Prostate biopsy

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.

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, or abnormalities in "reflex" blood or urine tests). (See '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 may be deferred indefinitely (in most cases) or until there is evidence of disease progression [1]. 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 — Prostate biopsy can be systematic, targeted, or both, the choice of which depends on demonstration of suspicious findings on prebiopsy magnetic resonance imaging (MRI). The requirement for prebiopsy MRI further depends on whether the patient has had prior prostate biopsy (algorithm 1).

Initial biopsy — For patients undergoing prostate biopsy for the first time, an MRI may be performed, and if there is a suspicious lesion(s), a targeted biopsy should be performed with a concurrent systematic biopsy. There are limited data to suggest that this approach may increase the detection rate of clinically significant prostate cancer. (See 'Targeted biopsy' below.)

However, due to issues related to the quality of imaging and interpretation, targeting strategies, as well as cost and availability [2,3], there are insufficient data to recommend routine MRI prior to every initial biopsy [2]. Systematic biopsy alone remains a reasonable approach to the initial biopsy [4,5]. (See "The role of magnetic resonance imaging in prostate cancer", section on 'Initial presentation with no prior biopsy'.)

Patients should proceed with a systematic biopsy if there are no suspicious findings on MRI.

Patients with negative systematic biopsy — A negative systematic 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 systematic biopsy alone [6,7], and this advantage is more pronounced when MRI-targeted biopsy is performed in men with a prior negative biopsy than biopsy-naïve men [8]. (See 'Targeted biopsy' 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 systematic biopsies. MRI-targeted biopsy should be performed with concurrent systematic sampling, or else clinically significant cancer can be missed by targeted biopsies alone [9-11]. (See 'Targeted biopsy' below.)

If there are no suspicious findings on the MRI, the patient should proceed with a repeat systematic biopsy. A more elaborate scheme of sampling such as saturation biopsy or template-guided biopsy may be considered. (See 'Repeat systematic biopsy' below and 'Template-guided transperineal biopsy' below.)

Active surveillance — Repeat prostate biopsy for men under active surveillance for low-risk clinically localized prostate cancer is generally recommended to rule out high-grade disease missed on the original biopsy. (See "Active surveillance for males with clinically localized prostate cancer".)

The current American Urologic Association recommendation is to obtain prostate MRI if the initial (diagnostic) prostate biopsy was performed without MRI guidance. If the MRI demonstrates suspicious findings (Prostate Imaging Reporting and Data System [PI-RADS] 4 or 5), a repeat (confirmatory) targeted biopsy should be performed as soon as possible. If the MRI is assessed as PI-RADS 1, 2, or 3, then repeat systematic biopsy may be performed within approximately 12 months. Thereafter, serial surveillance biopsies are recommended every one to four years depending on patient condition [12].

PREPARATION

Test for and treat urinary tract infection — 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

Transrectal biopsy — We recommend antibiotic prophylaxis prior to transrectal prostate biopsy [17,18]. We typically use a single dose of an oral fluoroquinolone one hour prior to prostate biopsy (table 1). Gentamicin plus ceftriaxone is the most commonly used intramuscular alternative to fluoroquinolone; another intravenous alternative is aztreonam.

A 2011 Cochrane 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) [19]. Severe 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 [20].

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, resistance to fluoroquinolones is rising. Thus, clinicians should review their local antibiograms and, if the fluoroquinolone-resistance rate for Escherichia coli is >20 percent, choose another class of antibiotics [17]. 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 [21-25]. In a trial, rectal cultured-based prophylactic antibiotics reduced the seven-day infection rate from 4.3 to 2.5 percent compared with empirical antibiotics [26].

Practices vary worldwide. 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 [27]. In countries with a ban on fluoroquinolones, fosfomycin is a good alternative, as is augmented prophylaxis, although no established standard combination exists to date.

Transperineal biopsy — Whether antibiotic prophylaxis is required for transperineal prostate biopsy is controversial because transperineal biopsy is associated with a lower risk of infection compared with transrectal biopsy. Our contributors do not find it necessary except for patients with risk factors (eg, immunocompromised).

