Prostate Biopsy

This topic addresses indications for, preparation for, and performance of prostate biopsy—in particular, transrectal ultrasonography (TRUS)-guided biopsy of the prostate gland.[3] Although a number of different methods may be used to perform TRUS-guided prostate biopsy, the authors find that those described in this topic facilitate mastery of this procedure.

The basics of office-based procedures such as this are easily overlooked in urology training. Mastery of such seemingly simple procedures sometimes eludes the urology resident during times when the spotlight may be on major surgery. However, the increasing focus on office-based procedures, combined with the observation that large numbers of urologists now function primarily in an ambulatory setting, makes facility with such procedures an increasingly important part of urologic specialty care.

Relevant anatomy

A normal prostate gland (see the image below) is approximately 20 g in volume, 3 cm in length, 4 cm wide, and 2 cm in depth. As men get older, the prostate gland is variable in size secondary to benign prostatic hyperplasia. The gland is located posterior to the pubic symphysis, superior to the perineal membrane, inferior to the bladder, and anterior to the rectum. The base of the prostate is in continuity with the bladder and the prostate ends at the apex before becoming the striated external urethral sphincter. The sphincter is a vertically oriented tubular sheath that surrounds the membranous urethra and prostate. For more information about the relevant anatomy, see Prostate Anatomy and Seminal Vesicle Anatomy.

See Prostate Cancer: Diagnosis and Staging, a Critical Images slideshow, to help determine the best diagnostic approach for this potentially deadly disease.

Also, see the Advanced Prostate Cancer: Signs of Metastatic Disease slideshow for help identifying the signs of metastatic disease.

Indications for prostate biopsy are not set in stone. Initially, patients with a prostate-specific antigen (PSA) value higher than 4.0 ng/mL were believed to have an absolute indication. Biopsy typically was also recommended for patients with suspicious findings on digital rectal examination (DRE).

However, the current established practice is that no PSA value exists that can establish with absolute certainty whether a patient does or does not have prostate cancer. Thus, the decision whether to proceed with prostate biopsy must be individualized in every case. Nomograms and predictive models have been developed to assist in this decision, but none have been able to provide a definite go/no go decision.

The introduction of markers (eg, prostate cancer antigen 3 gene [PCA3]) is an advantage of a nomogram or risk calculator over a PSA cut-point. Urinary PCA3 has been shown to be a useful tool in identifying patients at risk for prostate cancer prior to initial prostate biopsy.[4]

Even more difficult is the decision whether to perform a repeat biopsy.[5, 6] Patients with atypical small acinar neoplasia (ASAP) essentially have an absolute indication for repeat biopsy within a brief period after the initial biopsy. However, the situation is different for patients with high-grade prostatic intraepithelial neoplasia (HGPIN).

In the past, automatic repeat biopsy was recommended for patients with HGPIN. However, it is now generally considered that patients with focal HGPIN do not need to undergo automatic biopsy, because they are not at significantly higher risk for prostate cancer in the future. By contrast, patients with multifocal HGPIN are at significant risk for prostate cancer in the future; therefore, they should undergo delayed interval biopsy every 3 years as long as they remain healthy.[7, 8, 9, 10]

Patients who have persistently abnormal or rising PSA levels or very low percentages of free PSA (< 13%) are at some risk for harboring unrecognized prostate cancer and thus should be considered for repeat biopsy.[11] However, if a repeat biopsy is performed and it is negative, the likelihood of finding clinically significant prostate cancer in the future is very low, and a high threshold should be maintained for recommending further biopsy.

Contraindications for prostate biopsy include the surgical absence of a rectum or the presence of a rectal fistula.

Best practices

Today’s typical patient justifiably expects to undergo minimal pain and to be treated with respect for his or her privacy and modesty. Patient comfort is paramount to successful use of TRUS and prostate biopsy. This begins with the room setup. Respect for modesty is not only medicolegally advisable but also, and more importantly, the right thing to do. Using sheets to cover the legs allows the patient to feel some control over an embarrassing situation.

