Transrectal Ultrasonography of the Prostate

Prostate cancer is the most common noncutaneous cancer in males in the United States. It is estimated that about 60-70% of older men on autopsy have some degree of prostate cancer, compared with 15-20% of men diagnosed with prostate cancer during their lifetime and with the 3% lifetime risk of death from prostate cancer.[1, 2, 3]  An estimated one in six white men and one in five African-American men will be diagnosed with prostate cancer in their lifetime, with the likelihood increasing with age. Prostate cancer is rarely diagnosed in men younger than 40 years, and it is uncommon in men younger than 50 years.[4]

Management of prostate cancer can include active surveillance, radiation therapy, cryotherapy, hormone therapy, and/or surgery. In active surveillance, patients are followed by their urologist by means of periodic physical exams, prostate-specific antigen (PSA) testing, digital rectal exam (DRE), and/or periodic repeat prostate biopsies. The decision regarding whether one can pursue active surveillance depends on the biopsy results, PSA levels, and the clinical stage of the cancer. The American Urological Association (AUA) deems active surveillance an option in prostate cancer patients who have a low PSA level, clinical stage, and Gleason score, making accurate biopsy results extremely important in considering patients for this option.[2]

A useful tool that can help supplement various diagnostic and treatment modalities for prostate cancer is transrectal ultrasonography (TRUS). TRUS has become an extension of the urologist’s finger in the early detection of prostate cancer. The evolution of end-firing probes has further enhanced urologists’ ability to monitor the entire process of a prostate biopsy.[3] TRUS is also widely used to deliver treatments such as brachytherapy and to monitor cryotherapy treatment for prostate cancer.

The use of sound waves to detect distant objects on the basis of their reflective properties became popular after World War II. In medicine, the initial use of ultrasound was in the detection of brain tumors. In urology, ultrasound was first used to detect renal stones during surgery.

The early applications of ultrasonography in medicine involved sound-wave generators, cathode-ray tubes, Polaroid photography, or 35-mm film recording. However, the invention of the silicone microchip gave birth to the modern ultrasonography revolution.

Early investigators in prostatic ultrasonography conducted experiments with ultrasound probes and recording devices. One of the earliest devices was a chair-type apparatus with a probe mounted in the center of the chair. The patient sat on the probe, which was guided into the rectum. Improvements in gray-scale ultrasound display and multiplanar scanning have resulted in user-friendly hand-held probes.

Earlier studies concentrated on the ultrasonographic appearances of prostate abnormalities such as benign prostatic hyperplasia (BPH), carcinoma of the prostate (CAP), prostatitis, prostatic abscess, and prostatic calculi. Since the introduction of the PSA screening test and early detection of prostate cancer, the role of TRUS has changed; it is mainly used to visualize the prostate (see the image below) and to aid in guided needle biopsy.

Real-time prostate biopsy has emerged as a potential replacement for conventional systematic biopsy in an effort to improve quality, reduce the number of clinically insignificant cancer diagnoses, and improve targeting of high-grade and clinically significant tumors.

PSA guidelines

The American Urological Association (AUA) has published updated guidelines for the early detection of prostate cancer (CAP) to guide urologists in the screening of asymptomatic men.[5] The panel recommended against screening men younger than 40 years and the routine screening of men aged 40 to 54 years who are at average risk for CAP. Men younger than 55 years who are at increased risk for CAP (family history or African American race) should discuss an individualized approach to prostate cancer screening with their urologists. Men aged 55 to 69 years appear to derive the greatest benefit from screening. For men in this age group, the panel strongly recommended shared decision-making regarding PSA screening and proceeding at 2-year intervals depending on the individual’s values and preferences. PSA screening is not recommended for men older than 70 years or for any man with less than 10-15 years of life expectancy.[5]

Future applications

Possible future applications involving TRUS include the following:

• Color Doppler scanning

• Contrast-enhanced prostate biopsy

• Intermittent and harmonic ultrasonography

• High-intensity focused ultrasound (HIFU)

• Elastography

• MRI ultrasound coregistration

Color Doppler

Color Doppler scanning has been used to enhance the diagnosis of CAP as an adjunct to TRUS. Several investigators have demonstrated that the addition of color Doppler improved the specificity of prostate biopsy findings. However, differentiating a focus of prostatitis from cancer was difficult. The addition of power Doppler was not advantageous.

