INTRODUCTION
Transrectal ultrasound (TRUS) is a useful imaging modality to guide a biopsy in men with elevated prostate specific antigen (PSA) [1-3]. Many radiologists and urologists believe that TRUS is not a screening test but only a guiding tool to do a systematic biopsy for cancer detection. They have general consensus that many cancers are not seen on TRUS and do not concern well how to set up TRUS sequence, to control image quality, and to TRUS features of significant prostate cancer. Accordingly, they do not have good idea about what TRUS features suggest peripheral or transition cancer. However, as hardware and software of TRUS scanners have been developed constantly, it can enable so many prostate cancers to be depicted on TRUS images [4-6]. To reach an accurate histologic diagnosis, they need to be familiar with how to prepare good imaging quality, what to suggest cancer and how to differentiate insignificant and significant cancers. Then, they can target a lesion precisely with TRUS without relying on magnetic resonance imaging (MRI)-TRUS fusion techniques. Besides, they can obtain biopsy cores in men whose anus are stenotic from recurrent inflammation or absent following Miles’ operation.
The current Prostate Imaging and Reporting and Data System (PI-RADS) does not rely on TRUS findings but MRI findings to determine the likelihood of significant prostate cancer [7-9]. Therefore, they prefer to use MRI-TRUS image fusion to target a lesion but frequently encounter mis-targeting due to in-born error such as mis-registration of MRI and TRUS images. To our knowledge, there are only a few investigations dealing with the TRUS sequence, imaging findings, and target biopsy of prostate cancer [10-12]. The aim of this review is to show how to prepare TRUS for good scan setting, to describe TRUS features of peripheral and transition cancer, how to differentiate insignificant and significant cancers, and how to apply TRUS features for biopsy.
NECESSITY OF PRE-BIOPSY MRI
Currently, the number of MRI scans is being increased in men with elevated PSA. This imaging modality can be scanned in multi-parametric (mp) sequences, in which anatomical and functional magnetic resonance (MR) imaging helps to detect prostate cancer [13-15]. T2-weighted and diffusion-weighted imaging are the key MR sequences in determining PI-RADS category. Basically, peripheral lesion is categorized with diffusion-weighted imaging and transition lesion is categorized with T2-weighted imaging. mpMRI can precisely predict or stratify the risk of significant cancer in most cases [7-9]. Besides, contrast-enhanced MR imaging offers added value to T2-weighted and/or diffusion-weighted imaging [16]. Accordingly, mpMRI prior to biopsy is strongly recommended to plan how to do a target biopsy in PI-RADS 3–5 lesions. It can reduce unnecessary biopsy, complication, and cost [13-15]. Also, the number of TRUS-guided biopsy cores will be decreasing due to precise targeting a lesion which is depicted on MR images [17]. Post-biopsy bleeding or infection will be reduced because the number of systematic cores can become smaller. For these reasons, mpMRI is now a trend prior to biopsy in men with high PSA. However, there are many things to concern about how to scan and read mpMR images. The current PI-RADS system accepts various kinds of MRI scanners (1.5T vs. 3.0T), coils (surface coil vs. endorectal coil) and MR sequences obtaining T2-weighted, diffusion-weighted, and dynamic contrast-enhanced images. Therefore, image qualities of mpMRI are widely ranged in many institutions and hospitals. Besides, radiologists’ experience and education are not clearly stated in the PI-RADS system. No one knows how many MRI scans they should read per year, how many times they should be educated in the refresher courses or related conferences or how long they should be trained prior to formally reporting prostate mpMR images.
HOW TO PREPARE TRUS
Transducer preparation
A TRUS transducer should be well prepared with ultrasonic gel and condoms to avoid air-induced artifacts. Enough gel is put on the transducer tip and next, transducer is wrapped tight with a condom. This preparation alone is good enough for TRUS imaging. To proceed to biopsy setting, a biopsy guide is placed appropriately on the transducer. Then, sufficient gel is put on the transducer tip and the transducer is wrapped tight with another condom again. Air-trapping should be avoided during these whole preparations. The external orifice of anus is searched and touched by the tip of transducer to gently introduce it into the rectum air. Then, the prostate gland, seminal vesicle, and vas deference are to be centered and magnified to occupy at least half of the whole screen by controlling the scan depth and focal zone. Also, it should be kept in mind that these organs are included as much as possible in the TRUS monitor. Especially, hyperechoic band is frequently created at the anterior rectal wall due to strong reflection of ultrasound (US) and is optimized by timegain control or automatic control such as i-scan. Radiologists and urologists need to check out gray-scale frequently. The entire prostate, seminal vesicle, and vas deference are carefully scanned on gray-scale US and next, abnormal hypervascular area should be searched with color or power Doppler US. The bilateral margins of the prostate are likely to be neglected in the transverse scan and thus, the transducer should be moved laterally not to miss a cancer.
