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The Use of Transrectal Prostatic Ultrasonography in the Evaluation of Patients with Prostatic Carcinoma
0022-504 '7 /89/14:l2-023:3SC2 .00/0 'JoL 141, February
THS JOURNAL Ot'' U:tOLOGY
Copyright (() 1989 by ':'he \1'filhams
Vlilkir1s Co.
Printed in U.S.A.
State of the A THE USE OF TRANSRECTAL PROSTATIC ULTRASONOGRAPHY IN THE EVALUATION OF PATIENTS WITH PROSTATIC CARCINOMA ROBERT L. WATERHOUSE
AND
MARTIN L RESNICK~
From the Division of Urology, Case Western Reserve University, School of Medicine, Cleveland, Ohio
This year adenocarcinoma of the prostate gland will likely be the second most common malignancy diagnosed in American men older than 50 years. Estimates for 1988 suggested that approximately 99,000 new cases of prostate cancer were diagnosed and that about 28,000 men died of the disease. 1 • 2 It is well recognized that the clinical course of a patient with prostate cancer is unpredictable but many tumors will follow a gradually progressive pattern.3-4 Initially, it is believed that prostatic carcinomas often are well differentiated and slow growing but as the tumor enlarges it becomes more poorly differentiated and more invasive. It is likely that men diagnosed with the disease when they are 70 to 80 years old may have possessed the malignancy in an undetected stage at 40 to 50 years and postmortem studies have estimated that the prevalence of the disease in American men more than 50 years old is 30 per cent. 5 As in the approach to other malignancies, the clinical stage at presentation usually determines the most appropriate mode of treatment. With increased awareness of the clinical significance of prostate cancer and the advances made in surgical treatment, there is renewed clinical interest in attempting to identify patients with surgically curable disease. Most patients are not diagnosed as having the disease until a digital rectal examination reveals a prostatic nodule. The examination most frequently is performed as part of the annual physical or results from an evaluation of patient complaints of voiding dysfunction or bony pain. Others with unsuspected malignancy are diagnosed incidentally when they undergo simple prostatectomy (transurethral resection or open procedure) for presumed benign hyperplasia, and cancer is found on histological examination of the removed tissue. Imaging studies, such as computerized tomog· raphy and nuclear magnetic resonance imaging, have been disappointing in identifying these early malignancies and the need for improved techniques is evident." Recently, many clinicians are advocating transrectal prostatic ultrasound as an aid in not only early detection but staging and post-treatment evaluation as well. These aspects of this technique will be reviewed but before commenting on these roles it will be helpful to review the history and background of ultrasound of the prostate gland. HISTORY
Dussik in Austria performed the first medical application of ultrasound when he used transducers in an attempt to locate brain tumors in the early 1940s. 7 In 1949 Wild and Neal began their early investigation in ultrasonography and later reported on its value in the detection of differences between normal and diseased tissue by using an A-mode display. 8 Wild and Reid reported 2-dimensional scans in 1952 that included a breast carcinoma, normal kidney and normal muscle. 9 They noted that malignant tissue reflected more sound than normal tissue, * Requests for reprints: Division of Urology, University Hospitals of Cleveland, 2065 Adelbert Rd., Cleveland, Ohio 44106.
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and that tissue of nonmalignant tumors reflected less sound than normal tissue. These same investigators attempted transrectal studies of the prostate during this time but the scans were so poor that the results were not reported. In 1963 Japanese urologists reported disappointing results with the use of A-mode scans to view the prostate. They observed that while A-mode scans can be informative, time-amplitude echograms of the pelvic organs with their thousands of interfaces are too complex for reliable interpretation. It was not until 1964 that Takahashi and Ouchi used a transrectal probe equipped with a radial scanning device to obtain the first tomographic pictures of the prostate. 10 Unfortunately, these early pictures were of poor quality and were considered to be of no clinical value. Watanabe and associates obtained the first clinically useful transrectal sonograms of the prostate in 1967. 11 - 13 B-mode instrumentation was used and prostatic images were displayed on a black and white screen. The transducer was covered with a water-filled balloon and the examinations were performed with patients in the sitting position. The bladder was filled with water via a urethral catheter to aid in demonstration of the prostate, seminal vesicles and other pelvic organs. They studied a large number of patients with various types of prostatic abnormalities and demonstrated consistent, reproducible images. In 1973 King and associates first reported on the use of prostate echography in the United States and they used similar equipment as their Japanese counterparts. 14 Later, investigators from the same laboratory reported on using gray scale imaging associated with transrectal ultrasonography. 15 Further studies followed with the development of improved gray scale instrumentation, higher frequency transducers and real-time imaging so that enhanced visualization of the prostate was achieved. In addition, transabdominal, perineal and transurethral ultrasonic techniques were studied to improve visualization of the prostate gland but most investigators concluded that the most consistent, reproducible prostate images were obtained with transrectal techniques. 16 · 17 INSTRUMENTATION AND TECHNIQUE
The term ultrasound refers to sound waves that are propagated in a material element with a frequency greater than that of audible sound (20,000 cycles per second, or 20 KHz.). For medical purposes sound waves with frequencies of 1 to 10 million cycles per second (1 to 10 MHz.) are applicable. The production of ultrasound is based on the piezoelectric principle in that an electric potential applied across certain crystals results in vibration that produces sound waves, and that sound waves directed against the crystal produce an electric potential. Ultrasound transducers that are composed of piezoelectric crystal elements, therefore, function as transmitters and receivers of sound waves. 18 • ' 9 Ultrasound is transmitted in short bursts lasting 10 msec. and for the majority of the time the transducer is in the "listening" mode. The thickness of the crystal element determines the frequency of the sound waves and the higher
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the wavelength the lower the degree of tissue penetration but the greater the resolution. Early prostate images were obtained with a 3.5 MHz. transducer but recently 7.0 MHz. transducers have been used. The propagated sound is focused with an acoustical lens that produces a narrow beam of only a few millimeters in diameter. 20 Ultrasound does not pose any risk of radiation or electromagnetic field but it does deliver a negligible amount of mechanical energy to the tissues through which it passes. No detrimental effects of this energy have been demonstrated. The transducer and its mechanism of action (mechanicalsector and radial; array-linear and phased) are another important component of the instrumentation. Most current transrectal radial ultrasonic probes consist of a freely moving inner assembly and a stationary outer assembly. The outer unit has inflow and outflow ports for the fluid that acts as a coupling medium between the transducer and rectal wall. Some sound waves are reflected at the interface between the fluid-filled condom and the rectal wall but the impedance difference between the 2 mediums is minimized when there is a good, tight seal. 20 The transducer in the radial scanner rotates 360 degrees and propagates sound waves perpendicular to the long axis of the transrectal probe. Within the human body and with respect to the prostate gland, the sound waves are directed perpendicular to the long axis of the body and prostate. This direction is called transaxial or axial and it is similar to the transverse plane of a computerized tomography scan. Newer array and mechanical sector scanners have eliminated the need for the rectal balloon and the probe is placed in direct contact with the rectal wall. A decided advantage of these instruments is that transrectal prostate biopsies or aspirations can be performed with ultrasonic guidance. In the linear array scanner many small transducers are aligned side by side much like the teeth of a comb, and when the scanner is oriented parallel to the long axis of the body the sonographic images obtained are in the longitudinal or sagittal plane. 21 Mechanical sector and phased array scanners can provide images in either plane and new bimodal probes incorporate both transducers in 1 unit. Transverse images yield more information about the lateral margins and symmetry of the prostate, while longitudinal images show the apex and base of the gland more clearly (fig. 1). The transverse image may seem easier to understand than the longitudinal image to the neophyte in sonography. 22 However, the linear array longitudinal orientation appears to be more ideal for ultrasonic guidance of prostate biopsy even though the technique was demonstrated first with radial scanners. 23·24 Some investigators believe that using axial and longitudinal projections provides increased sensitivity in examination of the prostate and probes having both capabilities have been developed.22,2s In addition to the transducer and scanner, the imaging screen and mode of display are essential components of the examina-
tion. As mentioned previously, early equipment used A-mode (amplitude mode) displays that appear as waves on an oscilloscope with the X axis as the distance from the transducer and the Y axis as the amplitude of the returned sound wave. Later, the B-mode (brightness mode) was developed, which displayed a composite 2-dimensional image of the examined area. Current technology uses gray-scale imaging, which varies the brightness of the dots in proportion to the intensity of the returned sound wave amplitude. In addition, instead of providing static images, real-time gray-scale imaging constantly scans the tissue and continually updates the images. 20 ·26 Real-time scanning can provide dynamic studies of the bladder, bladder neck and urethra during voiding and it may yet prove to be a valuable diagnostic tool in patients with voiding dysfunction. 27 Finally, it is important to emphasize that a hard copy image should be obtained when an ultrasound examination is performed. These can be obtained with photographic or x-ray film, digital printers or video tape. 13 ' 26 Technically, transrectal ultrasonography is minimally invasive and easy to perform. The entire examination takes 15 to 20 minutes, and can be performed in the office and on an outpatient basis without the need for anesthesia. Before starting the study a rectal examination is performed to exclude the presence of anal or rectal abnormalities that may contraindicate transrectal probe insertion. The prostate should be examined digitally at this time and the findings recorded. The probe then is inserted approximately 8 to 9 cm. above the anal verge and serial sonographs are obtained. Depending on the type of probe used the rubber condom then is inflated and the transducer is placed in direct contact with the rectal wall. It is important to perform the study systematically. If transverse images are obtained typically sonograms are obtained at 5 mm. increments beginning at the bladder and seminal vesicles and progressing towards the apex. If a longitudinal scanner is used images are obtained at 5 degree increments right and left of center. All images should be appropriately marked and hard copies obtained so that they may be referred to at a later date. IMAGE CHARACTERISTICS
The normal prostate and benign prostatic hyperplasia. The normal prostate as viewed on a transrectal radial ultrasonogram appears as a symmetrical, triangular, ellipsoid structure that is delineated circumferentially by a continuous prostatic capsule. The capsule usually is well defined, highly echogenic and free of distortion. The anteroposterior diameter appears shorter than the transverse diameter, since the posterior portion of the prostate becomes concave due to distortion produced by the inflated balloon or compression by the probe during the examination. The internal sonographic structure of the prostate is composed of multiple fine, diffuse, homogeneous echoes that probably represent acoustic interfaces created by the numerous glands that are present. 13·28
FIG. 1. A, transverse image demonstrates capsular symmetry and normal prostatic architecture (7.0 MHz.). Arrows designate prostate capsule. B, longitudinal image shows visualization of apex and base. Note presence of urethral catheter and catheter balloon, and round or ovoid appearance of gland when viewed in midline (7.0 MHz.).