Contrast-enhanced prostate biopsy

The use of microbubble contrast agents can enhance gray-scale imaging and Doppler imaging. Newer agents that remain in the vascular compartment have been used for prostate imaging. Currently available agents include the following:

• Perflenapent emulsion (EchoGen)

• Galactose–palmitic acid (Levovist)

• Perflexane lipid microspheres (Imavist)

• Galactose suspension (Echovist)

• Perflutren lipid microsphere (DMP 115, Definity)

• Perfluorobutane microspheres (NC100-100, Sonazoid)

Several investigators have evaluated contrast-enhanced prostate ultrasonography. Ragde et al used EchoGen to study 15 patients with rising PSA levels and previous negative biopsy findings and found that the addition of this contrast agent helped guide biopsies to appropriate sites.[6]

Similarly, Watanabe et al studied 9 cases in which Levovist was used and demonstrated enhanced images of all cancers.[7] Halpern et al evaluated 26 patients with elevated PSA levels and found significant image enhancement after using Imavist.[8] However, the extra cost of this technique may be the limiting factor in its widespread use.

Intermittent and harmonic ultrasonography

The rationale for intermittent and harmonic ultrasonography is that conventional ultrasonography destroys the microbubbles of the contrast agents used in ultrasonographic imaging. Intermittent ultrasonography increases the enhancement provided by the contrast agents. In harmonic imaging, the reverberations produced by the contrast agent are visualized at a different frequency than the insonating frequency, which can provide a better image.

High-intensity focused ultrasound

With extracorporeal HIFU, temperatures higher than 60°C can be achieved in the target tissue. The prostate can be easily treated with this modality via a transrectal probe. The size of the thermal lesion can be controlled by the power and the duration of the ultrasound pulse. Higher in situ intensities (>3055 W/cm2) create the cavitation phenomenon and bubble effect, which are difficult to monitor.

The currently available HIFU devices use 3-4 MHz transducers. Experimental studies have shown core temperatures of 75°C, with a peak of 99°C during insonification.

Gelet et al pioneered the use of transrectal HIFU in the treatment of prostate cancer.[9]  The procedure is used to treat localized prostate cancer and is performed with the patient under anesthesia and in a decubitus position. Rectal cooling is employed to prevent rectal burns. Prostates smaller than 40 mL or those with an anteroposterior diameter of less than 5 cm are best suited for this treatment. During the procedure, the whole gland is treated (in contrast to focal therapy). After the procedure, a suprapubic tube is left in place for 5-7 days. In a multicenter trial of 402 patients treated with HIFU, the median duration for catheter use was 5 days.[10] Prolonged retention occurred in 9% of patients, and 3.6% developed urethral strictures. Incontinence following HIFU was rare (0.6%). Rectourethral fistula developed in 1.2% of the patients.

Complication rates are higher with salvage HIFU after radiation therapy, radical prostatectomy, or HIFU. Erectile function can be preserved in 20-46% of patients who undergo only 1 session of HIFU.

After a minimum follow-up period of 6 months, Thuroff et al reported negative biopsy results in 87% of patients and a median nadir PSA level of 0.4 ng/mL after HIFU.[10] Gelet at al reported that 78% of low-risk patients were disease-free and had negative biopsy results at an actuarial 5-year follow-up.[9]

Gelet et al also reported salvage HIFU after failed radiation in 71 patients.[11] Among these patients, biopsy results were negative in 80%, and 61% had a PSA level nadir below 0.5 ng/mL. Complication rates after salvage HIFU were higher: total incontinence developed in 6%, rectourethral fistula in 6%, and vesical neck contracture in 17%.

Prostate elastography

DRE, PSA testing, and color Doppler TRUS-guided systematic biopsy are the basis for the diagnosis of prostate cancer. As alluded to earlier, TRUS has not been proven as a reliable imaging technique for localizing cancer foci within the prostate. Krouskop et al[12] theorized that cell density is greater in neoplastic tissue, causing a change in tissue elasticity. This line of thinking formed the basis for elastography, which was developed in the early 1990’s. As elastography developed, it has been increasingly applied for prostate cancer imaging. Konig et al[13] studied 404 patients with suspected prostate cancer and found that elastography detected 84% of the 151 true positive cancer patients.

Elastrography is an ultrasound tool that is capable of mapping tissue stiffness of the prostate. There are 2 elastography techniques: quasi-static and shear-wave.[14] Quasi-static technique involves the analysis of prostate tissue deformation before and after compression by the ultrasound transducer. This difference in deformation is used to estimate the tissue stiffness. Reduced deformation typically indicates neoplastic tissue; additionally, if this tissue appears hypoechoic, it is likely a malignancy. The shear-wave technique requires no compression of the rectal wall and is based on the measurement of shear-wave velocity propagating through the tissues. Elastic properties are typically provided in kilopascals (kPa), where neoplastic nodularity is suspicious at levels greater than 35 kPa.[15]