TRUS sequence
Harmonic imaging is a default setting for currently available TRUS scanners, but it is recommended to be replaced with fundamental imaging (Table 1) [18-22]. Even though the latter looks noisier and coarser, it offers better tissue contrast between prostate cancer and normal tissue compared to the latter (Fig. 1). Dynamic range of current TRUS scanners is set more than 60 as a default, but it should be lowered to 40–50 to increase tissue contrast (Fig. 2) [18,19,23]. Fundamental imaging and dynamic range are two key factors in keeping tissue contrast good (Table 1). Even though this TRUS sequence or technique decreases image resolution as a tradeoff, it helps radiologists or urologists to identify a prostate cancer which becomes contrasted from normal tissue clearly [18,19]. Tissue contrast can provide good information on analyzing tumor size, demarcation, and margin. If it becomes high, a tumor becomes well demarcated, and tumor size can be measured precisely. But also, it helps to determine if tumor margin is smooth or irregular.
INSIGNIFICANT VS. SIGNIFICANT CANCERS
Tumor echogenicity
Peripheral cancer is frequently seen as a hypoechoic mass on TRUS (Table 2) [10-12]. Reportedly, tumor echogenicity is related to the Gleason score (GS). As cancer echogenicity becomes hypoechoic, the GS becomes greater. Insignificant cancer (GS 6 or less) looks slightly hypoechoic compared to normal peripheral tissue and thus is difficult to detect on TRUS. However, significant cancer (GS 7 or greater) tends to be more hypoechoic than insignificant cancer (Fig. 3). If a lesion is clearly hypoechoic on TRUS, it can be identified and targeted easily. This tumor proves to be histologically a significant cancer [10-12]. However, many benign lesions such as inflammation, infection, infarction, and abscess are seen also as hypoechoic lesions. Therefore, radiologists or urologists need to correlate patients’ clinical signs or symptoms, past medical history, and laboratory findings. But also, MRI findings should be correlated with TRUS findings prior to lesion detection and biopsy.
Transition cancer in contrast to peripheral cancer is not hypoechoic but hyperechoic compared to adjacent transition tissue (Table 2) [10-12,17,24]. Still, radiologists and urologists are not familiar with this TRUS finding because they stick to traditional concept that prostate cancer is hypoechoic regardless of tumor location. As transition cancer becomes hyperechoic, the GS becomes higher (Fig. 4). Lesion conspicuity becomes clearer and thus tumor targeting becomes more precise. Many benign prostate nodules also can be seen as hyperechoic lesions. If a hyperechoic lesion is lenticular within the benign prostate hyperplastic nodule, it is likely to be a significant cancer which can be categorized as a PI-RADS 4 or 5. When a lesion is difficult to differentiate prostate cancer and benign prostate hyperplasia, radiologists or urologists should review mpMR images for lesion correlation.
Tumor size
The size of peripheral or transition tumor is another important finding to differentiate insignificant and significant cancers (Table 2, Figs. 3, 4). If a tumor increases in size, the GS becomes higher. PI-RADSv2.1 suggests that 1.5 cm is a size threshold to distinguish PI-RADS 4 and 5 [7-9]. The proportion of significant cancers is much higher in PI-RADS 5 compared to PI-RADS 4. However, Park et al. [25,26] reported that the size criteria should be changed from 1.5 to 1.0 cm because significant cancer detection rate in a tumor of 1.0 cm or greater becomes higher and is not different from that that in a tumor of 1.5 cm or greater. Further investigations are necessary to determine what size is optimal to differentiate PI-RADS 4 and 5. Many men with serious co-existing diseases frequently does not need systematic biopsy requiring many biopsy cores when they have PI-RADS 5. For this reason, re-adjusting size criteria are of great importance in men who can have high post-biopsy morbidity or mortality.
Tumor texture
Tumor texture is also useful TRUS finding to differentiate insignificant and significant cancers (Table 2) [18,19,27]. As a tumor becomes heterogeneous, the GS becomes higher (Figs. 3, 4). Otherwise, as a tumor becomes homogeneous, it is likely to be insignificant cancer. Frequently, higher GS cancer tends to have necrosis, degeneration, hemorrhage, or calcification. These pathologic features can make the tumor texture look heterogeneous on TRUS image. Evaluating tumor texture seems to be easier on TRUS compared to mpMRI because of higher image resolution because transducer’s frequences can be widely controlled in the commercially available TRUS scanners. If a tumor becomes heterogeneous, the GS becomes various according to where target cores are obtained within the tumor. Therefore, target cores should be sampled in the tumor periphery as well as tumor center [28].
