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Research News: Prostate Cancer

Recent Kimmel Center at Jefferson studies shed light on how prostate cancer spreads – and how physicians can reduce the number of unnecessary biopsies

If you or someone you care about has been diagnosed with prostate cancer, turn to the Kimmel Cancer Center at Jefferson’s Multidisciplinary Genitourinary Center. Founded in 1996, the Multidisciplinary Genitourinary Center gives you access to not only Jefferson urologists but also experts in radiation oncology, medical oncology and integrative medicine. The center’s progressive approach enables patients to benefit from these multiple areas of expertise in a single visit.

Just as important, patients of the Center benefit from the ongoing research initiatives at Kimmel Cancer Center at Jefferson. Two recent examples: studies into how prostate cancer spreads and how physicians can use a special ultrasound technique to reduce unnecessary prostate biopsies.

Study #1: Blocking the spread of prostate cancer

Researchers at the Kimmel Cancer Center at Jefferson have shown that by blocking a signaling protein, they can prevent prostate cancer cells from metastatic dissemination. The work opens the door to future studies examining the protein as a target for therapies aimed at keeping prostate cancer at bay.

In a series of experiments in both the laboratory and animal models, Marja Nevalainen, MD, PhD, associate professor of Cancer Biology at Jefferson Medical College of Thomas Jefferson University, and her co-workers found that the protein, Stat3, is key to the metastatic progression of prostate cancer. Dr. Nevalainen’s group reported its findings in the June 2008 issue of the American Journal of Pathology.

According to Dr. Nevalainen, previous studies have shown that Stat3 is very active in metastatic prostate cancer, and the protein has been linked to cancer metastasis in several different cancer types. Because metastatic prostate cancer lacks effective therapies, understanding the molecular changes involved is critical.

To clarify Stat3’s role in prostate cancer progression, she and her co-workers performed several studies. In one case, the scientists used an antibody for Stat3, for example, to show that it is activated in 77 percent of lymph nodes and 66 percent of bone metastases in human prostate cancer. In another experiment, the scientists prompted mouse prostate cancer cells to overproduce the normal Stat3 protein by delivering it through a virus vehicle. They saw a dramatic increase in prostate cancer metastases compared to controls. Specifically, in mice lacking a working immune system, they showed that Stat3 caused a 33-fold increase in metastases.

“This is the first proof that Stat3 may have a major effect on metastatic dissemination of prostate cancer,” Dr. Nevalainen says. “Stat3 now becomes a potential drug target to interfere with the metastatic progression of prostate cancer.”

Study #2: Reducing unnecessary biopsies

In another study, urologists and radiologists at the Jefferson Prostate Diagnostic Center and the Kimmel Cancer Center at Jefferson found that using a special ultrasound technique to spot areas of blood flow in the prostate gland may substantially reduce the number of unnecessary biopsies.

The researchers found that biopsies targeted to areas of increased blood flow in the prostate were twice as likely to be positive for cancer compared with conventional prostate biopsy techniques. 

According to Prostate Diagnostic Center co-director Edouard Trabulsi, MD, assistant professor of Urology at Jefferson Medical College of Thomas Jefferson University, finding the best areas to perform biopsies in the prostate has always been difficult. Standard methods entail simply dividing the prostate into a dozen regions within the gland, almost randomly. Center co-director Ethan Halpern, MD, who is principal investigator on the four-year, National Cancer Institute-supported trial, has been developing and refining techniques to enhance targeted biopsy of the prostate for more than a decade.

With their co-workers, Dr. Trabulsi and Dr. Halpern, professor of Urology and Radiology respectively at Jefferson Medical College, randomly divided 63 prostate biopsy patients into two groups. One group was given the drug dutasteride, which can reduce the blood flow in benign prostate tissue, while the other half received a placebo. They then compared the results from biopsies targeted by blood flow changes using contrast-enhanced ultrasound to those that were done the standard way. The study involved 979 biopsies.

“We’ve previously shown that a two-week course of the drug Avodart (dutasteride) before biopsy reduces the benign blood flow, or background noise – allowing us to see subtle flow changes to target for biopsy,” Dr. Trabulsi explains. “When we did this, we found that targeted biopsies based on the contrast-enhanced ultrasound are much more likely to detect prostate cancer. That’s the exciting part about this.”

Dr. Halpern explains that standard procedures fail to diagnose prostate cancer in approximately 30 percent of men with the disease, even though the biopsy protocol may sample 12 to 18 tissue cores from the prostate. “In the future, our goal is to perform a limited number of targeted biopsies and leave the rest of the prostate alone,” he says. “This will provide a safer, more cost-effective approach to diagnosing prostate cancer.”

The doctors say that the current study involves a novel ultrasound algorithm called flash replenishment imaging to show fine vascular flow differences: “The novelty is using the dutasteride before biopsy, using contrast-enhanced ultrasound and using the latest ultrasound technology to look for blood flow changes associated with prostate cancer,” says Dr. Halpern.

“We are beginning to have patients who were operated on come back in,” Dr. Trabulsi notes. “If we can show that we reliably hit the areas of cancer based on the ultrasound results and didn’t miss any, it’s a home run.”

The trial is continuing and the team is hoping to enroll about 450 men in the trial. To learn more, please see the Prostate Diagnostic Center site, www.prostate.tju.edu.

For more information

Make an appointment with a Jefferson physician online or by calling 1-800-JEFF-NOW.