MEN SEEK 'THE TRUTH' ON PROSTATE TREATMENTS

By Anne Barnard

Boston Globe Staff

At a robust 56, he faced surgery for prostate cancer, terrified that it would leave him impotent. He made the rounds, visiting top urologists at Harvard hospitals. He chose a surgeon who told him that 80 percent of his patients end up able to have sex without the help of devices.

Last week, unable to get an erection and suffering from incontinence, he went to a support group at Beth Israel Deaconess Medical Center, where he learned that the vast majority of the group have significant trouble with sexual function, even years after surgery or radiation treatment.

It turns out that the 80 percent success rate may be more hope than reality, achieved only by a few highly practiced surgeons on selected patients. One large-scale study of prostate cancer survivors found that, 18 months after treatment, 60 percent could not get an erection firm enough for intercourse.

As a result, many men, including some in the (Us Too!) Beth Israel support group, feel they were misled about the sexual side effects of their treatment.

"Why can't we get good solid information?" said the Boston man at Beth Israel, who, at four months after surgery, still hopes for improvement and did not want his name used for fear of alienating his doctor. "If people knew the truth, if there was more - I hate to use the word honesty - but I think people could deal with this disease a little bit better.

Doctors agree that there is a broad gap between the more optimistic potency rates widely quoted in surgeons' books and Web sites- especially those of celebrity specialists like Johns Hopkins Hospital's Dr. Patrick C: Walsh - and the more typical experience. Published studies report post surgical rates of impotence ranging from less than 15 percent to more than 80 percent, depending on the patients' ages and conditions and the experience of the surgeon.

Radiation treatment offers a somewhat lower risk of impotence, but, because long-term survival is not so good, doctors usually recommend surgery for younger patients, the ones most likely to be sexually active.

However, doctors say they tell patients up front about the risks and trade-offs. They also say that support groups overstate the degree of dissatisfaction because they tend to attract more men who are having problems.

But some doctors, as well as many patients, believe the prostate cancer survivors have a point: Surgeons sometimes downplay the chances of impotence as they focus on curing cancer. They sometimes quote potency rates for celebrity surgeons who do nothing but remove prostates, rather than their own rates, said Dr. Jeffrey Steinberg, acting chief of surgery at Cambridge Health Allance, who advises the support group. Or they don't emphasize that the best numbers come from groups of younger, healthier patients.

The result, said group leader Stan Klein, is that with 180,000 men diagnosed and 55,000 undergoing prostate-removal surgery each year, thousands of survivors are glad to be alive, but painfully disappointed with their sexual function.

"It's devastating," he said. "We've had them coming in with tears in their eyes."

"I understand the frustration and anger on the part of many of those patients," Steinberg said, adding that doctors have to be extra rigorous in preparing patients for side effects, since men sometimes hear only what they want to hear when doctors predict their sexual future.

"It's important for surgeons to tell patients what their experience is in their own practice, how many they've done, what age range they've done" he said. About 50 percent of his own patients are potent a year after surgery, he said, with better results in younger patients.

Klein, cancer-free nine years after surgery, is on a mission to paint what he calls a more realistic picture. His goal is not to discourage treatment: with almost 32,000 men dying each year, we don't want men to say, I'll take my chances.'"

Rather, he said, realizing that impotence is more likely than not will prepare men better to cope with the problem and seek treatment - Viagra, rejections, vacuum pumps and penile implants - that usually brings "an almost normal sex life"

Dr. Irwin Goldstein, director of the Institute of Sexual Medicine at Boston University School of Medicine, had this advice for prostate patients, whether they opt for surgery or radiation: Doctors exaggerate their ability to save your erections. Expect to be impotent. But worry only about surviving. Then, call the sexual dysfunction specialists.

If a man owns a penis, he said, "we can make them have an erection."

Prostate cancer victims face a particularly difficult choice since the treatment options force them to decide between a greater risk of death or a greater risk of impotence. Unlike most cancers, their disease can be treated effectively with two very different techniques, surgery and radiation. While radiation causes less impotence and incontinence, surgery has better survival rates beyond 10 years. And radiation patients sometimes develop sexual side effects well after the treatment.

And for doctors, measuring safety and effectiveness of surgery is always contentious, since so much depends on individual skill and patient selection. There is some mistrust between surgeons and the epidemiologists and others who measure their outcomes. The debate over prostate surgery has even tapped into the rivalry between Boston's hospitals and Johns Hopkins of Baltimore - home of Walsh, the surgeon who helped raise expectations so high.

