REVIEW ARTICLE Prostate Biopsy for the Interventional Radiologist Cheng William Hong, BS, Hayet Amalou, MD, Sheng Xu, PhD, Baris Turkbey, MD, Pingkun Yan, PhD, Jochen Kruecker, PhD, Peter A. Pinto, MD, Peter L. Choyke, MD, and Bradford J. Wood, MD ABSTRACT Prostate biopsies are usually performed by urologists in the office setting using transrectal ultrasound (US) guidance. The current standard of care involves obtaining 10–14 cores from different anatomic sections. Biopsies are usually not directed into a specific lesion because most prostate cancers are not visible on transrectal US. Color Doppler, US contrast agents, elastography, magnetic resonance (MR) imaging, and MR imaging/US fusion are proposed as imaging methods to guide prostate biopsies. Prostate MR imaging and fusion biopsy create opportunities for diagnostic and interventional radiologists to play an increasingly important role in the screening, evaluation, diagnosis, targeted biopsy, surveillance, and focal therapy of patients with prostate cancer. ABBREVIATIONS BPH = benign prostatic hyperplasia, PSA = prostate-specific antigen, US = ultrasound Indications for prostate biopsy include a positive digital rectal examination (focal nodule, stiffness, or asymmetry), clinical symptoms, high serum prostate-specific antigen (PSA), or PSA velocity (increase in PSA per year). Prostate biopsy is also performed to monitor known cancers for transformation to a more aggressive pheno- type. The standard of care involves obtaining 10–14 cores from different anatomic sections of the prostate. How- ever, transrectal ultrasound (US) has low sensitivity and is limited by significant overlap in the appearances of benign changes and malignancy (1–3). Prostate cancer remains the only solid tumor in which biopsy is not directed at visualized lesions. Interest in imaging methods to guide biopsy is rapidly growing, which creates opportunities for interventionalists to leverage their expertise in image- guided procedures to contribute to this field. Until more recently, PSA screening has been the primary determinant for prostate biopsies in the general population, but it has resulted in overdiagnosis and overtreatment, without a definite survival benefit(4–6). The role of PSA screening in prompting biopsies has been called into question by the United States Preventive Task Force (7). PSA screening is now performed on an individualized basis after discussion of the risks and benefits of screening. Before imaging methods were available, prostate biopsy was guided by direct palpation. The use of transrectal US began in the early 1970s with the advent of ultrasound (US), and the original sextant biopsy scheme (six cores from the base, middle, and apex bilaterally) improved detection over digital guidance (8). Meta-analysis of 87 studies showed that doubling the number of cores (to 12, by obtaining medial and lateral cores in the traditional 6- sextant scheme) improved cancer detection by 31% (9). The 12–18 core systematic biopsy became the standard in the 2000s. The increase in biopsy cores from 6 to 12 is not associated with measurable increased morbidity after biopsy (10). The logical extension of this increase in biopsy cores was saturation biopsy, which involves sampling the entire gland. Saturation biopsy is reserved for patients with persistently increasing PSA and a history of negative biopsy results (11). In an attempt to provide better image guidance of prostate biopsies, numerous US-based technologies were & SIR, 2014 J Vasc Interv Radiol 2014; 25:675–684 http://dx.doi.org/10.1016/j.jvir.2013.12.568 P.Y. and J.K. are salaried employees of Philips Research North America. NIH and Philips Healthcare have a cooperative research and development agree- ment and may have intellectual property in this field. In Vivo Corp. is a subsidiary of Philips Healthcare. From the Center for Interventional Oncology, Clinical Center (C.W.H., H.A., S.X., P.Y., J.K., B.J.W.), and Molecular Imaging Program (B.T., P.L.C.) and Urologic Oncology Branch (P.A.P.), National Cancer Institute, National Insti- tutes of Health, 10 Center Drive MSC 1182, Bethesda, MD 20892; and Philips Research North America (P.Y., J.K.), Briarcliff Manor, New York. Received September 26, 2013; final revision received December 14, 2013; accepted December 22, 2013. Address correspondence to: B.J.W.; E-mail: bwood@ nih.gov
Transcript
REVIEW ARTICLE
Prostate Biopsy for the Interventional Radiologist
Peter A. Pinto, MD, Peter L. Choyke, MD, and Bradford J. Wood, MD
ABSTRACT
Prostate biopsies are usually performed by urologists in the office setting using transrectal ultrasound (US) guidance. Thecurrent standard of care involves obtaining 10–14 cores from different anatomic sections. Biopsies are usually not directed into aspecific lesion because most prostate cancers are not visible on transrectal US. Color Doppler, US contrast agents, elastography,magnetic resonance (MR) imaging, and MR imaging/US fusion are proposed as imaging methods to guide prostate biopsies.Prostate MR imaging and fusion biopsy create opportunities for diagnostic and interventional radiologists to play anincreasingly important role in the screening, evaluation, diagnosis, targeted biopsy, surveillance, and focal therapy of patientswith prostate cancer.
