INTRODUCTION — Prostate biopsy is a minimally invasive procedure in which tissue samples are obtained from the prostate gland for the purpose of detecting the presence of cancer.
The two main anatomic approaches to prostate biopsy are transrectal and transperineal. Transrectal ultrasound-guided biopsies are typically performed in the office setting by urologists, while transperineal procedures (ultrasound or magnetic resonance imaging [MRI] guided) are most often performed in an outpatient hospital setting by a urologist alone or in conjunction with a radiologist, although newer MRI fusion biopsies can be performed by urologists in the office setting.
Prostate biopsy techniques and periprocedural management will be reviewed here. Other aspects of prostate biopsy are discussed in other topics:
●(See "Screening for prostate cancer".)
●(See "Clinical presentation and diagnosis of prostate cancer".)
●(See "The role of magnetic resonance imaging in prostate cancer".)
●(See "Active surveillance for males with clinically localized prostate cancer".)
PROSTATE ANATOMY — The prostate gland is a firm, walnut-shaped structure located at the base of the urinary bladder; the apex is caudal and the base cranial. The prostate is composed of both glandular and stromal (smooth muscle) tissue. Secretions from the prostate, vas deferens, and seminal vesicle empty into the prostatic urethra (ie, section of the urethra that traverses the prostate); each of these structures contributes to the composition of the semen (figure 1).
The prostate gland is divided into three general zones (figure 2).
●Peripheral – Approximately 70 percent of the prostate gland is contained within the peripheral zone, and the majority of prostate cancers originate within this zone.
●Central – The central zone comprises 25 percent of the volume of the normal prostate with an increased proportion in men with benign prostatic hyperplasia. The stroma of the prostate gland is the densest in this zone. Approximately 5 percent of prostate cancers originate within the central zone.
●Transition – The transition zone comprises 5 percent of the normal volume of the prostate and is the site of benign prostatic hyperplasia. Approximately 10 percent of cancers originate within the transition zone.
INDICATIONS — Prostate biopsy is usually performed to diagnose or exclude prostate cancer.
Indications for the initial prostate biopsy include:
●Abnormal serum prostate-specific antigen (PSA) level. However, what constitutes an abnormal PSA level, and which patients with an abnormal PSA level should be biopsied, are complicated and evolving questions, which are discussed elsewhere. (See "Clinical presentation and diagnosis of prostate cancer", section on 'PSA testing' and "Clinical presentation and diagnosis of prostate cancer", section on 'Decision to biopsy'.)
●Abnormal digital rectal examination (DRE). Abnormal findings on DRE include the presence of nodules, induration, or asymmetry. (See "Clinical presentation and diagnosis of prostate cancer", section on 'Digital rectal examination'.)
Indications for repeat prostate biopsies include:
●Inadequate initial biopsy, atypical findings on initial biopsy, or continued high clinical suspicion for prostate cancer after initial negative biopsy based upon rising PSA levels or a variety of other PSA-based parameters (eg, PSA velocity, PSA density). (See 'Need for repeat biopsy' below.)
●Active surveillance of low-risk, clinically localized prostate cancer. Active surveillance for men with clinically localized prostate cancer at low risk for progression utilizes observation rather than immediate therapy, with curative-intent treatment deferred indefinitely (in most cases) or until there is evidence of disease progression. Repeat prostate biopsy is generally recommended within the first year or two, then every two to five years to rule out high-grade disease missed on the original biopsy. (See "Active surveillance for males with clinically localized prostate cancer".)
The approach and method of prostate biopsy should be tailored to the indication. (See 'Choice of biopsy method by indication' below.)
CHOICE OF BIOPSY METHOD BY INDICATION
Biopsy-naive patients — Transrectal ultrasound (TRUS)-guided prostate biopsy is the standard approach for most patients undergoing prostate biopsy for the first time. We suggest extended 10 to 12 core biopsy rather than sextant biopsy in order to increase the detection of prostate pathology. Patients with a small prostate volume may be biopsied with a smaller number of core samples. (See 'Extended core' below.)
Despite growing interest and numbers of studies, magnetic resonance imaging (MRI)-targeted techniques cannot be recommended for routine initial biopsy until issues related to the quality of imaging and interpretation, targeting strategies, and cost and availability have been addressed [1,2]. Currently there are insufficient data to recommend routine MRI prior to every initial biopsy [1]. (See "The role of magnetic resonance imaging in prostate cancer", section on 'Initial presentation with no prior biopsy'.)
Other guidelines allow clinicians to choose either TRUS-guided or MRI-targeted biopsy as the initial biopsy [3]. Regardless, saturation biopsy is not an appropriate technique for initial biopsies.
Patients with a negative TRUS biopsy — A negative TRUS biopsy in the face of clinically determined need or indication for a prostate biopsy is the most validated and accepted indication for prostate MRI and MRI-targeted biopsy. There is increasing evidence that MRI-targeted biopsy can increase clinically significant cancer detection over standard TRUS biopsy alone [4,5], and this advantage is more pronounced when MRI-targeted biopsy is performed in men with a prior negative biopsy than biopsy-naïve men [6]. (See 'MRI' below and "The role of magnetic resonance imaging in prostate cancer".)
At facilities where prostate MRI and MRI-targeted biopsy are available, they should be performed for patients with one or more prior negative TRUS biopsies. MRI-targeted biopsy should be performed with concurrent systematic sampling, or else clinically significant cancer can be missed by targeted biopsies alone [7-9]. (See 'MRI' below.)
The decision about repeat prostate biopsy depends on many factors. If MRI is performed and a suspicious lesion (PI-RADS 3 or greater) is identified, then the MRI-targeted biopsy should follow. If MRI is not available or shows no suspicious lesion, further management depends on the clinical suspicion for prostate cancer (based on PSA level, size of the prostate, etc): low-risk patients may be followed, intermediate-risk patients may undergo repeat TRUS biopsy, and high-risk patients may undergo saturation/template-guided biopsy. (See 'Saturation' below and 'Template-guided' below.)
Active surveillance — Repeat prostate biopsy for men under active surveillance for low-risk clinically localized prostate cancer is generally recommended within the first year or two, then every two to five years to rule out high-grade disease missed on the original biopsy. (See "Active surveillance for males with clinically localized prostate cancer".)
Current information is not sufficient to support repeat MRI without biopsy for monitoring men on active surveillance [1]. Several methods of repeat biopsy have been evaluated for active surveillance, including transperineal template-guided biopsy [10] and MRI/TRUS fusion biopsy.
