Prostate and PSA
Some say testing for prostate cancer leads to overtreatment. Others disagree.

BY JIM HUTCHISON

You know, it’s been two years since your last PSA test,” nudged Vancouver physician Dr. Peter House during my annual checkup in October, 2004. I didn’t need reminding that I was avoiding the issue.

I was 59 when he did a rectal exam of my prostate—the gland that produces fluid for semen—to check for suspicious lumps and then sent me to the lab for a PSA (prostate-specific antigen) blood test. A week later I was back in his office. “Your PSA is 4.8,” he told me. At my age, a blood level over four nanograms per decilitre of the protein produced by the prostate raised a red flag for increased cancer risk. I left his office with a referral to a specialist and an unwelcome dread.

Dr. Ercole Leone, a young urologist at the Seymour Medical Clinic, suspected my increased PSA might be due to benign prostatic hyperplasia (BPH)—an enlargement of the walnut-size prostate, which is located under the bladder and in front of the rectum. BPH is a common legacy of being male and middle-aged.

The only way to rule out prostate cancer as the cause of my elevated PSA was a biopsy. Guided by ultrasound, a thin, hollow needle is in- serted through the rectum wall into the prostate to withdraw tissue and check for cancer.

“I feel like I’m on a slippery slope heading towards surgery,” I told Dr. Leone. He understood my concern and had suggested “watchful waiting”—no biopsy for now, but an annual PSA test and rectal exam to keep an eye on any changes.

Now, as I went for my annual checkup that October, my friend of 30 years, Brian Airth, was much in my mind. Gamely he was enduring weekly chemotherapy for prostate cancer that had spread outside the gland—discovered after a high PSA reading. In the early stages of prostate cancer, there are most often no symptoms—the reason many doctors recommend PSA screening after 50, or at 45 if there is family history.

The Canadian Task Force on Preventive Health Care, and its counterpart in the United States, are against PSA screening, however, citing lack of hard evidence that it lowers the overall death rate in men.

Who is right?

Urologist Dr. Thomas Stamey, a pioneer of the PSA test in the early 1980s at Stanford University, captured head-lines around the world with a study published in the October 2004 issue of the U.S. Journal of Urology. Using data collected from over 1,300 prostates removed by urologists at Stanford over the past 20 years, Stamey’s team compared the volume of cancer in the glands and PSA levels before they were removed.

In the first five years studied, they found a 50-percent relationship between volume of cancer and blood PSA, but for every subsequent five-year period it plummeted. “In the last five years only two percent of the radical prostatectomies done here at Stanford had any relationship to blood PSA,” says Stamey. “In the early days those cancers were big. Now we get prostates every day in my lab where we can hardly find the cancer it is so small.” He says the PSA test is so inaccurate that you may as well biopsy men because of the colour of their eyes.

How did PSA’s ability to predict significant prostate cancer go from nearly 50 percent to two percent? Stamey believes widespread screening is partly responsible. He also points to a postmortem study done on the prostates of men killed accidentally in Detroit. Eight percent of those in their 20s already had prostate cancer, rising to a staggering 80 percent of men 70 or older.

“Something every man and urologist should know is that we all get prostate cancer if we live long enough,” he says.

In light of the Detroit study and others, he says that any reason used to biopsy the prostate in men over 50— such as elevated PSA—is likely to find cancer, but most will never cause problems: The vast majority of men will die with prostate cancer, not from it. Stamey firmly believes the way the PSA test is being used has led to overtreatment.

“What we badly need is a new marker,” he says, “one that will accurately predict which cancer is going to turn deadly.”

Not everyone agrees that the PSA test is finished. “The PSA test is not a useless test at all,” says urologist Dr. Larry Goldenberg, director of the Prostate Centre at Vancouver General Hospital. Twenty years ago, he recalls, it was routine for men to hobble in on crutches because prostate cancer had spread to their bones. “I don’t see that very often anymore because of widespread awareness. Men are finally starting to pay attention to their health,” he says.

He agrees with Stamey that today PSA just doesn’t correlate to volume or severity the way it did 20 years ago. “But PSA is still the best biological marker we have. We have to change how we use the test now.”

The PSA level is not as important as the PSA velocity or how it changes over time, says Goldenberg. Taking that into account with prostate size and age offers useful clues. If PSA rises dramatically between tests, or it is very high to start with, for example, that increases the chance of a fast-growing cancer.

When a biopsy is done, the Gleason grade—a formula for assessing tumours—is a strong predictor of how cancer will progress. Goldenberg looks at the grade, the size of the cancer, what the prostate feels like and changes in PSA levels. Together, these factors can add up to a better prediction of whether the cancer is what he calls a turtle, a bird or a rabbit—one that moves slowly and rarely gets out to cause trouble, one that flies away quickly and there’s little one can usually do to catch it, and one that bounces around and if not caught will get out of control eventually. “This is the best way we have to decide whether a man needs treatment now or if it can be delayed, perhaps forever.”

Making decisions about PSA, he says, must arise from a partnership between doctor and patient. “It is the doctor’s responsibility to inform the patient of pros and cons of each treatment option,” he says.
Surgeon Dr. Laurence Klotz, head of the prostate cancer group at Sunnybrook and Women’s College Health Sciences Centre in Toronto, agrees. “What we’ve been doing for ten years is offering patients watchful waiting—active surveillance is the term we use. We track patients’ PSA and rebiopsy them every few years. If the PSA rises rapidly or the grade increases, we treat them aggressively at the point where they are still curable.”
Of the 400 patients on Klotz’s program diagnosed with significant prostate cancer, about a third end up being treated radically with combinations of surgery, radiation and hormone treatments. The other two thirds end up with no treatment. The strategy is paying off in less surgery and saved lives.

According to the Canadian Cancer Society, prostate cancer is the most commonly diagnosed cancer for men, with 20,100 cases annually, and is the third leading cause of cancer deaths for men, at 4,200. But of 11,900 men diagnosed annually with lung cancer, a whopping 10,700 will die.

“Patients need to understand that although the word ‘cancer’ is there, it is not what they think,” says Klotz. “Prostate cancer is really a very slow process. We have 400 patients who have decided they can live with this.”

Goldenberg still recommends getting a PSA test done as a baseline at 50, or 45 if there is a family history. And, he says, there is plenty a man can do to reduce his risk of prostate cancer.

“Asian men living in North America have higher rates of prostate cancer than those in Asia. Animal fat may be a culprit in predisposing men and may speed up the progression of the disease,” Goldenberg says. Indeed, studies show that a diet high in animal or saturated fat increases risk.

Exercise, keeping weight down, a diet balanced with healthy grains, fruit and vegetables, all can help lower risk. Some studies show selenium may have some protective properties as
do micronutrients like lycopene in tomatoes.

Wine is definitely on the menu. A new study at Seattle’s Fred Hutchison Cancer Research Centre compared over 700 men newly diagnosed with prostate cancer with 700 who were cancer-free. Moderate drinkers of red wine reduced their risk by a whopping 50 percent; the researchers also found vitamins C and E helped.

On November 18, 2004, armed with the facts, I went for another PSA test. My level had dropped from 4.8 to 3.8. I felt relieved, but until a better test is discovered, I plan on having an annual PSA test to be sure it has not suddenly risen.

“I see guys all the time who at 55 have caught their cancer in time with surgery. In the days before screening, they would have found themselves at age 60 with an incurable disease. PSA screening can still be life-saving,” says Klotz.

Prostate and PSA    • Protect Your Prostate