Tumor margin
Tumor margin is another important finding to differentiate insignificant and significant cancers (Table 2) [18,19]. As it becomes irregular, infiltrative, or spiculated, the GS becomes higher (Figs. 3, 4). Insignificant cancer tends to have smooth tumor margin where the GS is 6 or less. If a tumor margin becomes partly irregular, infiltrative, or spiculated, it should be targeted to discover higher GS cancer. When a tumor shows becomes locally aggressive, the tumor margin is infiltrative or spiculated in most cases. Fundamental imaging offers better information on tumor margin which is clearly identified under strong tissue contrast. Therefore, radiologists and urologists need to replace harmonic imaging with fundamental imaging to precisely analyze tumor margin on TRUS.
Tumor vascularity
If GS becomes higher, a tumor tends to be hypervascular because of increased vascularity [29]. Color or power Doppler TRUS shows significant cancer to have strong frequency shift, suggestive of tumor hypervascularity [30,31]. This finding is frequently seen in the peripheral significant cancer. However, it is not seen in many transition significant cancer. Probably, it is due to the distance between transducer and tumor. Generally, transition cancer is far from the transducer compared to peripheral cancer. Therefore, analyzing tumor vascularity is difficult when a tumor is close to the anterior capsule. When a tumor is detected with gray-scale TRUS, a transducer should not be pushed to the posterior capsule because of banana-shape deformity of the prostate. However, it should be pushed if a lesion is close to the anterior capsule to shorten the distance between transducer and tumor. If an anterior tumor becomes close to the transducer, analyzing vascularity and tumor targeting are more accurate.
HOW TO BIOPSY WITH TRUS
Correlation of MRI and TRUS
TRUS-guided biopsy is usually performed when a PI-RADS 4 or 5 lesion is detected on mpMR images because significant cancer is likely or highly likely to exist. Many radiologists or urologists do not know well how it is precisely identified or targeted on TRUS images. There is a significant difference between MRI and TRUS images in terms of tumor location, size, and shape because of different scan axis between TRUS and MRI (Fig. 5). Usually, MRI is scanned perpendicular to the pros tate urethra, whereas TRUS is scanned oblique to it [18,19]. As a tumor is closer to anterior capsule on MR images, it looks closer to the apex on TRUS images (Fig. 5) [18,19]. As a tumor is closer to the posterior capsule on MR images, it looks closer to the base on TRUS images (Fig. 5) [18,19]. This location difference also results in different tumor size and shape on TRUS. Even though a tumor is round and 1.0 cm or greater, it is not surprising that it looks oval or less than 1.0 cm on TRUS images. Therefore, if radiologists or urologists are not familiar with these differences, they have difficulty in detecting a tumor on TRUS images. When TRUS is scanned to search for a tumor, a transducer should not be pushed to the posterior capsule because a tumor is embedded or deformed. Also, the prostate tends to look like a banana. This shape deformation is more severe in peripheral tumor than transition tumor. These imaging findings or techniques are also useful when an ultra-resolution TRUS scanner is performed. Systematic biopsy barely can be skipped because it offers added value to significant cancer detection [32]. However, if men with severe co-existing diseases have locally aggressive tumor and lymphatic or hematogenous metastasis, target biopsy alone is good enough to detect a significant cancer. Only a few target cores are sufficient to confirm a significant cancer in men who have extra-capsular extension, seminal vesicle invasion or metastasis if he does not wean anti-coagulant therapy [17].
Target and systematic biopsies
Before radiologists and urologists begin TRUS-guided biopsy, they need to perform local anesthesia to reduce pain [33-35]. Lidocaine should be injected around the bilateral neurovascular bundles at the level of base. They should wait for 10 minutes until lidocaine works and then begin target and systematic biopsies.
If a tumor is targeted and biopsied with 1–2 cores alone (oligo-targeting), the GS can be underestimated [28]. Even though a biopsy needle is bound for the tumor center, it is slightly off centered in many cases [18]. Therefore, if 5–6 cores should be sampled from the tumor, multi-targeting may increase the likelihood of detecting higher GS [28]. A 12-core systematic biopsy is recommended to do a biopsy of PI-RADS 2–3 lesions. Adding systematic biopsy to target biopsy contribute to detect higher GS cancer in PI-RADS 1–3 compared to PI-RADS 4–5. Performing multi-target and/or systematic biopsy increases the likelihood of significant cancer detection [32,36]. However, it is doubtful if systematic biopsy with many biopsy cores should be performed always in men with PIRADS 5 showing clearly extra-capsular extension, seminal vesicle invasion or metastasis. When a lesion is close to the posterior capsule, a transducer should not be pushed to the tumor because it is frequently invisible. However, when a lesion is close to the anterior capsule, a transducer should be pushed slightly to the posterior capsule. This procedure makes the tumor-to-transducer distance shortened for precise tumor targeting. When systematic biopsy is performed, pushing transducer is useful to obtain longer cores and to reduce post-biopsy bleeding, as well.
