Prostate Exam Deaths From ‘Superbugs’ Spur Inquiry Into Cancer Tests
Dr. Robert Nam
Doug Nicholson/Sunnybrook Odette Cancer Centre via Bloomberg
Dr. Robert Nam, head of genitor-urinary cancer at Toronto's Odette Cancer Centre.
Dr. Robert Nam, head of genitor-urinary cancer at Toronto's Odette Cancer Centre. Photographer: Doug Nicholson/Sunnybrook Odette Cancer Centre via Bloomberg
May 6 (Bloomberg) -- Among the millions of men tested for prostate cancer around the world each year, doctors are detecting an increasing number of cases in which patients become sick from potentially lethal, drug-resistant infections. The trend is forcing doctors to rethink their approach to screening for the most common malignancy in men. Bloomberg's Shannon Pettypiece reports on Bloomberg Television's "InBusiness With Margaret Brennan." (Source: Bloomberg)
Shane Greenstein only vaguely recalls being told that a prostate biopsy he had in June was negative for cancer. That’s because within two days of the exam he was in the hospital with a potentially deadly blood infection.
“It was the worst illness I have ever felt in my life,” said Greenstein, 50, an economics professor at Northwestern University who sought emergency-room treatment in Evanston, Illinois, 10 hours after feeling “mild flu-like symptoms.”
Doctors gave him intravenous fluids to maintain blood pressure and prevent shock, a complication that could lead to a cascade of symptoms including organ failure and death. Greenstein was saved when the third antibiotic he was prescribed, an intravenous one, managed to kill the bacteria.
Among the millions of men tested for prostate cancer around the world each year, doctors are detecting an alarming trend: An increasing number of patients are getting sick from potentially lethal, drug-resistant infections.
Studies emerging during the past year have uncovered that a small, yet growing percentage of those undergoing routine needle biopsy tests are becoming critically ill and dying from bacterial infections. Infectious complications including sepsis, the condition Greenstein had, from prostate biopsies have more than doubled in less than a decade, studies from three countries show. Nine out of 10,000 men whose tests were negative died within a month, researchers in Toronto reported in the Journal of Urology in March last year.
More Harm Than Good
The new reports, by urologists from Baltimore to Singapore, are forcing doctors to rethink their approach to screening for prostate cancer, the most common malignancy in men. The newly uncovered risk of dangerous infections is adding to concern that the tests are being overused, leading to aggressive treatment that may cause some men more harm than good.
The studies also are exposing another deadly risk attributed to the global rise of infections that can’t be readily treated by existing antibiotics.
“We’re all beginning to see more and more sepsis as a result of resistant bacteria after prostate biopsies,” said Peter T. Scardino, chief of surgery at the Memorial Sloan- Kettering Cancer Center in New York, which does about 2,000 of the tests annually. “This is an extremely worrisome problem.”
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, can be dangerous if the bacteria are resistant to antibiotics given at the time of the biopsy.
‘Significant Threat’
“It’s a significant threat,” said Florian Wagenlehner, head of urology at University Hospital Giessen, near Frankfurt, who is researching infectious complications from prostate biopsies in Europe. “If you have 1 million procedures a year in Europe and you have a 1-to-5 percent infectious complication rate, it’s unacceptable.”
More than 1 million transrectal prostate biopsies are done in the U.S. each year to diagnose cancers in men whose screening blood tests suggest they may have the disease. No studies have examined the risk of sepsis globally. Instead doctors are trying to gauge the scope of the problem from studies beginning to emerge from North America, Europe and Asia.
Death Toll
“The fact that there is a mortality rate associated with the procedure, that’s concerning,” said Robert Nam, head of genitor-urinary cancer at Toronto’s Odette Cancer Centre, who led the largest study to date of hospitalizations after biopsy.
Nam helped uncover the emerging infection risk last year after he trawled through more than 75,000 electronic records of biopsy patients treated in Ontario between 1996 and 2005. When he looked at hospital admissions among patients whose biopsy was negative for cancer, Nam discovered the chance of being hospitalized within a month of the procedure had increased fourfold in less than a decade, reaching 4.1 percent in 2005 from 1 percent in 1996, according to the Journal of Urology report.