Based on prior anatomical studies the p:rostate can be divided into 3 distinct ;;w,uu,cu,u regions: the peripheral, transition and central zones. Tissue of the peripheral zone comprises about 70 to 75 per cent of the prostatic volume and occupies the posterior, lateral and apical aspects of the gland. This area is homogeneous and is the primary region where adenocarcinoma of the prostate is believed to originate.'30 Recent data from McNeil and associates indicate that malignancies can arise in the transition and central zones, and these malignancies comprise the majority of stage A tumors diagnosed after transurethral prostatectomy. 01 Recent evidence currently indicates that approximately 30 per cent of all malignancies arise in these zones and are not associated with the peripheral zone"'' The central zone occupies 20 per cent of the glandular volume of the prostate and is associated with few disease processes. Benign prostatic hyperplasia originates from the transition zone, and with advancing patient age increases in size and compresses the peripheral zone."" 29 · 10 Before the onset of benign hyperplasia this zone occupies only 5 per cent of the glandular volume but with progressive growth it can occupy as much as 95 per cent of the total prostatic tissue. By moving the transrectal axial probe in a cephalad-caudal direction the entire prostate gland can be visualized. The apex, mid section and base can be delineated but it may be difficult to differentiate between the base of the gland and the bladder neck, especially if a prominent median lobe is present. Also, in this region the seminal vesicles are typically visualized as symmetrically paired structures, which are seen better as is the base of the prostate when the bladder is filled partially. The seminal vesicles may vary somewhat in shape but they can usually be imaged clearly. These structures are slightly less
Fm" 2. Typical appearance of benign prostatic hyperplasia (7.0 MHzo).
echoic than the prostate gland. The seminal vesicles extend cephalad and at the base of the bladder they continue laterally, tending to parallel the distended rectal wall. 1 " In the young male patient the gland assumes a triangular shape but with development of benign prostatic hyperplasia the gland increases in size typically in the anteroposterior dimension to a greater degree than the transverse dimension. Due to growth in all directions it should be emphasized that the anteroposterior diameter rarely exceeds the transverse diameter. The capsule often thickens but it remains uniform and continuous. The gland maintains a symmetrical appearance and tends to have a uniform, homogeneous echo pattern. Not infrequently, areas of high and low echogenicity are observed (fig. 2). The linear array scanner images the prostate in the longitudinal plane parallel to the long axis of the body as described previously. Other types of scanners also can provide images in this plane. The acoustic characteristics of the prostate gland are similar to those seen with the radial scanner but in this plane the prostate appears round or ovoid in the midline. When examining the lateral margins of the gland the round capsule of the prostate is defined further. At the mid portion of the prostate the pubic symphysis and space of Retzius, with its fat and venous tissue, usually are well delineated. The apex of the prostate is well outlined as in the base and bladder. The seminal vesicles appear as having reduced echogenicity and their relationship to the posterior wall of the bladder is especially well defined. 11 Often, a typical beak is demonstrated at which point the ducts of the seminal vesicles and vasa deferentia enter the base of the prostate. As with its appearance in the transverse scan the hyperplastic prostate assumes a more circular appearance and enlarges in a uniform manner. Similar echo patterns are observed in the longitudinal as in the transverse plane. Carcinoma of the prostate. Unlike the usual homogeneous sonographic appearance of the normal prostate, the ultrasonic characteristics of carcinoma of the prostate are varied. Cancer originates and commonly is seen in the peripheral zone of the prostate but it can be found in the anterior portion of the gland as well. 31 ''32 Early studies with B-mode and initial gray-scale imaging reported that prostatic carcinomas appeared as echo dense or hyperechoic areas. 12- 15 • 28 ' 03 With improvement in instrumentation and the use of higher frequency transducers, the appearance of tumors changed. Some investigators began to demonstrate that prostatic malignancies, particularly when they are small and localized, appear as hypoechoic areas but others demonstrated that tumors can be hyperechoic, hypoechoic, isoechoic or of mixed echogenicity (fig. 3). 25 • 30, 34 • 35 As a explanation of these differing appearances, it can be theorized that earlier equipment detected cancer at a later or more advanced stage. Newer high resolution equipment visualizes a prostate tumor as an echopenic focus before it invades other tissue and obtains a more echogenic appearance" Often associated with tumor growth and invasion is a desmoplastic
FIG. 3. A, localized carcinoma demonstrates typical hypoechoic appearance (arrows, 7.0 MHz.). B, advanced carcinoma demonstrates mixed echo pattern (arrows, 7.0 MHz.)"
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reaction and those changes certainly may contribute to the mixed pattern observed with advanced tumors. Experience indicates that early cancers tend to be of lower echogenicity. If the presence of collagen in the stroma of prostatic tissue determines its echogenicity, then prostate cancer may appear hypoechoic because the stroma is replaced by infiltrating glandular tumor elements. 36 Other considerations include the fact that large prostate cancers can replace all of the normally isoechoic peripheral zone, thereby obliterating any ultrasound reference for normal tissues to contrast with the hypoechogenicity of prostate cancer, and the inherent inaccuracies of biopsy localization in determining the nature of an ultrasonographic area. Unfortunately, many structures and benign processes within the prostate can have ultrasonic characteristics similar to the hypoechoic appearance of small prostate malignancies, including small nodules of hyperplasia, cysts, infarcts, inflammatory processes, cystic atrophy, blood vessels and muscle tissue. Greater echogenicity also is likely secondary to the development of increased tissue interfaces that occur as the tumor grows and invades other areas of the prostate and surrounding tissues, and the presence of calcification. Hyperechoic areas of prostate cancer are often subtle and differ from the hyperechoic images of prostate calculi, which are brighter and usually associated with acoustic shadowing.5 ' 32 It also must be remembered that many carcinomas are isoechoic and cannot be imaged with this technique. Additionally, anterior tumors often cannot be distinguished reliably from the normal hypogenie appearance of this region of the gland. Another important consideration in the ultrasound examination of patients with prostate cancer is the appearance of the prostatic capsule and seminal vesicles. In patients with confined carcinoma of the prostate the capsule usually is well delineated circumferentially and free of distortion or disruption. Occasionally, there may be acoustic shadowing of the capsule adjacent to tumor areas. More obvious deformity is associated with invasive disease as it causes loss of the symmetric, continuous, hyperechoic pattern of the prostate capsule (fig. 4). Deformity of the capsule may appear as subtle irregularities or more distinct capsular echoes. With extension of cancer into the seminal vesicles the ultrasonic image becomes distorted with dense echoes continuous with sonographic abnormalities of the tumor within the prostate gland. More invasive prostate cancer may completely obliterate the seminal vesicle sonographic image (fig. 5). 13 It is important to emphasize that microscopic capsular invasion into the periprostatic fat and microscopic invasion of the seminal vesicles cannot be detected by transrectal ultrasound. In summary, there is no single pathognomonic appearance
FIG. 4. Radial scan shows distortion of prostatic capsule (arrows) associated with invasive carcinoma (7.0 MHz.).