The examining room layout should minimize the chance that someone opening the door will be able to see the patient in a compromising position. Ideally, doors open in a manner that puts them between the person or persons entering and the patient until they have opened completely. This increases the time available for visitors to stop and leave if they find they are entering the wrong room (or the right room at the wrong time). Placing curtains in front of the door helps with this and undoubtedly makes the patient feel less vulnerable.

When possible, the examining table should be placed so that a patient who is in an exposed position is not situated in such a way that private body areas are visible from the door. The temperature should accommodate the comfort of the partially clothed patient.

Lubrication for urologic instruments is vital. The value of anesthetic-based lubricants has not been definitively demonstrated, but the role of lubrication to minimize the shearing forces of friction against rectal mucosa is undeniable. The authors use water-based lubricants (eg, KY Jelly) for TRUS because nothing has been demonstrated to provide better protection from pain.

Modern transrectal ultrasound probes are relatively small (often no larger than an examining finger) and thus are easily tolerable by most patients. Adequate (even abundant) lubrication minimizes the coefficient of kinetic friction and shearing forces against the anus. Given that attempts at anal mucosa and sphincteric anesthesia have yielded mixed results, lubrication and gentle technique remain the mainstays of comfort measures.

For patients with anorectal pain issues, application of Hurricaine or Urojet lubrication appears to decrease the pain of probe placement; however, it adds some discomfort in the course of its own application. Consequently, such lubrication is rarely used in the authors’ practice.

Complication prevention

Antibiotic prophylaxis

The authors have found no statistically significant difference in complications between a single dose of a fluoroquinolone and a 3-day course of antibiotics plus enema. The single-dose regimen has the advantage of ensuring full patient compliance, which cannot be guaranteed by more protracted courses requiring actions that must occur outside the clinic setting (eg, additional antibiotic doses and enemas).

Moreover, the single-dose fluoroquinolone regimen potentially minimizes the risk of emergence of resistant strains that may arise with unnecessarily prolonged courses of antibiotics. Finally, it saves considerable discomfort and some of the costs associated with more complex approaches that have shown no clear evidence of benefit.

Nevertheless, given the increase in microbial resistance to fluoroquinolones, the authors now recommend adding a single dose of gentamicin. The dose should be approximately 1 mg/kg, rounded to the next highest 40-mg vial measurement. Thus, for example, a 90-kg man should receive 120 mg of gentamicin.

Antiplatelet and anticoagulation therapy

Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) should be discontinued for 5-7 days prior to the biopsy. In patients with coronary artery stents, aspirin should be continued to prevent stent thrombosis. Anticoagulation should be stopped for 5-7 days prior to biopsy or with an international normalized ratio of 1.5 or lower. However, in patients with a high risk of coagulopathies, heparin therapy should be started.[12]

Biopsy devices

Biopsies are best performed with a spring-driven needle core biopsy device (or biopsy gun), which can be passed through the needle guide attached to the ultrasound probe. Most instrumentation provides optimal visualization of the biopsy needle path in the sagittal plane.

In most cases, 18-gauge needles are used, and the tips of the needles are etched with small ridges or pits to render them more echogenic. A ruled puncture trajectory corresponding to the probe’s needle guide should be superimposed on the ultrasound images; this allows anticipation of the needle path.

Ultrasound probes

Two types of prostate ultrasound probes exist: side-fire and end-fire.[13] Understanding their differences is important for mastery of transrectal ultrasonography (TRUS) because they provide entirely different views, which can lead to confusion if one type is used in the manner that is appropriate for the other. The direction of imaging should be obvious from the names of the probe types, but the implications of their differences may not be.

Side-fire probes project laterally. For this reason, twisting the probe while keeping its axis neutral with respect to the sagittal plane laterally enables lateral visualization. End-fire probes project an imaging plane either directly or at a slight angle from the end of the probe. Thus, the probe handle must be angled away from the side of interest in order to visualize the lateral areas, with the anus used as a fulcrum.

