Clues to prostate cancer.

Death, taxes...and prostate cancer.

Cancer cells are pretty much inevitable in the prostates of men who live to their 70s or 80s. But dying of prostate cancer isn't.

"You see the same incidence of microscopic clusters of cancer cells throughout the world," says Warren Heston of the Memorial Sloan-Kettering Cancer Center in New York. "But Europe and the U.S. have a higher rate of progression to clinical cancer than Asia."

It's not just older men who have prostate cancer cells. "In autopsies of men who die of other causes, a third of those over 50--maybe a third over 30--have microscopic clusters of prostate cancer cells," says William Fair, chief of urology at Sloan-Kettering. "What keeps some of them microscopic and stimulates others to grow so that they take a life, we don't know."

Early evidence suggests that a low-saturated-fat diet and lycopene--a carotenoid found largely in tomatoes--might keep those tiny prostate cancers in check. And that gives researchers hope.

"Even if the cancer is there, if it doesn't grow it doesn't matter," says Heston. "If we could just delay the clinical appearance of the disease, we'd have a real winner."

PIZZA PARTY

"A new study says men who eat ten pizzas a week are less likely to develop prostate problems," joked Jay Leno last December. "They're more likely to develop size 54 pants."

The media ate up the latest findings from Harvard's Health Professionals Follow-up Study. Edward Giovannucci and colleagues analyzed the diets reported in 1986 and again in 1990 by nearly 48,000 male dentists, optometrists, pharmacists, and other health professionals, then aged 40 to 75.(1) By 1992, 812 of the men had been diagnosed with prostate cancer, almost always in its earliest, localized stage.

Giovannucci wanted to see whether the five major carotenoids--which give some fruits and vegetables their orange or green colors-were linked to the cancer. Alpha-carotene, beta-carotene, beta-cryptoxanthin, and lutein all struck out. Lycopene--and the tomatoes that are so rich in it--hit a home run.

SPAGHETTI & LYCOPENE SAUCE

"The risk of prostate cancer was a third lower in men who ate tomato-based products more than ten times a week than in men who ate them less than twice a week," explains Giovannucci. "Even the men who ate tomato sauce once a week had a 23 percent lower risk than those who never ate it."

Tomato juice was not linked to a lower risk, perhaps because people don't absorb much of its lycopene. The men who ate raw tomatoes had a lower risk, but not as low as those who ate pizza or tomato sauce.

"Tomato sauce had the strongest association with prostate cancer risk," says Giovannucci, perhaps because the tomatoes in spaghetti sauce are usually cooked in oil. "You need a little bit of oil to release the lycopene in tomatoes, so spaghetti sauce may be the ideal way to get it."

One study isn't proof, of course. "It's a good study, but I'd like to see it supported by several other equally good studies," says Geoffrey Howe, a cancer expert at Columbia University.

Giovannucci is also cautious. "We want to make sure it's not a chance finding that just popped up," he says. But he's encouraged by several observations.

"On average, lycopene is the highest of all the carotenoids in the blood and in prostate tissues," he says. And in test tubes, it has twice beta-carotene's potency as an antioxidant.

Where does that leave health-conscious men? "The findings add support to the advice to eat a variety of fruits and vegetables, but with an emphasis on tomatoes," says Giovannucci.

Those findings also make him concerned about olestra, the artificial fat that will soon appear in potato chips and other foods (see p. 4)."Studies have shown that olestra reduces blood levels of a lot of carotenoids, but that its effect on lycopene is the strongest," he cautions. "If someone is eating tomato sauce, a little bit of olestra would eliminate the benefit."

FINGERING FAT

"Let me explain how it all started," says Sloan-Kettering's William Fair. "As a surgeon, I'd see patients with detectable PSAs a year after having their prostates removed."

Doctor use blood levels of PSA (prostate specific antigen) to monitor the progression of prostate cancer. Men without a prostate should have a PSA of zero. Anything higher is a sign that cancer cells escaped the diseased prostate and are still growing.

