October 18, 2004 /PSA Rising/- SEATTLE -In the largest known study of its kind, scientists have confirmed that men with high grade prostatic intraepithelial neoplasia or PIN, characterized by abnormal cells in the lining of prostate ducts, are at high risk for invasive prostate cancer.
The study, presented today at the American Association for Cancer Research Third Annual International Conference on Frontiers in Cancer Prevention Research, showed that about one in three men with high grade PIN are at high risk for prostate cancer within a year of detection and should be closely monitored for disease progression.
"This study confirms that the increased risk factor associated with high-grade PIN is real and not just a coincidence," said Dr. Mitchell S. Steiner, chief executive officer with GTx, Inc.
GTx makes a drug, toremifene, which the company has been testing in Phase 2 trials to prevent prostate cancer. The data about what happens to untreated high grade PIN come from observing men in the placebo arm of one of these trials.
"The next step is to develop an effective therapy for treating high grade PIN, before prostate cancer has a chance to take root. We know that there is a measurable window of opportunity for treatment before the cancer appears. We must take advantage of that opportunity as a key step toward prostate cancer prevention," Steiner said.
In GTx's prospectively designed study, some 109 men with high-grade PIN and no prostate cancer at baseline were analyzed. In addition to the baseline biopsy, patients were re-biopsied at six and 12 months to test for the presence of prostate cancer. Results demonstrate that within one year, men in the placebo group had a 31.4 percent risk of being diagnosed with prostate cancer.
A sub-set analysis of the placebo patients in a year long, chemopreventive toremifene study, which was also presented at the AACR meeting here, confirmed that men with high-grade PIN have an increased, cumulative risk of being diagnosed with prostate cancer after one year.
Toremifene citrate (trade name Acapodene), a drug currently used to treat breast cancer in women, is a nonsteroidal selective estrogen receptor modulator (SERM).
For more on the drug's effect on high grade PIN see:
Acapodene (toremifene citrate) shows promise to prevent prostate cancer in men at high risk.
GTx plans to initiate a Phase III clinical trial in 2004 following discussions with the Food and Drug Administration (FDA).
About High Grade PIN
High grade PIN is a premalignant lesion with strong potential to progress to prostate cancer.
In the United States, about 1,300,000 prostate biopsies are performed per year to detect 230,000 new cases of prostate cancer. About 115,000 new cases of high grade PIN are diagnosed each year. This amounts to some 9% of prostate biopsies.
Currently, patients diagnosed with high grade PIN have to be followed closely by their urologist and are checked by means of repeat prostate biopsies.
What does high grade PIN look like on a biopsy? See this slide at webpathology.com http://www.webpathology.com/image.cfm?case=19&n=1
Concern about PIN led to a clinical trial of Proscar (finasteride) to prevent prostate cancer:
PIN: Precursor to Prostate Cancer? Winter 1995-1996. Eric Klein M.D.
The Proscar trial was halted in June 2003 when a small but statistically significant number of men developed highly aggressive prostate cancer while taking Proscar.
About prostate cancer
Prostate cancer is the most commonly diagnosed cancer in America among men. With an estimated 220,000 new cases diagnosed each year, one in every five men will get prostate cancer during his lifetime. African-American men are at special risk for the disease. In fact, the incidence rate in African-Americans is 60 percent higher than that in white males and double the mortality rate. An estimated 29,900 American men lose their lives to prostate cancer each year.