●In a 2022 meta-analysis of 106 cohort studies, antibiotic prophylaxis was not associated with a lower incidence of septic complications (0.05 versus 0.08 percent) or overall infectious complication (1.22 versus 1.35 percent) compared with nonantibiotic prophylaxis [28].

●In a randomized trial of 555 patients, no patient developed sepsis or urinary tract infection requiring hospitalization after transperineal biopsy; only one patient who received antibiotic prophylaxis and three patients who did not receive antibiotic prophylaxis developed a urinary tract infection that did not require hospitalization [29].

Rectal cleansing — Rectal cleansing with enemas, suppositories, or iodine lavage is not necessary as long as appropriate antibiotic prophylaxis is provided [30]. 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 [31]. In patients who have received antibiotic prophylaxis, a clinically significant benefit from rectal cleansing has not been found [19,32]. In addition to lack of benefit, improper or incomplete enema technique may hinder visualization and increase patient discomfort [33].

Equipment sterilization — 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 [34]. Some authors have recommended formalin disinfection of the biopsy needle after each core is taken to minimize postbiopsy infection [35].

Antiplatelet therapy/anticoagulation — Many patients undergoing prostate biopsy are taking anticoagulants or antiplatelet agents for cardiovascular diseases. The decision to withhold or continue these agents requires clinical judgment weighing the risk of a significant cardiovascular event against the risk of bleeding [36].

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.

Data suggest that the continued use of low-dose aspirin or warfarin therapy at the time of prostate biopsy may not be associated with an increase in risk for local bleeding complications [37-40].

●For patients on aspirin, two trials did not identify an increased risk of clinically significant hemorrhage in patients who remained on aspirin in the periprocedural period [38,39]. 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 [38]. 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 [37].

There are no data on the risk of bleeding with other antiplatelet medications, including clopidogrel, or with direct oral anticoagulants. In the absence of data, these agents are typically withheld [41]. The general principles of perioperative antiplatelet/anticoagulation management are discussed in detail elsewhere. (See "Perioperative medication management", section on 'Medications affecting hemostasis'.)

Sedation/analgesia — Patients are understandably anxious and may benefit from administration of an anxiolytic prior to undergoing prostate biopsy [42]. Multiple randomized trials have found that local anesthetic administration significantly reduces patient discomfort during prostate biopsy, especially in younger patients [43-50]. In addition, the administration of local analgesia does not appear to increase the rate of complications following prostate biopsy [48,51].

●Most urologist perform a periprostatic nerve block with plain lidocaine (2.5 mL of 1% or 2%) injected under ultrasound guidance at each junction between the seminal vesicle and the prostate [52,53].

●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 [54-57].

●Nitroglycerin (glyceryl trinitrate) ointment may be useful in some patients due to its ability to relax the anal sphincter [58].

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) [59,60]. (See "Pudendal and paracervical block".)

SYSTEMATIC VERSUS TARGETED BIOPSY — There is increasing evidence that MRI-targeted biopsy can increase clinically significant cancer detection over transrectal ultrasound (TRUS)-based systematic biopsy alone, and this advantage is more pronounced when MRI-targeted biopsy is performed in men with a prior negative biopsy than biopsy-naïve men.

Systematic biopsy — 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 [61]. Multiple sampling schemes have been developed in an effort to improve the accuracy in the detection of cancer.

Initial systematic biopsy — For an initial TRUS-guided biopsy, society guidelines from North America and Europe generally recommend obtaining 10 to 12 cores systematically by incorporating apical and far-lateral regions of the prostate [62]. Compared with a 10- or 12-core biopsy, a 6-core biopsy could miss a third of the cancer, whereas 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 [63].

●10- to 12-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 [64-67]. 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 [62].

●6-core – In the early era of TRUS-guided biopsy, a 6-core or sextant biopsy technique was commonly employed, taking one sample each from the apex, base, and mid-prostate on each side [68]. 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 6-core approach [69]. Compared with 6-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 [69,70]. (See 'Complications' below.)

●18-core – 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 [71].

Prostate volume should also be taken into account [63,72]. In a study of 500 men, for example, an 8-core prostate biopsy was sufficient for the detection of cancer in men whose prostate volume was less than 35 cm³ [63].

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 prostate-specific antigen between 2 to 10 ng/mL, suggested that at a given prostate volume, fewer cores are needed as age increases [73].

