Prostate Surgery Center

October 1, 2007

STANDARD TREATMENT FOR PROSTATE CANCER MAY ENCOURAGE SPREAD OF DISEASE

A popular prostate cancer treatment called androgen deprivation therapy may encourage prostate cancer cells to produce a protein that makes them more likely to spread throughout the body, a new study by Johns Hopkins researchers suggests.

Although the finding could eventually lead to changes in this standard treatment for a sometimes deadly disease, the Johns Hopkins researchers caution that their discovery is far too preliminary for prostate cancer patients or physicians to stop using it. The therapy is effective at slowing tumor growth, they emphasized.

David Berman, an assistant professor of pathology, urology and oncology at The Johns Hopkins University School of Medicine, and his colleagues identified the unsuspected potential problem with treatments that suppress testosterone after discovering that the gene that codes for the protein, called nestin, was active in lab-grown human prostate cancer cells.

Curious about whether prostate cancer cells in people also produce nestin, the researchers looked for it in cells taken from men who had surgery to remove locally confined cancers of their prostates and found none. But when they looked for nestin in prostate cancer cells isolated from patients who had died of metastatic prostate cancer - in which cancer cells spread out from the prostate tumor - they found substantial evidence that the nestin gene was active.

What was different, Berman speculated, is that androgen deprivation therapy, a treatment that reduces testosterone in the body, is generally given only when prostate cancers become aggressive and likely to metastasize.

Because prostate cancer growth is typically stimulated by testosterone, the treatment is thought to slow tumor growth and weaken the disease. Patients who eventually die because their disease metastasizes are almost certain to have received this type of therapy, he says.

Speculating that depriving cells of androgens might also, however, affect nestin expression, the researchers experimented on a prostate cancer cell line that depends on androgens to grow. When they removed androgens from the chemical mixture that the cells live in, their production of nestin increased.

Aware that the nestin gene has long been suggested to play some role in cell growth and development, Berman and his colleagues used a bit of laboratory sabotage called RNA interference to decrease the genetic expression of nestin and found that these cells weren’t able to move around and through other cells nearly as well as cells with normal nestin levels.

Prostate cancer cells with hampered nestin expression were also less likely than normal prostate cancer cells to migrate to other parts of the body when transplanted into mice. However, while nestin expression seemed pivotal for metastasis in these experiments, it didn’t seem to make a difference in tumor growth.

“What all this suggests is that nestin levels increased when prostate cancer cells are deprived of androgens and may encourage the cells to metastasize,” says Berman.

Besides Berman, other Johns Hopkins researchers involved in this study were Wolfram Kleeberger, M.D., G. Steven Bova, M.D., Matthew E. Nielsen, M.D., Mehsati Herawi, M.D., Ph.D., Ai-Ying Chuang, M.D., and Jonathan I. Epstein, M.D.

The research, published in the Oct. 1 issue of Cancer Research, was funded by grants from the National Institutes of Health, National Cancer Institute, Evensen Family Foundation, and German Cancer Aid Foundation.

Press release source

Prostate Cancer Research Institute adds Bernhoff A. Dahl, M.D. to their Helpline staff.

Bangor, ME 04496 — October 18 2007 — The Prostate Cancer Research Institute (PCRI) was founded in 1996 by internationally recognized prostate-focused oncologists Stephen B. Strum, M.D. and Mark C. Scholz, M.D. with support from the Daniel Freeman Hospital Foundation in Southern California.

The objective of PCRI is to educate patients and their families about prostate cancer, including new advances in diagnosis, staging, treatments and available resources. PCRI believes that a patient who understands his disease and treatment is empowered to communicate more effectively with his physicians and obtain a better outcome.

The PCRI Helpline is a support service available to people dealing with prostate cancer via phone and email. It is staffed by survivors of prostate cancer, some of which are physicians, but the focus is on directing inquirers to information and not practicing medicine.

Bernhoff A. Dahl, M.D. is the former Chief of Pathology at the Eastern Maine Medical Center and co-founder of Dahl-Chase Pathology Associates, which serves twenty hospitals and laboratories in Maine. Although he had no family history of prostate cancer, after years of monitoring his PSA and a negative biopsy, in September 2004 his second biopsy showed aggressive cancer.

Dr. Dahl the set about to gain all the current concepts in prostate cancer diagnosis and treatment and opted for all four major treatment modalities: androgen-depravation therapy (ADT3), radical prostatectomy, chemotherapy, and external beam radiation therapy, all of which he received in one year.

