Cover Story 5/22/00 U.S. News & World Report
Early detection is forcing more men to weigh the difficult treatment options
BY SUSAN BRINK
“In the shower, you feel all soft, like a woman.”
“I feel like my brain has been feminized.”
“It’s like the male hysterectomy.”
“It’s a delicate subject. There’s a virility issue.”
“Your wife ain’t too happy.”
“I was in the airport, nervous about flying and . . . whoosh. I lost control. Thank God I had clean clothes with me.”
–Comments from prostate cancer survivors
Prostate cancer is an inglorious disease, rife with indignities that cut to the core of male sexuality and self-esteem, as these men suffering the aftermath of treatment attest. More and more men share that awareness. New York Mayor Rudolph Giuliani, 55, diagnosed with prostate cancer last month and still weighing his treatment options, is part of a generation of men in their 40s and 50s who are forced to understand the male body and its betrayals in a way never required of their fathers. “A lot of men who come to our meetings didn’t even know they had a prostate. Even fewer know how to pronounce it,” says Darryl Mitteldorf, who leads a Manhattan support group called Malecare.
The catalyst for this change is a blood test that can find cancer at earlier stages than ever before. The cancer mostly kills men over 65, but the test, called the prostate specific antigen (PSA) test, has forced it into the baby boom generation’s consciousness, causing men as young as 40 to make a decision on whether or not to screen for early signs of this cancer. The test detects an enzyme made by the prostate, and its sensitivity to early cancer is both a blessing and a terrible burden. A series of wrenching options can begin to unfold if the PSA test gives a positive result that is confirmed as cancer, as is the case for 180,000 men each year. Treatments today are more effective and less debilitating than they once were, but they still carry a significant risk of impotence and incontinence, the result of damage to nerves or to the urethra, which the prostate straddles.
Most men choose surgery to remove the prostate, the quickest route to a cure provided the cancer has not escaped the pros-tate. But even men in the best of health face three weeks or more of recovery.
Standard radiation is an option for men too old or frail to withstand surgery. If it fails to eliminate the cancer, however, surgery is seldom possible. Radiation alters the gland, leaving it all but inoperable.
Another treatment is implanting “seeds” of radioactive material directly in the prostate, in an outpatient procedure. Many men have short-term urinary problems following the implant, however, and while promising, this procedure is new enough to lack long-term results.
In skilled hands, surgery or radiation can cure 80 percent or more of early cancers. Yet paradoxically, some of the cancers detected by PSA might never pose a threat if untreated. The balance between lives saved by early detection and lives blighted by unnecessary treatments for harmless cancers is still so uncertain that the country’s leading cancer research organization, the National Cancer Institute, is silent on whether or not men should get regular screening.
At each stage in a man’s journey from a positive test result through treatment, doctors can come up with numbers that help point to the best course: the odds that surgery or radiation will lead to a cure, for example, and the chance that a man will emerge from treatment with his functions intact. The odds, many times, are good. But for each patient, every decision is a roll of the dice.
Most men get it. Next to skin cancer, prostate cancer is the most common cancer in American men. An estimated 37,000 men will die of the disease this year, and the lifetime risk of being diagnosed with prostate cancer–1 in 6–is higher than the 1-in-8 risk of breast cancer in women. (The breast cancer death toll is higher, however, at nearly 44,000 women a year.) Nearly every man shows evidence of prostate cancer if he lives long enough. Autopsies show that as many as 80 percent of men in their 80s probably have some prostate cancer cells when they die–cells that have never caused any harm. But the problem comes from those cancers that start early enough or are aggressive enough to eventually spread.
Finding those cancers early is the goal of the PSA test, and few researchers doubt that it is saving lives. The disease has no symptoms until after it has escaped from the prostate. The first sign can be the pain of cancer in the bones–at which point it is essentially incurable. “I would urge everyone to get the PSA test,” Mayor Giuliani said unequivocally at the press conference disclosing his disease.
Many doctors would second Giuliani’s call, at least for men whose genes put them at risk of the disease. A family history of prostate cancer can double a man’s risk. The risk is even greater if more than one relative had the disease, and greater still if family members were diagnosed at relatively young ages–in their 50s, say.
The highest-risk families seem to carry genes that almost always lead to can- cer. But other men may inherit normal genes in forms that are prone to turn cancerous when set off by some outside factor, perhaps a high-fat diet. Such genes may explain why African-American men are also at higher risk. They are diagnosed with the disease at least 50 percent more often than white men, and their death rate from it is nearly twice as high. The American Cancer Society, the National Comprehensive Cancer Network, and the American Urological Association all recommend that higher-risk men, including African-Americans and men with a family history of prostate cancer, talk with their doctors about annual PSA screening starting at age 40. For other men, these organizations suggest starting at 50.