Repeat systematic biopsy — 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 [74-77], 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 [78,79].

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 [78,79]. 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 [80].

Limited value of FNA — Fine needle aspiration (FNA) smears lack architectural detail and are not considered sufficiently accurate to definitively diagnose prostate cancer [81]. 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.

Targeted biopsy — MRI-defined lesions can be targeted for biopsy in several ways [64,82-93]:

●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 [94].

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 [64,91,95-98]. 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. When performing an MRI-targeted biopsy with fusion software, the urologist needs to take 4- to 6-core biopsies around the target to identify the most aggressive portion of the tumor [99]. (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 [100]. 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 [101]. 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 [102]. 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 [103].

●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 [7]. 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]) [8].

Whether MRI-targeted biopsy should be performed with or without concurrent systematic sampling is controversial [6]. Based on the following data, we suggest concurrent targeted and systematic sampling:

●In the Prospective Assessment of Image Registration in the Diagnosis of Prostate Cancer (PAIREDCAP) trial, 248 biopsy-naïve men with MRI-visible lesions underwent systematic, cognitive fusion, and software fusion biopsies [11]. 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) [104]. 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).

IMAGE GUIDANCE — Prostate biopsy was historically performed with manual guidance, but transrectal ultrasound (TRUS)-guided or MRI-guided biopsies are most commonly performed nowadays.

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.

●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 a PSA level higher than normal due to increased prostate volume [105]. (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 [106]. 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 [107,108]. 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 and their advantage over standard TRUS biopsy is debated [109-112].

●Enhanced ultrasound techniques have been introduced to manage some of the limitations of traditional grayscale ultrasound-guided biopsy techniques, primarily the relatively low sensitivity for prostate cancer [106,113-117].

•One technique uses Doppler imaging to identify areas of increased vascularity, which can be further augmented using contrast agents [118-125].

•Another technique, elastosonography, evaluates differences in tissue response to manual compression [126-130]. 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 [131-134].

•Another emerging technique, microultrasound-guided biopsy [135-138], allows use of Prostate Risk Identification Using Microultrasound (PRI-MUS) protocol to characterize and target lesions similar to the Prostate Imaging Reporting and Data System (PI-RADS) protocol for multiparametric MRI [139]. Microultrasound seems to be equivalent to MRI for imaging prostate cancer [138]. A head-to-head trial of microultrasound- versus MRI-guided prostate biopsy is ongoing [140].

MRI — MRI provides superior resolution of prostate anatomy and potential targets for biopsy (especially anterior tumors) compared with other imaging modalities [141]. Major technical improvements in prostate multiparametric MRI with the standard approach to interpretation using the Prostate Imaging Reporting and Data System (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 [93,142-145]. (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) [146]. 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 [6]. In the Prospective Assessment of Image Registration in the Diagnosis of Prostate Cancer (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) [11]. (See 'Targeted biopsy' above.)

●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 velocity, PSA density, or biomarkers). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scanning may be helpful. This is controversial and further discussed in another topic. (See "Clinical presentation and diagnosis of prostate cancer", section on 'Decision to biopsy'.)

ANATOMIC APPROACHES — The two main anatomic approaches to prostate biopsy are transrectal (TRUS) and transperineal, the use of which varies widely by country and within regions of specific countries [147]. The reported cancer detection rates associated with transrectal versus transperineal biopsy route are not significantly different [148-151].

Transrectal biopsy — TRUS biopsy is typically performed by urologists in the office setting.

●The patient is placed in a lateral decubitus position, with the knees and hips flexed 90 degrees [152].

●With appropriate lubrication, the ultrasound probe (figure 3) is gently inserted into the rectum.

●A preprocedure TRUS and digital rectal examination are performed to confirm previous findings. The prostate is imaged, and prostate volume is 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 [153]. 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 [62].

Transperineal biopsy — Transperineal procedures 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.

Transperineal biopsy can be performed with conventional ultrasound, microultrasound, computed tomography, or MRI guidance, and the overall diagnostic accuracy appears to be equivalent to that of transrectal TRUS [154-157].