Elastography has proved to be a useful tool in the detection of prostate cancer. In Miyanaga’s study,[16] of 29 patients with untreated prostate cancer, the sensitivity of elastography, TRUS, and DRE were 93%, 59%, and 55%, respectively. Pallwein et al[17] studied 15 patients who were initially studied with standard ultrasound and elastography before undergoing robot-assisted laparoscopic prostatectomy, and they found that elastography was 88% sensitive for detecting cancer foci and that 78.3% of the cases correlated with the histologic findings. Further analysis showed that the best sensitivity and specificity were found in the apex region.  Additionally, elastography has been shown to have a negative predictive value of up to 99% for the detection of prostate cancer, making it unlikely that cancers will be missed with this technique.[15]

In terms of targeted prostate biopsy, a larger study, by Pallwein et al,[18] concluded that elastography was 2.9 times more likely to detect prostate cancer than systematic TRUS biopsy. Furthermore, elastography required fewer than half the number of biopsy cores. When evaluating elastography for the staging of prostate cancer, Salomon et al[19] evaluated 15 patients who underwent elastography after radical prostatectomy and found that 14 of 15 patients were correctly identified for the presence or absence of extracapsular disease.

Elastography certainly has shown promise as an alternative to conventional TRUS, and further clinical trials are being conducted, which will likely lead to better understanding of the exact role for elastography in the management of prostate cancer.

MRI ultrasound coregistration

Prostate MRI was first reported over 30 years ago.[20] MRI "in bore" biopsy, where targeting biopsies are performed within the MRI gantry, has been the most widely examined prostate biopsy procedure; however, because of increased cost, lack of availability, and overall clinical outcomes, it is unlikely to replace systematic biopsy. MRI coregistration with ultrasound, commonly referred to as MR-US fusion, has been an area of increasing research and is a potential replacement for systematic biopsy moving forward.

MR-US fusion allows MRI data to be used to obtain biopsies under ultrasound guidance. Cognitive fusion refers to the operator viewing lesions on MRI, allowing one to attempt biopsy of the visualized location from memory using real-time US. Obvious disadvantages include potential for human error and the steep learning curve and variability of results. In an effort to reduce this variability, several fusion devices have been developed and are now approved by the FDA.[20, 21, 22, 23, 24, 25, 26]

The Artemis device (Eigen) utilizes tracking of the TRUS probe by a directly attached robotic arm that translates the 2D US into a 3D model, which is fused with the preprocedure MRI and allows targeting of suspicious lesions.[20] The device also tracks biopsy sites, allowing rebiopsy of the exact site at a later time.

Sonn et al[21] found that in men undergoing active surveillance with previously negative biopsy results, the Artemis device detected cancer in 55% of men overall and 94% of those with the highest level of suspicion on MRI. They also found that there was a clinically significant increase in the detection of significant cancers and a decreased detection of insignificant cancers, as compared to systematic biopsy.

Disadvantages of using the Artemis device include the bulkiness of the device and difficulty with in-office use. The UroNav device (Invivo) utilizes a sensor that attaches to the TRUS probe, and using a small electromagnetic field placed in close proximity to the patient, it fuses the MRI data.[20] It is a free-hand technique that is generally more familiar to urologists. However, it has the disadvantage of an electromagnetic field, as opposed to the accuracy of the robot.

Vourganti et al[22] found that in patients with previous negative biopsy results, UroNav detected cancer in 37% of patients, including 11% with high-grade disease. The Urostation device (Koelis) utilizes real-time 3D TRUS in a recreated model of the prostate to localize each biopsy site.[20] The model is reset with each probe firing to adjust for any changes. This device has the advantage of a free-hand platform, though the inherent error in any free-hand technique still exists.

Delongchamps et al[27] compared cognitive and fusion MR-US devices with systematic biopsy. In their study of 391 patients, they found no difference in the rate of cancer detection for visually targeted versus random biopsy. The fusion MR-US devices did increase the detection of high-grade cancer with fewer cores, while decreasing the rate of micro focal cancer detection.

Puech et al[23] studied men with a suspicious lesion on MRI, and each man underwent 12 random core biopsies, 2 visually guided biopsies, and 2 MR-US fusion software-targeted biopsies. The study found that targeted biopsy detected clinically significant cancer in more men than random biopsy; however, there was no significant difference in cancer detection between cognitive fusion and MR-US fusion software.

MR-US coregistration has shown promise as a targeted method of sampling the prostate leading to more accurate identification of clinically significant prostate cancer. However, it remains unclear whether the biopsy results can be applied to the conventional risk-stratification systems that were designed for systematic and random biopsy. It is also unclear how exactly this will impact the practicing urologist. Long-term studies are certainly required. Nonetheless, it is an important advancement in the ongoing effort to improve the management of prostate cancer.