●For patients with an MRI-visible lesion, MRI-targeted biopsy is preferred. In a meta-analysis of 741 men with low-risk prostate cancer in active surveillance with at least one index lesion on imaging, MRI-targeted biopsy had slightly greater sensitivity (0.79 versus 0.67) and area under the curve (0.99 versus 0.92) than systematic TRUS biopsy [11].
●Men on active surveillance with no MRI-visible lesions may undergo standard 12 core TRUS biopsy or transperineal biopsy.
PREPARATION — Patients are understandably anxious and may benefit from administration of an anxiolytic prior to undergoing prostate biopsy [12]. The presence of bacteriuria or an indwelling catheter at the time of biopsy increases the risk of postbiopsy urinary tract infection and other infectious complications [13-16]. Thus, a urinalysis should be performed prior to biopsy. If the urinary findings are suspicious for bacteriuria, the biopsy is postponed, urine cultures are obtained, and a short course (five to seven days) of culture-appropriate antibiotics is administered. (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Genitourinary surgery' and 'Infection' below.)
Prophylactic antibiotics — We recommend antibiotic prophylaxis prior to prostate biopsy. The main effect of antibiotic prophylaxis is a lowered incidence of postbiopsy bacteriuria. Although not all patients with bacteriuria are symptomatic, all patients who develop infectious complications following rectal biopsy are bacteriuric [17]. (See "Acute bacterial prostatitis".)
We typically use a single dose of an oral fluoroquinolone one hour prior to prostate biopsy [18,19]. An oral alternative is trimethoprim-sulfamethoxazole. Gentamicin (dosed by weight) and ceftriaxone (1 gram) are the most commonly used intramuscular alternatives to fluoroquinolone, which should also be given at least one hour prior the procedure [20].
Prophylactic antibiotics are recommended prior to prostate biopsy [21-24]. Prostate biopsy performed without antibiotic prophylaxis is associated with increased rates of bacteriuria (8 to 44 percent) and bacteremia (16 to 70 percent) [13,14,25-33]. Major infectious complications, such as sepsis, Fournier gangrene, and urinary tract infection requiring hospital admission, have been reported in patients who did not receive prophylactic antibiotics [29]. A meta-analysis of nine trials found that antibiotic administration prior to prostate biopsy reduces the risk of bacteriuria (risk ratio [RR] 0.25, 95% CI 0.15-0.42), bacteremia (RR 0.67, 95% CI 0.49-0.92), fever (RR 0.39, 95% CI 0.23-0.64), urinary tract infection (RR 0.37, 95% CI 0.22-0.62), and need for hospitalization (RR 0.13, 95% CI 0.03-0.55) [23].
Selection of antibiotics for genitourinary procedures is based upon coverage of urinary tract flora, which includes both gram-positive and gram-negative organisms (table 1) [34]. In the meta-analysis, there were no significant differences between several classes of antibiotics for the outcomes tested (bacteriuria, bacteremia, fever, and the need for hospitalization). No differences were identified for oral versus systemic (intravenous or intramuscular) antibiotics. Seven trials reported a one-day versus three-day course of antibiotics. A single day of antibiotics was associated with an increased risk of bacteriuria (RR 1.98, 95% CI 1.18-3.33), but there were no significant differences in the incidences of more important clinical outcomes. The data were insufficient to recommend multiple doses or treatment for longer than 24 hours.
Fluoroquinolones are the most widely used antibiotic for prophylaxis due to their broad spectrum of activity, easy oral administration, good penetration to prostate gland tissue, and long-lasting bactericidal activity. However, the development of resistant organisms is becoming an increasing problem and may lead to a need to alter the antibiotic regimen [26,35-38].
In the era of fluoroquinolone prophylaxis, infection after transrectal prostate biopsy is most often caused by fluoroquinolone-resistant Escherichia coli [39,40]. Overall resistance to fluoroquinolones is rising. Thus, clinicians should review their local antibiograms and, if the fluoroquinolone-resistance rate for E. coli is >20 percent, choose another class of antibiotics [20]. Alternatively, for patients at high risk of harboring resistant organisms (eg, diabetes, immunosuppression, recurrent urinary tract infections, antibiotics within six months, health care workers, or recent international travel), rectal swab cultures may be taken to direct antibiotic selection [41-45].
Given that practices vary, a meta-analysis of 59 trials comparing seven different prophylactic antibiotic regimens found that in countries where fluoroquinolones are allowed as antibiotic prophylaxis, a minimum of a full one-day administration as well as targeted therapy in case of fluoroquinolone resistance is recommended [46]. In countries with a ban on fluoroquinolones, fosfomycin is a good alternative, as is augmented prophylaxis, although no established standard combination exists to date.
For procedures in which ultrasonography is performed, sterile ultrasound transmission gel should be used. Outbreaks of infection due to resistant organisms have been traced to contaminated gel from multiple-use tubes [47]. Some authors have recommended formalin disinfection of the biopsy needle after each core is taken to minimize postbiopsy infection [48].
Patients who develop sepsis after transrectal prostate biopsy should be empirically treated with intravenous carbapenems, amikacin, or a second- or third-generation cephalosporin until blood culture data are available. If bacteremia is suspected, oral fluoroquinolone or trimethoprim-sulfamethoxazole is not an adequate choice given the high risk of resistance [20].
Rectal cleansing — Rectal cleansing with enemas, suppositories, or iodine lavage is not necessary as long as appropriate antibiotic prophylaxis is provided [49]. The potential benefit of enema administration or povidone-iodine lavage prior to prostate biopsy is based upon the supposition that these measures will reduce infectious complications due to transmission of bacteria from the rectal vault [50]. In patients who have received antibiotic prophylaxis, a clinically significant benefit from rectal cleansing has not been found. In addition to lack of benefit, improper or incomplete enema technique may hinder visualization and increase patient discomfort [51].
A Cochrane systematic review identified four trials evaluating rectal preparation and found no significant differences for any outcome (bacteriuria, bacteremia, fever, urinary tract infection, the need for hospitalization) for prophylactic antibiotics versus enema [23]. A decreased risk of bacteremia, however, was found for the use of "antibiotic plus enema" versus "antibiotic" (relative risk 0.25, 95% CI 0.08-0.75). However, the authors noted that the quality of the evidence for these comparisons was overall poor because of the limited number of studies, patients, and events. A subsequent randomized trial also did not find a significant benefit for rectal cleansing [52].
Antiplatelet therapy/anticoagulation — Most patients undergoing prostate biopsy are middle-aged or older men with significant cardiovascular risk factors. Many of these patients are being treated with low-dose aspirin and some with an anticoagulant such as warfarin. The decision to withhold or continue these agents requires clinical judgment weighing the risk of a significant cardiovascular event to the risk of bleeding.
