows them to compare notes and get feedback on treatment decisions. Many prostate cancer doctors post messages to mailing lists and answer patient questions.

"I'm not sure I'd be alive today if it weren't for information I've gotten on the Internet," says prostate cancer patient Russ Ingram, who has located experts online who have helped him select the latest treatments for his spreading cancer.


For More Information

Contact any of these organizations for more on prostate cancer, support groups, and joining Internet mailing lists.

American Cancer Society
1-800-ACS-2345 (1-800-227-2345)

American Foundation for Urologic Disease
1128 N. Charles St.
Baltimore, MD 21201

National Cancer Institute
Building 31, Room 10A03
31 Center Drive, MSC 2580
Bethesda, MD 20892-2580
1-800-4-CANCER (1-800-422-6237

National Prostate Cancer Coalition
1158 15th St., N.W.
Washington, DC 20005
(202) 463-9455

US Too International Inc.
930 N. York Road, Suite 50
Hinsdale, IL 60521-2993

Noncancerous Prostate Disorders

Up to 90 percent of men over age 80 have some symptoms of the condition known as benign prostatic hyperplasia (BPH). Half of men over 50 have it.

BPH is not cancer, but it can display similar symptoms: prostate specific antigen (PSA) levels may be elevated, and the prostate gland itself is enlarged. The condition is rarely dangerous, but it can be aggravating for men because of the prostate's proximity to the urethra, which runs through the gland. When the prostate becomes enlarged, it chokes off the flow of urine, and strain may be necessary to start the flow. Men may have frequent urges to urinate, especially at night, or they may have a lingering sensation that the bladder isn't empty.

Treatment options include:

Heat treatments--These are minimally invasive and generate heat within the prostate by microwave, radio-frequency (RF), or laser energy. FDA approved the first microwave device, the Prostatron, in 1996, and since has approved the Targis and Urowave systems. Transurethral Needle Ablation (TUNA) was cleared in 1996 and uses RF needles inserted into the prostate to heat the tissue. FDA has cleared three types of lasers for treating BPH: a side-firing device that delivers laser energy from a fiber in the urethra; contact systems, which come in direct contact with the prostate; and the interstitial laser, which heats the prostate from probes placed within the gland.

Surgery--Transurethral resection of the prostate (TURP) removes excess prostate tissue with special instruments inserted into the urethra. For smaller prostates, the less invasive transurethral incision of the prostate (TUIP) involves one or two cuts made in the gland.

Stents--In 1997, FDA approved the Urolume, a tube to hold open the urethra and relieve obstruction due to BPH.

Alpha blockers--These oral drugs relax the prostate muscles, easing pressure on the urethra. FDA has approved Hytrin (terazosin), Cardura (doxazosin), and Flomax (tamsulosin hydrochloride).

Proscar (finasteride)--This drug shrinks the prostate by reducing the body's conversion of testosterone to the hormone DHT. FDA approved Proscar in 1992, and in 1998 allowed the drug to be labeled as the first medication to reduce the need for prostate surgery and to lower the risk of developing acute urinary retention, a serious and painful complication of BPH. Proscar also is being tested as a prostate cancer preventive in a massive clinical trial sponsored by the National Cancer Institute.

Another noncancerous condition, prostatitis, can be a bacterial infection of the prostate occurring in men of any age. Doctors typically prescribe antibiotics for the condition, which may occur only once (acute prostatitis) or several times (chronic prostatitis). Sometimes the condition clears up on its own, but men should always seek treatment, say health professionals.



Publication No. (FDA) 00-1297

This article originally appeared in the September-October 1998 FDA Consumer.
This version is from a reprint of the original article and contains revisions made in May 2000.