But among those prostate-less patients with worrisome PSAs, "some men would later come back with PSAs that were much lower than before," says Fair. "The common thread was that most were following diets that were low in fat."

To see if what happened to those men wasn't just a coincidence, Fair and his co-workers injected human prostate cancer cells into mice on diets that got 40, 30, 20, 11, or 2 percent of their calories from fat.(2)

"The most dramatic finding was that when the diet was 20 percent of calories from fat or less, the tumors didn't disappear, but they did stop growing," says Fair.

His animal study isn't the first clue that fat may promote prostate tumors. In humans, most studies suggest that diets high in saturated fats are to blame (a theory that no one has tested on animals).

In 1993, Giovannucci's team found that men who got about 30 grams of fat a day from red meat--what you'd get in about five ounces of cooked hamburger--had more than double the risk of prostate cancer of men who ate a tenth as much fat from red meat.(3)

Others have found links with the saturated fats not just in meat, but also in high-fat dairy products.(4) "When you look at all the studies on prostate cancer, the most consistent finding is that saturated fat or animal fat is associated with a higher risk," says Giovannucci.

But the case against animal fats i far from closed. "There's still a lack of consistency in the data," says Howe. We need more solid evidence from studies that follow healthy men for decades to see who gets cancer and who doesn't, he adds. But in the studies that are under way, "the men simply aren't yet old enough to look at prostate cancer rates."

And, says epidemiologist A,ice Whittemore of Stanford University, "it may be that diet during puberty or early manhood is what really matters." If that's true, researchers wouldn't find a strong link between prostate cancer and foods consumed later in life.

WHY WAIT?

Rather than just wait for long-term study results, Fair and Heston are mounting two pilot trials to test a low-fat diet on two groups of men.

1. Men at high risk of getting prostate cancer. Sometimes a blood test shows a suspiciously high PSA, but a biopsy finds no cancer cells. The elevated PSA could be due to an enlarged prostate, which is called benign prostatic hypertrophy (BPH).

"Or it could mean that the man has a tumor so small that the biopsy missed it," says Fair. "In fact, in 25--some say in 50--percent of these men we find a tumor on a second biopsy."

But meanwhile, the men are in limbo, not knowing if they have cancer and not able to do anything to stop it. "I don't have to tell you how anxious these men are," says Fair.

Most of the men in his "high risk" trial have PSAs between four and ten and are under 55. "If you're over 65 and have a PSA of 6.5, that's not high risk," explains Fair, "because PSAs go up with age, probably because of benign prostatic hypertrophy."

The men will be randomly assigned to one of two diets:

* 30 percent of calories from fat. This diet--which the National Cancer Institute recommends for all Americans--has slightly less fat than most people typically eat.

* 15 percent of calories from fat. This very-low-fat diet--rich in fruits, vegetables, and grains--is also low in saturated fat.

"The neat thing is that we can monitor all the men's PSAs," says Fair. "Unlike studies on breast or colon cancer, we don't have to wait for a cancer to occur."

2. Men who have no prostates but PSAs above zero. "In half of the men who have tumors at the margin of the capsule surrounding the prostate, surgery to remove the prostate will fail to get all the cancer cells, and their PSAs will start rising within two years," explains Heston.

That's a sign that some cancer cells are still in the body, and it puts physicians in a quandary. Some treat the area where the prostate was with radiation, but that causes complications, says Fair. "If they weren't impotent after surgery, they will be after the radiation. And for all you know, the tumor could have traveled to the lung or the shoulder."

The only other treatment, says Heston, is "hormone therapy that turns off the man's ability to make testosterone." But no testosterone means no interest in sex. "And hormones may not hold back the tumor for long if it's aggressive," he adds. In most men taking hormones, the disease begins to recur within two or three years.

So the Prostate intervention Nutrition Study (PINS) will randomly assign men to one of two diets and will monitor their PSA's and tumors:

* 30 percent of calories from fat. That's the same diet used in the "high risk" trial.