When Nam searched for the cause of the hospitalizations, he found 72 percent had an infection-related diagnosis. Nam’s research group is examining individual case files to determine the cause and severity of the infections and which patients had drug-resistant bacteria.
‘Not Just Smoke’
“When you’re admitted to hospital, that’s an indication of a pretty severe infection,” he said. “I firmly believe the source of sepsis is from antibiotic-resistant strains.”
Nam’s research was presented at the American Urological Association’s annual meeting in San Francisco last June. Four other studies with similar findings were presented by researchers from the U.S., Czech Republic, Singapore and South Korea. Ten studies related to prostate biopsies and infection are slated for this year’s meeting in Washington on May 14-19.
“There’s not just smoke, there is a fire. No question,” said Gilbert J. Wise, 78, clinical professor of urology at New York’s Weill Cornell Medical Center, who has practiced urology since 1969. “I’m personally aware of two deaths -- they’re not mine, thank God -- in patients following biopsy. So it can happen. It’s a shame. You do something, there is no cancer, and they die of the procedure.”
Screening Controversy
Infectious complications are adding to debate over so- called PSA screening, a blood test for a protein produced by prostate cells known as prostate-specific antigen. About 30 million American men get the test annually, costing at least $3 billion, said Richard J. Ablin, the scientist who discovered PSA in 1970. Still, the basis of the exam is flawed because it can’t detect prostate cancer or distinguish between benign tumors and deadly malignant ones.
“Despite accumulating evidence to the contrary of the effectiveness of the test, it continues to lead to a hugely expensive public health disaster,” said Ablin, 70, a research professor of pathology at the University of Arizona College of Medicine in Tucson. “The medical community must confront the reality and stop the inappropriate use of PSA testing.”
Men most susceptible to harboring resistant bacteria include those who have taken antibiotics in the year before the procedure; who have recently visited countries where resistance is common in the community; and those who work in a hospital or live with someone who does, said David Bell, a urologist in Halifax, Nova Scotia.
Doctors Vulnerable
Bell, who is head of the urology department at Dalhousie University, and colleagues reported three cases of sepsis from multidrug-resistant bacteria in doctors who underwent prostate biopsy in the Canadian Journal of Urology in April last year. One of the physicians, a 44-year-old whose biopsy was negative for cancer, died.
“I have personally sent two other departmental chiefs into the ICU because of biopsies,” Bell, 52, said. “This is a huge issue. This is actually catastrophic.”
Bell, who completed his urology training in 1990, said he’s now “much more reluctant” to recommend a biopsy unless there’s good evidence a patient has a malignancy, and that it needs to be identified and treated.
Two days after his biopsy, Don Beer, a resident of Canberra in Australia, began feeling sick. His chills worsened shortly after he went to bed at about 7 p.m.
‘Shivering and Shaking’
“Pretty soon I was shivering and shaking,” said Beer, a 69-year-old former history professor. His case was described by doctors in a letter to the Medical Journal of Australia in February.
At the time of the procedure, Beer was given ciprofloxacin, a pill from the antibiotic class known as fluoroquinolones, favored by most urologists for their ability to concentrate in the prostate gland and fight a broad spectrum of so-called Gram- negative bacteria including E. coli that inhabit the bowel.
Blood and urine tests on Beer found his infection was caused by E. coli, the most common cause of urinary tract infections. Tests found that the bacterial strain coursing through Beer’s bloodstream was resistant to ciprofloxacin and four other classes of antibiotics.
Beer’s infection came and went three times before it was finally cleared with the help of seven courses of four different antibiotics over nine weeks, according to the letter.
Beer probably picked up the superbug from the food and water he consumed while traveling overseas, said Peter Collignon, head of infectious diseases at Canberra Hospital, where Beer was treated. The government-run center has seen 16 cases of sepsis following prostate biopsy since 2009. E. coli resistant to two or more antibiotic classes was found in 13 patients and ciprofloxacin-resistant E. coli was found in 10.