The practices of urologists vary. Some continue low-dose aspirin but discontinue clopidogrel, warfarin, or direct oral anticoagulants, and others continue all anticoagulants if clinically indicated (ie, discontinuation could increase the risk of cardiovascular adverse events), while others favor discontinuing all anticoagulants if clinically safe.
For patients undergoing extended-core or saturation prostate biopsy, the risk of bleeding for patients on low-dose aspirin and warfarin has not been established. In addition, the risk of bleeding with other antiplatelet medications, including clopidogrel, has not been extensively evaluated. In the absence of sufficient evidence, these agents are typically withheld. In a survey that included 297 respondents, more than 90 percent of urologists discontinued clopidogrel prior to prostate biopsy [53].
The continued use of antiplatelet/anticoagulation therapy at the time of prostate biopsy may not be associated with an increase in risk for local bleeding complications that are sufficiently severe to require further intervention (ie, endoscopy, surgery) [54-57]. For patients on low-dose aspirin, two trials did not identify an increased risk of clinically significant hemorrhage in patients who remained on aspirin in the periprocedural period [55,56]. In the larger of these trials, 200 men on low-dose aspirin were randomly assigned to continue low-dose aspirin, discontinue low-dose aspirin, or replace low-dose aspirin with low-molecular-weight heparin (LMWH); systematic 10 core prostate biopsy was performed [55]. No severe bleeding complications occurred in any of the patients, although the duration of minor bleeding was significantly longer in the patients on low-dose aspirin or LMWH.
For warfarin therapy, a prospective observational study evaluating the risk of bleeding in patients undergoing sextant biopsy identified no significant differences in the incidence or severity of rectal bleeding, hematuria, or hematospermia in the patients who remained on warfarin compared with those who were not anticoagulated [54].
The general principles of perioperative antiplatelet/anticoagulation management are discussed in detail elsewhere. (See "Perioperative medication management", section on 'Medications affecting hemostasis'.)
TRANSRECTAL BIOPSY — Transrectal ultrasound (TRUS)-guided biopsy is the most common approach for prostate biopsy. TRUS biopsy is most often performed in the urologist's office with local anesthesia and no sedation.
Image guidance — Prostate biopsy was historically performed with manual guidance, but this technique has been completely replaced by TRUS guidance. TRUS-guided and magnetic resonance imaging (MRI)-guided biopsies are most commonly performed.
Ultrasound — TRUS-guided biopsy is easy to perform, widely available, and generally well tolerated (picture 1) [58-60].
Two-dimensional TRUS is typically used for measuring prostate volume. Prostate height and width are measured in a longitudinal plane, and then the probe orientation is switched on the machine to measure length and width in the transverse plane. The software contains an algorithm that reliably computes prostate volume based upon these measurements. Prostate volume and prostate-specific antigen (PSA) density (PSA level/prostate volume) are easily calculated and may aid in determining the sample size on prostate biopsy. Patients with larger prostates (eg, those with benign prostatic hyperplasia) may have higher than normal PSA levels due to increased prostate volume [61]. (See "Measurement of prostate-specific antigen", section on 'PSA density'.)
The prostate should be visualized in both the sagittal and longitudinal planes, and the overall echotexture of the prostate and seminal vesicles are assessed and correlated with the findings of digital rectal examination and potential underlying histology [62]. The normal prostate has a uniform echotexture (image 1). Hypoechoic lesions and those that correlate with an abnormality on digital rectal examination have a higher likelihood of harboring cancer; however, up to one-third of (and possibly more) prostate cancers are isoechoic [63,64]. Hyperechoic areas represent areas of prostatic calcification (ie, stones).
Three-dimensional TRUS can provide additional information about the location and extent of prostate cancer (eg, seminal vesicle invasion, extension through the prostatic capsule); however, three-dimensional imaging devices are not widely available in the office setting [65-67].
Enhanced ultrasound techniques, including contrast-enhanced Doppler ultrasound and elastosonography, have been introduced to manage some of the limitations of traditional grayscale ultrasound-guided biopsy techniques, primarily the relatively low sensitivity for prostate cancer [62,68-72].
One technique uses Doppler imaging to identify areas of increased vascularity, which can be further augmented using contrast agents [73-80]. Another technique, elastosonography, evaluates differences in tissue response to manual compression [81-85]. Elastosonography has shown promise for enhancing the resolving power of ultrasound, and, although results are conflicting, several reports indicate that elastosonography is capable of identifying foci of cancer, with improved sensitivity for higher-grade cancers. Potential limitations of this technology include the need for specialized ultrasound probes and the reliance upon operator skill to define areas of differential elasticity [86-89].
Another emerging technique, microultrasound-guided biopsy [90-93], allows use of Prostate Risk Identification Using Micro-Ultrasound (PRI-MUS) protocol to characterize and target lesions similar to the Prostate Imaging-Reporting and Data System (PI-RADS) protocol for multiparametric MRI [94]. Microultrasound seems to be equivalent to MRI for imaging prostate cancer [93].
MRI — Although ultrasound has been the primary imaging modality used to guide prostate biopsy, other imaging modalities, including MRI and computed tomography (CT), can also be used. In particular, MRI provides superior resolution of prostate anatomy and potential targets for biopsy (especially anterior tumors) compared with other imaging modalities [95].
MRI-defined lesions can be targeted for biopsy in several ways [96-108]:
●Cognitive targeting refers to a method in which the clinician identifies the lesion on MRI and uses the anatomic information to select the area during TRUS-guided prostate biopsy.
●Targeting within the magnet (ie, "in-bore" targeting) is a technique in which MRI is used to directly guide prostate biopsy in real-time.
●The use of registration or fusion software (eg, Koelis Urostation, UroNav, Artemis) allows a lesion targeted on MRI to be identified again during a later TRUS-guided biopsy procedure, either with or without a tracking device [109].
The superiority of any specific approach has not been established. However, among these three options, the most useful for urologists, who perform the majority of prostate biopsies, may be the MRI/TRUS fusion-guided technique [105,107,110-113]. At some institutions, including those of most of the authors and editors of this topic, all men who have access to it undergo prostate MRI prior to planned TRUS biopsy. (See "The role of magnetic resonance imaging in prostate cancer", section on 'Multiparametric imaging'.)
The available evidence suggests that incorporation of prebiopsy MRI in the diagnostic pathway for a clinically suspected prostate cancer improves the diagnosis of clinically significant disease, reduces adverse effects from biopsy, and can potentially prevent unnecessary biopsies in some individuals.