Indications for prostate biopsy include a positive digitalrectal examination (focal nodule, stiffness, or asymmetry),clinical symptoms, high serum prostate-specific antigen(PSA), or PSA velocity (increase in PSA per year).Prostate biopsy is also performed to monitor knowncancers for transformation to a more aggressive pheno-type. The standard of care involves obtaining 10–14 coresfrom different anatomic sections of the prostate. How-ever, transrectal ultrasound (US) has low sensitivity and islimited by significant overlap in the appearances of benignchanges and malignancy (1–3). Prostate cancer remainsthe only solid tumor in which biopsy is not directed atvisualized lesions. Interest in imaging methods to guidebiopsy is rapidly growing, which creates opportunities for
& SIR, 2014
J Vasc Interv Radiol 2014; 25:675–684
http://dx.doi.org/10.1016/j.jvir.2013.12.568
P.Y. and J.K. are salaried employees of Philips Research North America. NIHand Philips Healthcare have a cooperative research and development agree-ment and may have intellectual property in this field. In Vivo Corp. is asubsidiary of Philips Healthcare.
From the Center for Interventional Oncology, Clinical Center (C.W.H., H.A.,S.X., P.Y., J.K., B.J.W.), and Molecular Imaging Program (B.T., P.L.C.) andUrologic Oncology Branch (P.A.P.), National Cancer Institute, National Insti-tutes of Health, 10 Center Drive MSC 1182, Bethesda, MD 20892; and PhilipsResearch North America (P.Y., J.K.), Briarcliff Manor, New York. ReceivedSeptember 26, 2013; final revision received December 14, 2013; acceptedDecember 22, 2013. Address correspondence to: B.J.W.; E-mail: [email protected]
interventionalists to leverage their expertise in image-guided procedures to contribute to this field.Until more recently, PSA screening has been the
primary determinant for prostate biopsies in the generalpopulation, but it has resulted in overdiagnosis andovertreatment, without a definite survival benefit (4–6).The role of PSA screening in prompting biopsies hasbeen called into question by the United States PreventiveTask Force (7). PSA screening is now performed on anindividualized basis after discussion of the risks andbenefits of screening.Before imaging methods were available, prostate biopsy
was guided by direct palpation. The use of transrectal USbegan in the early 1970s with the advent of ultrasound(US), and the original sextant biopsy scheme (six coresfrom the base, middle, and apex bilaterally) improveddetection over digital guidance (8). Meta-analysis of 87studies showed that doubling the number of cores (to 12,by obtaining medial and lateral cores in the traditional 6-sextant scheme) improved cancer detection by 31% (9).The 12–18 core systematic biopsy became the standard inthe 2000s. The increase in biopsy cores from 6 to 12is not associated with measurable increased morbidityafter biopsy (10). The logical extension of this increase inbiopsy cores was saturation biopsy, which involvessampling the entire gland. Saturation biopsy is reservedfor patients with persistently increasing PSA and a historyof negative biopsy results (11).In an attempt to provide better image guidance of
prostate biopsies, numerous US-based technologies were
Hong et al ’ JVIR676 ’ Prostate Biopsy for the Interventional Radiologist
introduced, including Doppler-targeted strategies, real-timeelastography, and US contrast agents. Other US techniquesinclude three-dimensional US (TargetScan; EnvisioneeringMedical Technologies, Pittsburgh, Pennsylvania) and tissuecharacterization algorithms (HistoScanning; AdvancedMedical Diagnostics SA/NV, Waterloo, Belgium).MR imaging of the prostate appears to be the most
sensitive method for detecting prostate cancer by imag-ing. Direct biopsies under MR imaging guidance havebeen attempted but prove to be inefficient and uncom-fortable for patients. Higher cancer detection rates weredemonstrated when MR imaging obtained before biop-sy was fused to real-time transrectal US to guide thebiopsy to lesions seen on MR imaging (12). Techniquesfor fusion guidance include electromagnetic tracking(UroNav; Invivo Corporation, Gainesville, Florida) im-age processing (MIM Symphony; MIM Software Inc.,Cleveland, Ohio, and Urostation; KOELIS, La Tronche,France), optical tracking (Hologic, Bedford, Massa-chusetts), and encoded mechanical arm/passive robotic(Artemis; Eigen, Grass Valley, California).