Transperineal biopsy has a lower risk of infectious complications and thus could potentially avoid the need for broad-spectrum antibiotic prophylaxis [158,159], although whether routine antibiotic prophylaxis is required before transperineal prostate biopsy remains controversial [29]. (See 'Transperineal biopsy' above.)

However, the overall complication rates of transperineal biopsy were found to be similar to [160] or higher than [161,162] those of TRUS in older studies due to unique complications such as perineal hematoma. The risk of hematuria and hematospermia is similar between transperineal and transrectal biopsy [163]. Transperineal biopsy is also typically more painful and requires general anesthesia to carry out in an operating room [164], although in-office transperineal biopsy under local anesthesia has been proposed [165,166]. (See 'Complications' below.)

Template-guided transperineal biopsy — A template-guided transperineal approach combines TRUS with transperineal biopsy guided by a brachytherapy template [167-169]. 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 'Repeat biopsy' below.)

Core samples are obtained at 5 mm intervals throughout the prostate. Template-guided transperineal biopsy provides value to rule out prostate cancer, prevent overtreatment of those that can remain on active surveillance, evaluate focal therapy candidacy, and identify those needing whole-gland management [109,110]. In one retrospective series of 117 men with prior negative biopsies, cancer and clinically significant cancer was detected in 64 and 50 percent, respectively; for 86 men on active surveillance, 42 percent had Gleason upgrading [170]. In that study, template-guided transperineal biopsy changed management for 69 percent of patients, with 44 percent proceeding to whole-gland therapy and 24 percent electing focal therapy. Complication rate was 17 percent, with the majority of complications being minor.

In-office transperineal biopsy — A new system that uses a trocar to minimize the number of skin punctures allows transperineal 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 [171,172].

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 [173,174]. 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 [173]. However, the evolution of MRI technology and template biopsy techniques have largely eliminated the need for TURP as a prostate biopsy technique. The transurethral route is diagnosing prostate cancer is now rarely used, perhaps only when the rectum is absent.

POSTBIOPSY FOLLOW-UP

Patient instructions — Postbiopsy pain is not common and generally responds to acetaminophen. Nonsteroidal anti-inflammatory drugs 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.)

Patient follow-up — 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 or specialist physician, who may obtain "reflex" biomarker tests to estimate whether the biopsy has missed an aggressive cancer. Benign biopsy tissue may also be sent for DNA methylation abnormality testing (ConfirmMDx test) if available. (See "Clinical presentation and diagnosis of prostate cancer", section on 'Nonmetastatic disease'.)

By 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 recurrent or metastatic castration-sensitive prostate cancer".)

Repeat biopsy — The decision about repeat prostate biopsy depends on many factors. If MRI is performed and a suspicious lesion (Prostate Imaging Reporting and Data System [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 prostate-specific antigen [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 'Repeat systematic biopsy' above and 'Template-guided transperineal biopsy' above.)

Yield of 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 [175]. 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 [176-180]. 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 [176,178].

Indications for repeat biopsy — Indications for repeat biopsy are the finding of abnormal but nonmalignant pathology, rising PSA after a negative biopsy, and concerns for inadequate sampling.

Abnormal histology — The presence of certain abnormal nonmalignant histology in the initial biopsy specimen may warrant further testing, which may include repeat systematic biopsy with consideration of MRI targeted biopsy, PSA, as well as urine or serum biomarkers [5].

●High-grade 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 [181]. PIN is divided into low-grade and high-grade subtypes. A majority of pathologists will not comment on findings of low-grade PIN, as evidence suggests that this histologic pattern is not premalignant [182].

When discovered, high-grade PIN (HGPIN) is often multifocal (defined as HGPIN found on at least four biopsy cores) and typically located within the peripheral zone of the prostate [183-185]. Multifocal HGPIN is associated with a 50 to 80 percent rate of cancer detection on repeat biopsy [185-187]. Thus, patients with multifocal HGPIN should undergo early repeat biopsy, whereas patients with unifocal HGPIN may not require repeat biopsy unless PSA velocity is elevated or there are changes in the digital rectal examination. (See "Precancerous lesions of the prostate: Pathology and clinical implications", section on 'Management of high-grade PIN'.)