In 1981, Walsh published a paper describing the nerves that are close to the prostate and help control erections. He developed the technique of removing the walnut sized gland without cutting either of the nerves, called bilateral nerve sparing.

His most famous study, quoted frequently on his Web site, was published in 2000. Of 62 relatively young, healthy patients he operated on, 86 percent could have sex spontaneously after a year and 93 percent were completely continent. He and five other top surgeons also reported 90 percent potency on 50 patients under age 60.

"He's a very good surgeon and he's honest, but he's very selective" in Choosing patients, said Dr. Jeremy Rich, chief of urology at Brigham and Women's Hospital, who says his own potency rate is 85 percent for patients in their 40s, 60 percent for those in their 60s.

In a larger study of 1,291 patients, about half over 65, University of Washington epidemiologist Janet Stanford found- that 18 months after surgery, 60 percent of men reported having no erections or erections that were not adequate for sex. Even among those under 60, just 40 percent had erections adequate for intercourse.

Since not everyone can go to a to specialist, it's important for all surgeons to measure and report their own outcomes, said Dr. James Talcott, of Massachusetts General Hospital's Center for Outcomes Research. But he believes most don t - partly because the expectations are so high that real numbers would be damaging.

Talcottstudied 49 patients who had surgeries at Boston teaching hospitals. He found that most were impotent, including 15 of 19 patients who had bilateral nerve-sparing surgery. He said his results were more realistic because the patients had a wider mix of ages and were asked about their conditions by independent researchers, not doctors.

Anne Barnard can be reached at: <abarnard@globe.com.>

This story ran on page A1 of the
Boston Globe on 1/18/2003.

This article is about genistein which is a substance found in soy products. I use the powder - 25 grams of genisee powder in OJ and Sprite and ice - which is mixed in a blender. For more information on where genistein is found do a webb search on "genistein".

SOY PRODUCT GENISTEIN QUELLS CANCER GROWTH MECHANISMS
AT GENETIC LEVEL
by Sonia Nichols
AP Senior Medical Writer
The soybean product genistein is purported to influence the course of a number of diseases, including cancer. Researchers in the U.S. have confirmed that genistein targets genes responsible for controlling signals associated with prostate cancer dissemination.

Health care professionals believe that by sensitizing prostate cancer cells to chemotherapy, some individuals might avoid cancer cell metastasis. Several studies have shown that isoflavones such as genistein alter the course of prostate cancer in animals. The coauthors of a Wayne State University School of Medicine study say genistein controls prostate cancer by control of processes such as angiogenesls at the transcription level.

"To better understand the precise molecular mechanism(s) by which genistein exerts its effects on PC3 (prostate cancer) cells, we utilized cDNA microarray to interrogate 12,558 known genes to determine the gene expression profiles altered by genistein treatment," said Yiwei Li and colleagues, who work at the Detroit, Michigan medical school.

Genistein more than doubled the response of over 800 genes. Thirteen of those genes have been linked in some way to angiogenesis and the spread of cancer. Eleven of the 13 genes were down-regulated after geniste!n treatment, whereas the 2 remaining genes, associated with connective tissue signaling, were up-regulated.

Several more laboratory tests confirmed the results of the microarray analysis (Down-regulation of invasion and angIogenesis-related genes identified by cDNA microarray analysis of PC3 pros tate cancer cells treated with genistein. Cancer Letters, 2002; 186(2): 157-164).

"We concluded that genistein down-regulates the transcription and translation of genes critically involved in the control of angiogenesis, tumor cell invasion, and metastasis, suggesting the possible therapeutic role of genistein for metastatic prostate cancer, said Li and coauthors.

The investigators proposed that genistein might be particularly suited for making prostate cancer cells more receptive to control by chemothempies already on the market.

Key points reported in this study include:
* Genistein is an isoflavone that is believed to have anticancer properties

* Genistein down-regulates or up-regulates a number of genes linked with angiogenesis, tumor invasion, and metastasis in prostate cancer

* The soy product may be valuable as an adjuvant for chemotherapies that treat or prevent metastatic prostate cancer

UCLA scientists report that 11 days of daily exercise and a low-fat, high-fiber diet induce prostate cancer cells to die.

The research, published in the new issue of the journal Cancer Causes and Control, is the first to show that diet and exercise can kill prostate cancer cells.

"You can make changes in a short period of time that have a dramatic Impact on your health - in this case, on the growth and death of prostate tumor cells," said R. James Barnard, Professor of Physiological science at UCLA and lead investigator on the study.