PROSTATE ANATOMY AND ZONAL
DISTRIBUTION
The prostate gland is composed of peripheral, transitional,and central zones. The peripheral zone is disc-shaped andconstitutes 70% of the prostate gland (Fig 1a, b). Its ductsradiate laterally from the urethra lateral and distal to theverumontanum (13). The central zone constitutes 25% ofthe prostate gland and surrounds the prostatic urethra. Itsducts arise close to the ejaculatory duct orifices at theverumontanum and branch laterally near the prostate base.The transitional zone, which is not separable from thecentral zone on MR imaging, is found anterior and lateralto the prostatic urethra and constitutes the remaining 5%of the glandular prostate. In benign prostatic hyperplasia(BPH), the central zones grow disproportionately andeventually surpass the volume of the peripheral zone (3).
INDICATIONS AND CONTRAINDICATIONS
FOR PROSTATE BIOPSIES
Indications for prostate biopsy include suspicion ofprostate cancer, abnormal digital rectal examination,
Figure 1. Normal anatomy of the prostate on (a) axial and (b) sagitta
elevated serum PSA, or PSA velocity. Detailed screeningguidelines are available from the National Compre-hensive Cancer Network guidelines for early cancerdiagnosis (14). The benefit of PSA screening is greaterin African-Americans, patients with a positive familyhistory, and patients taking 5-alpha-reductase inhibitors(which increase the predictive capacity of PSA). PSA isnonspecific; in addition to prostate cancer, prostatitisand BPH can cause the PSA level to increase (15). TheAmerican Cancer Society recommends that average-riskmen expected to live at least 10 more years shoulddiscuss screening for prostate cancer at age 50 with theirphysician (16). Practically speaking, these recom-mendations may be difficult to interpret or to translateinto real-life guidance. The benefits of PSA screeningmust be weighed against the risks of overdiagnosis.The most commonly used threshold for PSA is 4.0 ng/
mL. Lowering the normal threshold for PSA to 2.5 ng/mL has been suggested, but this doubles the number ofmen defined as abnormal and does not clearly result in abenefit (17). Use of PSA velocity is also controversial.One study demonstrated an association between prostatecancer and PSA velocity 4 0.75 ng/mL/y (18); however,data from the European Randomized Study of ScreeningProstate Cancer in Rotterdam did not show that PSAvelocity improved detection (19).Relative contraindications to prostate biopsy include
coagulopathy, painful anorectal conditions, significantimmunosuppression, acute prostatitis, and an absentrectum.
CARE BEFORE BIOPSY PROCEDURE AND
ANTIMICROBIAL PROPHYLAXIS
The use of prophylactic antibiotics before transrectalprostate biopsy to reduce infection risk is recommendedby the American Urological Association Best PracticePolicy Statement on Urological Surgery Antimicrobi-al Prophylaxis guidelines (20). There is no single stan-dard protocol, and practice patterns vary widely, oftenby geography and relative levels of bacterial antibio-tic resistance in the community. However, fluoro-quinolones are generally preferred because of theirbroad-spectrum coverage against Escherichia coli, the most
l view. The peripheral zone is indicated by arrows.
Figure 2. Coronal view of standard extended 12-core prostate
Figure 3. Axial image demonstrating central calcifications and
a hypoechoic lesion (cursors).