●In the PROMIS trial, 576 biopsy-naïve men underwent prostate MRI followed by both TRUS-guided systematic biopsy and template biopsy. Compared with TRUS biopsy, MRI was more sensitive (93 versus 48 percent) but less specific (41 versus 96 percent) in detecting clinically significant cancer [114]. Using MRI to triage men might have negated biopsy in about a quarter of patients and diagnosed 5 percent fewer clinically insignificant cancers.
●In the PRECISION trial, 500 biopsy-naïve men were randomly assigned to undergo MRI with (72 percent) or without (28 percent) targeted biopsy (depending on whether MRI revealed a target lesion) or standard TRUS biopsy [115]. The MRI "pathway" detected more clinically significant cancers (38 versus 26 percent; adjusted difference 12 percent, 95% CI 4-20) and fewer clinically insignificant cancers (9 versus 22 percent; adjusted difference -13 percent, 95% CI -19 to -7) than standard TRUS biopsy.
●In another trial, 212 biopsy-naïve men were randomly assigned to either undergo MRI followed by either MRI-targeted biopsy (76 percent) or TRUS biopsy (24 percent without an MRI-visible lesion) or undergo standard TRUS biopsy [116]. This slightly different MRI "pathway" also detected more cancers overall (51 versus 30 percent) and more clinically significant cancers (44 versus 18 percent) than standard TRUS biopsy.
●In another Canadian trial, 453 biopsy-naïve men underwent either TRUS biopsy or multiparametric MRI followed by MRI-targeted biopsy of any PI-RAD ≥3 lesions. MRI-targeted biopsy identified more clinically significant prostate cancers than TRUS biopsy (35 versus 30 percent) while sparing biopsy in 37 percent of men who had a negative MRI. MRI-targeted biopsy also resulted in fewer complications and identified fewer clinically insignificant cancers compared with TRUS biopsy [117].
●A 2019 Cochrane review compared the test accuracy of prostate MRI, MRI-targeted biopsy, MRI pathway (MRI with or without MRI-targeted biopsy), and systematic TRUS biopsy in prostate cancer diagnosis in both men with and without a prior biopsy, using template-guided biopsy as the reference standard [5]. It concluded that, within the limitation of the studies analyzed, the MRI pathway has the most favorable diagnostic accuracy in clinically significant prostate cancer detection (pooled sensitivity 0.72 [95% CI 0.60-0.82]; pooled specificity 0.96 [95% CI 0.94-0.98]) [6].
Whether MRI-targeted biopsy should be performed with or without concurrent systematic sampling is controversial [4]. Based on the following data, we suggest concurrent targeted and systematic sampling:
●In the PAIREDCAP trial, 248 biopsy-naïve men with MRI-visible lesions underwent systematic, cognitive fusion, and software fusion biopsies [9]. Targeted biopsies had higher cancer detection rates per core than systematic biopsy (38 percent software versus 33 percent cognitive versus 15.7 percent systematic), but fewer cores are taken with targeted biopsy (6 versus 12); thus, the overall cancer detection rate was similar at 60 percent for systematic and targeted biopsy. The overall cancer detection rate was greatest (70 percent) when systematic and targeted results were combined, as discordance of tumor locations suggested that the different biopsy methods detect different tumors. Overall, 21 percent had cancer detected by systematic biopsy that was missed by an MRI-targeted biopsy, while 10 percent had cancer detected by targeted biopsy that was missed by systematic biopsy. A control group of 52 men without MRI-visible lesion underwent systematic biopsy, which detected cancer in 15 percent. Thus, a negative MRI result should not obviate the need for prostate biopsy when otherwise clinically indicated.
●In another study, 2103 men with MRI-visible lesions underwent both MRI-targeted and systemic biopsy (79 percent had prior biopsy) [118]. Combined biopsy detected more cancers than either method alone (62.4 percent combined; 51.5 percent with MRI; 52.5 percent with systematic biopsy) and was associated with the fewest clinically significant upgrades (defined in this study as grade group 3 or higher (table 2)) in those who underwent prostatectomy (3.5 percent combined; 8.7 percent with MRI; 16.8 percent with systematic biopsy). The corresponding rates for upgrades to grade group 2 or higher disease were 6.7 percent for combined biopsy versus 18.3 and 30.2 percent for targeted and systematic biopsies, respectively. Downgrading to clinically insignificant cancer (grade group 1) on histopathologic analysis of the prostatectomy specimen was uncommon overall and not significantly different among the three groups (3.5 percent of those undergoing combined biopsy versus 2.2 and 2.5 percent for systematic and MRI-targeted biopsy, respectively).
Major technical improvements in prostate multiparametric MRI with the standard approach to interpretation using the PI-RADS have rapidly expanded the role of MRI in prostate cancer management in many clinical contexts, both prior to and following diagnosis, which is discussed in detail elsewhere [108,119-122]. (See "The role of magnetic resonance imaging in prostate cancer".)
Patients with a PI-RADS category 3 to 5 lesion warrant repeat biopsy with image-guided, targeted biopsy. The MRI/TRUS fusion or in-bore targeting technique is more reliable, especially for small lesions or lesions in difficult locations (eg, anterior or apical prostate) [123]. However, they are expensive. Cognitive targeting of other more accessible lesions is acceptable in skilled hands. At least two core samples should be obtained from each MRI target [4]. In the PAIREDCAP trial, the cancer detection rate was higher for PI-RADS 4 (64 percent) and 5 (80 percent) lesions than for PI-RADS 3 lesions (23 percent) [9].
Patients with a PI-RADS category 1 or 2 lesion may or may not need a repeat biopsy, depending on clinical suspicion and other ancillary markers (eg, PSA). This is controversial and further discussed in another topic. (See "The role of magnetic resonance imaging in prostate cancer".)
Sampling methods — TRUS-guided prostate biopsy is based on systematic prostate sampling and augmented by additional sampling of any abnormal areas (eg, hypoechoic) found on ultrasound or rectal examination [124]. Multiple sampling schemes have been developed in an effort to improve the accuracy in the detection of cancer.
For an initial TRUS-guided biopsy, society guidelines from North America and Italy generally recommend obtaining 10 to 12 cores systematically by incorporating apical and far-lateral regions of the prostate [125]. Collecting more than 12 cores or sampling the transition zone offers no additional benefit for an initial biopsy. A smaller number of cores may be adequate for patients with low prostate volumes [126].
Six core — In the early era of TRUS-guided biopsy, a six-core or sextant biopsy technique was commonly employed, taking one sample each from the apex, base, and mid-prostate on each side [127]. However, this method misses approximately 30 percent of clinically significant cancers [128-131]. Because of these data, sextant biopsy has been largely replaced by extended-core biopsy.