FIG. 5. Radial scan demonstrates obliteration of seminal vesicle (arrows) due to invasive carcinoma (4.5 MHz.).
of prostate cancer when viewed sonographically. However, there are criteria that are suggestive of malignancy as demonstrated by Rifkin and associates on 443 pathologically confirmed transrectal sonographic examinations. 34 Smaller cancers are more hypoechoic than larger ones but few larger tumors are purely hypoechoic. Malignanices usually are irregularly marginated and prostatic capsule distortion is a sign of invasive cancer. Although carcinoma originates in the peripheral zone of the prostate the tumor may grow to invade the central and transition zones, thus, the location of an abnormal area is helpful but not diagnostic of its etiology. As noted previously tumors can arise de novo in these latter 2 zones. 31 Approximately, 30 per cent of all malignancies originate anteriorly. Additionally, it is important to emphasize that not all prostatic carcinomas can be detected with ultrasonography. Patients with normal prostate ultrasound examinations have undergone prostatectomy for benign disease and been found to have occult carcinoma on histological review of the specimen.37' 38 CLINICAL IMPLICATIONS
Screening. Probably the most controversial area related to the use of transrectal ultrasonography is its application as a screening or early detection study for early prostate cancer. Thompson illustrated several criteria that must be met before screening is advocated for a disease. 39 The disease should have a high prevalence within the population tested. With prostate cancer the prevalence is significant but the yield may be increased by defining the population at risk as men more than 50 years old. Similarly, the upper age limits of the population to be screened must be defined because presumably further evaluation and treatment will be initiated in patients having a positive study. The biological behavior of the disease must be understood. The problem with prostate tumor biology is that not all cancers progress to invasive and metastatic disease. To date it is not known how to differentiate the indolent behaving prostatic carcinoma from the aggressive one. 40 • 41 However, some aspects of prostate cancer biology are understood. As mentioned previously, as most prostatic cancers enlarge they become less differentiated and more invasive, and there are data indicating that tumors less than 1 cm. large do not possess the potential to metastasize. 3 Therefore, ideally, successful screening should allow for identification of prostatic cancers less than 1 cm. in diameter. Finally, to gain benefit from diagnosing early disease there must be a method of treatment for that diagnosis. Prostate cancer can be treated and in many instances cured in the early stages with appropriate intervention. Therefore, prostate cancer fulfills these 3 criteria as a disease in which screening may be appropriate; however, before screening can be initiated
TRANSRECTAL PROSTATIC ULTRASONOGRAPHY IN PATIENTS WITH PROSTATIC CARCINOMA
it must be demonstrated that patients will benefit from such an endeavor. Before initiating a screening program the test used also should fulfill certain criteria. The test should be rapid, inexpensive, noninvasive and well accepted by patients. A cost versus benefit analysis has not been done for prostate cancer detection by transrectal ultrasound and reports of the cost of the study have varied from $50 to $400. Transrectal ultrasound is tolerated well and minimally invasive but the study is of considerably greater duration than a digital rectal examination. The test also should have high sensitivity, specificity, and positive and negative predictive values. These criteria are primarily the ones responsible for the debate over whether transrectal ultrasound is a worthwhile screening study to detect early prostate cancer. To date, with analysis of available technology and data by several investigators the use of transrectal ultrasound in such a screening capacity is not supported. Watanabe and associates reported the only large study using transrectal ultrasound as a screening modality in asymptomatic, nonselected men but they did not report specificity data.4 2 Unfortunately, transrectal ultrasonic detection of prostate cancer has a low sensitivity and specificity with regard to the values necessary for screening purposes. Sensitivity rates for transrectal sonographic diagnosis of prostatic carcinoma range from 71 to 92 per cent by various investigators 23 , 43 - 47 and for detection of subclinical disease sensitivity values of 60 to 85 per cent have been reported. 33 • 44 ' 48 Furthermore, in retrospective reviews of prostate glands removed as treatment for histologically proved cancer 24 to 30 per cent of the cases had ultrasonic patterns that were uniform, isoechoic and not suggestive of cancer. 31 ·'15 Specificity data have a more detrimental effect on the positive predictive value of ultrasound, with specificity rates ranging from 41 to 79 per cent.4 4 - 47 Experience indicates that false positive rates are high because ultrasound cannot always reliably differentiate benign conditions (benign prostatic hyperplasia, prostatic cysts, prostatic calculi, prostatic infarcts and prostatitis) and normal tissue structures (blood vessels and muscle) from cancer. 28·'31 • 34 ·'37 There may be a 30 per cent overlap between benign and malignant lesions that have similar acoustic appearances.4 9 Statistical analyses also reveal that the positive predictive value of transrectal sonography is not significantly greater than that for digital rectal examination of the prostate.4 5 • 47 .,so,si Because the digital examination is inexpensive and easy to perform, there appears to be little to gain screening with ultrasound. Many patients without prostatic carcinoma but with positive sonograms would be subjected to further invasive studies and expense that would unnecessarily create patient and family anxiety. Whether transrectal ultrasound will have any role in the evaluation of an asymptomatic population with palpably benign glands is unknown to date. Possibly, when combined with other studies (for example prostatic specific antigen) or when used selectively in certain high risk populations based on age, race or symptoms the study may be of value. As with mammography in the evaluation of women for detection of breast carcinoma this new technology must be evaluated further. Several large cooperative trials have either been initiated or are being planned and the results of such investigations will be forthcoming. Therefore, the routine use of this study is premature and presently cannot be recommended. Staging. Despite its unproved role as a screening tool for prostate cancer, transrectal ultrasonography has useful applications in the evaluation of patients diagnosed as having this disease. Ultrasound is sensitive in assessing prostatic size and unrecognized invasive disease. Early reports showed that the stage ofprostatic carcinoma as determined by transrectal ultrasonography corresponded with the stage diagnosed pathologically on radical prostatectomy specimens. s:i In a study by Pontes and associates a sensitivity of 89 and 100 per cent was demonstrated for preoperative ultrasonic detection of capsular
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and seminal vesicle involvement, respectively."" The of detecting capsular penetration and seminal vesicle involvement was only 50 and 28 per cent, respectively, due to the inability of the study to detect microscopic disease. Fujino and Scardino reported the ability of ultrasound to detect invasive disease in 8 of 18 patients who had no extension of the disease by rectal examination.'" 3 As emphasized, transrectal ultrasound is not as accurate for determining microscopic invasion. 54 There also does not appear to be any definite correlation between histological grade and ultrasonic pattern other than the fact that small tumors that tend to be well differentiated often appear hypoechoic and larger, higher grade tumors tend to have a mixed pattern. Monitoring response to treatment. Transrectal ultrasonography is useful to document prostate gland volume and it is accurate within 5 per cent to determine true prostatic weight. 15, 5 "," 6 This ability allows ultrasound to provide information regarding the response of the tumor to therapy. It must be emphasized that these determinations are of total gland volume and not tumor volume. No reported study to date has correlated the volume of tumor as determined by ultrasound with the true volume as determined by pathological examination. Prostate sonography has documented reduction in prostatic size after administration of endocrine therapy as treatment for disseminated cancer. Within 3 to 6 months after either orchiectomy or estrogen therapy a sonographically detectable 20 to 30 per cent decrease in prostatic volume occurs. 33' 57 Changes with estrogen therapy are slightly slower to occur than those with surgical castration. Individuals who have progressive disease within 1 year after castration have been shown to have a significantly smaller decrease in prostate size than those with a sustained clinical response. Carpentier and associates found that in patients whose prostatic volume decreased to at least 50 per cent of the pretreatment volume after 3 months none had progression of the malignancy. 57 The clinical value of this application of prostate ultrasound may be of even greater importance when effective treatment becomes available for hormone-unresponsive prostatic carcinoma. Further usefulness of ultrasound has been demonstrated in evaluation of prostatic cancer patients treated with radiotherapy and chemotherapy. Pontes and associates showed that 10 of 14 patients treated with a National Prostatic Cancer Project Protocol had a decrease in the sonographic volume of the prostate. 58 Fujino and Scardino concurred with these results and reported that a maximal reduction in size of the prostate usually occurred by 9 months after radiotherapy and 3 months after chemotherapy. 58 As a response to therapy in addition to a decrease in size, the prostate resumed a more normal symmetrical shape, the capsule reformed and thickened, the degree of extracapsular extension diminished and the seminal vesicles became normal in appearance. These investigators illustrated a substantial 20 per cent decrease in the volume of the prostate in all 19 patients treated with definitive radiotherapy for stages B, C and D prostatic carcinoma. 59 Furthermore, prostatic size decreased significantly more slowly and to a lesser extent in patients who had disease progression during followup. Accordingly, prostate ultrasound may become useful to identify patients who will not have maximal responses to radiotherapy alone so that other therapy may be instituted more promptly. Although systemic progression of prostate cancer after hormonal therapy or radiotherapy usually is not manifested by an increase in prostatic size, the tumor does recur locally after radical prostatectomy. Local tumor recurrence often is around the bladder neck in an area inaccessible to the examining finger. Prostatic ultrasound is useful to detect recurrence during followup of these patients. 33 • 60 • 61 Ultrasound guided biopsy and interstitial radiation therapy. Transrectal prostatic ultrasonography is useful as an aid in the placement of a biopsy needle within a specific suspicious area of the prostate. 23 • 62 A special needle guide attachment can be