Volume 25 ’ Number 5 ’ May ’ 2014 677
likely infectious organism after biopsy. In addition, fluo-roquinolones demonstrate excellent tissue penetration inthe prostate. Alternatives to ciprofloxacin include amino-glycosides with metronidazole or clindamycin (20).Quinolone resistance is responsible for most infectious
complications after prostate biopsy, with overall ratesvarying between o 1% and 5% (21). If patients presentwith symptoms after prostate biopsy, empiric treatmentwith ceftriaxone, ceftazidime, or amikacin is indicatedbecause approximately 50% of etiologic agents arequinolone-resistant (22). There is currently no definiteevidence for the superiority of a longer course ofantibiotics (3 d vs 1 d) or multiple-dose treatment oversingle-dose treatment (23). The prescription of a self-administered enema before biopsy is common, but thevalue of doing so is debated (24).
STANDARD TECHNIQUES
Nerve BlockBilateral nerve blockade facilitates the procedure byhelping to keep the patient immobile and markedlyimproving patient comfort for an otherwise uncomfort-able procedure. Blockade can be done quickly with USguidance targeting the lateral edge of the periprostatictissues in several injections on each side, taking care toinfiltrate the tissue planes surrounding the capsule andadjusting the needle injections slightly to promote broaddistribution to the nerve plexus. The needle should beadvanced and retracted to ensure injections occur inmultiple planes. Typical regimens include 10 mL of 1%lidocaine delivered bilaterally (20 mL total) via the USneedle guide slowly injected in several different trans-rectal punctures. The echogenic “fat triangle” betweenthe posterior-lateral surface of the prostate and theseminal vesicles is a common landmark. The anestheticcan also be administered adjacent to the apex or into theDenonvilliers fascia (1).Regardless of the site chosen, both sides of the
periprostatic nerve plexus should be injected, and severalminutes should be given to allow the lidocaine todistribute and take effect. Injecting directly into theprostate gland is of no benefit (1). Care needs to betaken not to move the US transducer with the needledeployed, or rectal mucosa would be torn. Tracking theamount of the hub side of the needle outside the patientis the best way to guarantee that the needle is notinserted in the rectum and that it is safe to move the USprobe. Topical lidocaine gel can also be used to reducethe discomfort of US probe insertion and needlepuncture. Because the patient is awake, the nerveblock can be repeated if it is inadequate.
Standard 12-Core Transrectal US BiopsyPatients are generally positioned in the left lateraldecubitus position with knees to the chest and flexedhips on the table edge, allowing mobility of the US
transducer. Core biopsy specimens are obtained using adisposable spring-loaded biopsy needle (Bard BiopsySystems, Tempe, Arizona) inserted parallel to the end-fire US probe through an attached disposable transrectalneedle guide (CIVCO Medical Solutions, Kalona, Iowa).The spring is much stronger than from standard percu-taneous coaxial biopsy kits. The conventional biopsyconsists of 12 cores: the base, middle, and apex sextantregions are sampled in both the lateral and the medialaspects of each sextant region bilaterally (Fig 2).
US-Guided BiopsyA standard transrectal US–guided biopsy begins with abrief survey of the prostate gland to identify nodules,which are most often in the peripheral zone and usuallyhypoechoic but may be hyperechoic (Fig 3). Gray-scaletransrectal US has low sensitivity and specificity forprostate cancer compared with MR imaging.To confirm the presence of a nodule, scanning should
be performed in two planes, typically the axial andsagittal planes. This scanning can be accomplished byrotating the probe slowly while maintaining the nodulein view (Fig 4a, b). Sagittal plane imaging is typically in
Figure 4. (a) Hypoechoic lesion (cursors) on axial view. (b) US probe was rotated to show lesion (arrows) on sagittal view.