●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 [188]. An ASAP finding alone on prostate biopsy is associated with a 30 to 50 percent risk of prostate cancer detection on repeat biopsy, with approximately 10 to 20 percent of these being clinically significant [189-194]. 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 additional testing. (See "Precancerous lesions of the prostate: Pathology and clinical implications", section on 'Atypical small acinar proliferation'.)

●Atypical intraductal proliferation – Atypical intraductal proliferation (AIP) describes lesions with greater architectural complexity and/or cytologic atypia than HGPIN but lacking definitive criteria for the diagnosis of intraductal carcinoma (IDC-P) [195]. AIP encompasses many of the lesions formerly designated cribriform HGPIN, exhibiting loose cribriform architecture with moderate cytologic atypia, but lacking marked pleomorphism or necrosis [196]. Given the association between AIP and undiagnosed IDC-P [197-199], a finding of AIP as either alone or together with low-risk cancer warrants additional testing.

Rising PSA after biopsy — Repeat biopsy may be considered in patients with a rising serum PSA after a negative initial biopsy [200]. In these patients, PSA velocity, free-to-total PSA, and other urine or serum biomarkers 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 [177,178,200-202]. The lateral peripheral zone should be thoroughly sampled preferentially over the anterior aspect or transition zone because the anterior regions have a lower yield [179,180,203-205]. (See 'Patients with negative systematic biopsy' 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 — Common complications of prostate biopsy include bleeding, infection, and urinary obstruction. There are more infectious complications after transrectal than transperineal biopsies, but the overall complication rates of the two approaches are similar. (See 'Transperineal biopsy' above.)

Bleeding — Minor urinary or rectal bleeding is common and to be expected after prostate biopsy, which is generally self-limited, and <1 percent require intervention [206,207].

●Hematuria – Visible hematuria following biopsy is common with reported rates ranging from 10 to 84 percent [207]. In a retrospective review of 5802 transrectal ultrasound (TRUS)-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 [208]. 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 [163].

●Rectal bleeding – The risk of rectal bleeding varies between 1.3 and 58.6 percent and increases with an increasing number of sample cores and with anticoagulation [70,207,209], but severe rectal bleeding requiring intervention occurs in fewer than 1 percent of procedures [207,210].

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 [211]. Alternatively, a Foley catheter can be inserted into the rectum and inflated to 50 mL to tamponade the bleeding [212]. 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, endoscopic (eg, epinephrine injection, Endoclip) or surgical (ie, ligation) intervention may be required [211,213].

●Hematospermia – Hematospermia (hemoejaculate) 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 [214]. Prebiopsy counseling is required to alleviate anxiety. (See "Hematospermia".)

Infection — Infectious complications are the most common complications of prostate biopsy and the most common reason for hospitalization. They occur in 0.1 to 7 percent (sepsis 0.3 to 3.1 percent) of patients who undergo transrectal prostate biopsy [215-217]. Between 1.1 and 1.9 percent of patients are hospitalized due to an infectious complication [21,218]. The most common cause of infection after transrectal prostate biopsy is fluoroquinolone-resistant E. coli, the presence of which increases the risk of infection by four-fold [219-221]. (See 'Transrectal biopsy' above.)

Infectious complications include urinary tract infection, urosepsis, and prostatitis. Antibiotic prophylaxis before biopsy decreases the rate of infectious complications, but some patients are still at risk for serious infectious complications despite prophylaxis. (See 'Prophylactic antibiotics' above.)

●Urinary tract infection – Urinary tract infection is the most common infectious complication of prostate biopsy, occurring in 1 to 11 percent of patients [14,30,207,222-224]. Treatment with oral antibiotics (eg, fluoroquinolone, trimethoprim-sulfamethoxazole) is generally sufficient, though hospitalization and intravenous antibiotics may be required [209,225]. (See "Acute simple cystitis in adult and adolescent males", section on 'Treatment'.)

●Urosepsis – In an observational study of 2023 patients who received antibiotics prior to prostate biopsy, 3 percent became septic [226]. 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 [227,228]. (See 'Prophylactic antibiotics' above.)

Patients who present with a fever after prostate biopsy should be assessed for sepsis. 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 [17]. (See "Evaluation and management of suspected sepsis and septic shock in adults".)