Extended core — Extended-core biopsy is performed by obtaining five to seven evenly distributed specimens from each side, sampling more extensively from the lateral aspects of the prostate [107,130,132,133]. A systematic review of 87 studies found that schemes with 12 core samples that took additional laterally directed cores detected 31 percent more cancers (95% CI 25-37) compared with a six-core approach [134]. Compared with six-core biopsy, extended-core biopsy is not associated with an increased risk of infection, abdominal or rectal pain, or voiding difficulties. However, rectal bleeding and hematospermia may be more frequent [134,135]. (See 'Complications' below.)
In selecting locations for sampling, the biopsy template should ensure adequate sampling of the apex or anterior apex, the far-lateral region (including the base, mid-gland, and apex), and the traditional sextant sites. Additional sampling from the transition zone does not improve yield [125].
Another method extends initial biopsy to include 18 cores. This approach may be more effective in detecting premalignant pathology, but the overall success in diagnosing true cancer appears to be equivalent to a 12 core biopsy, except for those patients with prostate volume exceeding 55 cm3 [136].
Prostate volume should also be taken into account [126,137]. In a study of 500 men, for example, an eight-core prostate biopsy was sufficient for the detection of cancer in men whose prostate volume was less than 35 cm3 [126].
Age may also play an important role in guiding the number of core samples obtained. The Vienna nomogram, developed from a large European cohort of men with a serum PSA between 2 to 10 ng/mL, suggested that at a given prostate volume, fewer cores are needed as age increases [138].
Sampling considerations for repeat prostate biopsy are discussed below. (See 'Need for repeat biopsy' below.)
Saturation — Saturation biopsy is a form of TRUS-guided biopsy that involves extensive sampling of the prostate, obtaining up to 24 core samples. Compared with standard extended-core TRUS biopsy, saturation biopsy takes a greater number of cores in a better symmetric array throughout the entire prostate gland. Saturation techniques do not provide increased cancer detection when used for first-time biopsy but may provide increased sensitivity when repeat biopsies are performed and should be considered after one or more negative TRUS biopsies [139-142], especially in areas where MRI-targeted biopsy is not available. Saturation biopsy detects prostate cancer in 22 to 33 percent of patients undergoing repeat biopsy [143,144]. (See 'Need for repeat biopsy' below.)
Saturation biopsy is typically performed in the outpatient setting under regional or general anesthesia due to concerns for pain control, and because it is thought to be associated with an increased incidence of morbidity (eg, severe hematuria) requiring hospital admission [143,144]. However, a systematic review that identified eight studies comparing saturation with extended biopsy found no significant differences in infection, hematuria, or bleeding between the groups [145]. (See 'Complications' below.)
Limited value of FNA — Fine needle aspiration (FNA) smears lack architectural detail and are not considered sufficiently accurate to definitively diagnose prostate cancer [146]. As a result, some premalignant histology cannot be adequately distinguished from prostate cancer, even by an experienced pathologist. FNA of the prostate gland is particularly unreliable in men who have undergone hormonal or radiation therapy. However, FNA may have a role in confirming advanced prostate cancer or metastatic disease in men with a prior history of localized cancer.
Anesthesia — Although some clinicians feel that prostate biopsy is generally well tolerated without analgesia [147], most perform a periprostatic nerve block with lidocaine. Multiple randomized trials have found that local anesthetic administration significantly reduces patient discomfort during prostate biopsy, especially in younger patients [148-154]. In addition, the administration of local analgesia does not appear to increase the rate of complications following prostate biopsy [152,155].
Traditionally, pain control with local anesthesia has been achieved with the administration of plain lidocaine (2.5 mL of 1% or 2%) injected at each junction between the seminal vesicle and the prostate (periprostatic nerve block), which is easily seen with ultrasound [156,157].
Some investigators have found that the addition of intraprostatic lidocaine administration may provide better analgesia than periprostatic blockade alone, despite the risk of increased pain at the time of administration [158-160].
Periprostatic nerve block combined with various topical or local anesthetics significantly controlled pain better than nerve block alone in a systematic review that included 18 studies involving 2076 men undergoing ultrasound-guided biopsy [161]. In randomized trials, topical anesthetic agents alone are less effective [149-152,162,163]. Among the available topical anesthetics, no significant differences regarding pain of probe insertion have been found. Nitroglycerin (glyceryl trinitrate) ointment may be useful in some patients due to its ability to relax the anal sphincter [164].
For patients who are particularly anxious and those undergoing a saturation biopsy, prostate biopsy can also be performed with regional anesthetic techniques (eg, saddle block, pudendal block) [165,166]. (See "Pudendal and paracervical block".)
Procedural details — TRUS biopsy is typically performed in the office setting.
●The patient is placed in a lateral decubitus position, with the knees and hips flexed 90 degrees [58].
●With appropriate lubrication, the ultrasound probe (figure 3) is gently inserted into the rectum.
●A preprocedure transrectal ultrasound and digital rectal examination are performed to confirm previous findings. The prostate is imaged and prostate volume determined. (See 'Ultrasound' above.)
●An 18 gauge spring-loaded core biopsy needle (eg, Tru-Cut) is advanced into the rectum adjacent to the ultrasound probe and guided into the prostate to obtain core samples, one at a time.
●The specimen is removed from the biopsy gun and examined. The core should measure 0.1 cm in diameter and 1.0 to 1.5 cm in length [167]. Inadequate cores require resampling from the same region. The specimens are labeled according to location before being sent for pathologic analysis. Society guidelines recommend putting no more than two cores in each specimen container to avoid tissue fragmentation or tangling [125].
Postprocedure instructions — Postbiopsy pain is not common and generally responds to acetaminophen. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not commonly used, because of the concern for bleeding.
Patients may resume their normal activities, including sexual intercourse, following the procedure. Routine use of stool softeners after uncomplicated TRUS-guided biopsy is not necessary, although patients who develop prostatitis or urinary tract obstruction may benefit from their use. (See 'Infection' below and 'Urinary obstruction' below.)
Patients are alerted to seek medical attention if they develop fever or difficulty voiding. A small amount of bright red blood per rectum is expected, but persistent rectal bleeding warrants immediate evaluation. Similar considerations apply to moderate hematuria, which should also be self-limited. Hematospermia is common after prostate biopsy, and discoloration of the semen may persist for weeks. (See 'Complications' below.)
TRANSPERINEAL BIOPSY — An alternative to transrectal biopsy of the prostate is a transperineal approach that can be used to perform a prostate biopsy in men who cannot undergo a transrectal procedure (eg, those with a prior abdominoperineal resection or severe anal stenosis) [168,169] or when there is a concern that the prostate is not being completely sampled via a transrectal approach.
