Diagnosing prostate cancer can be frustrating. Standard methods, such as the prostate specific antigen (PSA) test and the digital rectal examination, often turn up false positives. The digital rectal exam, in particular, is simple and inexpensive - and subjective and inexact. And screening studies can't pinpoint a cancer's exact location. As a result, biopsies of the prostate are performed on areas that are only best guesses where cancer may lie. Some 200,000 cases of prostate cancer are diagnosed annually in the United States, yet only one in three persons receiving a biopsy is found to have cancer. Physicians and patients would like a better way. The key to the trial's success, says Ethan Halpern, M.D., professor of radiology and urology at Jefferson Medical College of Thomas Jefferson University, who is leading the study, lies in the nature of the cancerous tumor itself. Cancerous tissue in the prostate may have up to twice as many blood vessels as does healthy tissue. Many researchers believe that without this additional blood supply, cancerous tumors cannot grow and spread.
But Dr. Halpern, who is co-director of the Jefferson Prostate Diagnostic Center, says that conventional Doppler ultrasound may not be good enough to find those tumors that contain more blood vessels than usual. In addition, it can only detect vessels larger than 1 to 2 mm in size. Contrast-enhanced ultrasound, he says, can detect vessels smaller than 1 mm.
Dr. Halpern believes that by using contrast-enhanced ultrasound, "we can find areas in the prostate that have more blood vessels," enabling physicians to direct biopsies there. At the same time, he says, "we hope to show that those areas in the prostate that don't have more vessels don't require biopsy."
Once cancer is suspected, say by a high or rising PSA, says Dr. Halpern, the standard procedure is the sextant biopsy - six biopsies distributed on the prostate gland. But since no one knows where the cancer is, a negative result doesn't rule out cancer. If the PSA continues to go up, another sextant biopsy is performed three to six months later.
Dr. Halpern and his team hope to be able to improve cancer detection with fewer biopsies. "We'd like to find the clinically significant cancers that will impact a person," he says. "By looking for cancers located in vessel-rich tissue, we're hoping that not only will we improve the detection of cancer, we'll improve the detection of clinically significant cancers that will more likely be dangerous to the patient. It may not be important if we miss tumors with fewer vessels because we think they will be less dangerous." Cancers that are vascular-rich, he notes, are more likely to spread.
While prostate cancer is the most common male cancer in the Western world and the second leading cause of cancer death in men, it is a disease men often die with, not of. It can be extremely slow growing; half of all men who die at age 80 have prostate cancer, though they may not necessarily have any symptoms or even know it.
In the study, every patient is evaluated first with both standard "gray scale" and Doppler ultrasound. The exam is repeated twice, once before infusion of the contrast agent and again during the infusion. A biopsy of suspicious areas in each part of the prostate is performed during infusion of the contrast agent.
The contrast agent being studied, Imavistä (AF0150), is awaiting final approval from the U.S. Food and Drug Administration (FDA). Dr. Halpern is evaluating the enhancement provided by Imavist with conventional Doppler imaging as well as a newer harmonic gray scale inversion technique. "The phase inversion technique provides better spatial and temporal resolution," he notes. He adds that these techniques may enable them to identify slight irregularities in the normal prostate blood flow pattern that are not seen with conventional Doppler. The researchers plan to follow the patients with positive biopsies for three years to see if contrast-enhanced imaging can also predict which cancers are more aggressive and more likely to return after treatment.
"If this new method is shown to be sensitive for detection of moderate- to-high-grade cancers of the prostate, many future patients could avoid biopsy," he says.
The Jefferson Prostate Diagnostic Center aims to improve the detection of cancer within the prostate, providing state-of-the-art prostate imaging and biopsies. Physicians who want to refer patients for biopsy and evaluation by the center should call 215-955-7544.
For more information regarding the study, please call the study coordinator, Dara DelCollo, at 215-955-2686 or 1-800-JEFF-NOW.