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mounted directly on the transrectal probe and biopsies can be performed via the perinea! or transrectal route. Patients have been reported in whom ultrasound guidance led to a prostate needle biopsy diagnosis of cancer, whereas digitally directed biopsies were benign. 24 Currently, there is debate concerning the superiority of this technique over digitally directed biopsies in patients with palpable abnormalities. Some believe that all prostate biopsies should be performed under ultrasound guidance, and others believe the digitally directed approach should be used first. In a study of 15 patients with biopsy proved adenocarcinoma of the prostate, only 9 were diagnosed correctly using conventional digitally directed perineal biopsy, while all 15 were diagnosed accurately with the ultrasound directed method. 63 All patients had palpable abnormalities but it was unclear from the report as to the correlation of the palpable abnormality and the site of the positive biopsy. In another study of patients with prostatic nodules dissimilar results were obtained. 64 In 11 patients cancer was detected by both techniques, while of the remaining 3 patients 2 were positive only by digitally directed perineal biopsy and 1 was positive only with the ultrasound directed method. The conclusion from this last study was that ultrasound guided biopsy is not needed routinely when a distinct nodule is palpable. Transrectal ultrasonically guided biopsies also are becoming increasingly popular, and new aspiration and core biopsy needles with spring loaded "guns" continue to be developed. 65 Problems exist because not all tumors can be visualized ultrasonically and more studies are required to correlate the area of the ultrasound biopsy with the physical findings. Some believe that because of the ease of the study transrectal aspiration may become the method of choice in the evaluation of patients with palpable abnormalities. 66 • 67 However, ultrasound guided biopsies do have a role in the evaluation of patients with or suspected to have prostate cancer. Repeat ultrasound guided biopsy after a negative digitally directed biopsy appears to be worthwhile in patients with suspicious palpable abnormalities. In patients with nonpalpable but suspected prostate malignancy ultrasound directed biopsy of sonographically suspicious areas may establish the diagnosis. Additionally, the technique has a role in the evaluation of patients treated with definitive radiotherapy who have no palpable abnormalities but suspicious ultrasonic findings. Ultrasound also can be used to direct radioactive seed implantation into the prostate when using this treatment modality. 68 A puncture attachment can be applied to the transrectal ultrasound probe and the radioactive seeds placed under ultrasound guidance. Permanent implantation of radioactive seeds offers some advantages to external beam irradiation. The dose is adapted accurately to tumor size and shape, and a higher minimum tumor dose can be obtained with less damage to normal tissue due to the protracted irradiation from the longlived isotope. Additionally, the implantation technique is less time-consuming for the patient and staff than a full course of external beam therapy. Ultrasound guidance with placement of the seeds eliminates the disadvantages of an operation, which is used most often for seed placement, but more importantly it permits a more satisfactory distribution of the seeds than is obtained with the freehand technique. Additionally, a higher concentration of seeds can be placed in and around the area of malignancy. The disadvantage of the technique is that extracapsular tumors with ill-defined margins may not be irradiated adequately and that regional lymphatics are not treated appropriately. Therefore, more experience and followup are needed before this method gains wide acceptance. SUMMARY
Transrectal ultrasonography is a relatively new diagnostic technique that has received much of the same enthusiasm that often is associated with the introduction of other new diagnostic
or therapeutic instruments. The study allows for imaging of the prostate but benign conditions often cannot be differentiated reliably from malignant ones. The technique has clinical application in staging, monitoring tumor response to therapy and assisting in biopsy. Its role as a screening study when used either alone or in combination with other diagnostic tests has yet to be determined and well controlled, carefully performed investigations with state of the art instruments probably will help to establish the role of this examination when used for this purpose. REFERENCES
1. Spirnak, J.P. and Resnick, M. I.: Prostatic ultrasonography. Urology Grand Rounds. Chicago: Sieber & McIntyre, Inc., No. 18, 1987. 2. Silverberg, E. and Lubera, J.: Cancer statistics, 1988. CA, 38: 5, 1988. 3. McNeal, J.E., Bostwick, D. G., Kindrachuk, R. A., Redwine, E. A., Freiha, F. S. and Stamey, T. A.: Patterns of progression in prostate cancer. Lancet, 1: 60, 1986. 4. Whitmore, W. F., Jr.: The natural history of prostatic cancer. Cancer, 32: 1104, 1973. 5. Stamey, T. A.: Personal communication. 6. Catalona, W. J. and Stein, A. J.: Staging errors in clinically localized prostatic cancer. J. Urol., 127: 452, 1982. 7. Martin, J. F.: History of ultrasound. In: Ultrasound in Urology, 2nd ed. Edited by M. I. Resnick and R. C. Sanders. Baltimore: The Williams & Wilkins Co., chapt. 1, pp. 1-12, 1984. 8. Wild, J. J. and Neal, D.: Use of high-frequency ultrasonic waves for detecting changes in texture in living tissues. Lancet, 1: 655, 1951. 9. Wild, J. J. and Reid, J.M.: Application of echo-ranging techniques to the determination of structure of biological tissues. Science, 115: 226, 1952. 10. Takahashi, H. and Ouchi, T.: The ultrasonic diagnosis in the field of urology. Proceedings of the 4th Meeting of the Japanese Society of Ultrasonics in Medicine. Tokyo: Osaka, No. 2, pp. 3537, 1964. 11. Resnick, M. I.: Transrectal ultrasonography of the prostate. In: Urology Annual 1988. Edited by J. N. Rous. East Norwalk, Connecticut: Appleton & Lange, p. 59, 1988. 12. Watanabe, H., Kato, H., Kato, T. and Terasawa, Y.: Diagnostic application of the ultrasonotomography to the prostate. J ap. J. Urol., 59: 273, 1968. 13. Spirnak, J. P. and Resnick, M. I.: Ultrasound and the evaluation of the prostate. In: New Techniques in Urology. Edited by R. W. deVere White and J.M. Palmer. Mt. Kisco, New York: Futura Publishing Co., chapt. 16, pp. 251-268, 1984. 14. King, W. W., Wilkiemeyer, R. M., Boyce, W. H. and McKinney, W. M.: Current status of prostatic echography. J.A.M.A., 226: 444, 1973. 15. Boyce, W. H., McKinney, W. M., Resnick, M. I. and Willard, J. W.: Ultrasonography as an aid in the diagnosis and management of surgical disease of the pelvis: special emphasis on the genitourinary system. Ann. Surg., 184: 477, 1976. 16. Henneberry, M., Carter, M. F. and Neiman, H. L.: Estimation of prostatic size by suprapubic ultrasonography. J. Urol., 121: 615, 1979. 17. Holm, H. H. and Northeved, A.: A transurethral ultrasonic scanner. J. Urol., 111: 238, 1974. 18. Carlsen, E. N.: Ultrasound physics for the physician: a brief review. J. Clin. Ultrasound, 3: 69, 1975. 19. Brandt, B.: Physical principles. In: Ultrasound in Urology. Edited by S. Koury. Reims, France: The Fondation Internationale pour !'Information Scientifique, chapt. 1, pp. 13-27, 1985. 20. Spirnak, J. P. and Resnick, M. I.: Ultrasound. In: Adult and Pediatric Urology. Edited by J. Y. Gillenwater, J. H. Grayhack, S.S. Howards and J. W, Duckett. Chicago: Year Book Medical Publishers, Inc., vol. 1, chapt. 3D, pp. 150-168, 1987. 21. Dahnert, W.: Ultrasound of the prostate: equipment. Read at Ultrasonography in Urology meeting, San Diego, California, September 18-20, 1987. 22. Rifkin, M. D.: Transrectal prostatic ultrasonography: comparison of linear array and radial scanners. J. Ultrasound Med., 4: 1, 1985. 23. Holm, H. H. and Gammelgaard, J.: Ultrasonically guided precise needle placement in the prostate and the seminal vesicles. J.