Transperineal biopsy can be performed with ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) guidance, and the overall diagnostic accuracy appears to be equivalent to that of transrectal ultrasound (TRUS) [169-172]. In light of increasing fluoroquinolone resistance, transperineal biopsy is generally considered safer than TRUS because it prevents sepsis risk and avoids the need for broad-spectrum antibiotic prophylaxis [173,174]. However, the overall complication rates of transperineal biopsy are similar to [175] or higher than [176,177] those of TRUS, due to unique complications such as perineal hematoma. Transperineal biopsy is also typically more painful and requires general anesthesia to carry out in an operating room [178], although in-office transperineal biopsy under local anesthesia has been proposed [179,180].
Template-guided — A template-guided transperineal approach combines transrectal ultrasound with transperineal biopsy guided by a brachytherapy template [181-183]. The template is a tool that maximizes symmetric biopsy throughout the entire prostate gland. This enhanced localization augments the biopsy technique and may prove especially beneficial for repeat biopsy when premalignant pathology is found on initial biopsy. (See 'Need for repeat biopsy' below.)
Core samples are obtained at 5 mm intervals throughout the prostate. This approach may potentially provide more accurate staging in patients harboring prostate cancer, and its ability to accurately define tumor location may render this approach particularly helpful for determining suitability for focal therapy [65,66]. In addition, one study found that, in patients with rising prostate-specific antigen (PSA), transperineal biopsy was able to detect prostate cancer in 39 percent of patients undergoing repeat biopsy with this technique after an initially negative transrectal biopsy [181]. Potential disadvantages of this approach are the need for anesthesia and a higher complication rate than with transrectal biopsy (7.7 percent in one report, with two patients requiring bladder irrigation for hematuria) [65].
In-office transperineal biopsy — A new system that uses a trocar to minimize the number of skin punctures allows transperitoneal template prostate biopsy to be performed in office (or at an outpatient facility) with local anesthesia. It is performed under TRUS guidance. Initial results showed acceptable cancer detection rate and no infectious complications [184,185].
TRANSURETHRAL RESECTION — For patients in whom suspicion for prostate cancer remains high in spite of aggressive negative sampling, transurethral resection of the prostate (TURP) can be performed [186,187]. However, the evolution of magnetic resonance imaging (MRI) technology and template biopsy techniques have largely decreased the need for TURP as a prostate biopsy technique. In a retrospective review, TURP detected cancer in 35 of 375 patients (9.3 percent) with one prior negative biopsy and in 6 of 35 patients with two prior negative biopsies [186]. (See "Surgical treatment of benign prostatic hyperplasia (BPH)".)
PATIENT FOLLOW-UP AND COUNSELING — Under most circumstances (providing the patient does not experience any complications), initial follow-up to discuss the pathology results will be over the phone. The results of the biopsy may be positive or negative for cancer or equivocal with respect to adequacy or histology. The interpretation of prostate biopsy histology is discussed in detail elsewhere. (See "Interpretation of prostate biopsy", section on 'Histologic features'.)
Men with adequate and negative extended biopsies should resume follow-up with their primary care clinician. In contrast, face-to-face consultation with an appropriate specialist is warranted in patients with positive or suspicious pathology. Patients with a diagnosis of prostate cancer will require additional staging prior to treatment. (See "Clinical presentation and diagnosis of prostate cancer" and "Initial approach to low- and very low-risk clinically localized prostate cancer" and "Overview of systemic treatment for advanced, recurrent and metastatic castration-sensitive prostate cancer and local treatment for patients with metastatic disease".)
Need for repeat biopsy — Despite the acceptable diagnostic yield of prostate biopsy, it remains a sampling technique with a substantial potential for misdiagnosis.
The potential yield of a repeat biopsy was illustrated by a series of 10,400 men undergoing prostate biopsy in the linked Surveillance, Epidemiology, and End Results (SEER) and Medicare database [188]. The overall proportion of repeat biopsies found to contain prostate cancer was 32 percent and increased with age: 26 percent at 65 to 69 years, 31 percent at 70 to 74 years, 35 percent at 75 to 79 years, and 41 percent at ≥80 years. Among men whose first recorded biopsy did not detect prostate cancer, the need to have a subsequent biopsy was 12 percent at one year and 38 percent at five years.
Similar findings were noted in other studies as prostate cancer was detected in up to 39 percent of patients at second biopsy [189-193]. Further biopsies were not likely to be helpful, since the likelihood of detecting cancer was only to 10 to 17 percent on a third biopsy and 4 to 14 percent on a fourth biopsy [189,191].
Indications for repeat biopsy are the finding of abnormal but nonmalignant pathology (eg, small acinar proliferation (see 'Atypical small acinar proliferation' below)), rising prostate-specific antigen (PSA) after a negative biopsy, and concerns for inadequate sampling.
Abnormal histology — The presence of abnormal nonmalignant histology (ie, atypical small acinar proliferation or high-grade prostate intraepithelial neoplasia) in the initial biopsy specimen warrants repeat prostate biopsy in many patients.
Atypical small acinar proliferation — Atypical small acinar proliferation (ASAP) is defined as highly suspicious glandular architecture that is insufficient for the diagnosis of prostate cancer [194]. Although prostatic inflammation may be confused with ASAP, the independently predictive value of ASAP indicates that all patients with this diagnosis at the time of initial biopsy should undergo repeat biopsy [194,195].
ASAP is detected in approximately 1 to 5 percent of extended-core biopsies and is associated with a 40 to 59 percent risk of cancer detection on repeat biopsy [194-196]. The number of cores positive for ASAP, serum PSA levels, and PSA density do not appear to influence the subsequent detection of prostate cancer in patients with ASAP [194,195]. (See "Precancerous lesions of the prostate: Pathology and clinical implications", section on 'Atypical small acinar proliferation'.)
Prostatic intraepithelial neoplasia — Prostatic intraepithelial neoplasia (PIN) is defined pathologically as abnormal cellular change within the prostatic ductal cells consistent with prostate cancer but without invasion of the basement membrane [197]. PIN is divided into low-grade and high-grade subtypes. When discovered, high-grade PIN is often multifocal (defined as high-grade PIN found on at least four biopsy cores) and typically located within the peripheral zone of the prostate [198-200]. A majority of pathologists will not comment on findings of low-grade PIN, as evidence suggests that this histologic pattern is not premalignant [201].
Multifocal high-grade PIN is associated with a 50 to 80 percent rate of cancer detection on repeat biopsy [200,202,203]. Thus, patients with multifocal high-grade PIN should undergo early repeat biopsy, whereas patients with focal high-grade PIN may not require repeat biopsy unless PSA velocity is elevated or there are changes in the digital rectal examination. (See "Screening for prostate cancer".)