●Prostatitis – Acute postbiopsy prostatitis is a relatively uncommon but potentially life-threatening complication that warrants immediate evaluation and intervention. Prior fluoroquinolone use and extended postbiopsy antibiotic regimens appear to increase the risk for postbiopsy prostatitis [216,229,230]. Treatment of 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 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 [17]. 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 [231,232]. 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

●Indications for prostate biopsy – Prostate biopsy is performed in patients with abnormal prostate-specific antigen (PSA) levels or abnormal digital rectal examination, or as a part of active surveillance. (See 'Introduction' above and 'Indications' above.)

●Choice of biopsy methods – Prostate biopsy can be systematic, targeted, or both, the choice of which depends on demonstration of suspicious findings on prebiopsy MRI. The requirement for prebiopsy MRI further depends on whether the patient has had a prior systematic biopsy (algorithm 1) (see 'Choice of biopsy method by indication' above):

•Initial biopsy – Patients undergoing prostate biopsy for the first time may either have a systematic biopsy or an MRI first. If there are suspicious findings on MRI, a targeted biopsy should be performed with or without a concurrent systematic biopsy; if there are no suspicious findings on MRI, a systematic biopsy is performed. (See 'Initial biopsy' above.)

•Repeat biopsy – For patients undergoing a repeat biopsy, we perform a prebiopsy MRI if one has not been done previously. If there are suspicious findings on MRI, a targeted biopsy should be performed with a concurrent systematic biopsy; if there are no suspicious findings on MRI, a systematic biopsy is performed; for repeat systematic biopsy, a more extensive sampling method such as saturation biopsy or template-guided biopsy may be considered. (See 'Patients with negative systematic biopsy' above and 'Active surveillance' above.)

The choice of image guidance and anatomic approaches does not affect biopsy performance and are determined by operator preference.

●Systematic versus targeted biopsy – There is increasing evidence that MRI-targeted biopsy can increase clinically significant cancer detection over standard transrectal ultrasound (TRUS) biopsy alone, and this advantage is more pronounced when MRI-targeted biopsy is performed in men with a prior negative biopsy than biopsy-naïve men. (See 'Systematic versus targeted biopsy' above.)

•TRUS-guided prostate biopsy is the most common approach for patients undergoing prostate biopsy for the first time. For initial TRUS biopsy, we perform an extended 10- to 12-core biopsy rather than a sextant biopsy or a more extensive (eg, 18-core) biopsy. Apical and far-lateral regions of the prostate should be adequately sampled. (See 'Systematic biopsy' above.)

•At facilities where prostate MRI and MRI-targeted biopsy are available, MRI-targeted biopsy should be performed with concurrent systematic sampling for patients. (See 'Targeted biopsy' above.)

●Transrectal versus transperineal biopsy – Use of transperineal versus transrectal biopsy varies widely by country and within regions of specific countries. The reported cancer detection rates associated with transrectal versus transperineal biopsy route are not significantly different in contemporary studies. (See 'Anatomic approaches' above.)

●Antibiotic prophylaxis – For patients undergoing prostate biopsy, we recommend antibiotic prophylaxis prior to transrectal prostate biopsy (Grade 1B). For patients without risk factors (eg, immunocompromised), antibiotic prophylaxis is not required before transperineal biopsy because of a lower risk of infection. (See 'Prophylactic antibiotics' above.)

●Need for repeat biopsy – Indications for repeat biopsy include abnormal but nonmalignant pathology (see below), rising PSA after a negative biopsy, and concerns for inadequate sampling (see 'Repeat biopsy' above):

•Patients with atypical small acinar proliferation (ASAP), atypical intraductal proliferation (AIP), or high-grade prostatic intraepithelial neoplasm (HGPIN) on initial biopsy should undergo further testing, including repeat biopsy.

•Repeat biopsy may be considered in patients with a rising serum PSA after a negative initial biopsy after considering PSA velocity, free-to-total PSA, and other urine or serum biomarkers.

●Complications – Common complications of prostate biopsy include infection, bleeding, and urinary obstruction. There are fewer infectious complications after transperineal than transrectal biopsies, but the overall complication rates of the two approaches are similar. (See 'Complications' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Gerald L Andriole, MD, who contributed to earlier versions of this topic review.