The above geometric requirements mean that when a patient undergoes TRUS of the prostate with a side-fire probe, the probe should remain essentially in the midline and should be twisted to reach the lateral aspects. Consequently, patient positioning is relatively unimportant, provided that the anus is accessible.

Conversely, when a patient undergoes TRUS of the prostate with an end-fire probe, the probe must be positioned so that its handle can be dropped far enough to reach beneath the plane of the examination table when the right lateral border of the prostate is visualized. To facilitate this, the patient’s buttocks should be directly over the corner of the table, with the legs flexed toward the chest and held by the table extension.

With either type of probe, limited visualization of the lateral aspects can result in 2 problems. First, periprostatic block is performed laterally at the junction of the seminal vesicles and prostate. Second, and equally important, the lateral aspects of the peripheral zone are the areas most likely to harbor cancer; limiting lateral access increases the risk of inadequate and false-negative biopsies.

The authors find that lateral visualization is most readily achieved with an end-fire probe, though they routinely perform biopsies successfully with either type. Another advantage of the end-fire probe is that the trajectory of the biopsy needle as it exits its guide is aimed more directly toward the prostate rather than tangentially. This allows easier biopsy of the apex and anterior horn of the peripheral zone, further minimizing the possibility of a false-negative biopsy.

Rectal swab

Some authors have found that they can identify the presence of resistant bacteria, which might change antibiotic prophylaxis prior to biopsy, by performing a rectal swab culture on a previous visit. This practice has not been widely accepted, probably because of the complexity of adding a visit for many patients to perform the swab. Nevertheless, it is intriguing and might be especially applicable for patients who are likely to have bacterial resistance, such as those who have taken multiple doses of antibiotics in the past or those who have traveled extensively internationally where antibiotic resistance may be higher than in the United States.[14]

Anesthesia

Periprostatic block is performed by placing a needle into the notch between the prostate and the seminal vesicle laterally. This is identified ultrasonographically as a white (hyperechoic) pyramidal area that the authors call the Mount Everest sign (because of its resemblance to a snowy mountain peak). Fat in this location makes the area easy to visualize on TRUS.

The authors find that trainees often fail to advance the probe far enough into the rectum to reach the Mount Everest sign. Difficulty in finding this notch immediately upon probe placement is usually due either to inadequate depth of probe placement (which is easily remediable) or to inadequate visualization laterally, often because the novice is twisting the end-fire probe or angling the side-fire probe, either of which can lead to loss of visual orientation and perspective.

Injection of 5 mL of a local anesthetic agent (either lidocaine or bupivacaine) creates a hypoechoic fluid area in the same site as the Mount Everest sign. The “ultrasonic wheal” describes visualization of the anesthetic agent reaching the periprostatic nerves.

Although some authors advocate multiple injections along either side, anesthesia is assured if the hypoechoic agent can be visualized dissecting along the nerve bundles between the prostate and rectum. This confirms that the anesthetic has reached the entire neurovascular bundle coursing along each side of the prostate. If the agent dissects caudally along the neurovascular bundles, prostatic anesthesia is assured regardless of whether a single injection or multiple injections were administered.

Ensuring that the anesthetic reaches the proper plane is facilitated by injecting as the needle enters the space in order to expand its distance, then pulling back slightly in order to open up the potential space until anesthetic is seen dissecting caudally. Note that the space between the rectal wall and the prostate widens when the fluid dissects into this plane.

Because apical sampling is more painful than biopsy of the remainder of the gland, the authors recently introduced rectal wall injection as the lidocaine needle traverses the tissue, which further reduces pain during apical biopsy. Furthermore, a rectal sensation test can be done by touching the biopsy needle against the rectal wall, for proper positioning of the needle in order to not traverse the sensitive anus as the first step of apical biopsy.[15]

Other methods of providing pain control are intrarectal application of local anesthetic gel[16] and intraprostatic injection of local anesthetic[17] ; however, periprostatic block is the most critical.