Hong et al ’ JVIR678 ’ Prostate Biopsy for the Interventional Radiologist
an extreme lateral plane because the image at this planeis composed almost entirely of peripheral zone.End-fire probes have curved array detectors on the
probe tip, whereas side-fire US probes have longitudinaltransducers. End-fire transrectal US probes are reportedto have higher cancer detection rates compared withside-fire US probes (25,26), which are limited to alongitudinal biopsy trajectory. End-fire probes allowbetter sampling in lateral and anterior aspects of pro-static tissue, which are typically undersampled (26).However, in one prospective study involving experi-enced urologists, US probe configurations did not dif-fer in cancer detection rates (27).Calcifications and linear hypoechoic “bands” in the
peripheral zone with very straight edges (which are bestvisualized in only one plane) are common benignfindings. Central region nodules can have a wide varietyof appearances but commonly represent BPH. Trans-rectal US generally is poor at determining the presenceof extracapsular extension. When the targets are identi-fied, core biopsy specimens can be obtained with thetransrectal US biopsy guide electronically superimposedover the US image. Movement of the transrectal USprobe should be carefully considered because it is easy tobecome anatomically disoriented. Transrectal USmanipulations should be performed in one plane at atime; this allows for better control over the planning ofthe needle pathway with real-time imaging feedback.Also, it is easier to retrace steps to retarget the biopsy if asystematic approach is used.
Saturation BiopsyWith a saturation biopsy, many cores (often 4 20) areobtained throughout the prostate aiming to samplevirtually all of the tissue at regular intervals. Saturationbiopsy is not used as the initial form of prostate biopsy(11) and typically has been reserved for patients withprevious negative biopsy results for whom there con-tinues to be a high degree of clinical suspicion forprostate cancer. The risks of missing significant cancershould be balanced with the possibility of detecting aclinically unimportant cancer. The increased number ofcores does not appear to be associated with a detectable
increased risk of complications (11). However, the highcost (each biopsy procedure is often separately billed)and requirement for deeper levels of anesthesia in thehospital setting make it less attractive.
Fine-Needle AspirationMost prostate biopsy specimens are obtained as coresamples. Although controversial, some studies haveshown that fine-needle aspiration biopsy of the prostategland may be as effective as core biopsies in cancerdetection but not in characterization or scoring (28).However, because Gleason scoring is such an importantpart of prostate cancer management, fine-needle aspira-tion is unlikely to replace core biopsies.
Transperineal BiopsyAlthough most prostate biopsy specimens are obtainedtransrectally, there are reasons to consider the trans-perineal approach. Anatomically, the transperineal ap-proach may identify proportionally more anteriortumors (29). In addition, the biopsy does not entailcrossing the rectal mucosa with presumably lower ratesof infections. Detection rates, cancer core rates, and compli-cations are generally comparable between the trans-perineal and transrectal approach (30). Transperinealbiopsy may be used for patients in whom there is norectal access because of surgery.One disadvantage is that transperineal biopsies may
require spinal or general anesthesia or deep sedation,limiting its use in the office setting. However, thetransperineal approach may be useful in guiding biopsiesunder MR imaging. A brachytherapy grid or stepper,which is a plastic block with predrilled holes, is used todirect the needles to the proper location. Robotic orsemiautomatic needle guide devices are also available foruse with MR imaging guidance via the transperinealapproach (Invivo Corporation).Such approaches may also prove useful for focal laser
ablation or cryoablation. When thermal energy methods(eg, laser ablation) are used, MR imaging guidance canprovide real-time thermometry of the treatment to theoperator of the ablation device.
Figure 5. Region of the left base peripheral zone demonstrates
hypervascularity (arrow). (Available in color online at www.jvir.org.)
Volume 25 ’ Number 5 ’ May ’ 2014 679
COMPLICATIONS
Prostate biopsy is generally considered to be safe. Oninitial biopsy, the risk of sepsis is o 0.1%, and the risk ofrectal bleeding is 2.1%. Mild hematuria and hemato-spermia are common, occurring in 62% and 9.8% ofpatients, respectively. The morbidity of repeat biopsydoes not differ significantly from morbidity of the initialbiopsy (31). Patients should be counseled to hydrate wellafter biopsy and to expect to see blood in their urine forseveral days. Because hematospermia is typically notclinically meaningful but may last many weeks, it shouldbe discussed to avoid anxiety. Persistent blood, dizziness,or fever should be reported immediately. In a study ofMedicare participants, the overall risk of hospitalizationwithin 30 days of a prostate biopsy (6.9%) was sig-nificantly higher than randomly selected controls (2.7%)(32). When a transrectal prostate biopsy specimen isobtained, fecal matter may be introduced into theprostate and presents an infection risk. Although it isplausible that a self-administered enema may reduce thefecal matter present, it has not been shown to decreasecomplication rates, and serious infections can occurnotwithstanding enemas done before the biopsy proce-dure (24).