Now three year since the diagnosis was made he has an undetectable PSA, changed his diet drastically, and living every day. During these years of therapy he wrote the book Optimize Your Life!which has become an international best-seller (www.TrionicsUSA.com).

His current work-in-progress is Take Charge of Your Life…or Someone Else Will! which includes material on taking charge of one’s healthcare.

In addition to the Helpline, PCRI works closely with other prostate support groups, planning and presenting eight national and regional conferences. It also maintains a powerful web sites (www.Prostate-Cancer.org) with a full range of literature on prostate cancer, as well as a quarterly newsletter PCRI Insights.

The services of PCRI depend on contributions from the public. Donations can be made via www.PCRI.org.

Bernhoff Dahl, M.D. (DrBDahl@aol.com)
President
Trionics International, Inc.
9 Shore Lane
Winterport, ME
Phone : 207-223-9998
Fax : 207-848-5649

Prostate Cancer Research Institute

Shrinkage of Prostate Led to Overestimation of Cancer Risk in Trial

Reanalysis of data from the Prostate Cancer Prevention Trial of a chemopreventive agent for prostate cancer shows that the excess prevalence of high-grade prostate cancer in the drug-treated group may be attributable to shrinkage of the prostate at the time of biopsy.

Newswise — Reanalysis of data from the first long-term randomized trial of a chemopreventive agent for prostate cancer shows that the excess prevalence of high-grade prostate cancer in the drug-treated group may be attributable to shrinkage of the prostate at the time of biopsy.

The study of the Prostate Cancer Prevention Trial, led by University of Illinois at Chicago professor of pathology Dr. Peter Gann, is published in the Sept. 12 issue of the Journal of the National Cancer Institute.

The Prostate Cancer Prevention Trial evaluated the drug finasteride, which blocks production of a male hormone within the prostate and is proven effective in treating benign prostatic hyperplasia, or enlargement of the prostate. The trial was stopped in 2003 when finasteride was found to reduce the risk of prostate cancer by nearly 25 percent. However, men assigned to the finasteride group had a greater prevalence of high-grade cancer.

Gann said the results were confusing for clinicians and patients because the drug appeared to retard the development of prostate cancer and decrease its prevalence, but the increased risk of high-grade cancer was unexplained and worrisome.

Researchers reasoned one possible explanation was that because finasteride shrinks the prostate gland, it increases the likelihood that a biopsy will detect high-grade cancer.

“It’s logical that if you shrink the size of the gland and then stick needles in it, you’re more likely to find cancer if it exists,” Gann said.

A second possible source of bias in the trial that may have contributed to overestimation of prostate cancer risk in the finasteride group is that the drug lowers the blood level of prostate-specific antigen by approximately 50 percent. The PSA level is a biological marker doctors use to detect disease, so PSA levels measured in men taking finasteride are routinely adjusted upward. This calculation may have led to overestimation of baseline PSA levels among men in the finasteride group who were already harboring high-grade tumors at the start of the study.

“This is a very unusual situation — though it will become more common in the future — where the drug affects the marker we use to find the cancer,” said Gann.

Using data from the Prostate Cancer Prevention Trial study, Gann and colleagues developed statistical models that took into account the size of the prostate gland and the number of needle cores that were taken during biopsy. In essence, the researchers compared finasteride to placebo among men with an equivalent number of needle samples per unit of gland volume.

The analyses showed that adjusting for changes in gland size due to the drug could account for all of the excess high-grade tumors.

“Once we did this adjustment, all the excess high-grade went away, and the effect of the drug on low-grade cancer was even stronger, as we would expect,” Gann said.

“This drug may have been much better than people thought,” Gann said, “and the fears about its impact on high grade tumors may have been exaggerated based on this bias alone.”

However, he said, the findings must be interpreted cautiously, and the new results alone do not justify definitive changes in clinical practice or widespread use of the drug.

“Our goal is to improve scientific understanding of what happened in this very important and expensive trial.”

Gann’s co-authors include Yael Cohen of Gamida Cell Ltd. in Israel and Kenneth Liu, Norman Heyden, Alexandra Carides, Keaven Anderson, and Anastasia Daifotis of Merck & Co. Inc. Merck markets finasteride as Proscar.

For more information about UIC, visit http://www.uic.edu

We have posted a new article to the Articles section of the website. This article is an overview of the various prostate cancer treatment that are currently available.

As with any form of cancer, it’s important for patients to educate themselves on all treatment options — and to seek the advice of more than one specialist — before making a decision. This new article is by no means an all-inclusive explanation of prostate cancer treatment options, but it does serve as a good starting point for your further research.

Read the article: Prostate Cancer Treatment Options