But as the National Cancer Institute’s silence about screening indicates, its benefits are still unproven. While prostate cancer death rates have dropped about 2.5 percent a year since widespread PSA screening began in the early 1990s, there’s no conclusive evidence linking those improved outcomes to early detection. A clinical trial of 75,000 men, half screened and half not screened, was begun in 1993 to see if screening prolongs life. Results are years away.
What remains clear is that screening finds a large number of cancers that don’t pose an immediate threat–and may not need immediate treatment. An analysis of about 300 patients at Johns Hopkins Hospital in Baltimore who most likely had early cancers and had their prostates removed found that between 25 percent and 33 percent had such small tumors that they were potentially insignificant. “In fact, 4 to 5 percent of tumors are so small, it’s hard to find them in pathology. We’ve seen that increasing over the years as a result of PSA screening,” says Jonathan Epstein, professor of pathology, urology, and oncology at Johns Hopkins.
Whether to begin screening is controversial, but most experts agree on the wisdom of an age-related end to screening–though no one will pinpoint a specific age. Most suggest that if a man has a life expectancy of 10 years or less, he should not be tested. Patrick Walsh, chairman of urology at Johns Hopkins, says, “I won’t test anyone in his 80s–unless he’s brought in by both his parents.”
Interpreting PSA. For men who opt for screening, the PSA count is not the last word. Ejaculation up to two days before the test can artificially raise the numbers (normal is below 4, high is above 10, and borderline is in between). Proscar or Propecia, two hair-growth drugs, can lower PSA numbers, as can certain herbs, including saw palmetto. And even if real, a high PSA can mean simpler, nuisance conditions rather than cancer: benign prostatic hyperplasia (BPH), an enlarged prostate that interferes with urination, for which Proscar can also be prescribed, or prostatitis, an infection that can be treated with drugs.
Prostate cancer is definitively diagnosed only after a biopsy, which entails probing a man from the rear. A biopsy gun shoots in a needle and removes prostate tissue in a fraction of a second, usually taking six to 18 samples from suspicious areas–a procedure most patients describe as, at best, highly uncomfortable. Those samples supply numbers that help determine how advanced any cancer is. The first is the stage of the tumor–how far it has spread. The second is the Gleason grade, a score of 1 to 10. A low score is given if the cancer cells look largely similar to normal cells, a higher score if they move in angry swirls, indicating a more aggressive cancer.
Men with borderline PSA and low Gleason numbers sometimes choose to do nothing more than “watchful waiting,” a strategy of closely monitoring PSA numbers and taking action only if they begin to rise. If the numbers are higher but still add up to a probable cure–an early-stage tumor with a Gleason grade of 7 or less, generally–surgery, external beam radiation, or radiation seed implants are the options. With higher numbers, suggesting an incurable cancer, a man might again opt to do nothing or try to limit its growth with radiation or hormonal therapy.
Yes, no, maybe. But again, the numbers aren’t always accurate. “The
If the numbers suggest treatment, a man can start exploring his options. About 100,000 men a year with newly diagnosed cases opt for a radical prostatectomy–surgical removal of the prostate. Some 30,000 men choose external beam radiation, and a new technology, called three-dimensional conformal radiation therapy, allows the oncologist to more precisely aim the radiation at higher doses, improving cure rates with fewer side effects. But only about 40 percent of cancer centers have the required state-of-the-art equipment. An additional 10,000 men opt for radiation seed implants, called brachytherapy, in which a doctor guided by ultrasound imaging shoots pencil-lead-size radioactive pellets into the prostate, through the rectum.
But no matter how reliable a man’s numbers and how careful his calculation, each step is clouded in uncertainty, as Richard Howe discovered. Howe’s numbers, including a low PSA and Gleason score, made him a good candidate for watchful waiting. But the former president of Pennzoil Corp. chose surgery because he wanted an early shot at a cure. Physicians found his cancer was more aggressive than they had predicted. “I probably had a very close call,” says Howe, who is not a physician but has studied prostate cancer enough to have had a paper published in 1994 in the Journal of Urology called “Prostate Cancer: A Patient’s Perspective.” Since his surgery eight years ago, he has informally counseled nearly 3,000 men about their options.
For Steve Weglarz of Lynn, Mass., the predictive numbers proved accurate, but he gambled on favorable lifestyle odds–and lost. “The good news is my PSA is zero and has been since surgery” eight years ago, he says. That means the cancer has been cured. But the price the 72-year-old retired internist paid is incontinence. Weglarz was devastated. “I didn’t expect to be incontinent. My urologist said the chances were 5 percent, so naturally I thought I’d be among the 95 percent,” he says. A study published in January in the Journal of the American Medical Association found that of 1,291 men who had undergone a radical prostatectomy, 8.4 percent were incontinent after 18 months and 60 percent were impotent. Both exter- nal beam radiation and radiation seed implants carry similar risks, though experienced surgeons and radiologists at centers that do a lot of prostate procedures report significantly lower rates.