TRANSRECT\4.L PR.OS'I'ATIC ULTRASOI\!OGRAPHY IN PArfIEI~r-_f'S \,;/ITH PROSTATIC CARCI1~01\!A Urol., 125: 385, 1981. 24, Rifkin, M, D,, Kurtz, A, R and Goldberg, R R: Prostate biopsy utilizing transrectal ultrasound guidance: diagnosis of nonpalpable cancers, J, Ultrasound Med,, 2: 165, 1983, 25, Lee, F,, Gray, J, M,, McLeary, R, D,, Meadows, T, R, Kumasaka, G, H,, Borkaza, G, S,, Straub, W, H,, Lee, F,, Jr,, Solomon, M, H,, McHugh, T, A, and Wolf, RM,: Transrectal ultrasound in the diagnosis of prostate cancer: location, echogenicity, histopathology, and staging, Prostate, 7: 117, 1985, 26, Angell, A, H, and Resnick, M, L: Office-based ultrasound for urologists, AUA Update Series, voL 5, lesson 33, 1986, 27, Shapeero, L, G,, Friedland, G, W, and Perkash, L: Transrectal sonographic voiding cystourethrography: studies in neuromuscular bladder dysfunction, Amer, J, Roentgen,, 141: 83, 1983, 28, Resnick, M, L, Willard, J, W, and Boyce, W, H,: Recent progress in ultrasonography of the bladder and prostate, J, UroL, 117: 444, 1977, 29, McNeal, J, K: The prostate gland: morphology and pathobiology, Monogr, UroL, 4: 1, 1983, 30, Lee, F,, Gray, J, M,, McLeary, R D,, Lee, F,, Jr,, McHugh, T, A, Solomon, M, H,, Kumasaka, G, H,, Staub, W, H,, Borlaza, G, S, and Murphy, G, P,: Prostatic evaluation by transrectal sonography: criteria for diagnosis of early carcinoma, Radiology, 158: 92, 1986, 3L McNeal, J, K, Price, H, M,, Redwine, K A,, Freiha, F, S, and Stamey, T, A,: Stage A versus stage B adenocarcinoma of the prostate: morphological comparison and biological significance, J, UroL, 139: 61, 1988, 32, Salo, J, 0,, Rannikko, S,, Makinen, J, and Lehtonen, T,: Echogenic structure of prostatic cancer imaged on radical prostatectomy specimens, Prostate, 10: 1, 1987, 33, Resnick, M, L, Willard, J, W, and Boyce, W, H,: Transrectal ultrasonography in the evaluation of patients with prostatic carcinoma, J, UroL, 124: 482, 1980, 34, Rifkin, M, D,, Friedland, G, W, and Shortliffe, L,: Prostatic evaluation by transrectal endosonography: detection of carcinoma, Radiology, 158: 85, 1986, 35, Dahnert, W, F,, Hamper, U, M,, Eggleston, J, C,, Walsh, P, C, and Sanders, R C,: Prostatic evaluation by transrectal sonography with histopathologic correlation: the echogenic appearance of early carcinoma, Radiology, 158: 97, 1986, 36, Rosenfield, A, T,, Taylor, K J, W, and Jaffe, C, C,: Clinical applications of ultrasound tissue characterization, Rad, Clin, N, Amer,, 18: 31, 1980, 37, Resnick, M, L: Evaluation ofprostatic carcinoma: noninvasive and preoperative techniques, Prostate, 1: 311, 1980, 38, Chancellor, M, R, McHugh, T, A,, Dorr, RP, and VanAppledorn, C, A,: Transrectal prostate ultrasonography before transurethral prostatectomy, its value in screening for stage A cancer, J, UroL, part 2, 137: 241A, abstract 550, 1987, 39, Thompson, L M,: The early detection of genitourinary neoplasms, AUA Update Series, voL 6, lesson 26, 1987, 40, Jewett, H, J,, Eggleston, J, C. and Yawn, D, R: Radical prostatectomy in the management of cal'cinoma of the prostate: probable causes of some therapeutic failures, J, UroL, 107: 1034, 1972, 4L Whitmore, W, F,, Jr,: Natural history and staging of prostate cancer, UroL Clin, N, Amer<, 11: 205, 1984, 42, Watanabe, H,, Ohe, H,, Inaba, T,, Itakura, Y,, Saitoh, M, and Nakao, M,: A mobile mass screening unit for prostatic disease, Prostate, 5: 559, 1984, 43, Dahnert, W, F,, Hamper, U, M,, Walsh, P, C,, Eggleston, J, C, and Sanders, RC,: The echogenic focus in prostatic sonograms, with xenoradiographic and histopathologic correlation, Radiology, 159: 95, 1986, 44, Brooman, P, J, C,, Peeling, W, R, Griffiths, G, T,, Roberts, E, and Evans, K: A comparison between digital rectal examination and per-rectal ultrasound in the evaluation of the prostate, Brit, J, UroL, 53: 617, 198L 45, Chodak, G, W,, Wald, V,, Parmer, K, Watanabe, H,, Ohe, H, and Saitoh, M,: Comparison of digital examination and transrectal ultrasonography for the diagnosis of prostatic cancer, J, UroL, 135: 951, 1986, 46, Fritzsche, P, J,, Axford, P, D,, Ching, V, C,, Rosenquist, R W, and
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Moore, R J,: Correlation of transrectal sonographic findings in patients with suspected and unsuspected prostatic disease, J, UroL, 130: 272, 1983, Guinan, P,, Ray, P,, Bhatti, Rand Rubenstein, M,: An evaluation of five tests to diagnose prostate cancer, In: Prostate Cancer, Part A: Research, Endocrine Treatment, and Histopathology, New York: Alan R Liss, Inc,, pp, 551-558, 1987, Cohen, J, M, and Resnick, IVL L: The use of transrectal ultrasonography in the diagnosis of stage A prostatic carcinoma, World J, UroL, 1: 12, 1983, Rifkin, M, D,: Ultrasonography of the lower genitourinary tract, UroL Clin, N, Amer,, 12: 645, 1985, Chodak, G, W, and Schoenberg, H, W,: Early detection of prostate cancer by routine screening, J,A,M,A,, 252: 3261, 1984, Guinan, P,, Bush, L, Roy, V,, Vieth, R, Rao, R and Bhatti, R: The accuracy of the rectal examination in the diagnosis of prostate carcinoma, New EngL J, Med,, 303: 499, 1980, Pontes, J, K, Eisenkraft, S,, Watanabe, H,, Ohe, H,, Saitoh, M, and Murphy, G, P,: Preoperative evaluation of localized prostatic carcinoma by transrectal ultrasonography, J, UroL, 134: 289, 1985, Fujino, A, and Scardino, P, T,: Transrectal ultrasonography for prostatic cancer: its value in staging and monitoring the response to radiotherapy and chemotherapy, J, UroL, 133: 806, 1985, Egender, G,, Furtschegger, A,, Schachtner, W,, Pirker, K and Bartsch, G,: Transrectal ultrasonography in diagnosis and staging ofprostatic cancer, World J, UroL, 4: 163, 1986, Bartsch, G,, Egender, G,, Hubscher, H, and Rohr, H,: Sonometrics of the prostate, J, UroL, 127: 1119, 1982, Hastak, S, M,, Gammelgaard, J, and Holm, H, R: Transrecta! ultrasonic volume determination of the prostate-a preoperative and postoperative study, J, UroL, 127: 1115, 1982. Carpentier, P, J,, Schroeder, F, H, and Schmitz, P, L M,: Transrectal ultrasonometry of the prostate: the prognostic relevance of volume changes under endocrine management, WorldJ, UroL, 4: 159, 1986, Pontes, J, K, Ohe, R, Watanabe, H, and Murphy, G, P,: Transrectal ultrasonography of the prostate, Cancer, 53: 1369, 1984, Fujino, A, and Scardino, P, T,: Transrectal ultrasonography for prostatic cancer, IL The response of the prostate to definitive radiotherapy, Cancer, 57: 935, 1986, Resnick, M, L and Boyce, W, ff: Ultrasonography of the urinary bladder, seminal vesicles, and prostate, In: Ultrasound in Urology, Edited by M, L Resnick and R C, Sanders, Baltimore: The Williams & Wilkins Co,, chapt, 12, pp, 220-250, 1979, Parra, R 0,, Wolf, RM, and Huben, RP,: Echogenic patterns of local pelvic recurrences following radical pelvic surgery as evaluated by trans rectal ultrasonography, J, U roL, part 2, 13 7: 243A, abstract 557, 1987, Rifkin, M, D,, Kurtz, A, B, and Goldberg, B, R: Sonographically guided transperineal prostatic biopsy: preliminary experience with a longitudinal linear-array transducer, Amer, J, Roentgen,, 140: 745, 1983, Liddell, H, T,, McDougal, W, S,, Burks, D, D, and Fleischer, A, C,: Ultrasound versus digitally directed prostatic needle biopsy, J, UroL, 135: 716, 1986, Resnick, M, L: Transrectal ultrasound guided versus digitally directed prostatic biopsy: a comparative study, J, UroL, 139: 754, 1988, Lee, F,, Littrup, P, J,, McLeary, RD,, Kumusaka, G, H,, Borlaza, G, S,, McHugh, T, A,, Soiderer, M, H, and Roi, L, D,: Needle aspiration and core biopsy of prostate cancer: comparative evaluation with biplanar transrectal US guidance, Radiology, 163: 515, 1987, Ljung, R-M,, Cherrie, Rand Kaufman, J, J,: Fine needle aspiration biopsy of the prostate gland: a study of 103 cases with histological followup, J, UroL, 135: 955, 1986, Carter, H, R, Riehle, RA,, Jr,, Koizumi, J, H,, Amberson, J, and Vaughan, K D,, Jr,: Fine needle aspiration of the abdominal prostate: a cytohistological correlation, J, UroL, 135: 294, 1986, Holm, H, H,, Juul, N,, Pedersen, J, F,, Hansen, H, and Str¢yer, L: Transperineal 125 iodine seed implantation in prostatic cancer guided by transrectal ultrasonography, J, UroL, 130: 283, 1983,
THS JOURNAL Ot'' U:tOLOGY
Copyright (() 1989 by ':'he \1'filhams
Vlilkir1s Co.
Printed in U.S.A.
State of the A THE USE OF TRANSRECTAL PROSTATIC ULTRASONOGRAPHY IN THE EVALUATION OF PATIENTS WITH PROSTATIC CARCINOMA ROBERT L. WATERHOUSE
AND
MARTIN L RESNICK~
From the Division of Urology, Case Western Reserve University, School of Medicine, Cleveland, Ohio
This year adenocarcinoma of the prostate gland will likely be the second most common malignancy diagnosed in American men older than 50 years. Estimates for 1988 suggested that approximately 99,000 new cases of prostate cancer were diagnosed and that about 28,000 men died of the disease. 1 • 2 It is well recognized that the clinical course of a patient with prostate cancer is unpredictable but many tumors will follow a gradually progressive pattern.3-4 Initially, it is believed that prostatic carcinomas often are well differentiated and slow growing but as the tumor enlarges it becomes more poorly differentiated and more invasive. It is likely that men diagnosed with the disease when they are 70 to 80 years old may have possessed the malignancy in an undetected stage at 40 to 50 years and postmortem studies have estimated that the prevalence of the disease in American men more than 50 years old is 30 per cent. 5 As in the approach to other malignancies, the clinical stage at presentation usually determines the most appropriate mode of treatment. With increased awareness of the clinical significance of prostate cancer and the advances made in surgical treatment, there is renewed clinical interest in attempting to identify patients with surgically curable disease. Most patients are not diagnosed as having the disease until a digital rectal examination reveals a prostatic nodule. The examination most frequently is performed as part of the annual physical or results from an evaluation of patient complaints of voiding dysfunction or bony pain. Others with unsuspected malignancy are diagnosed incidentally when they undergo simple prostatectomy (transurethral resection or open procedure) for presumed benign hyperplasia, and cancer is found on histological examination of the removed tissue. Imaging studies, such as computerized tomog· raphy and nuclear magnetic resonance imaging, have been disappointing in identifying these early malignancies and the need for improved techniques is evident." Recently, many clinicians are advocating transrectal prostatic ultrasound as an aid in not only early detection but staging and post-treatment evaluation as well. These aspects of this technique will be reviewed but before commenting on these roles it will be helpful to review the history and background of ultrasound of the prostate gland. HISTORY
Dussik in Austria performed the first medical application of ultrasound when he used transducers in an attempt to locate brain tumors in the early 1940s. 7 In 1949 Wild and Neal began their early investigation in ultrasonography and later reported on its value in the detection of differences between normal and diseased tissue by using an A-mode display. 8 Wild and Reid reported 2-dimensional scans in 1952 that included a breast carcinoma, normal kidney and normal muscle. 9 They noted that malignant tissue reflected more sound than normal tissue, * Requests for reprints: Division of Urology, University Hospitals of Cleveland, 2065 Adelbert Rd., Cleveland, Ohio 44106.
