Making Active Surveillance Safer
“Our infectious disease experts have helped us develop an appr oach to repeat prostate biopsies that is safer for men in active surveillance, and also for men undergoing routine prostate biopsies for an elevated PS A.”
Active surveillance, in carefully selected men, can prevent unnecessary treatment of prostate cancer. However, this approach is not without potential side effects. “Men on surveillance need periodic prostate biopsies for disease monitoring, and a major risk of prostate biopsy is infection,” says urologist H. Ballentine Carter, M.D.
To get a needle into the pr ostate, a urologist needs to go through the rectum; there is a risk that a biopsy - related infections can develop if bacteria in the rectum, such as E. coli, find their way to the prostate and, eventually, the bloodstream. To prevent this, urologists administer an antibiotic called a fluoroquinolone (Ciprofloxacin) before and after the procedure. However, says Carter, it has become evident that about one out of fiv e men has fluoroquinolone (FQ) resistance — which means that an infection could develop that might be more difficult to treat. “Two and a half years ago at the Brady we began a program to test, using a simple rectal swab sample, whether or not men have FQ resistance before biopsy. With this information, we can select the best antibiotic to prevent infection.” In the Hopkins Active Surveillance Program, men have been getting these rectal swabs every six months and now Carter has new information on how resistance develops over time.
HERE’S HOW IT WORKS:
MRI uses a magnetic field to form images of the body, and mpMRI identifies prostate cancers based on three characteristics of cancerous tissue:
• Abnormal signals that emanatefrom prostate tissue after exposure to a strong magnetic field;
• High cellular density and disorganized tissue architecture, leading to abnormal diffusion of water molecules within tissue; and
• New blood vessel formation,
which creates abnormal perfusion
of contrast within tissues.
Jason Cohen, a Hopkins medical student who has studied these swabs, found that diabetes is a risk factor for FQ resistance. He also identified a substantial number of men with E. coli who are resistant to other antibiotics commonly used to prevent post-biopsy infections. “This study, for the first time, evaluated the longitudinal patterns among men with repeat rectal swabs,” says Carter. “Two of three men who harbored resistant organisms maintained this resistance on a follow-up swab six months to a year later, and 9 percent of those who had no resistant organisms developed a resistant organism at the second swab.” Multiple biopsies were not associated with increased FQ resistance, he adds. Using these data, “our infectious disease experts have helped us develop an approach to repeat prostate biopsies that is safer for men in active surveillance, and also for men undergoing routine prostate biopsies for an elevated PSA.”
Lowering the risk of misclassifying cancer: “Misclassification is the problem of relying on a prostate biopsy, which samples only a small fr action of the prostate, to reflect the biology of the entire gland,” says Carter. “If a diagnosis of low-grade prostate cancer is made on prostate biopsy and a patient chooses active surveillance, the risk that a higher-grade, more aggressive cancer is present within the prostate can range from 10 to 30 percent.” A new technique called multi-parametric magnetic resonance imaging (mpMRI) could lower the risk by helping select which men truly have low-grade cancers; it could also reduce the number of prostate biopsies needed by men on active surveillance.
By assessing all three of these parameters, mpMRI can detect prostate cancers that were missed on a prostate biopsy, particularly tumors arising from sites that are not commonly sampled, such as the anterior area of the gland.
In a study of men on active surveillance, “our group demonstrated that when mpMRI suggested the absence of prostate cancer in a particular ar ea of the prostate, there was a high probability that cancer was absent on multiple biopsies taken from these negative mpMRI areas,” Carter explains. Carter, with Sayed Dianat, a radiology fellow, and Kasia Macura an MRI expert, recently studied 96 men who met the strictest criteria for entering the Hopkins Active Surveillance program and had an mpMRI within one year of entering the program. In follow-up biopsies, “we found cancer in 8 percent of those without any abnormality on the baseline mpMRI, as compared to cancer in 41 percent of those who showed an mpMRI abnormality on their baseline scans.” The scientists concluded that men without any mpMRI abnormality have a 65- percent lower likelihood of “a positive follow-up prostate biopsy that would have triggered prostate cancer treatment. We are now using mpMRI routinely to help select the mos t appropriate candidates for active surveillance, and to help reduce the frequency of prostate biopsies.”
New technology is also making it possible for the team to merge the mpMRI with a live ultrasound image, “so that during a prostate biopsy, specific areas within the prostate that are abnormal on mpMRI can be targeted,” Carter says.