The AUA and Society of Abdominal Radiology (SAR) has issued a consensus statement on the role of MRI in prostate biopsies.[28] The joint commission recognizes that the use of prostate MRI followed by MRI-targeted core biopsy is more useful in detecting clinically significant disease over standardized repeat biopsy. As a result, the organizations recommend that physicians strongly consider prostate MRI in patients with a prior negative biopsy who are undergoing repeat biopsy for clinically suspicious cancer. The authors state that the MRI should be reported in accordance with the Prostate Imaging Reporting and Data System (PI-RADS) version 2 (V2) guidelines. In these guidelines, each lesion is assessed a number (1-5) on the basis of the likelihood of the lesion correlating with the presence of cancer (see Table 1).[29]   The committee recommends image-targeted biopsy for any lesions with a PI-RADS category of 3 to 5.

The recommendations also note that although TRUS-MRI fusion and in-bore MRI targeting biopsies may be useful for smaller lesions, cognitive fusion will suffice if this equipment is not readily available. During the procedure, it is recommended that at least 2 targeted cores be taken from each suspected lesion, although this number could vary on the basis of the specific case and the physician’s clinical judgment.  Furthermore, in patients with negative or lower-suspicion MRI findings, ancillary tests (eg, PSA, PSAD) may be helpful in determining which patients warrant rebiopsy.

Two important trials that assessed the use of MP-MRI in the detection of CAP include the PROMIS[24]  and PRECISION trials. Both trials were large, multicenter studies. The PROMIS trial compared the use of MP-MRI or TRUS-guided biopsy with template prostate mapping biopsy (TPM-biopsy) in the detection of clinically significant CAP (Gleason score 3+4=7 or greater) and demonstrated that MP-MRI was more sensitive and had a higher NPV (93% and 89%, respectively) than TRUS-guided biopsy, but MP-MRI had a lower specificity and PPV (41% and 51%, respectively). The PROMIS trial did not assess the use of MRI-ultrasound fusion-guided biopsy.

The PRECISION[30]  trial was a non-inferiority trial that appraised the clinical value of using MP-MRI in both the screening and, if radiologically positive, the guided biopsy and subsequent diagnosis of CAP, as compared to TRUS-guided biopsy. The results demonstrated that MP-MRI was associated with an increase in the detection of clinically significant CAP (absolute adjusted increase of 12%, P=.005), a reduction in the detection of clinically insignificant CAP (absolute adjusted decrease of 13%, P=0.053), and a reduction in the number of patients who underwent biopsy (28% of randomized men did not undergo biopsy because of a negative MP-MRI result, compared to 0 men who did not undergo biopsy in the TRUS-guided group). The study also demonstrated that MP-MRI was associated with fewer required core biopsies (median of 4 cores in the MP-MRI arm, compared to 12 in the standard TRUS-guided arm) and a reduced complication rate at 30 days. Of note is that this trial was quite practical in its inclusion/exclusion criteria and protocols; thus, its results can likely be reasonably generalized to common urological practice.

Table. (Open Table in a new window)

TRUS has both diagnostic and therapeutic indications. Diagnostic indications for TRUS include early diagnosis of CAP. However, ultrasonographic findings alone cannot be used to establish or exclude the diagnosis of CAP. Definitive diagnosis must be based on biopsy results, along with abnormal DRE findings, elevated PSA levels, or both.

TRUS is also used diagnostically to determine the volume of the prostate gland and thereby facilitate the planning of brachytherapy, cryotherapy, or minimally invasive BPH therapy (eg, radiofrequency or microwave therapy). In addition, TRUS is used to evaluate prostate volume during hormonal downsizing for brachytherapy. Finally, TRUS is used in the evaluation of men with azoospermia to rule out ejaculatory-duct cysts, seminal vesicular cysts, mullerian cysts, or utricular cysts.

Therapeutic indications for TRUS include the following:

• Brachytherapy for CAP

• Cryotherapy for CAP

• Deroofing or aspiration of ejaculatory ducts, prostatic cysts, or prostatic abscesses

Contraindications for TRUS-guided biopsy of the prostate include an acute painful perianal disorder and a hemorrhagic diathesis. As a rule, patients should be discouraged from taking aspirin or nonsteroidal anti-inflammatory drugs for at least 10 days before the procedure, but recent use of these agents should not be considered an absolute contraindication for prostate biopsy.

Prostate anatomy

The adult prostate is a chestnut-shaped organ enveloped in a fibrous capsule. The base of the prostate is attached to the bladder neck, and the apex is fixed to the urogenital diaphragm. The prostatic urethra traverses the gland. The verumontanum is a longitudinal ridge in the prostatic apex onto which the ejaculatory ducts open.

The prostate is located superior and posterior to the seminal vesicles. The ampullae of the vas deferens run medial to the seminal vesicles along the posterior surface of the prostate. Anteriorly, the fibrous capsule thickens at the level of the apex to form puboprostatic ligaments, which attach the prostate to the back of the symphysis pubis.