Currently, the term ‘target biopsy’ is not well known because many radiologists and urologists are unfamiliar with the new TRUS techniques and imaging features as describe above. They still insist that it is cognitive biopsy. However, cognitive biopsy should be defined only when cores are obtained when a tumor is expected to exist on TRUS. If a tumor is identified on TRUS, we should not use cognitive but target biopsy [37].
Prostate biopsy in stenotic anus
If radiologists or urologists are familiar with new TRUS techniques and imaging features, they can try to do a prostate biopsy in men with stenotic anus as follows. TRUS-guided biopsy is successfully performed in many cases without relying on general anesthesia. Those who have anal stenosis are likely to have recurrent fistula, fissure, and/or hemorrhoid. The anus becomes so stenotic that it cannot be easily dilatated greater than the diameter of TRUS transducer. They complain of severe pain when a transducer is forced to introduce into the stenotic anal canal. Enough lidocaine gel is carefully put on external and internal orifices with a gloved finger and wait for 10 to 15 minutes before a transduce is introduced [38-40]. Then, a transducer can gently pass through the anal canal in many cases without so pain or resistance. Radiologists or urologists try to move the transduce tip to the posterior prostate capsule as close as possible in order to shorten the distance between transducer tip and prostate tumor. Shortening the tumor-to-transducer distance is useful for precise tumor targeting. If these procedures do not work, general anesthesia is recommended for prostate biopsy.
Prostate biopsy in absent anus
Those who have a history of Miles’ operation due to ano-rectal cancer do not have anus. Therefore, radiologists or urologists cannot perform TRUS but transperineal US-guided biopsy. Most peri-rectal fat as well as the rectal cancer is surgically removed and thus prostate becomes closer to the perineum (Fig. 6) [37,41,42]. Accordingly, a PI-RADS 4 or 5 lesion can be depicted when transducer tip is pushed to the perineum [37,41,42]. As a tumor becomes larger or closer to the apex, cancer detection rate increases. Park et al. [41] reported that PI-RADS 5 lesions were all depicted and targeted on transperineal biopsy.
Important technical tips of transperineal biopsy are sufficient local anesthesia, pushing transducer constantly, and keeping US images good for lesion targeting [41]. Perineum is very sensitive to the pain and thus local anesthesia is repeated many times to kill pain completely. Pushing transducer is important to shorten the tumor-to-transducer distance for good tumor depiction and targeting. Unlike TRUS, keeping a transducer constant to the perineum is difficult because it is not introduced into hollow viscus. Besides, lidocaine or US gel makes it slippery and difficult to fix at the skin entry site of a biopsy needle.
HOW TO REDUCE BIOPSY COMPLICATIONS
Prior to biopsy, patients need to fast for at least 6 hours and to empty their recto-sigmoid colon to remove fecal material as much as possible [43]. Acute prostatitis is one of the frequent complications and can result in life-threatening complications such as abscess formation and sepsis [44-46]. Antibiotic medication is recommended from one day before biopsy to post-biopsy 3 to 5 days [47-49]. During the biopsy procedures, a biopsy needle should be draped with sanitizer just before each core is sampled. This sterile procedure reduced the incidence of acute prostatitis in my institute. Radiologists and urologists are recommended to perform TRUS immediately after biopsy is completed [50]. They can detect biopsy tracts to determine if they target a tumor precisely and bleed actively. The tracts are seen as hyperechoic or hypoechoic lines [36,50]. When the hyperechoic lines are crossing the tumor, this finding indicates that tumor targeting is precise. When blood flow is seen in the hypoechoic lines, transducer compression is useful under the guidance of color Doppler TRUS [50]. If the bleeding is stopped, blood flow is not seen any longer on color Doppler TRUS. The hypoechoic line frequently becomes hyperechoic because of thrombosis.
CONCLUSION
Current TRUS cannot be merely a guiding tool for prostate biopsy but used for cancer detection. This imaging modality has potential to depict many significant cancers which are detected or missed on MR images. Therefore, radiologists or urologists need to be familiar with new TRUS imaging features and techniques to target a significant cancer.
PDF Links
PubReader
ePub Link
XML Download
Full text via DOI
Download Citation
Print
