The simultaneous, and fortuitous, introduction and approval of widespread prostate-specific antigen (PSA) testing and transrectal ultrasonography in the late 1980s resulted in the development of new biopsy techniques with a marked increase in the number of prostate biopsies performed yearly by urologists. With this came a stage migration and increase in the number of lower grade/organ-confined prostate cancer cases in those newly diagnosed. As evidence continues to mount regarding the role of active surveillance in management of low-risk prostate cancer, a challenge for many urologists is to determine which patients will in fact benefit from prostate biopsy in order to define potentially lethal disease. Recent data suggests that the number of biopsies performed by a urologist in the United States was a median of 29 cases per year.1 However, with the 2012 United States Preventive Services Task Force (USPSTF) D recommendation on PSA testing, there has been a reported 28.7% decrease in the number of biopsies performed annually after this controversial governmental decision, resulting in a drop to 21 biopsies annually per urologist.1,2 Nonetheless, more than 1 million biopsies are performed annually.3
Complications arising from traditional sextant transrectal ultrasound-guided prostate biopsy (TRUSBx) are uncommon but can be broadly categorized as infectious, bleeding, urinary obstruction/retention, and erectile dysfunction.4 It has been well documented that the number of infection-related complications (IRC), which can range in severity from a urinary tract infection to full-blown sepsis necessitating in-patient hospitalization, as a direct result of prostate biopsy has been increasing.5 The transrectal approach with direct introduction of fecal flora from the GI tract, thus seeding the prostate tissue, has been presumed to be the major source of these pathogens.6 There are conflicting data on whether the number of cores taken result in a higher incidence of infection.7,8 Obtaining a detailed patient medical history is critical (Table 1) as a number of these associated factors appear to render the patient at higher risk for infectious events.4
In 2012, the American Urological Association (AUA) published a white paper/best practice policy guideline for the prevention and treatment of IRC related to prostate needle biopsy; this guideline was updated in 2016.4 Oral fluoroquinolones (FQ) were the recommended antibiotic. It has been shown, however, that there is an emergence of fluoroquinolone resistance (FQR) worldwide, which may explain the increasing incidence of post-biopsy infection in certain patients treated with FQ antibiotics.9 Specifically, FQR Escherichia coli prevalence has been estimated at 23.5% in North America.10 There are a number of mechanisms that appear to be contributing, including target-site mutation, transmissible plasma–mediated FQR genes, changes in membrane permeability, and the presence of chromosomal multidrug efflux pumps.11 Table 2 lists associated risk factors that appear to increase the susceptibility for development of a clinical infection with a FQR pathogen.12
Because of these FQR patterns, multiple strategies have been adopted to address this burgeoning problem. These would include routine use of targeted prophylaxis with rectal swab cultures prior to prostate biopsy, augmented prophylaxis (defined as >2 antibiotics with extended E coli coverage based on local antibiograms), and a movement back towards a transperineal approach for prostate biopsy.13
In 2016, LUGPA (https://lugpa.org), partnering with Integra Connect (https://www.integraconnect.com) and the Department of Urology at the Feinberg School of Medicine, Northwestern University, conducted a prospective, multi-center trial utilizing nine LUGPA member practices to determine if the development of a standardized prostate biopsy protocol that included tissue handling and the use of an augmented prophylaxis antibiotic regimen would result in a decrease number of IRC compared with the practice’s historical data. Additionally, with the transition from volume- to value-based care, we recognize that in order to succeed, practices will be increasingly called upon to adopt and adhere to clinical protocols. Therefore, we wanted to determine if urology groups would be able to broadly operationalize standardized antibiotic prophylactic regimens, and if such regimens, once adopted, lead to a decreased incidence of IRC and/or healthcare savings.
A total of nine geographically distinct integrated LUGPA member practices with aggregate number of 220 urologists participated in this prospective study providers (Table 3). A lead-in, historical prospective phase (based on 819 patients who received a prostate biopsy between January 1, 2016 and July 31, 2016, self-reported by the groups) was used to determine the current antibiotic protocol for prostate biopsy at each practice. Utilizing an internally developed case report form, the existing infectious complication and subsequent hospitalization rate was determined for each practice as part of this data collection.
The second phase involved the development of locally derived augmented prophylaxis regimens (>2 antibiotics) based on local antibiograms and consistent with AUA best practice guidelines regarding antibiotic duration. These regimens were reviewed by the physicians on the project leadership team (ES, GK, RC). In general terms, regimens were selected with a goal of >90% E coli sensitivity for each of two antibiotics, based upon the local antibiogram. Secondary regimens, with similar sensitivity targets, were also formulated for reported penicillin allergy. Once developed and implemented, the practices were to enroll all patients undergoing prostate needle biopsy continuously over an 8-week period. Monitoring with clinical follow up for 2 to 3 weeks post-biopsy was used to determine if an IRC had occurred. Tables 4 and 5 detail the complete protocol and augmented prophylaxis regimens for each practice.