The dorsal venous complex (ie, the Santorini plexus) runs along the puboprostatic ligaments. The prostate gland lies beneath the endopelvic fascia. Posteriorly, the 2 layers of Denonvilliers fascia separate the prostate from the rectum. The rectourethralis muscle attaches the rectum to the prostatic apex.

A rich plexus of veins encompasses the prostate gland between the true fibrous capsule of the gland and the lateral prostatic fascia; these are visible landmarks on sonograms (see the image below). The neurovascular bundles run craniocaudally along the posterolateral aspects of the prostate. The prostate gland is supplied by the prostatic artery, which is usually a branch of the inferior vesical artery. The prostatic artery divides into a urethral branch, which supplies the transition zone, and a capsular branch.

Venous drainage from the prostate moves into the Santorini plexus and eventually into the internal iliac vein. The prostatic venous plexus communicates freely with the extradural venous plexus (ie, the Batson plexus), and this communication is thought to be a factor in the spread of prostate cancer. Initially, lymphatic drainage of the prostate is into the obturator lymph nodes and into the hypogastric chain.

The nerve supply to the prostate is both sympathetic, from the hypogastric plexus (L1-2), and parasympathetic, from the pelvic nerve (nervi erigentes, S2-S4). Although the cavernous nerves run along the posterior aspect of the prostate, the 2 distinct areas from which prostatic nerves leave the gland are thought to be the superior and inferior pedicles. These areas are the first sites of extraprostatic spread of cancer.

Internal anatomy

According to the classic work by McNeal, the prostatic urethra, which is the main reference point of the prostate, divides the gland into an anterior fibromuscular stroma and a posterior glandular organ. The urethra is angled 35° anteriorly in the proximal portion of the prostate. The ejaculatory ducts run in the same plane as the distal prostatic urethra to join the verumontanum.

Lowsley’s concept of a 5-lobed prostate has been replaced by McNeal’s concept of zonal architecture. In this scheme, the prostate has 4 glandular zones, each with its own ductal system. The peripheral zone, the transition zone, and the periurethral glands have a similar histologic appearance and are derived from the urogenital sinus. However, the central zone is histologically distinct from the other 3 zones and is derived from mesonephric tissues (ie, wolffian tissue).

Peripheral zone

The peripheral zone constitutes almost 75% of the normal prostate gland. It occupies the distal prostate gland, the area around the urethra distal to the verumontanum. The acini are small, round, and smooth-walled, and their ducts drain into the urethra distal to the verumontanum. The stroma is loosely woven with randomly oriented muscle fibers. Approximately 70% of CAP cases arise in this zone.

Central zone

The central zone constitutes 25% of the normal prostate and occupies the part of the prostate behind the proximal prostatic urethra. The ejaculatory ducts pass through the central zone. The acini are large and irregular, with significant intraluminal folds and ridges. They are also surrounded by muscular tissue that closely follows the shape of the acini. Approximately 5-10% of CAP cases arise in this zone.

Transition zone

The transition zone makes up approximately 5-10% of the normal prostate gland (see the image below). The transition zone lies on either side of the proximal prostatic urethra, lateral to the internal sphincter. The glandular architecture is similar to that of the peripheral zone; however, the stroma is more compact. The transition zone is where BPH originates and where approximately 20% of CAP cases arise.

Periurethral glands

The periurethral glands make up less than 1% of the glandular tissue. These glands are embedded in the smooth muscle of the prostatic sphincter. This is the site of origin of the large median lobe of BPH.

Anterior fibromuscular stroma

The anterior part of the prostate is composed mainly of fibromuscular stroma, which is continuous with detrusor fibers. Toward the apex of the gland, this fibromuscular tissue blends with striated muscle from the levator. Puboprostatic ligaments also blend with this area.

Invaginated extraprostatic space

As the ejaculatory ducts enter the prostate posteriorly, an invaginated extraprostatic space (IES) surrounds them and invaginates into the prostate. The IES surrounds the ejaculatory ducts, ends at the verumontanum, and communicates with the periurethral space.

In 1989, Lee introduced the concept that invasion of the IES may be the first sign of extraprostatic extension of prostate cancer and an early sign of invasion of seminal vesicles. In 2005, Amin et al evaluated the pathological significance of the invasion of IES in 80 patients with prostate cancer and concluded that IES involvement was consistently seen in cases with seminal vesicle invasion.[31]

Bladder neck and internal sphincter

The internal sphincter runs from the bladder neck to the level of the verumontanum. The smooth muscle fibers of the sphincter are continuous with the superficial layer of the trigone. In healthy males, the bladder neck and the internal sphincter are closed. In males with a neurogenic bladder, the bladder neck and the prostatic urethra are wide open, and some investigators have used TRUS to monitor the lower urinary tract in patients with spinal injuries.

See Prostate Anatomy and Seminal Vesicle Anatomy for more information.

