Transrectal Ultrasonography of the Prostate 

Introduction

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

The early application 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 ultrasonic 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 prostate-specific antigen (PSA) screening test and early detection of prostate cancer, the role of transrectal ultrasonography (TRUS) has changed; it is mainly used to visualize the prostate and to aid in guided needle biopsy.

Urologists have incorporated TRUS in their practices; moreover, TRUS is also widely used to deliver treatments such as brachytherapy and to monitor cryotherapy treatment for prostate cancer. 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 prostate biopsy.

For more information, see Prostate Cancer.

Indications

TRUS has both diagnostic and therapeutic indications. Diagnostic indications for TRUS include early diagnosis of CAP. Ultrasonographic findings alone cannot be used to establish or exclude the diagnosis of CAP, however; definitive diagnosis must be based on biopsy results, along with abnormal digital rectal examination findings, elevated PSA levels, or both.

TRUS is also used diagnostically to determine the volume of the prostate gland, in order to plan treatment with brachytherapy, cryotherapy, or minimally invasive BPH therapy (eg, radiofrequency, microwave). 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, müllerian 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

Contraindications to biopsy include an acute painful perianal disorder and hemorrhagic diathesis. Patients should be discouraged from taking aspirin or nonsteroidal anti-inflammatory drugs for 10 days prior to the procedure, but recent use should not be considered an absolute contraindication to biopsy.

Anesthesia

In the past, transrectal ultrasonography (TRUS) was performed without any infiltrative anesthesia. Currently, however, it is a common practice to use lidocaine infiltration in the periprostatic area.

Pareek et al described a technique of periprostatic nerve blockade.^[1] They injected 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). In a randomized, double-blind, placebo-controlled study, they showed significant pain control during and after biopsy.

Alavi et al compared the efficacy of intrarectal lidocaine gel with that of periprostatic nerve block and concluded that the nerve block was superior for pain control.^[2] Using this technique, saturation biopsies, with up to 20 cores, could be performed.

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

In their periprostatic block technique, 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. The needle is slowly withdrawn to the prostatic apex, and an additional 5 mL of lidocaine is injected at the apex.

Equipment

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

Positioning

Positioning for TRUS should be left lateral, lithotomy, or knee-elbow.

Complication Prevention

Gill and Ukimura have reported on the use of TRUS monitoring using Doppler during laparoscopic radical prostatectomy to identify the blood flow in the neurovascular bundles. Identifying and preserving pulsatile blood vessels within neurovascular bundles resulted in superior recovery of erectile activity postoperatively.^[4]

Preprocedural Enema

More than 80% of urologists administer an enema prior to TRUS and prostate biopsy. Some authors feel this is unnecessary, however.

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 1-17 days.

Increasing support has been garnered for a simpler prophylactic regimen in patients with uncomplicated medical conditions. Two doses of a fluoroquinolone, the first given prior to the procedure and the second, 12 hours later is the protocol most commonly recommended. In patients with prosthetic implants or valvular heart disease, additional prophylaxis with 1 g of intramuscular ampicillin (or 1 g intravenous vancomycin in penicillin-allergic patients) and 80 mg of intramuscular gentamicin is recommended.

Overview of 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 superiorly and posteriorly to the seminal vesicles. The ampullae of the vas deferens run medial to the seminal vesicles along the posterior surface of the prostate (see the image below). 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, 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. 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, Batson plexus), which is thought to be 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 of the Prostate

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 angulates 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. The prostate has 4 glandular zones, each with its own ductal system. The peripheral zone, transition zone, and periurethral glands have a similar histologic appearance and are derived from the urogenital sinus. However, the central zone is histologically distinct 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 distal to the verumontanum into the urethra. The stroma is loosely woven with randomly oriented muscle fibers. Approximately 70% of carcinoma of the prostate (CAP) cases arise in this zone. See image below.

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 traverse 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. The central zone is embryologically distinct from other zones and is derived from the mesonephric system (wolffian). 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. The transition zone lies on either side of the proximal prostatic urethra lateral to the internal sphincter. The glandular architecture is similar to the peripheral zone; however, the stroma is more compact. The transition zone is where benign prostatic hyperplasia (BPH) originates, and approximately 20% of CAP cases arise. See image below.

Periurethral glands

The periurethral glands comprise 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.^[5]

Bladder neck and the 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.

Overview

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 on either side of the midline. 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 mid gland 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 to 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. Several formulas have been used, the most common of which is the ellipsoid formula, which requires measurement of 3 prostate dimensions.

Dimensions are first determined in the axial plane by measuring the transverse and anteroposterior dimension at the estimated point of widest transverse dimension. 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

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 general, 18-gauge needles are used, and the tips of the needles are etched with small ridges or pits to render them more echogenic. Sonograms should be superimposed with a ruled puncture trajectory that corresponds to the needle guide of the probe, which allows anticipation of the needle path.