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and that tissue of nonmalignant tumors reflected less sound than normal tissue. These same investigators attempted transrectal studies of the prostate during this time but the scans were so poor that the results were not reported. In 1963 Japanese urologists reported disappointing results with the use of A-mode scans to view the prostate. They observed that while A-mode scans can be informative, time-amplitude echograms of the pelvic organs with their thousands of interfaces are too complex for reliable interpretation. It was not until 1964 that Takahashi and Ouchi used a transrectal probe equipped with a radial scanning device to obtain the first tomographic pictures of the prostate. 10 Unfortunately, these early pictures were of poor quality and were considered to be of no clinical value. Watanabe and associates obtained the first clinically useful transrectal sonograms of the prostate in 1967. 11 - 13 B-mode instrumentation was used and prostatic images were displayed on a black and white screen. The transducer was covered with a water-filled balloon and the examinations were performed with patients in the sitting position. The bladder was filled with water via a urethral catheter to aid in demonstration of the prostate, seminal vesicles and other pelvic organs. They studied a large number of patients with various types of prostatic abnormalities and demonstrated consistent, reproducible images. In 1973 King and associates first reported on the use of prostate echography in the United States and they used similar equipment as their Japanese counterparts. 14 Later, investigators from the same laboratory reported on using gray scale imaging associated with transrectal ultrasonography. 15 Further studies followed with the development of improved gray scale instrumentation, higher frequency transducers and real-time imaging so that enhanced visualization of the prostate was achieved. In addition, transabdominal, perineal and transurethral ultrasonic techniques were studied to improve visualization of the prostate gland but most investigators concluded that the most consistent, reproducible prostate images were obtained with transrectal techniques. 16 · 17 INSTRUMENTATION AND TECHNIQUE
The term ultrasound refers to sound waves that are propagated in a material element with a frequency greater than that of audible sound (20,000 cycles per second, or 20 KHz.). For medical purposes sound waves with frequencies of 1 to 10 million cycles per second (1 to 10 MHz.) are applicable. The production of ultrasound is based on the piezoelectric principle in that an electric potential applied across certain crystals results in vibration that produces sound waves, and that sound waves directed against the crystal produce an electric potential. Ultrasound transducers that are composed of piezoelectric crystal elements, therefore, function as transmitters and receivers of sound waves. 18 • ' 9 Ultrasound is transmitted in short bursts lasting 10 msec. and for the majority of the time the transducer is in the "listening" mode. The thickness of the crystal element determines the frequency of the sound waves and the higher
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WATERHOUSE AND RESNICK
the wavelength the lower the degree of tissue penetration but the greater the resolution. Early prostate images were obtained with a 3.5 MHz. transducer but recently 7.0 MHz. transducers have been used. The propagated sound is focused with an acoustical lens that produces a narrow beam of only a few millimeters in diameter. 20 Ultrasound does not pose any risk of radiation or electromagnetic field but it does deliver a negligible amount of mechanical energy to the tissues through which it passes. No detrimental effects of this energy have been demonstrated. The transducer and its mechanism of action (mechanicalsector and radial; array-linear and phased) are another important component of the instrumentation. Most current transrectal radial ultrasonic probes consist of a freely moving inner assembly and a stationary outer assembly. The outer unit has inflow and outflow ports for the fluid that acts as a coupling medium between the transducer and rectal wall. Some sound waves are reflected at the interface between the fluid-filled condom and the rectal wall but the impedance difference between the 2 mediums is minimized when there is a good, tight seal. 20 The transducer in the radial scanner rotates 360 degrees and propagates sound waves perpendicular to the long axis of the transrectal probe. Within the human body and with respect to the prostate gland, the sound waves are directed perpendicular to the long axis of the body and prostate. This direction is called transaxial or axial and it is similar to the transverse plane of a computerized tomography scan. Newer array and mechanical sector scanners have eliminated the need for the rectal balloon and the probe is placed in direct contact with the rectal wall. A decided advantage of these instruments is that transrectal prostate biopsies or aspirations can be performed with ultrasonic guidance. In the linear array scanner many small transducers are aligned side by side much like the teeth of a comb, and when the scanner is oriented parallel to the long axis of the body the sonographic images obtained are in the longitudinal or sagittal plane. 21 Mechanical sector and phased array scanners can provide images in either plane and new bimodal probes incorporate both transducers in 1 unit. Transverse images yield more information about the lateral margins and symmetry of the prostate, while longitudinal images show the apex and base of the gland more clearly (fig. 1). The transverse image may seem easier to understand than the longitudinal image to the neophyte in sonography. 22 However, the linear array longitudinal orientation appears to be more ideal for ultrasonic guidance of prostate biopsy even though the technique was demonstrated first with radial scanners. 23·24 Some investigators believe that using axial and longitudinal projections provides increased sensitivity in examination of the prostate and probes having both capabilities have been developed.22,2s In addition to the transducer and scanner, the imaging screen and mode of display are essential components of the examina-
tion. As mentioned previously, early equipment used A-mode (amplitude mode) displays that appear as waves on an oscilloscope with the X axis as the distance from the transducer and the Y axis as the amplitude of the returned sound wave. Later, the B-mode (brightness mode) was developed, which displayed a composite 2-dimensional image of the examined area. Current technology uses gray-scale imaging, which varies the brightness of the dots in proportion to the intensity of the returned sound wave amplitude. In addition, instead of providing static images, real-time gray-scale imaging constantly scans the tissue and continually updates the images. 20 ·26 Real-time scanning can provide dynamic studies of the bladder, bladder neck and urethra during voiding and it may yet prove to be a valuable diagnostic tool in patients with voiding dysfunction. 27 Finally, it is important to emphasize that a hard copy image should be obtained when an ultrasound examination is performed. These can be obtained with photographic or x-ray film, digital printers or video tape. 13 ' 26 Technically, transrectal ultrasonography is minimally invasive and easy to perform. The entire examination takes 15 to 20 minutes, and can be performed in the office and on an outpatient basis without the need for anesthesia. Before starting the study a rectal examination is performed to exclude the presence of anal or rectal abnormalities that may contraindicate transrectal probe insertion. The prostate should be examined digitally at this time and the findings recorded. The probe then is inserted approximately 8 to 9 cm. above the anal verge and serial sonographs are obtained. Depending on the type of probe used the rubber condom then is inflated and the transducer is placed in direct contact with the rectal wall. It is important to perform the study systematically. If transverse images are obtained typically sonograms are obtained at 5 mm. increments beginning at the bladder and seminal vesicles and progressing towards the apex. If a longitudinal scanner is used images are obtained at 5 degree increments right and left of center. All images should be appropriately marked and hard copies obtained so that they may be referred to at a later date. IMAGE CHARACTERISTICS
The normal prostate and benign prostatic hyperplasia. The normal prostate as viewed on a transrectal radial ultrasonogram appears as a symmetrical, triangular, ellipsoid structure that is delineated circumferentially by a continuous prostatic capsule. The capsule usually is well defined, highly echogenic and free of distortion. The anteroposterior diameter appears shorter than the transverse diameter, since the posterior portion of the prostate becomes concave due to distortion produced by the inflated balloon or compression by the probe during the examination. The internal sonographic structure of the prostate is composed of multiple fine, diffuse, homogeneous echoes that probably represent acoustic interfaces created by the numerous glands that are present. 13·28
FIG. 1. A, transverse image demonstrates capsular symmetry and normal prostatic architecture (7.0 MHz.). Arrows designate prostate capsule. B, longitudinal image shows visualization of apex and base. Note presence of urethral catheter and catheter balloon, and round or ovoid appearance of gland when viewed in midline (7.0 MHz.).