Complication prevention

Gill and Ukimura, in a study reporting on the use of TRUS monitoring with Doppler during laparoscopic radical prostatectomy to identify the blood flow in the neurovascular bundles, found that identification and preservation of pulsatile blood vessels within these bundles resulted in superior recovery of erectile activity postoperatively.[32]

Preprocedural enema

More than 80% of urologists administer an enema before TRUS and prostate biopsy. However, some authors consider this practice unnecessary.

Antibiotic prophylaxis

More than 90% of urologists administer prophylactic oral antibiotics. Reported regimens include a total of 11 different antibiotics, with 20 different dosages and treatment durations ranging from 1 to 17 days.

There is increasing support for a simpler prophylactic regimen in patients with uncomplicated medical conditions. The protocol most commonly recommended consists of 2 doses of a fluoroquinolone, with the first given before the procedure and the second 12 hours later. Targeted antimicrobial prophylaxis has been employed in cases of infections caused by fluoroquinolone-resistant organisms.[33]

In patients with prosthetic implants or valvular heart disease, additional prophylaxis with ampicillin 1 g IM (or, in penicillin-allergic patients, vancomycin 1 g IV) plus gentamicin 80 mg IM is recommended.

Transrectal ultrasonography (TRUS) of the prostate has made use of both side-fire and end-fire ultrasound probes. Understanding the differences between them is critical for mastery of TRUS, in that the 2 probe types yield entirely different view points that create confusion if one type is used in the manner that is appropriate for the other. The directions of imaging should be obvious from the names of the probe types, but the full implications for TRUS of the prostate may not be.

Side-fire probes project laterally. Thus, twisting the probe while keeping its axis neutral with respect to the sagittal plane laterally enables lateral visualization.

In contrast, end-fire probes project an imaging plane either directly or at a slight angle from the end of the probe. Thus, to visualize the lateral areas, the probe handle must be angled away from the side of interest, with the anus used as a fulcrum to gain accurate placement. For example, to visualize the right side of the prostate, the handle would be moved downward and toward the patient’s dependent left side.

The most widely used probe for TRUS is a 7-MHz transducer within an endorectal probe. This can produce images in both sagittal and axial planes.

Anesthesia

In the past, TRUS was performed without any infiltrative anesthesia. Currently, however, it is a common practice to infiltrate lidocaine into the periprostatic area.

Pareek et al, in a randomized, double-blind, placebo-controlled study using a technique of periprostatic nerve blockade, reported significant pain control during and after biopsy.[34] This technique involved injection of 2.5 mL of lidocaine on each side at the prostate base at the junction of the prostate and the seminal vesicle (using a 5-in, 22-gauge spinal needle through the ultrasound probe).

Alavi et al, in a study comparing the efficacy of intrarectal lidocaine gel with that of periprostatic nerve block, concluded that the nerve block was superior for pain control.[35] With this technique, saturation biopsies including as many as 20 cores could be performed.

Mutaguchi et al reported that local anesthesia with an intraprostatic block provided better pain control for prostate biopsy than the use of a periprostatic block.[36] In the intraprostatic block technique, 10 mL of 1% lidocaine was injected into 2-3 sites of each prostate lobe.

In the periprostatic block technique described by the investigators, 5 mL of 1% lidocaine was injected via a 7-in. 22-gauge spinal needle into the region of the prostatic vascular pedicle just lateral to the junction of seminal vesicles and the prostate.[36] The needle was slowly withdrawn to the prostatic apex, and an additional 5 mL of lidocaine was injected at the apex.

A randomized controlled trial comparing pelvic plexus block to periprostatic nerve block demonstrated better pain control with the former technique. While the procedure is more foreign to urologists, the patients experience less pain and this technique should be considered in men undergoing office prostate biopsy.[37]

Positioning

The left lateral, lithotomy, and knee-elbow positions have all been used for TRUS. If a patient is undergoing 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. Thus, patient positioning is relatively unimportant, as long as the anus is accessible.

Conversely, if a patient is undergoing TRUS of the prostate with an end-fire probe, he must be positioned so that the ultrasound probe handle can be dropped far enough to reach beneath the plane of the examination table when the right lateral border of the prostate is being visualized. This is most readily accomplished if the patient’s buttocks are directly over the corner of the table, with his legs flexed toward his chest and held by the table extension.

General procedure

In transrectal ultrasonography (TRUS) of the prostate, scanning begins in the axial plane, and the base of the prostate and seminal vesicles are visualized first. A small amount of urine in the bladder facilitates the examination.

Seminal vesicles are identified bilaterally, with the ampullae of the vas deferens on either side of the midline (see the image below). The seminal vesicles are convoluted cystic structures that are darkly anechoic. Men who have abstained from ejaculation for a long period may have dilated seminal vesicles.