High-grade PIN is a premalignant condition and is noted in 2 to 22 percent of extended-core prostate biopsy specimens [196,200,204]. However, it is commonly overdiagnosed. In a prospective study, for example, high-grade PIN was confused with benign pathology in nearly 25 percent of biopsy specimens [205]. Thus, the diagnosis of PIN should be confirmed by an experienced urologic pathologist. A more detailed discussion of the histology of high-grade PIN is found elsewhere. (See "Precancerous lesions of the prostate: Pathology and clinical implications", section on 'Prostatic intraepithelial neoplasia'.)
The need to perform a repeat biopsy in patients with high-grade PIN is controversial. Although many studies have suggested a strong correlation between high-grade PIN and the detection of prostate cancer on subsequent biopsy [200,206,207], other studies have found that the rate of cancer detection after a diagnosis of high-grade PIN does not differ significantly from those with benign pathology at the time of initial biopsy [195,196,208]. (See "Precancerous lesions of the prostate: Pathology and clinical implications", section on 'Management of high-grade PIN'.)
Rising PSA after biopsy — Repeat biopsy may be considered in patients with a rising serum PSA after a negative initial biopsy [206]. In these patients, PSA velocity, free-to-total PSA, and urinary prostate cancer antigen 3 gene (PCA3) have shown promise in guiding clinical decision making regarding repeat prostate biopsy. (See "Screening for prostate cancer".)
Sampling considerations — When performing a repeat biopsy, an MRI-targeted biopsy with systematic biopsy or extended-core sampling technique should be used [190,191,206,209,210]. The lateral peripheral zone should be thoroughly sampled preferentially over the anterior aspect or transition zone because the anterior regions have a lower yield [192,193,211-213]. (See 'Patients with a negative TRUS biopsy' above and 'Extended core' above.)
When interpreting the pathology report, it should be determined whether an appropriate number of core samples were of adequate quality; a core sample is not adequate if prostatic glands or stroma are not visualized. Patients with a negative biopsy who have undergone inadequate (ie, low number of quality cores) or prior limited (ie, sextant) biopsy are at increased risk for a missed diagnosis of prostate cancer and should be considered for repeat biopsy.
COMPLICATIONS — Transrectal ultrasound (TRUS)-guided prostate biopsy is generally uncomplicated and well tolerated [214]. With the administration of proper antibiotic prophylaxis, the rate of serious complications (eg, urosepsis, prostatitis) is low [14,15,215-218]. Among men enrolled in the Prostate, Lung, Colorectal, and Ovarian Screening (PLCO) trial who underwent biopsy (negative biopsy result), the incidences of any complication, postbiopsy infection, and noninfectious complications were 2.0, 0.78, and 1.3 percent, respectively [219]. On multivariate analysis, a history of prostate inflammation or enlargement (odds ratio [OR] 2.6, 95% CI 1.6-4.3) and being from a Black population (OR 2.6, 95% CI 1.2-5.9) were significantly associated with higher rates for any complication, while repeat biopsy was associated with a lower rate of noninfectious complications (OR 0.3, 95% CI 0.1-0.9). In a study of the Surveillance, Epidemiology, and End Results (SEER) database, the rate of hospitalization within 30 days of undergoing a prostate biopsy was 6.9, compared with 2.7 percent in a control population [215]. The need to perform repeat biopsy in itself is not associated with a greater risk of serious complications [220]. The need for hospitalization was primarily due to infectious complications. (See 'Prophylactic antibiotics' above.)
A higher rate of complications has been reported for transperineal biopsy. In a study that included 3000 patients, the overall rate of complications following a freehand transperineal biopsy guided by transrectal ultrasound was 40 percent (hematuria, hematospermia, urinary tract infection), but only 1.2 percent of patients required admission [176]. As with transrectal biopsy, complications were directly correlated with the number of needle cores, at 31.5 percent for 12 cores, 41.8 percent for 18 cores, and 57.4 percent for more than 24 cores. In a separate study using a template-guided method in 87 patients, the overall rate of complications was similar at 42.5 percent [177].
Bleeding — Minor urinary or rectal bleeding is to be expected after prostate biopsy [221,222]. Bleeding is generally self-limited and requires no intervention. Blood streaks on the ultrasound probe are noted in 17 to 27 percent of patients undergoing the procedure.
Hematuria — Visible hematuria following biopsy is common with reported rates ranging from 10 to 84 percent [222]. In a retrospective review of 5802 transrectal ultrasound-guided sextant biopsies, hematuria and/or hematospermia occurred in approximately 50 percent of patients and lasted more than three days in 23 percent of patients [223]. However, most hematuria that occurs after prostate biopsy is self-limited; only 0.4 percent require urethral catheterization and hospital admission for gross hematuria and/or clot retention [216].
Rectal bleeding — The risk of rectal bleeding varies between 1.3 and 58.6 percent and increases with an increasing number of sample cores [135,222,224], but severe rectal bleeding requiring intervention occurs in fewer than 1 percent of procedures [222,225].
In the hemodynamically stable patient who is experiencing brisk rectal bleeding, manual digital compression of the prostate is the first-line strategy; rectal packing with gauze can also be used [226]. As direct pressure is being applied, the patient's vital signs are monitored and coagulation parameters checked and corrected, as needed. In the event that bleeding continues or the patient becomes hemodynamically unstable, consultation for endoscopic (eg, epinephrine injection, Endoclip) or surgical (ie, ligation) intervention should be obtained [226,227].
A randomized trial of 275 patients evaluated the efficacy of placement of a rectal Foley catheter inflated to 50 mL in an attempt to prevent rectal bleeding [228]. Placement of the catheter was associated with a significantly reduced incidence of any amount of rectal bleeding compared with controls (1.5 versus 17.7 percent). We do not advocate the routine use of this technique for prevention, since it may cause undue discomfort for a marginal benefit. However, it may be useful for temporary control of significant rectal bleeding while awaiting consultation.
Hematospermia (hemoejaculate) — Hematospermia occurs in 1.1 to 93 percent of men after prostate biopsy. Although a minor complication, it can persist for as long as four weeks in a third of the patients [229]. Prebiopsy counseling is required to alleviate anxiety. (See "Hematospermia".)
Infection — Urinary tract infection is the most common infectious complication of prostate biopsy, occurring in 1 to 11 percent of patients [14,49,222,230-232]. A multinational prospective study found a high rate of symptomatic urinary tract infections (5.2 percent) but lower rate of hospitalization (3.1 percent) [230]. No statistically significant differences were found comparing the infection rate in Africa, Asia, or Europe.
