Prostate Cancer Test Causing Sepsis Spurs Biopsy ConcernsJason Gale
Doctors are changing their approach to prostate biopsies as evidence mounts that the danger of complications from the procedure may outweigh its usefulness identifying some cancers.
An increasing incidence of potentially lethal, difficult-to-treat bloodstream infections tied to prostate biopsies has become so serious that urologists are reassessing when, how and even if they do the procedure.
To reduce the risks, doctors are turning to a longer, costlier -- but ultimately safer -- approach to detect tumors that entails avoiding the bacteria-laden rectum. And though global evidence is scant, in Australia data shows doctors are scaling back their reliance on biopsies altogether. In the U.S., doctors say anecdotal evidence also suggests prostate biopsies are probably decreasing.
“People have started to sit up and say, ‘hey, maybe we need to rethink what we’re doing,’” said Nathan Lawrentschuk, an associate professor of surgery at the University of Melbourne and a urologist at Melbourne’s Austin Hospital.
The response reflects the growing threat of bowel-dwelling bacteria that even the world’s most powerful antibiotics are unable to snuff out. It’s also adding to the debate about the importance of diagnosing prostate cancer. While it’s one of the most common malignancies of men, tumors are slow-growing in most cases and treatment often causes impotence and incontinence.
Doing a tissue biopsy of the prostate to detect cancer typically entails sending an ultrasound-guided needle about a dozen times through the rectum to collect specimens from the walnut-sized gland that sits under the bladder.
The test carries an infection risk because the needle can take bacteria from the bowel into the prostate, bladder and bloodstream. The 15-minute procedure, usually performed in a doctor’s office under local anesthetic or light sedation, can be dangerous if the bacteria are resistant to antibiotics given at the time of the biopsy. Bacteria that escape into the bloodstream can cause sepsis, a condition that can lead to multiorgan failure and death.
“Greater recognition of the infectious risks of biopsy has led us to be much more careful about who we select for prostate biopsy,” said Stacy Loeb, assistant professor of urology and population health at New York University. “All patients should be evaluated for risk factors for resistant bacteria and infection, and should be counseled about the risks and benefits of proceeding to biopsy.”
The most common reason to perform a biopsy is an abnormal result from PSA screening, a blood test for a protein produced by prostate cells known as prostate-specific antigen. The test is controversial because, while it may signal the likelihood of prostate cancer, it can’t definitely detect it. Nor can it distinguish among benign tumors, slow growing cancers and deadly malignant ones. That’s led many doctors to question the wisdom of using PSA screening results to make treatment decisions.
“The risk of sepsis has made all of us think a little bit longer before recommending a biopsy,” said David Bell, head of urology at Dalhousie University in Halifax, Nova Scotia, adding that he tends to avoid the transrectal approach in repeat biopsies.
Bell says he’s now more tolerant of a slightly abnormal PSA and looks for other supporting reasons to indicate a biopsy is necessary, such as when PSA increases rapidly over time or is especially high. Other factors to consider include whether a palpable nodule develops, or if the patient has African ancestry or has a family history of early-onset prostate cancer or death from prostate cancer.
In Australia, the number of prostate biopsies performed per capita has declined the past three years from a peak in 2009, government records show.
More than 800,000 prostate biopsies are done in the U.S. each year. There isn’t good quality data in the U.S. to track frequency trends, New York University’s Loeb said. Anecdotal evidence, however, suggests the “overall number of biopsies is decreasing,” Otis Brawley, chief medical officer of the American Cancer Society, said in an e-mail.
The declining biopsy rate in Australia reflects concern about infection, as well as the availability of alternative tools, such as magnetic resonance imaging (MRI), to identify patients most likely to benefit from it, said Mark Frydenberg, head of urology at Monash Medical Centre in Melbourne.
“The best way to minimize the risk is by not having a biopsy at all,” Frydenberg said. “If you do need a biopsy, then the decision rests between going down the transperineal route or transrectal route.”
The perineum, the skin between the bottom of the scrotum and the anus, is a safer entry point because it can be cleaned with antiseptic, unlike the rectum, said Lindsay Grayson, Austin Hospital’s head of infectious diseases.
The lower risk of infections means urologists can take more core samples of the prostate, especially of the part of the gland that’s difficult to reach from the rectum, Frydenberg said.
On the downside, the procedure takes at least twice as long to perform, requires heavier patient sedation, six people in an operating theater, and equipment costing about $100,000, he said.
No studies have examined the infection risk from prostate biopsies globally. Instead doctors are trying to gauge the scope of the problem from studies emerging from North America, Europe and Asia.
The chance of being hospitalized within a month of a biopsy increased fourfold in Ontario in less than a decade, reaching 4.1 percent in 2005 from 1 percent in 1996, Robert Nam and colleagues at Toronto’s Odette Cancer Centre, wrote in a study published in the Journal of Urology in 2010. Almost three-quarters of the hospitalizations were infection-related.
“Given the recent spike in infection complications after prostate biopsy, the ideal method to diagnose prostate cancer must be pondered,” Matthew Gettman, professor of urology at the Mayo Graduate School of Medicine in Rochester, Minnesota, wrote in an editorial in the journal European Urology last May. “Despite local anesthetics, the whole procedure is barbaric, and it is surprising that the issue of infection has not come to light years ago.”
Infectious complications have typically occurred in 3 percent to 5 percent of prostate biopsy patients at Austin Hospital, Lawrentschuk said. Doctors have sought to curb rising rates of infection by using increasingly powerful antibiotics. The problem is resistance is building to even the broadest-spectrum drugs, forcing doctors to look for other ways to minimize risks. “That’s huge,” said Brawley, of the American Cancer Society.
“You do hear these anecdotal reports of deaths, but I have only heard of one in Melbourne in the last three or four years,” Lawrentschuk said. “In terms of sepsis and admissions to the ICU, they seem to be more common. Even if the sepsis rates aren’t higher, the stakes are higher because you are getting organisms that are trickier to treat.”
The Moffitt Cancer Center in Tampa, Florida, has revised its biopsy protocol over the past two years with the help of infectious disease physicians to minimize complications, said Wade Sexton, a urologist and director of the hospital’s urologic oncology fellowship program.
In addition to being as selective as possible with initial biopsies and repeat procedures, the center now performs rectal swabs on every patient undergoing a prostate biopsy within one month of the procedure to make better informed choices about what antibiotics to use based on any resistant bugs found, Sexton said.
“This is a step we’re taking to try to minimize the risks as best as possible until additional evidence becomes available,” he said. “Whether this approach is cost-effective remains to be determined.”
Patients who have traveled to South Asia, Southeast Asia and other regions where there is a high incidence of infections caused by multidrug-resistant bacteria are told to wait at least six months from their return to have a prostate biopsy, Lawrentschuk said. Where there is a more urgent need, travelers are given a different antibiotic -- one from the last-resort class known as carbapenems.
Doctors are also testing fosfomycin, a broad-spectrum antibiotic discovered in Spain in 1969, for its ability to penetrate the prostate. Preliminary results of research carried out at Austin Hospital suggest it’s promising, Lawrentschuk said.