Nine LUGPA member practices were chosen to participate in this project. In total, 819 patients (91 per practice site) who had undergone prostate biopsy, regardless of indication, were retrospectively reviewed to determine the historic IRC rate from January through July 2016. An IRC was defined as one or more of the following: chills/rigor, T >101°F, or documented positive blood or urine cultures. Using these criteria, a 3.1% overall incidence of IRC was noted across the reporting groups.
This historical review was also used to determine the individual current antibiotic protocol in place at the time of the biopsies: 3 of 9 (33%) had practice-wide prophylaxis not based on antibiograms and 6 of 9 (67%) had no protocols in place (Table 5). Figure 1 shows the IRC rate based on the historical protocol in place.
After submission of the local antibiogram, we noted geographic differences in FQR (Table 6). Site-by-site accommodations were made considering prohibitive drug costs to the practice and patient, when applicable in some markets, and the ability to administer IV antibiotics within a practice at the site of service for prostate biopsies. A total of 759 patients were accrued for evaluation by the nine practices over a consecutive 8-week period. Eight of the nine practices accrued patients from July 31, 2017 to September 22, 2017, with one practice accruing patients August 28, 2017 to October 20, 2017. An IRC was determined by a urologist review at each site. After implementation of the protocol, the infection rate dropped from 3.1% in phase 1 to 1.4% in phase 2 or a statistically significant 53% reduction in IRC (P = 0.031; Figure 2). This statistical analysis was performed using the IBM SPSS Statistics package. All comparisons were two-tailed and a P < 0.05 was considered statistically significant. Equal variances were not assumed.
Since the 1980s, one of the most common procedures performed by the practicing urologist has been transrectal ultrasound–guided biopsy of the prostate (TRUSBx).3 The genesis stems from the concomitant development and introduction of PSA testing and affordable transrectal ultrasonography, thus allowing the urologic provider to offer prostate biopsy in the office or outpatient setting. The result was a dramatic increase in the number of biopsies performed annually in the United States, with a significant percentage of those newly diagnosed patients having low-risk disease.14 We now possess a better understanding of the natural history of low-grade prostate cancer and that certain low-risk patients may be safely followed with active surveillance.15 Coupled with a notable risk of complications arising from TRUSBx, it becomes prudent for the urologist to be more judicious as to which patient needs to undergo prostate biopsy to identify the presence of significant prostate cancer, as well as limiting the possible complications and reducing the cost of care to manage these unplanned events.
The incidence of post-biopsy IRC has risen over the past decade, with some recent estimates at approximately 2.15/100 biopsies, up from 0.7/100 biopsies performed a decade earlier. It is also of note that there has been a rise in FQR E coli strains during this same time period.3 A number of studies have documented, in both the United States and abroad, that the hospitalization rate as a result of IRC may be as high as 4%.16 Given the number of biopsies performed annually, IRC and their subsequent management represent a significant cost. A recently published large retrospective study of over 5000 patients over a 1-year period from a large metropolitan community-based practice documented a 1.1% IRC after adopting a targeted prophylaxis antibiotic protocol.17 In the era of value-based medicine and pathway adherence, it was the goal of this study, in a prospective fashion, to standardize the biopsy protocol, including identification of risk factors, handling of tissue at the time of biopsy, and incorporation of an augmented antibiotic protocol that was based on local antibiograms. We observed a statistically significant 53% aggregate decrease (3.1% → 1.4%) in IRC across the nine groups that participated in the trial via implantation of the standardized, local antibiogram–based augmented prophylactic regimen.
Limitations of this study included the retrospective nature of determining the historic complication rate(s) of the individual practices based on a finite number of patients (819), as well as the limited number of patients (759) enrolled during the prospective phase. It is likely under-reporting of post-biopsy IRC was greater in the retrospective cohort, which would only strengthen our conclusions. Additionally, notwithstanding the geographic diversity of the participating groups, the total number of groups participating was less than 10.
By developing a standardized biopsy protocol with specific emphasis on incorporating an augmented antibiotic prophylactic regimen based upon local antibiograms, we were able to demonstrate in a prospective trial across nine geographically distinct community practices a significant reduction in the incidence of IRC.
This project was funded by LUGPA and Integra Connect.