Antibiotic prophylaxis before biopsy decreases the rate of urinary tract infection, but some patients are at risk for serious infectious complications independent of prophylaxis. In an observational study of 2023 patients who received antibiotics prior to prostate biopsy, 3 percent became septic [233]. Predictive risk factors for sepsis included presence of an indwelling urethral catheter, diabetes mellitus, or biopsy with more than 10 cores. In other reviews, these factors and others, including hospitalization in the month prior to biopsy, chronic obstructive pulmonary disease, a history of recent antibiotic usage, or international travel, were identified as increasing the risk for infection [234,235]. (See 'Prophylactic antibiotics' above.)
Treatment of urinary infection following prostate biopsy with oral antibiotics (eg, fluoroquinolone, trimethoprim-sulfamethoxazole) is generally sufficient, though hospitalization and intravenous antibiotics may be required [25,224]. Antibiotic treatment may be altered based upon the clinical response and the results of urine culture and antibiotic sensitivity testing. (See "Acute simple cystitis in adult males", section on 'Treatment'.)
Acute postbiopsy prostatitis is a relatively uncommon but potentially life-threatening complication that warrants immediate evaluation and intervention. Prior fluoroquinolone use and extended post-biopsy antibiotic regimens appear to increase the risk for post-biopsy prostatitis [37,236,237]. Issues related to acute prostatitis are presented separately. (See "Acute bacterial prostatitis".)
Urinary obstruction — Because patients may develop a degree of urinary obstruction due to acute postbiopsy prostatic inflammation, assessment of postvoid residual with a bladder scan should be performed for symptomatic patients. Alpha-blocker therapy can be initiated for patients with residual urine volumes of less than 100 mL, while insertion of a small-caliber (12 to 16 Fr) urethral catheter (or suprapubic catheter) is warranted in patients with higher residual volumes. Symptomatic patients should also be placed on stool softeners to ease mechanical strain on the prostate during bowel movements. (See "Acute urinary retention" and "Placement and management of urinary bladder catheters in adults".)
Erectile dysfunction (rare) — Erectile dysfunction (ED) is a rare, poorly understood complication of TRUS-guided prostate biopsy. The exact mechanism is unknown, but hypotheses about the cause include periprocedural anxiety, pain, apprehension about biopsy results, needle injury to the cavernosal nerves, cancer effects, and local tissue edema from the nerve block and hemorrhage [20]. Patients should be counselled about possible, at least short-term, changes in erectile function after TRUS-guided biopsy.
Tumor seeding (rare) — A common patient concern is the possibility of spreading cancer cells within the prostate. Although isolated cases of tumor seeding the needle tract have been reported, these are rare and more often associated with the transperineal compared with a transrectal approach [238,239]. The very low risk of tumor seeding should not preclude an indicated biopsy.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and management of prostate cancer".)
SUMMARY AND RECOMMENDATIONS
●Prostate biopsy is a safe and effective sampling technique in which tissue is obtained in a minimally invasive fashion from the prostate gland for the purpose of detecting cancer. Prostate biopsy is performed in patients with abnormal prostate-specific antigen (PSA) levels or abnormal digital rectal examination, or for active surveillance. (See 'Introduction' above and 'Indications' above.)
●Transrectal ultrasound (TRUS)-guided prostate biopsy is the standard approach for most patients undergoing prostate biopsy for the first time. We perform an extended 10 to 12 core biopsy, rather than a sextant (6 core) biopsy, in order to increase the detection of prostate pathology. Patients with a small prostate volume may be biopsied with a lower number of core samples. (See 'Biopsy-naive patients' above.)
●At facilities where prostate magnetic resonance imaging (MRI) and MRI-targeted biopsy are available, MRI-targeted biopsy should be performed with concurrent systematic sampling for patients with one or more prior negative TRUS biopsies. If MRI-targeted biopsy is not available or there are no MRI-visible lesions, repeat TRUS biopsy or saturation/template-guided biopsy can be performed, depending on the level of clinical suspicion. (See 'Patients with a negative TRUS biopsy' above.)
●The transperineal approach can be used to perform a prostate biopsy in men who cannot undergo a transrectal procedure (eg, those with a prior abdominoperineal resection or severe anal stenosis) or when there is a concern that the prostate is not being completely sampled via a transrectal approach. Compared with transrectal biopsy, transperineal biopsy carries a lower risk for infectious complications but causes more pain and is typically performed under anesthesia in an operating room (although new systems may permit in-office biopsy under local anesthesia). (See 'Transperineal biopsy' above.)
●Saturation biopsy and template-guided biopsies are performed transrectally or transperineally with TRUS guidance. Saturation and template biopsies are not indicated for initial biopsy but are for repeat biopsies after one or more failed standard TRUS biopsies, especially when there are no MRI-visible lesions or where MRI-targeted biopsy is not available. Such procedures are more extensive and may require anesthesia and hospitalization. (See 'Saturation' above and 'Template-guided' above.)
●For patients undergoing prostate biopsy, we recommend antibiotic prophylaxis prior to prostate biopsy (Grade 1B). We typically use a single dose of an oral fluoroquinolone, unless the Escherichia coli resistance rate to fluoroquinolone is >20 percent according to the local antibiogram, in which case we select an oral (trimethoprim-sulfamethoxazole) or intramuscular (gentamicin or ceftriaxone) alternative to fluoroquinolone. Cleansing enemas are unnecessary provided patients have received appropriate antibiotic prophylaxis. (See 'Prophylactic antibiotics' above and 'Rectal cleansing' above.)
●Indications for repeat biopsy include abnormal but nonmalignant pathology (see below), rising PSA after a negative biopsy, and concerns for inadequate sampling (see 'Need for repeat biopsy' above):
•All patients with atypical small acinar proliferation (ASAP) on initial biopsy undergo repeat biopsy. (See 'Atypical small acinar proliferation' above.)
•All patients with multifocal high-grade prostatic intraepithelial neoplasia (PIN) on initial biopsy undergo repeat biopsy. Patients with focal high-grade PIN or low-grade PIN may not require repeat biopsy unless PSA velocity is elevated or there are changes in the digital rectal examination. (See 'Prostatic intraepithelial neoplasia' above.)
●Minor urinary or rectal bleeding or hematospermia is common after prostate biopsy, is generally self-limited, and only on rare occasion requires some form of intervention. The risk of rectal bleeding increases with an increasing numbers of sample cores. The continued use of aspirin in the periprocedural period has not been associated with an increased risk of clinically significant hemorrhage; however, clopidogrel is generally stopped prior to prostate biopsy, especially extended or saturation biopsy. (See 'Bleeding' above and 'Antiplatelet therapy/anticoagulation' above.)
