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European UrologyVolume 61, issue 6, pages e53-e66, June 2012
To Biopsy or Not to Biopsy—Thou Shall Think Twice
Published online 8 February 2012, pages 1115 - 1117
Refers to article:
Infectious Complications and Hospital Admissions After Prostate Biopsy in a European Randomized Trial
Accepted 28 December 2011
June 2012 (Vol. 61, Issue 6, pages 1110 - 1114)
Prostate biopsy—generally considered a safe procedure, although beset by rare and worrisome major complications—has changed quite dramatically over the past two decades, as has the prostate cancer (PCa) field itself . We are far from the digitally directed biopsies of the 1980s. Most biopsies are now driven by prostate-specific antigen (PSA) testing rather than digital rectal examination. However, as the positive predictive value of PSA has been significantly reduced over the last several years, more unnecessary prostate biopsies are performed annually on millions of men worldwide.
We have also witnessed a sharp increase in the number of biopsies performed compared with the sextant scheme, with the most extreme schemes (saturation) including >50 biopsies . This inflation in the number of biopsies has come with a cost. A significant number of cancers that are very unlikely to ever become life threatening are diagnosed. The prevalence of PCa in the population is higher than the incidence of clinically significant disease. This fact has a profound impact on both patients and their physicians, as the best management and course of action for these “indolent” cancers remain unclear at the present time. In addition, it is both intriguing and frustrating to observe that despite the increased number of biopsy samples, some clinically significant PCa is still missed.
In addition to the huge burden on our health systems and on patients produced by the detection of so many low-risk cancers, PCa biopsies are associated with inherent risks. As they are performed through the transrectal route, and despite prophylactic antibiotics, the risk of infection associated with them is real and seems to have increased over time. Whether this increase is because of the increased number of biopsies performed, the liberal use of local anesthesia, the growing resistance to quinolone-based antibiotics, or a combination of these factors has not been completely established. What is clear is that when counseling a patient and advising him to undergo prostate biopsy in 2012, the discussion of risks versus benefits should not be neglected. As urologists, we should remain on the side of caution, as it is easy to become desensitized to the potential risks to our patients.
The risk of serious infectious complications requiring hospitalization after biopsy is not trivial. The incidence of serious complications and hospitalizations remains relatively low (<1%, according to the current paper by Loeb et al. ) and might fly under the radar and scrutiny of many of us; however, it seems that these numbers are at best an underestimation of the current situation, not an overestimation, particularly when the numbers are being monitored by clinical trial personnel within the studies. Interestingly enough and as expected intuitively, in the European Randomized Study of Screening for Prostate Cancer (ERSPC), not only comorbidities such as diabetes but also an enlarged prostate increased the risks of complications after prostate biopsies. As diabetes is very common, this aspect should not be underestimated. Most important, the rate of complications increased over the study period.
One of the coauthors of this editorial was the first to show, in a population-based study from Canada including >41 000 men with negative biopsy, that the 30-d hospital admission rate after prostate biopsy increased from 1.0% in 1996 to 4.1% in 2010 . The majority of hospital admissions (72%) were related to bacterial infections. Nine of 10 000 men died within a month. Loeb et al. subsequently showed similar findings from a 5% random sample of Medicare participants in the Surveillance Epidemiology and End Results study . At the onset of this US study in 1991, <0.5% of men were admitted to the hospital because of an infection diagnosed following a prostate biopsy. This rate remained stable until 2000, when rates of infection-related complications began to increase, to >1.2% in 2007. Some authors have even stated that there is a concerning mortality, not a mere morbidity, associated with prostate biopsies .
Given the astronomical number of prostate biopsies performed worldwide, even a relatively low incidence of serious morbidity—not to mention mortality—is to be taken very seriously and may translate into thousands and thousands of casualties. One should never forget that the phrase primum non nocere remains valid thousand of years after it was written. Everything in medicine boils down to a thin balance between benefits and weighted risks for the patients. And one can really wonder whether diagnosing a very low-volume Gleason 6 PCa in 1 of 16 cores in an otherwise healthy 74-yr-old man whose passion is golf amounts to a real benefit for him.