Next, the base of the prostate is visualized. The central zone comprises the posterior part of the gland and is often hyperechoic. The midgland is the widest portion of the gland. The peripheral zone forms most of the gland volume. Echoes are described as isoechoic and closely packed.

The transition zone is the central part of the gland and is hypoechoic. The junction of the peripheral zone and the transition zone is distinct posteriorly and is characterized by a hyperechoic region, which results from prostatic calculi or corpora amylacea. The transition zone is often filled with cystic spaces in patients with benign prostatic hyperplasia (BPH).

Scanning at the level of the verumontanum and observing the Eiffel tower sign (anterior shadowing) help identify the urethra and the verumontanum. The prostate distal to the verumontanum is composed mainly of the peripheral zone. The capsule is a hyperechoic structure that can be identified all around the prostate gland.

Several hypoechoic rounded structures can be identified around the prostate gland. These are the prostatic venous plexi.

The position of the neurovascular bundles can often be identified by the vascular structures. Imaging in the sagittal plane allows visualization of the urethra. The median lobes of the prostate are often visualized.

Volume measurement

Volume assessment of the prostate is an important and integral part of TRUS. Of the several formulas that have been developed for this purpose, the most commonly used is the ellipsoid formula, which requires measurement of 3 different prostate dimensions.

First, the transverse dimension and the anteroposterior dimension at the estimated point of the widest transverse dimension are measured in the axial plane. Next, the longitudinal dimension is measured in the sagittal plane just off the midline (because the bladder neck often obscures the cephalad extent of the gland). The ellipsoid volume formula is then applied, as follows:

Volume = height × width × length × 0.52

Biopsy

Directed biopsies are obtained from any area that is considered suggestive on the basis of ultrasonographic findings or palpable abnormalities found on DRE. 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.

Obtaining separate biopsy samples from each sextant of the prostate improves the odds of sampling clinically unapparent tumors. Originally, these biopsy sites included the midlobe parasagittal plane at the apex, the midgland, and the base bilaterally. Subsequently, however, changes to this protocol were recommended.

Various authors suggested that the 6 biopsy samples should be obtained from the lateral third of each lobe rather than from the mid lobe or that 2 lateral biopsy samples should be obtained from each lobe in addition to the original sextant samples. Some authors recommend obtaining even larger numbers of biopsy cores to increase the diagnostic sensitivity. (See Prostate Biopsy.)

Complications of prostate biopsy include hematuria, rectal bleeding, hematospermia, urosepsis, and perineal pain.[38] Although most of these complications subside within 48-72 hours, patients should be warned that hematospermia can last for 3-4 weeks. In rare cases (< 1%), bacteremia develops that necessitates hospitalization and administration of intravenous antibiotics.

Early diagnosis of prostate cancer

Advances in TRUS coincided with the development of prostate-specific antigen (PSA) testing. The PSA has proved the most valuable tumor marker test for early diagnosis of carcinoma of the prostate (CAP).

TRUS was also evaluated to determine whether it could be used for CAP screening. However, it was not found to be highly effective for this purpose, because of its lack of specificity. CAP lesions may appear hypoechoic, hyperechoic, or isoechoic on TRUS. Therefore, TRUS is used primarily to direct the physician to suggestive areas in the prostate (see the images below) or to guide the performance of prostate biopsies.

Prostate volume is assessed during the TRUS examination. The decision to perform biopsy in patients with abnormal PSA levels can be bolstered by PSA density (PSAD), which is defined as the PSA level divided by the prostate volume. The sensitivity of PSAD is enhanced by a cutoff value of 1.5.

BPH tissue produces one tenth as much PSA per gram as cancer tissue does; accordingly, a gland with a large amount of BPH tissue indicates an elevated PSA level. CAP is diagnosed in 30% patients with a PSA value of 4-10 ng/mL and in 60% of patients with a PSA value of 10-20 ng/mL. PSAD has been used to decrease the number of prostate biopsies performed.

Other methods that have been used to aid in the decision whether to perform biopsy include the following:

• Expected PSA value for a given prostate volume

• Volume and PSAD of the transition zone

• A PSA value that increases at a velocity greater than 0.75 ng/mL per year

The volume of the prostate gland can also be used to determine treatment options. Both perineal prostatectomy and brachytherapy are easier to perform when the gland is smaller than 50 g. In large glands, the anterolateral portion of the gland is behind the pubic arch, and these areas cannot be reached with the perineal brachytherapy needles. Hormonal downsizing is useful in such cases, and TRUS is used to monitor gland size.

Measuring prostate volume is also useful in large BPH glands to help determine whether transurethral resection or an open procedure is appropriate for prostatectomy.

Whether TRUS has a role in staging prostate cancer is debatable. Most early cancers are confined to the organ. Lee et al popularized staging biopsies of the neurovascular bundles and the seminal vesicles. Positive results from biopsy of the neurovascular bundles and seminal vesicles signified extracapsular disease and a poor outcome.