No More Drugs
“This is a major international public health problem --not just in prostate biopsies,” said Collignon, who also teaches at the Australian National University. “We are all seeing so many difficult or impossible to treat Gram-negative bacteria infections, and there’s nothing in the pipeline capable of fighting the most resistant of them.”
People may carry resistant bacteria for years, said Maurine Leverstein-van Hall, a clinical microbiologist at the University Medical Center in the Dutch city of Utrecht. A quarter of people whose bowels were colonized with the superbugs still had them a year later, her research found.
Beer traveled to Morocco and Spain 12 months before the procedure, and Vietnam and Cambodia two years prior. He’d also spent weeks traveling through China, Egypt, Jordan, Turkey, Chile, Argentina, Peru and Bolivia from 2002 to 2006.
India, China
Ciprofloxacin-resistant E. coli is uncommon in Australia, the only country where general practitioners require government authority to prescribe the medicine. A national survey found resistance in 4.9 percent of 762 specimens tested in 2006. In Europe, resistance ranges from 7 percent in Iceland to 36 percent in Italy and 43 percent in Cyprus. More than half of specimens tested in India, China and Thailand resist ciprofloxacin and three other antibiotic classes, a 2011 study found.
Researchers in Australia and Sweden testing rectal swabs of international travelers taken before and after their trips reported last year that a quarter to half returned home carrying multidrug resistant E. coli in their bowels. Of those who visited India, at least three-quarters were colonized with the superbugs.
Tailoring Treatment
Michael Liss, a chief resident in his final year of urology training at the University of California, Irvine, in Los Angeles, is researching a test that will help doctors predict the best antibiotic for preventing infections. Liss was prompted to look for ways to make the procedure safer after almost losing a patient to sepsis three years ago.
Biopsy candidates who recently traveled to India, China and other parts of Asia should wait six months after their return before having the procedure, said Anthony Costello, who does about 200 biopsies a year at prostate cancer clinics at the Royal Melbourne and Epworth hospitals in Melbourne. He estimates two of every 100 biopsy patients will develop sepsis. About 26,000 procedures were done in Australia last year, more than double the number a decade earlier, government statistics show.
Prostate biopsies are also controversial because a cancer diagnosis doesn’t necessarily save lives. A two-decade-long study led by Gabriel Sandblom of the Karolinska Institute in Stockholm found that PSA tests and digital rectal exams helped detect cancer but didn’t reduce deaths. A separate study from Sweden last year showed that 293 men needed to be invited for a cancer screening and 12 had to be treated to prevent one death.
$9.9 Billion in Costs
An estimated 217,730 men were diagnosed with prostate cancer and 32,050 men died of the disease in the U.S. last year. U.S. medical costs linked to prostate cancer care were estimated at $9.9 billion in 2006.
One in six men in the U.S. will be diagnosed with prostate cancer during their lifetime, according to the National Cancer Institute in Bethesda, Maryland. Even still, fewer than 3 percent of men will die from the malignancy.
The American Cancer Society changed its guidelines in 2010 to reflect a growing body of research suggesting screening tests may do more harm than good in some men. The cancer group said patients should be warned of the risk of misleading tests results and treatment side effects, which might in some cases cause more damage than the slow-growing disease.
Do No Harm
“There has been this huge enthusiasm for everyone getting their PSA checked, which has led to a lot of prostate biopsies that have not benefited anyone,” said James R. Johnson, an infectious diseases physician at the Veterans Affairs Medical Center in Minneapolis. “The more dangerous the biopsy becomes because of infection risk, the more likely it is that the balance is shifting toward harm, rather than benefit.”
Sepsis survivor Greenstein says the desire to get an early jump on prostate cancer is such that it wouldn’t dissuade him from a repeat biopsy if it’s recommended.
“The risks are too high,” the father-of-four said. “You’ve got to do what you can to avoid it.” But at the first sign of a problem, he said he would seek medical help. “I would go to the hospital at 8 o’clock, rather than wait until the next morning.”
To contact the reporter on this story: Jason Gale in Singapore at j.gale@bloomberg.net
To contact the editor responsible for this story: Jason Gale at j.gale@bloomberg.net
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