Based on prior anatomical studies the p:rostate can be divided into 3 distinct ;;w,uu,cu,u regions: the peripheral, transition and central zones. Tissue of the peripheral zone comprises about 70 to 75 per cent of the prostatic volume and occupies the posterior, lateral and apical aspects of the gland. This area is homogeneous and is the primary region where adenocarcinoma of the prostate is believed to originate.'30 Recent data from McNeil and associates indicate that malignancies can arise in the transition and central zones, and these malignancies comprise the majority of stage A tumors diagnosed after transurethral prostatectomy. 01 Recent evidence currently indicates that approximately 30 per cent of all malignancies arise in these zones and are not associated with the peripheral zone"'' The central zone occupies 20 per cent of the glandular volume of the prostate and is associated with few disease processes. Benign prostatic hyperplasia originates from the transition zone, and with advancing patient age increases in size and compresses the peripheral zone."" 29 · 10 Before the onset of benign hyperplasia this zone occupies only 5 per cent of the glandular volume but with progressive growth it can occupy as much as 95 per cent of the total prostatic tissue. By moving the transrectal axial probe in a cephalad-caudal direction the entire prostate gland can be visualized. The apex, mid section and base can be delineated but it may be difficult to differentiate between the base of the gland and the bladder neck, especially if a prominent median lobe is present. Also, in this region the seminal vesicles are typically visualized as symmetrically paired structures, which are seen better as is the base of the prostate when the bladder is filled partially. The seminal vesicles may vary somewhat in shape but they can usually be imaged clearly. These structures are slightly less
Fm" 2. Typical appearance of benign prostatic hyperplasia (7.0 MHzo).
echoic than the prostate gland. The seminal vesicles extend cephalad and at the base of the bladder they continue laterally, tending to parallel the distended rectal wall. 1 " In the young male patient the gland assumes a triangular shape but with development of benign prostatic hyperplasia the gland increases in size typically in the anteroposterior dimension to a greater degree than the transverse dimension. Due to growth in all directions it should be emphasized that the anteroposterior diameter rarely exceeds the transverse diameter. The capsule often thickens but it remains uniform and continuous. The gland maintains a symmetrical appearance and tends to have a uniform, homogeneous echo pattern. Not infrequently, areas of high and low echogenicity are observed (fig. 2). The linear array scanner images the prostate in the longitudinal plane parallel to the long axis of the body as described previously. Other types of scanners also can provide images in this plane. The acoustic characteristics of the prostate gland are similar to those seen with the radial scanner but in this plane the prostate appears round or ovoid in the midline. When examining the lateral margins of the gland the round capsule of the prostate is defined further. At the mid portion of the prostate the pubic symphysis and space of Retzius, with its fat and venous tissue, usually are well delineated. The apex of the prostate is well outlined as in the base and bladder. The seminal vesicles appear as having reduced echogenicity and their relationship to the posterior wall of the bladder is especially well defined. 11 Often, a typical beak is demonstrated at which point the ducts of the seminal vesicles and vasa deferentia enter the base of the prostate. As with its appearance in the transverse scan the hyperplastic prostate assumes a more circular appearance and enlarges in a uniform manner. Similar echo patterns are observed in the longitudinal as in the transverse plane. Carcinoma of the prostate. Unlike the usual homogeneous sonographic appearance of the normal prostate, the ultrasonic characteristics of carcinoma of the prostate are varied. Cancer originates and commonly is seen in the peripheral zone of the prostate but it can be found in the anterior portion of the gland as well. 31 ''32 Early studies with B-mode and initial gray-scale imaging reported that prostatic carcinomas appeared as echo dense or hyperechoic areas. 12- 15 • 28 ' 03 With improvement in instrumentation and the use of higher frequency transducers, the appearance of tumors changed. Some investigators began to demonstrate that prostatic malignancies, particularly when they are small and localized, appear as hypoechoic areas but others demonstrated that tumors can be hyperechoic, hypoechoic, isoechoic or of mixed echogenicity (fig. 3). 25 • 30, 34 • 35 As a explanation of these differing appearances, it can be theorized that earlier equipment detected cancer at a later or more advanced stage. Newer high resolution equipment visualizes a prostate tumor as an echopenic focus before it invades other tissue and obtains a more echogenic appearance" Often associated with tumor growth and invasion is a desmoplastic
FIG. 3. A, localized carcinoma demonstrates typical hypoechoic appearance (arrows, 7.0 MHz.). B, advanced carcinoma demonstrates mixed echo pattern (arrows, 7.0 MHz.)"
236
WATERHOUSE AND RESNICK
reaction and those changes certainly may contribute to the mixed pattern observed with advanced tumors. Experience indicates that early cancers tend to be of lower echogenicity. If the presence of collagen in the stroma of prostatic tissue determines its echogenicity, then prostate cancer may appear hypoechoic because the stroma is replaced by infiltrating glandular tumor elements. 36 Other considerations include the fact that large prostate cancers can replace all of the normally isoechoic peripheral zone, thereby obliterating any ultrasound reference for normal tissues to contrast with the hypoechogenicity of prostate cancer, and the inherent inaccuracies of biopsy localization in determining the nature of an ultrasonographic area. Unfortunately, many structures and benign processes within the prostate can have ultrasonic characteristics similar to the hypoechoic appearance of small prostate malignancies, including small nodules of hyperplasia, cysts, infarcts, inflammatory processes, cystic atrophy, blood vessels and muscle tissue. Greater echogenicity also is likely secondary to the development of increased tissue interfaces that occur as the tumor grows and invades other areas of the prostate and surrounding tissues, and the presence of calcification. Hyperechoic areas of prostate cancer are often subtle and differ from the hyperechoic images of prostate calculi, which are brighter and usually associated with acoustic shadowing.5 ' 32 It also must be remembered that many carcinomas are isoechoic and cannot be imaged with this technique. Additionally, anterior tumors often cannot be distinguished reliably from the normal hypogenie appearance of this region of the gland. Another important consideration in the ultrasound examination of patients with prostate cancer is the appearance of the prostatic capsule and seminal vesicles. In patients with confined carcinoma of the prostate the capsule usually is well delineated circumferentially and free of distortion or disruption. Occasionally, there may be acoustic shadowing of the capsule adjacent to tumor areas. More obvious deformity is associated with invasive disease as it causes loss of the symmetric, continuous, hyperechoic pattern of the prostate capsule (fig. 4). Deformity of the capsule may appear as subtle irregularities or more distinct capsular echoes. With extension of cancer into the seminal vesicles the ultrasonic image becomes distorted with dense echoes continuous with sonographic abnormalities of the tumor within the prostate gland. More invasive prostate cancer may completely obliterate the seminal vesicle sonographic image (fig. 5). 13 It is important to emphasize that microscopic capsular invasion into the periprostatic fat and microscopic invasion of the seminal vesicles cannot be detected by transrectal ultrasound. In summary, there is no single pathognomonic appearance
FIG. 4. Radial scan shows distortion of prostatic capsule (arrows) associated with invasive carcinoma (7.0 MHz.).
FIG. 5. Radial scan demonstrates obliteration of seminal vesicle (arrows) due to invasive carcinoma (4.5 MHz.).
of prostate cancer when viewed sonographically. However, there are criteria that are suggestive of malignancy as demonstrated by Rifkin and associates on 443 pathologically confirmed transrectal sonographic examinations. 34 Smaller cancers are more hypoechoic than larger ones but few larger tumors are purely hypoechoic. Malignanices usually are irregularly marginated and prostatic capsule distortion is a sign of invasive cancer. Although carcinoma originates in the peripheral zone of the prostate the tumor may grow to invade the central and transition zones, thus, the location of an abnormal area is helpful but not diagnostic of its etiology. As noted previously tumors can arise de novo in these latter 2 zones. 31 Approximately, 30 per cent of all malignancies originate anteriorly. Additionally, it is important to emphasize that not all prostatic carcinomas can be detected with ultrasonography. Patients with normal prostate ultrasound examinations have undergone prostatectomy for benign disease and been found to have occult carcinoma on histological review of the specimen.37' 38 CLINICAL IMPLICATIONS
Screening. Probably the most controversial area related to the use of transrectal ultrasonography is its application as a screening or early detection study for early prostate cancer. Thompson illustrated several criteria that must be met before screening is advocated for a disease. 39 The disease should have a high prevalence within the population tested. With prostate cancer the prevalence is significant but the yield may be increased by defining the population at risk as men more than 50 years old. Similarly, the upper age limits of the population to be screened must be defined because presumably further evaluation and treatment will be initiated in patients having a positive study. The biological behavior of the disease must be understood. The problem with prostate tumor biology is that not all cancers progress to invasive and metastatic disease. To date it is not known how to differentiate the indolent behaving prostatic carcinoma from the aggressive one. 40 • 41 However, some aspects of prostate cancer biology are understood. As mentioned previously, as most prostatic cancers enlarge they become less differentiated and more invasive, and there are data indicating that tumors less than 1 cm. large do not possess the potential to metastasize. 3 Therefore, ideally, successful screening should allow for identification of prostatic cancers less than 1 cm. in diameter. Finally, to gain benefit from diagnosing early disease there must be a method of treatment for that diagnosis. Prostate cancer can be treated and in many instances cured in the early stages with appropriate intervention. Therefore, prostate cancer fulfills these 3 criteria as a disease in which screening may be appropriate; however, before screening can be initiated
TRANSRECTAL PROSTATIC ULTRASONOGRAPHY IN PATIENTS WITH PROSTATIC CARCINOMA