Currently, however, the greatest amount of information is available on staging approaches using the PSA value and the Gleason score of prostate cancer based on several published nomograms (eg, Partin nomograms). Moreover, biopsy of the periprostatic venous plexus may result in pelvic hematoma. Perineural invasion found on prostate biopsy samples should not be considered an indicator of extraprostatic spread. TRUS can help identify extraprostatic CAP in advanced-stage T3 cases.

Brachytherapy

Localized prostate cancer can be treated by means of brachytherapy using permanent radioactive iodine seeds, with or without preimplant external beam irradiation (depending on the tumor grade). After initial volume assessment, the seeds are placed according to a computer-generated grid under ultrasonographic guidance.[39]

To exclude violation of the urethra or bladder, cystoscopic evaluation is necessary at the end of the procedure. Although iodine seeds are most commonly used, palladium seeds are often employed to treat more aggressive cancers (usually defined as those with a Gleason score higher than 7 and a PSA value higher than 10 ng/mL).

Alternatively, patients with more aggressive tumors may receive high-dose radiation therapy consisting of external beam irradiation during the second and fourth weeks along with a brachytherapy boost with temporary implants. With temporary seeds, trocars are placed under ultrasonographic guidance according to a computer-generated grid, and the radioactive source is threaded in and out of each of the trocars.

Cryotherapy

Gonder and associates were the first to use cryoablation in urologic disorders in the 1960s. In 1988, Onik et al used real-time ultrasonography to monitor the freezing process during radical cryoablation of the prostate. Currently, cryotherapy is acceptable as salvage therapy for radiation failures.

Radical cryoablation is defined as the freezing of the entire prostate, the periprostatic tissue, the neurovascular pedicles, and the proximal seminal vesicles. Probes are placed in the prostate gland via the perineum under ultrasonographic guidance, and cryotherapy is begun. The ice ball, which is an anechoic lesion with a hyperechoic edge that can be seen advancing or receding, is directly monitored as it occupies the entire prostate gland.

Most centers use a urethral warming device to prevent urethral necrosis. The following 3 techniques have been used:

• Single freeze-thaw cycle

• Double freeze-thaw cycles

• Pullback freeze technique

A suprapubic catheter is kept in place until the patient is able to void satisfactorily with minimal residual urine. Follow-up biopsies are performed at 6 months, 1 year, and 2 years.

Using the current double freeze-thaw technique, Cohen et al reported an 11% positive biopsy rate after 4 years of follow-up. All positive results occurred in patients with a PSA value higher than 10 ng/mL or tumors at stage T3.[40]

Ghafar et al reported the results of salvage cryotherapy for recurrence after external beam radiation therapy.[41] In this study, 38 men were treated with the double freeze-thaw technique on an argon-based system. The biochemical recurrence-free survival rate was 86% at 1 year and 74% at 2 years. Complications included rectal pain (39.5%), urinary tract infection (2.6%), incontinence (7.9%), hematuria (7.9%), and scrotal edema (10%). None of the patients developed rectourethral fistula, urethral sloughing, or retention.

The goals of pharmacotherapy are to reduce pain and morbidity and prevent complications.

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.

Lidocaine (Xylocaine)

Currently, however, it is a common practice to infiltrate lidocaine into the periprostatic area. Administer 2.5 mL of lidocaine on each side at the prostate base at the junction of the prostate and the seminal vesicle (using a 5-in, 22-gauge spinal needle through the ultrasound probe).

Class Summary

More than 90% of urologists administer prophylactic oral antibiotics. There is increasing support for a simple prophylactic regimen in patients with uncomplicated medical conditions.

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 2 doses of 500 mg ciprofloxacin, with the first given before the procedure and the second 12 hours later.

Ampicillin and sulbactam (Unasyn)

In patients with prosthetic implants or valvular heart disease, prophylaxis with ampicillin 1 g intramuscularly (IM) may be administered. Ampicillin interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. It covers skin, enteric flora, and anaerobes but is not ideal for nosocomial pathogens.

Gentamicin

In patients with prosthetic implants or valvular heart disease, prophylaxis with gentamicin 80 mg IM plus vancomycin 1 g intravenously (IV) is recommended. Gentamicin is an aminoglycoside antibiotic for gram-negative coverage. It is used in combination with an agent against gram-positive organisms and one that covers anaerobes.

Vancomycin

In patients with prosthetic implants or valvular heart disease, prophylaxis with vancomycin 1 g intravenously (IV) plus gentamicin 80 mg IM is recommended. Vancomycin is a potent antibiotic directed against gram-positive organisms and active against Enterococcus species. It is useful in the treatment of septicemia and skin structure infections.