Positioning

Although some physicians recommend the lithotomy position, the authors find that prostate biopsy can typically be performed more readily with the patient in the left lateral decubitus position. The patient’s buttocks should be at the corner of the bed, especially if the physician is using an end-fire probe, which must be angled to permit visualization of the lateral aspect of the right side of the prostate. The knees should be pulled toward the chest as much as possible to facilitate probe placement.

No specific recommendations exist for care after prostate biopsy. Most patients wish at least to return home for a shower, but it is acceptable for them to resume their previous activity level if they wish. It is important for patients to notify a physician if they experience any fevers or chills. Urine and blood cultures should be obtained on the basis of the potential for resistant bacteria.

It should be kept in mind that after a single negative biopsy result, at least 25% of patients may still harbor histologic prostate cancer; thus, careful monitoring is mandatory. In view of the slow development of prostate cancer and its slow progression in the overwhelming majority of patients, the authors recommend annual prostate-specific antigen (PSA) testing. Some authors recommend more frequent surveillance, and this is a reasonable option.

Placement of probe

For transrectal ultrasonography (TRUS), the probe should be placed in a controlled manner, with light but slowly increasing pressure applied against the probe as its tapered end dilates the sphincter during entry. Because the anal canal may be slightly angled in one anatomic direction or another, using this technique to allow the probe to find the path of least resistance should minimize pain. Holding the end of the probe between the thumb and forefinger allows greater range of motion than a tight-fisted grip would and makes biopsy easier on the surgeon.

The physician should remain mindful of the topical anatomy throughout the procedure (see the image below). Just as the laparoscopic surgeon should observe the body during instrument entry and exit, so should the ultrasonographer observe the probe to ensure that it points in the direction of the rectal course during placement.

Number and location of biopsy cores

Directed biopsies are obtained from any area considered to be suggestive on the basis of TRUS of the prostate or palpable abnormalities found on digital rectal examination. Because the incidence of nonpalpable isoechoic prostate tumors is high, limiting biopsy sites to either ultrasonographically hypoechoic lesions or to areas of palpable abnormality tends to miss many malignancies.

Obtain separate biopsy samples from each sextant of the prostate; this improves the odds of sampling clinically inapparent tumors. Originally, these biopsy sites included the midlobe parasagittal plane at the apex, the midgland, and the base bilaterally. However, many authors subsequently recommended changes to this protocol, involving alternative locations or greater numbers of biopsy samples.[18]

Currently, the authors recommend 14-core biopsy as an initial biopsy strategy on the basis of their findings that increasing the number of cores beyond that yields no benefit for initial investigation. The 14-core strategy involves the standard 12-core template with 1 core medially and laterally in both the parasagittal and lateral aspects of the gland plus 1 core on each side in the extreme apex (the site that has the highest likelihood of unique cancer detection).[19, 20]

The authors place 6 cores parasagittally in the same sites as originally described by Hodge et al[21] ; 6 additional cores are obtained lateral to those sites, with an emphasis on going as far laterally as will still permit full-length cores. Because the needle tract projects toward the base, it is appropriate to situate the entrance site more toward the apex so as to ensure that most of the tissue is not obtained from the superior portion of the gland (which is the area less likely to harbor malignancy).

For all repeat biopsies, the authors have confirmed that a 20-core transrectal saturation biopsy increases cancer detection by approximately 50% as compared with extended biopsy.[22] Morbidity is no higher with this approach, and patients tolerate it well under periprostatic block.

TRUS-guided prostate biopsy is one of the most frequently performed urologic procedures. Although it is generally a safe and well-tolerated outpatient procedure, it is associated with a complication rate of up to 63-73% in some series.