Directed biopsies are obtained from any area deemed as suggestive (ie, hyperechoic) based on ultrasonographic findings or on 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, which improves the odds of sampling clinically inapparent tumors. Originally, these biopsy sites included the midlobe parasagittal plane at the apex, the mid gland, and the base, bilaterally.

Many authors subsequently recommended changes to this protocol. They suggested that these 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 be obtained from each lobe in addition to the original sextant samples. This latter approach is termed the 10-biopsy scheme. Obtaining even larger numbers of biopsy cores has been recommended by some authors to increase the diagnostic sensitivity.

TRUS in the 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 if it could be used for CAP screening. However, lack of specificity made this difficult; CAP lesions may appear hypoechoic, hyperechoic, or isoechoic. Therefore, TRUS is used to direct the physician to suggestive areas in the prostate or to perform systematic biopsies. See image below.

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. Sensitivity of PSAD was enhanced by a cut-off value of 1.5.

BPH tissue produces one tenth of PSA per gram as compared with cancer tissue; therefore, a large BPH gland 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 decide whether to perform biopsy are as follows:

• The expected PSA value for a given prostate volume
• The volume and PSAD of the transition zone
• A PSA value that increases at a velocity greater than 0.75 ng/mL/y

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 decide if 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 and colleagues 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, most information is available on the PSA value and the Gleason score of prostate cancer based on several published nomograms (ie, 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.

TRUS and Brachytherapy

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

To exclude violation of the urethra or bladder, cystoscopic evaluation is necessary at the end of the procedure. Iodine seeds are commonly used; however, palladium seeds are often used to treat more aggressive cancers, usually defined as a Gleason score of higher than 7 and a PSA value above 10 ng/mL.

Alternatively, patients with more aggressive tumors may receive high-dose radiation therapy consisting of external beam radiation therapy during the second and the fourth week, 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 these trocars.

TRUS and Cryotherapy for Prostate Cancer

Gonder and associates were the first to use cryoablation in urological 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, periprostatic tissue, neurovascular pedicles, and 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. Three types of techniques have been used—single and double freeze-thaw cycles and the 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 of greater than 10 ng/mL or tumors at stage T3.^[6]

Ghafar et al reported results on salvage cryotherapy for recurrence after external beam radiation therapy.^[7] Using an argon-based system, 38 men were treated with the double freeze-thaw technique. The biochemical recurrence-free survival rate was 86% at 1 year and 74% at 2 years. Complications included rectal pain in 39.5%, urinary tract infection in 2.6%, incontinence in 7.9%, hematuria in 7.9%, and scrotal edema in 10%. No patients developed rectourethral fistula, urethral sloughing, or retention.

Possible future applications involving TRUS include the following:

• Color Doppler scanning
• Contrast-enhanced prostate biopsy
• Intermittent and harmonic ultrasonography
• High-intensity focused ultrasound

Color Doppler scanning

Color Doppler 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:

• EchoGen
• Levovist
• Imavist
• Echovist
• DMP 115
• NC100-100

Several investigators have evaluated contrast-enhanced prostate ultrasonography. Ragde and colleagues used EchoGen to study 15 patients with rising PSA levels and previous negative biopsy findings, and found that only 2 of the 8 patients with abnormal vascular patterns were diagnosed with cancer.^[8]

Similarly, Watanabe and colleagues studied 9 cases in which Levovist was used and demonstrated enhanced images of all cancers.^[9] Halpern and colleagues evaluated 26 patients with elevated PSA levels and found significant image enhancement after using Imavist.^[10] However, the extra cost of this technique may be the limiting factor in its widespread use.

Intermittent and harmonic ultrasonography

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

Using extracorporeal high-intensity focused ultrasound (HIFU), temperatures of greater 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 transducers with 3-4 MHz. 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.^[11] Currently, the procedure is used in Europe to treat localized prostate cancer and is used under anesthesia; patients are placed in a decubitus position. Rectal cooling is used to avoid 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 (as opposed to focal therapy).

Following 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.^[12] 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 one 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.^[12] 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.^[11]

Gelet et al have also reported salvage HIFU after failed radiation in 71 patients. Among these patients, biopsy results were negative in 80%, and 61% had a PSA level nadir of less than 0.5 ng/mL. The complications following salvage HIFU were higher; 6% developed total incontinence, 6% developed rectourethral fistula, and 17% developed vesical neck contracture.^[13]

Complications

Complications of prostate biopsy include hematuria, rectal bleeding, hematospermia, urosepsis, and perineal pain. 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%), patients develop bacteremia that requires hospitalization and administration of intravenous antibiotics.