it must be demonstrated that patients will benefit from such an endeavor. Before initiating a screening program the test used also should fulfill certain criteria. The test should be rapid, inexpensive, noninvasive and well accepted by patients. A cost versus benefit analysis has not been done for prostate cancer detection by transrectal ultrasound and reports of the cost of the study have varied from $50 to $400. Transrectal ultrasound is tolerated well and minimally invasive but the study is of considerably greater duration than a digital rectal examination. The test also should have high sensitivity, specificity, and positive and negative predictive values. These criteria are primarily the ones responsible for the debate over whether transrectal ultrasound is a worthwhile screening study to detect early prostate cancer. To date, with analysis of available technology and data by several investigators the use of transrectal ultrasound in such a screening capacity is not supported. Watanabe and associates reported the only large study using transrectal ultrasound as a screening modality in asymptomatic, nonselected men but they did not report specificity data.4 2 Unfortunately, transrectal ultrasonic detection of prostate cancer has a low sensitivity and specificity with regard to the values necessary for screening purposes. Sensitivity rates for transrectal sonographic diagnosis of prostatic carcinoma range from 71 to 92 per cent by various investigators 23 , 43 - 47 and for detection of subclinical disease sensitivity values of 60 to 85 per cent have been reported. 33 • 44 ' 48 Furthermore, in retrospective reviews of prostate glands removed as treatment for histologically proved cancer 24 to 30 per cent of the cases had ultrasonic patterns that were uniform, isoechoic and not suggestive of cancer. 31 ·'15 Specificity data have a more detrimental effect on the positive predictive value of ultrasound, with specificity rates ranging from 41 to 79 per cent.4 4 - 47 Experience indicates that false positive rates are high because ultrasound cannot always reliably differentiate benign conditions (benign prostatic hyperplasia, prostatic cysts, prostatic calculi, prostatic infarcts and prostatitis) and normal tissue structures (blood vessels and muscle) from cancer. 28·'31 • 34 ·'37 There may be a 30 per cent overlap between benign and malignant lesions that have similar acoustic appearances.4 9 Statistical analyses also reveal that the positive predictive value of transrectal sonography is not significantly greater than that for digital rectal examination of the prostate.4 5 • 47 .,so,si Because the digital examination is inexpensive and easy to perform, there appears to be little to gain screening with ultrasound. Many patients without prostatic carcinoma but with positive sonograms would be subjected to further invasive studies and expense that would unnecessarily create patient and family anxiety. Whether transrectal ultrasound will have any role in the evaluation of an asymptomatic population with palpably benign glands is unknown to date. Possibly, when combined with other studies (for example prostatic specific antigen) or when used selectively in certain high risk populations based on age, race or symptoms the study may be of value. As with mammography in the evaluation of women for detection of breast carcinoma this new technology must be evaluated further. Several large cooperative trials have either been initiated or are being planned and the results of such investigations will be forthcoming. Therefore, the routine use of this study is premature and presently cannot be recommended. Staging. Despite its unproved role as a screening tool for prostate cancer, transrectal ultrasonography has useful applications in the evaluation of patients diagnosed as having this disease. Ultrasound is sensitive in assessing prostatic size and unrecognized invasive disease. Early reports showed that the stage ofprostatic carcinoma as determined by transrectal ultrasonography corresponded with the stage diagnosed pathologically on radical prostatectomy specimens. s:i In a study by Pontes and associates a sensitivity of 89 and 100 per cent was demonstrated for preoperative ultrasonic detection of capsular
237
and seminal vesicle involvement, respectively."" The of detecting capsular penetration and seminal vesicle involvement was only 50 and 28 per cent, respectively, due to the inability of the study to detect microscopic disease. Fujino and Scardino reported the ability of ultrasound to detect invasive disease in 8 of 18 patients who had no extension of the disease by rectal examination.'" 3 As emphasized, transrectal ultrasound is not as accurate for determining microscopic invasion. 54 There also does not appear to be any definite correlation between histological grade and ultrasonic pattern other than the fact that small tumors that tend to be well differentiated often appear hypoechoic and larger, higher grade tumors tend to have a mixed pattern. Monitoring response to treatment. Transrectal ultrasonography is useful to document prostate gland volume and it is accurate within 5 per cent to determine true prostatic weight. 15, 5 "," 6 This ability allows ultrasound to provide information regarding the response of the tumor to therapy. It must be emphasized that these determinations are of total gland volume and not tumor volume. No reported study to date has correlated the volume of tumor as determined by ultrasound with the true volume as determined by pathological examination. Prostate sonography has documented reduction in prostatic size after administration of endocrine therapy as treatment for disseminated cancer. Within 3 to 6 months after either orchiectomy or estrogen therapy a sonographically detectable 20 to 30 per cent decrease in prostatic volume occurs. 33' 57 Changes with estrogen therapy are slightly slower to occur than those with surgical castration. Individuals who have progressive disease within 1 year after castration have been shown to have a significantly smaller decrease in prostate size than those with a sustained clinical response. Carpentier and associates found that in patients whose prostatic volume decreased to at least 50 per cent of the pretreatment volume after 3 months none had progression of the malignancy. 57 The clinical value of this application of prostate ultrasound may be of even greater importance when effective treatment becomes available for hormone-unresponsive prostatic carcinoma. Further usefulness of ultrasound has been demonstrated in evaluation of prostatic cancer patients treated with radiotherapy and chemotherapy. Pontes and associates showed that 10 of 14 patients treated with a National Prostatic Cancer Project Protocol had a decrease in the sonographic volume of the prostate. 58 Fujino and Scardino concurred with these results and reported that a maximal reduction in size of the prostate usually occurred by 9 months after radiotherapy and 3 months after chemotherapy. 58 As a response to therapy in addition to a decrease in size, the prostate resumed a more normal symmetrical shape, the capsule reformed and thickened, the degree of extracapsular extension diminished and the seminal vesicles became normal in appearance. These investigators illustrated a substantial 20 per cent decrease in the volume of the prostate in all 19 patients treated with definitive radiotherapy for stages B, C and D prostatic carcinoma. 59 Furthermore, prostatic size decreased significantly more slowly and to a lesser extent in patients who had disease progression during followup. Accordingly, prostate ultrasound may become useful to identify patients who will not have maximal responses to radiotherapy alone so that other therapy may be instituted more promptly. Although systemic progression of prostate cancer after hormonal therapy or radiotherapy usually is not manifested by an increase in prostatic size, the tumor does recur locally after radical prostatectomy. Local tumor recurrence often is around the bladder neck in an area inaccessible to the examining finger. Prostatic ultrasound is useful to detect recurrence during followup of these patients. 33 • 60 • 61 Ultrasound guided biopsy and interstitial radiation therapy. Transrectal prostatic ultrasonography is useful as an aid in the placement of a biopsy needle within a specific suspicious area of the prostate. 23 • 62 A special needle guide attachment can be
238
WATERHOUSE AND RESNICK
mounted directly on the transrectal probe and biopsies can be performed via the perinea! or transrectal route. Patients have been reported in whom ultrasound guidance led to a prostate needle biopsy diagnosis of cancer, whereas digitally directed biopsies were benign. 24 Currently, there is debate concerning the superiority of this technique over digitally directed biopsies in patients with palpable abnormalities. Some believe that all prostate biopsies should be performed under ultrasound guidance, and others believe the digitally directed approach should be used first. In a study of 15 patients with biopsy proved adenocarcinoma of the prostate, only 9 were diagnosed correctly using conventional digitally directed perineal biopsy, while all 15 were diagnosed accurately with the ultrasound directed method. 63 All patients had palpable abnormalities but it was unclear from the report as to the correlation of the palpable abnormality and the site of the positive biopsy. In another study of patients with prostatic nodules dissimilar results were obtained. 64 In 11 patients cancer was detected by both techniques, while of the remaining 3 patients 2 were positive only by digitally directed perineal biopsy and 1 was positive only with the ultrasound directed method. The conclusion from this last study was that ultrasound guided biopsy is not needed routinely when a distinct nodule is palpable. Transrectal ultrasonically guided biopsies also are becoming increasingly popular, and new aspiration and core biopsy needles with spring loaded "guns" continue to be developed. 65 Problems exist because not all tumors can be visualized ultrasonically and more studies are required to correlate the area of the ultrasound biopsy with the physical findings. Some believe that because of the ease of the study transrectal aspiration may become the method of choice in the evaluation of patients with palpable abnormalities. 66 • 67 However, ultrasound guided biopsies do have a role in the evaluation of patients with or suspected to have prostate cancer. Repeat ultrasound guided biopsy after a negative digitally directed biopsy appears to be worthwhile in patients with suspicious palpable abnormalities. In patients with nonpalpable but suspected prostate malignancy ultrasound directed biopsy of sonographically suspicious areas may establish the diagnosis. Additionally, the technique has a role in the evaluation of patients treated with definitive radiotherapy who have no palpable abnormalities but suspicious ultrasonic findings. Ultrasound also can be used to direct radioactive seed implantation into the prostate when using this treatment modality. 68 A puncture attachment can be applied to the transrectal ultrasound probe and the radioactive seeds placed under ultrasound guidance. Permanent implantation of radioactive seeds offers some advantages to external beam irradiation. The dose is adapted accurately to tumor size and shape, and a higher minimum tumor dose can be obtained with less damage to normal tissue due to the protracted irradiation from the longlived isotope. Additionally, the implantation technique is less time-consuming for the patient and staff than a full course of external beam therapy. Ultrasound guidance with placement of the seeds eliminates the disadvantages of an operation, which is used most often for seed placement, but more importantly it permits a more satisfactory distribution of the seeds than is obtained with the freehand technique. Additionally, a higher concentration of seeds can be placed in and around the area of malignancy. The disadvantage of the technique is that extracapsular tumors with ill-defined margins may not be irradiated adequately and that regional lymphatics are not treated appropriately. Therefore, more experience and followup are needed before this method gains wide acceptance. SUMMARY
Transrectal ultrasonography is a relatively new diagnostic technique that has received much of the same enthusiasm that often is associated with the introduction of other new diagnostic
or therapeutic instruments. The study allows for imaging of the prostate but benign conditions often cannot be differentiated reliably from malignant ones. The technique has clinical application in staging, monitoring tumor response to therapy and assisting in biopsy. Its role as a screening study when used either alone or in combination with other diagnostic tests has yet to be determined and well controlled, carefully performed investigations with state of the art instruments probably will help to establish the role of this examination when used for this purpose. REFERENCES
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