Fortunately, the complications encountered after TRUS biopsy are commonly minor and self-limited, including mild hematuria, hematospermia, and transient rectal bleeding. Occasionally, the resultant morbidities may be significant enough to require surgical intervention (eg, urinary retention [0.2-2.6%] and severe rectal bleeding [0.6%]).[23, 24]

After bleeding, urinary tract infection (UTI) is the second most frequently noted complication of prostate biopsy. It may be described as a minor or major complication, depending on its severity. Although simple UTI frequently occurs after biopsy (1.2-11.3% of cases), febrile UTIs also are not uncommon (1.4-4.5%). Sepsis, one of the most serious clinical sequelae, is encountered in 0.1-2.2% of cases after biopsy.[2]

Some reports have debated the benefit of antibiotic prophylaxis before biopsy, whereas other studies have demonstrated a 16-100% incidence of asymptomatic bacteriuria and transient bacteremia after biopsies performed without antibiotic prophylaxis.

Currently, most urologists agree on the importance of antibiotic-based prebiopsy preparation for maintaining acceptably low complication rates. In a survey conducted on 900 practicing urologists in the United States, prebiopsy regimens included prophylactic antibiotics in 98.6% of cases and a cleansing rectal enema in 81%. Additionally, 11 different antibiotics were used, with 20 variable doses and 23 different timing-duration regimens.

Although there are no published guidelines or prospective randomized trials on which urologists can rely when attempting to determine the optimal antibiotic type, dose, duration, and schedule in the prebiopsy setting, several studies have demonstrated the benefit offered by a single prebiopsy dose of oral antibiotics.

On the basis of their broad spectrum of activity, which covers most aerobic organisms residing in the bowel, fluoroquinolones have been considered the antibiotic type of choice for most of these regimens. However, because of emerging resistant bacterial patterns, the authors now recommend gentamicin in addition to fluoroquinolones.

Further extension of the antibiotic course may be specifically reserved for high-risk patients (eg, those with valvular heart disease and mechanical prostheses).

The use of enemas in prebiopsy protocols was initially based on the suspicion that the mechanism by which infection occurs might be seeding of rectal flora by the biopsy needle. Nevertheless, the real value of enemas in these protocols remains debatable. Some urologists consider them nothing more than cumbersome procedures that potentially increase patient cost and discomfort without offering any additional benefit over antibiotic prophylaxis alone. Given the absence of a clear justification for their use, the authors do not recommend enemas.

Murray et al reported that the effects of TRUS-guided prostate biopsy on erectile function have probably been “underestimated”; however, the cause of these effects has yet to be determined. Of the 220 patients who underwent TRUS-guided prostate biopsy, 38.6% reported no erectile dysfunction (ED), 22.3% mild ED, 15.5% mild to moderate ED, 10% moderate ED, and 13.6% severe ED.[25, 26]

A single dose of a fluoroquinolone plus a single dose of parenteral gentamicin is indicated. Alternatively, a cephalosporin may provide adequate coverage, but this option has not been studied extensively.

Finally, all patients should receive a prostatic block. This may be done with any local anesthetic injectable agent. The benefits of prolonged local anesthesia have not been established.

Class Summary

Prophylactic therapy should cover all likely pathogens in the context of this clinical setting.

Ciprofloxacin (Cipro)

Ciprofloxacin is a fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Ciprofloxacin has no activity against anaerobes. The protocol may consist of a single dose of 500 mg ciprofloxacin.

Class Summary

The use of a urethral anesthetic in female patients is controversial. The decision to anesthetize the urethra should be made in conjunction with the patient. Local anesthetics block the initiation and conduction of nerve impulses. Anesthetics used for the urethra include lidocaine and, possibly, bupivacaine.

Lidocaine (Xylocaine)

Lidocaine inhibits depolarization of type C sensory neurons by blocking sodium channels. The authors use 1% lidocaine without epinephrine.

Bupivacaine (Marcaine)

Bupivacaine decreases permeability to sodium ions in neuronal membranes. This results in the inhibition of depolarization, blocking the transmission of nerve impulses. The authors have used 0.25% bupivacaine successfully. Despite the traditional teaching that bupivacaine's onset of action is delayed in comparison with that of lidocaine, the authors have found that this is not the case and that the 2 agents work equally well.