* 15 percent of calories from fat, plus soy, vitamin E, and selenium. In addition to the same very-low-fat diet used in the "high risk" trial, this group will consume a total of 40 grams of soy protein a day (in two milkshakes or protein bars), 800 international Units (IU) of vitamin E, and 200 micrograms (mcg) of selenium, even though the evidence for soy and those nutrients is weaker.

Soy. We eat burgers and fries. In Asia, they eat tofu and tempeh (or at least they did before the Golden Arches invaded). Could soy foods explain the lower death rate from prostate cancer in Asian countries?

High doses of genistein, a phytoestrogen (plant estrogen) in soy foods, slowed the growth of prostate tumors in mice in a study that hasn't yet been published, says Fair. "It worked even when the mice were fed high-fat diets."

But in humans, says Stanford's Whittemore, "there just isn't a lot of data at present."

Meanwhile, if you're looking for genistein, stick to soybeans, tofu, or soy milk. Soy sauce and soy-based drinks like Ensure have little.(5)

Vitamin E. In 1994, researchers reported somewhat lower rates of prostate cancer in Finnish smokers who were given 50 IU of vitamin E a day for about five years.(6) But so far, other studies have come up empty.

"I've looked at men who used vitamin E at a high dose for 20 years and found absolutely no difference between them and non-vitamin-E-takers, not even a hint," says Giovannucci. "It's conceivable that men who are deficient in E could be at higher risk," he adds. But the evidence that high doses of E protect the prostate is weak.

Selenium. A few studies have found less selenium in the blood of people who later developed cancers of all kinds. But the evidence, says the National Cancer Institute's Richard Hayes, "is very speculative at this point."

And supplement-takers take note: Selenium is toxic in high doses. Don't exceed the Recommended Dietary Allowances, which are 55 mcg a day for women and 70 mcg for men,

AS GOOD AS A CURE

All in all, there just isn't enough evidence to make promises about any aspect of diet and prostate cancer. "Until the last five or seven years, the scientific literature was very scanty," says Hayes.

"Scientists didn't take prostate cancer seriously because it was a disease of older men, whose longevity wouldn't be altered much by the disease." But that's changing, he adds.

And some researchers are hopeful that this is one cancer that can be stopped...or at least slowed down. "If we're ever going to control health care costs, we've got to do it up front with prevention, not with the sexy stuff like gene therapy," says Fair.

"My dream is that we can find prostate cancer in a 60-year-old man and slow it down for 20 or 30 years. For most men, that's as good as a cure."

RELATED ARTICLE: THE BOTTOM LINE

* Eat a diet that's low in saturated fat. That means mostly plant foods (pasta, rice, breads, cereals, fruits, vegetables, and beans). If you eat animal foods, pick low-fat ones like fish, chicken breast, round steak, pork tenderloin, low fat cheeses or yogurt, or 1% milk.

* Eat five to nine servings of fruits and vegetables a day. Use tomatoes or tomato sauce several times a week in low-fat dishes like spaghetti or linguine with red clam sauce. Get your pizza or lasagna with lots of vegetables and little or no cheese or meat.

* The American Cancer Society (ACS) recommends a rectal exam once a year for men aged 40 and up and a PSA test for men 50 and up.

* No matter how old you are, tell your doctor if you have:

- weak or interrupted urine flow,

- inability to urinate (or difficulty starting or stopping),

- need to urinate frequently, especially at night,

- blood in the urine, or

- continuing pain in the lower back, pelvis, or upper thighs.

* Got a question about prostate (or any) cancer? Call the National Cancer institute at 1-800-4-CANCER.

* If you're interested in participating in one of Sloan-Kettering's prostate studies, call [phone].

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(1) Journal of the National Cancer Institute 87:1767, 1995. (2) Journal of the National Cancer Institute 87:1427, 1995. (3) Journal of the National Cancer Institute 85:1571, 1993. (4) Journal of the National Cancer Institute 87:629, 652, 1995. (5) Journal of the American Dietetic Association 94:739, 1995. (6) New England Journal of Medicine 330:1029, 1080, 1994.