Barnard and his UCLA colleagues studied two groups of men: 14 obese men, ages 42 to 73, without prostate cancer, who part!cipated in an 11-day diet and exercise program at the Pritikin Longevity Center; and 8 men, ages 38 to 74, who have exercised regularly and followed a low-fat, high-fiber diet for more than 14 years.

The researchers - who also include Tung Ngo and Christopher Tymchuk, UCLA graduate students working in Barnard's laboratory; Pinchas Cohen, a researcher at UCLA's Jonsson Cancer Center and professor of pediatrics at UCLA's David Geffen School of Medicine; and William Aronson, a researcher at UCLA's Jonsson Cancer Center and an associate clinical professor in the Department of Urology at UCLA's David Geffen School of Medicine - collected blood serum samples from the 14 men before they began the 11-day Pritikin program. At UCLA, the researchers mixed these serum samples in dishes with prostate cancer cells. At the end of the l 1-day program, the researchers collected a second set of blood serum samples from the same 14 men, and placed these samples in laboratory dishes with prostate cancer cells.

Prostate cancer cell death
Among the 14 men at the beginning of their diet and exercise program, fewer than three percent of the LNCaP cells - prostate cancer cells -in the cell culture showed apoptosis (programmed cell death). At the conclusion of the 11-day program, more than 40 percent of these cells were on their way to death, and in the 14-year group of eight men, more than 50 percent of these cells were on their way to apoptosis, or death.

"That was the finding that made our jaws drop," Bamard said. "We don't know yet whether these dramatic changes that occurred to prostate cancer cells cultured in a laboratory will also occur in patients; we have hope that these changes will occur."

In an attempt to understand What might be inducing the apoptosis of the tumor cells, the scienists measured blood serum levels of a hormone called IGF-I, which stimulates tumor cells to grow, a high level of IGF-I is a risk factor for prostate cancer, Bamard said.

At the end of the 11 days, IGF-I levels for the 14 men had decreased by 20 percent. The eight men who had followed the diet and exercise program for 14 years had IGF-I levels 55 percent lower than the 14 men had at the start of their diet and exercise program.

"Insulin is the primary factor that stimulates the liver to, produce IGF-I, Barnard said. In previous research, we have shown that diet and exercise lower the serum insulin level; we suspected that diet and exercise should lower the IGF-I level as well, and we have found that to be true."

While IGF-I floats in the bloodstream, it binds to a protein, IGFBP-I, which limits the amount of IGF-I that is available to interact with tissue. Higher levels of this binding protein are desirable, causing a drop in free IGF-I levels, Barnard said.

Over the 11-day program, IGFBP-I levels increased by 53 percent, while in the long-term group of eight men, IGFBP-I levels were 150 percent higher than the short-term group had at the outset of the program.

"We didn't expect the results would be this dramatic," Barnard said. "We found dramatic changes in both IGF-I and IGFBP-I levels with diet and exercise. The important message is you can change your levels of both IGF-I and IGFBP-I in a very short period of time, and that may have an Important impact on your prostate health."

Implications of the research
We've been telhng.people for years if they want to avoid most of the health problems we have in this country, they should go on a low-fat, high-fiber diet and do about an hour of aerobic exercise every day," Barnard said. "You make up your mind: Do you want to be healthy? It's not a tough choice."

Barnard, 65, has worked with the Pritikin Longevity Center since 1978, and serves as a consultant. He weighs five pounds less than when he graduated from college, and his cholesterol dropped from 235 when he was in his early 40s to 180 when he changed his diet; he has maintained his cholesterol around 180-190 for more than 20 years.

The Pritikin program focuses on a diet of whole grains, fruits and vegetables, and small portions of meat (no more than 3-and-a-half ounces a day), and 60 minutes of exercise a day.

Prostate cancer is the most common type o f cancer in American men, other than skin cancer, and the second leading cause of cancer death in men, exceeded only by lung cancer. Some 30,000 men in the United States die of prostate cancer each year.

Barnard noted that some people buy. growth hormone supplements, which stimulate the production of IGF-I. He "seriously questions" older people taking such supplements.

"Where you need IGF-I is in your muscle; the way to get it is to exercise," Bamard said. People want the easy way out; they want to take a pill."

You can find news you can use at the USToo International web site: http://www.ustoo.org/. Check it out for the latest references.

*Date & Time:*	Tuesday, January 21, 2003, 7:00 PM
*Place:*	Wilson N. Jones, North Senior Health Center
*Attendance:*	Est. 20 attendees


*Vol. 2, No. 2*	*February 2003*