No diapers. Weglarz found a way to cope. Two years after surgery, he went to a support group meeting and heard men tell similar tales. More important, he found out about a surgical procedure to implant an artificial sphincter, a device that releases urine only when triggered by external hand pumping. Weglarz no longer has to wear a pad.
Urologists can also counsel men on treatments to help overcome impotence following treatment, including the erectile dysfunction drug Viagra if treatment has not damaged the nerve bundles surrounding the prostate, and various injectible drugs and vacuum devices. “You can do a lot to overcome the side effects,” says Howe. “Would you rather be impotent and alive, or potent and dead?”
As Weglarz learned, even reassuring numbers are simply probabilities, and patients whose prospects look similar can fare very differently. When Mike Semenek of Downers Grove, Ill., found out four years ago that he had prostate cancer, he went to a support group, Us Too!, and met three other men who, like him, were recently diagnosed. Coincidentally, their PSA counts and Gleason scores were roughly the same. So, like businessmen with a lifesaving mission, they set about figuring their odds. “We tabulated survival rate charts by treatment types,” says Semenek. “We used a decision analysis for deciding what treatment would be best for each of us. We ended with a numerical value. All four of us ended up deciding that seed implant was the best for our particular objectives”: surviving the cancer and preserving their quality of life.
Spasm. Semenek, 71, went to the Mayo Clinic in Scottsdale, Ariz., for his radiation seed implant, and his PSA numbers are very low and holding, with few troubling side effects. Bob Jackson, 74, of Chicago went to the Northwest Tumor Institute at Swedish Medical Center in Seattle, where John Blasko pioneered seed implant therapy, and his numbers are equally low. He was troubled by severe urinary problems for about two weeks following the procedure, however. “My experience of going to the bathroom was a spasm of the whole lower abdomen. I didn’t know if I was urinating or defecating.” When that difficulty subsided, he still had extreme difficulty urinating until he had a surgical procedure called transurethral resection of the prostate to scrape away excess prostate tissue.
The two others, Bruce Sanfilippo, 61, and Dan Herman, 60, had treatment in the Chicago area. They both had only minor and temporary problems with urination, but their PSA numbers have fluctuated. Sanfilippo’s are now low and stable, but Herman’s are beginning to rise–a troubling sign that the cancer may return. None of them knows, of course, if the disease was simply more aggressive in the two men who are not doing as well or if an alternate procedure or institution would have made a difference. One thing the four friends have in common is that none became impotent following treatment.
Despite the agonizing trade-offs in making a treatment decision, the chilling reality is that cancer recurs in more than 35 percent of men, regardless of treatment. “For that group of people, the treatment options become pretty limited,” says Erik Goluboff, director of urology at the Allen Pavilion of the Columbia-Presbyterian Medical Center in New York.
Bill Blair, 70, of Blue Island, Ill., went into surgery hoping for a cure. Instead surgeons found his cancer had spread farther than his doctor thought. He was sewn up with his prostate still inside. “My surgery was aborted. I was given the prophecy by all the experts that I would not live long and I should get my house in order,” says Blair, who has already outlived predictions by two years.
Like other men whose cancer has advanced beyond the reach of the knife or the radiation beam, Blair faced some cruel choices. He could forgo any other medical treatments. Or he could try hormonal therapy, which he is doing. Hormonal therapy, a medical euphemism for surgical or chemical castration, drastically reduces testosterone, which slows the growth of the cancer. But the treatment also has profound side effects, including loss of the sex drive. “It makes an old man of you real fast. Anemia. Arthritis. Night sweats. Men finally figure out what women are going through,” says Blair. “You lose muscle mass. You feel weak. I gained 15 pounds. You get depressed. You have a lot of mood swings. I was weepy.” The side effects are troubling enough that Blair has chosen what he calls intermittent hormonal therapy, taking drugs to block testosterone when his PSA numbers are rising and getting off them when the numbers stabilize.
But where there is medical research, there is hope. Early this month, Goluboff presented a paper at the annual meeting of the American Urological Association with promising results about an experimental drug called Exisulind, which has been shown to kill prostate cancer cells in mice. He followed 96 prostate patients who had had surgery but whose PSA levels continued to rise, indicating that their cancer had not been cured. Half received a placebo, and the other half got Exisulind, which seems to block an enzyme unique to cancer cells. PSA levels either stabilized or rose more slowly among the men taking the drug. And, unlike hormonal therapy, says Goluboff, it had “almost no side effects. It’s like taking a vitamin pill.”
It’s a promising first step toward treating prostate cancer as a chronic disease that can be controlled. “People can live with an elevated PSA as long as they don’t ever develop a metastasis,” says Goluboff. The drug, still in clinical trials, may be approved by the Food and Drug Administration within a year.
For now, Giuliani and men like him can only juggle the numbers and come up with an educated guess about how to cope with their cancer. Each decision is equal parts scientific logic and leap of faith.