One limitation possibly preventing us from generalizing the data observed by Loeb and colleagues  to day-to-day practice in 2012 is that lateralized sextant biopsy, and not an extended scheme, was performed in the Rotterdam ERSPC. The authors note that it is unclear whether the rates of infectious complications would be different with a greater number of biopsy cores, as a randomized trial of 6-core biopsy compared with 12-core biopsy reported no significant difference in febrile complications . It is important to note that the study by Nam et al.  showed no difference in hospital admission rates between patients who underwent an initial biopsy and patients who underwent a repeat prostate biopsy after an initial negative biopsy (which generally involves more needle cores sampled).
The emergence of fluoroquinolone-resistant Escherichia coli as a cause of infection after prostate biopsy has been scrutinized in recent years, especially in the context of the increased number of biopsies performed. In 1446 patients who had undergone transrectal ultrasound-guided prostate biopsy from 2001 to 2010, with a mean number of 15.2 biopsies, results in line with those shown by Loeb et al.  in the ERSPC using sextant biopsies were observed by Zaytoun et al. . Of the 1446 patients, 2.14% had a febrile urinary tract infection, and 0.62% were diagnosed with sepsis requiring hospitalization. Of the 40 patients, 20 patients (50%) had urine cultures positive for E coli. Of these 20 patients, 11 patients (55%) had fluoroquinolone-resistant infection, and 9 patients had fluoroquinolone-sensitive E coli infection.
Toren and colleagues reported two cases of catastrophic complications following routine transrectal ultrasound-guided prostate biopsy . The first patient incurred near-fatal septic shock due to multiresistant E coli. Because of the severity of his shock, he developed bilateral leg gangrene requiring amputations. The second patient incurred significant hemorrhage, eventually requiring emergent general anesthesia and surgical management to control hemorrhage after other measures failed. While they describe rare events, these reports emphasize the caution needed by physicians who routinely order prostate biopsies.
This increased risk associated with PCa is real and present across the globe. After Nam presented his results at the 2009 American Urological Association (AUA) meeting, five additional groups presented their postbiopsy infectious complication rates at the 2010 annual AUA meeting. These presentations were a wakeup call for the urologic community, and serious lessons should be learned from them . Of 66 811 men undergoing biopsy in these studies, 1.2% developed urosepsis, with the majority being admitted to a hospital. This problem has been increasing over time. In the United Kingdom, Patel et al. reported recently that of 316 men, 16 were hospitalized with infection after prostate biopsies .
Given this increased risk observed with prostate biopsies over the last decade, several concluding comments are worth considering. First, as indicated by Loeb et al. , although prostate biopsy may be associated with serious complications, they were relatively rare, and this fact should not by itself deter healthy young men who would benefit from early detection from pursuing a recommended biopsy. Second, patients having a biopsy should have a full discussion with their physicians about recent antibiotic use, recent hospitalization, and anything else that might put them at risk for antibiotic-resistant organisms. Third, as urologists, we should pay attention to the increased and sometimes worrisome risks associated with prostate biopsies, as it is easy to become desensitized to the potential risks to our patients and fail to react as sepsis rates fly below the 1% rate. Fourth, efforts should be made to study new antibiotic prophylaxis for patients undergoing prostate biopsies. Finally, physicians should be encouraged to use a risk-adapted strategy and risk calculators to recommend prostate biopsies rather than use fixed cut-off levels for PSA, which is a single and imperfect marker, even if it boasts of being the best marker in oncology .
Conflicts of interest
The authors have nothing to disclose.
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a Department of Surgery, Urology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
b Department of Surgical Oncology, Urology, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada
c Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
Corresponding author. Department of Surgery, Division of Urology, University of Toronto, Mount Sinai Hospital and University Health Network, 60 Murray Street, 6th Floor, Box 19, Toronto, ON, M5T 3L9, Canada. Tel. +1 416 586 4800 ext. 3910; Fax: +1 416 586 4776.
© 2012 European Association of Urology, Published by Elsevier B.V.
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