ADVANCED BIOPSY GUIDANCE
TECHNIQUES
Doppler and ElastographyColor and power Doppler are based on the frequencyshift caused by the movement of specular reflectors(typically red blood cells) relative to the US probe.Detection of the Doppler shift can show the directionand speed of blood flow. Flow is usually minimal andsymmetric in the normal prostate gland, although colorDoppler signal may be seen in neurovascular bundlesand pericapsular and periurethral arteries as well as aweb of periprostatic veins (1). Areas of focal orasymmetric hypervascularity within the gland are morelikely to demonstrate malignancy (Fig 5). However, thefinding is nonspecific because some tumors are hypo-vascular, whereas some benign lesions, particularlyprostatitis, are hypervascular (33). Color Doppler canimprove sensitivity, but the effect on specificity is not aspronounced (34). The term “color Doppler” refers to thepeak Doppler shift measured by the probe. The term“power Doppler” (the Doppler display is also in color)refers to the area under the Doppler curve and tends tohave better signal-to-noise ratios. However, power Dop-pler is not markedly more accurate than color Doppler(35).Cancerous tissue often has increased blood flow,
which can be seen with US contrast agents. US contrastagents are microbubbles with a thin membrane contain-ing gas. In one large retrospective study, the per-patient
detection rate of contrast-enhanced Doppler US–tar-geted biopsy was 27% compared with 23% with system-atic biopsy, with a detection rate of 31% when bothmodalities were combined (36). When contrast-enhancedDoppler–targeted biopsy was positive, significantlyhigher Gleason scores were found (37).US elastography quantifies the stiffness of tissue
during the manual compression of the gland by thetransducer (1). Tumors typically have increased stiffnesscompared with the surrounding tissue. Tumor stiffnesscan also be detected with shear-wave elastography,which analyzes the US signal from propagating a shearwave through tissue to measure the elastic modulus in aquantitative and operator-independent way. TargetedUS elastography may improve cancer detection com-pared with systematic biopsy, even with fewer coresobtained, by having a significantly higher cancer detec-tion rate per core (38). Although the use of these tech-niques for targeted biopsy can potentially improve detec-tion rates of prostate cancer, limitations include therequirement for technical expertise, lack of updated eq-uipment, subjective interpretive criteria, and interuservariability.
MR Imaging as Diagnostic ToolFor noninvasive detection of prostate cancer, MRimaging has superior soft tissue resolution and bettervisualization of surrounding anatomy compared withconventional US. Classic prostate MR imaging involvesplacement of an endorectal coil in the patient’s rectum toobtain higher signal. Although a body or surface coil canbe used instead, sensitivity and specificity of MR imag-ing are reduced. Nonetheless, modern 3-tesla MR imag-ing scanners can obtain imaging of the prostate ofexcellent quality with only multichannel phased arraysurface coils. MR imaging relies on multiple parametersto achieve its accuracy. Multiparametric MR imagingconsists of a combination of T2-weighted imaging,diffusion-weighted imaging (which generates apparent
demonstrates increased choline-to-citrate ratio within the right peripheral zone lesion (arrow from asterisk to graph). Biopsy of this
lesion was performed under transrectal US/MR imaging fusion system guidance, and the biopsy specimen was found to include
Gleason 8 (4 þ 4) tumor. (Available in color online at www.jvir.org.)
Hong et al ’ JVIR680 ’ Prostate Biopsy for the Interventional Radiologist
diffusion coefficient maps), MR spectroscopy, anddynamic contrast enhanced MR imaging (Fig 6a–e).As more of these parameters turn positive, a lesion canbe assigned a higher suspicion level (Table) (39,40).To some extent, multiparametric MR imaging is
predictive of tumor aggressiveness or grade. On T2-weighted imaging, prostate cancers typically demon-strate lower signal intensity compared with the highsignal intensity of normal prostate tissue, especially inthe peripheral zone where most cancers reside (41).Gleason and D’Amico clinical risk scores are also nega-tively correlated with the apparent diffusion coefficientsderived from diffusion-weighted MR imaging (39). On
MR spectroscopy, prostate cancer foci are associatedwith decreases in citrate and an elevation of the cholinepeak, although this is the least commonly used of thefour MR sequences and requires considerable off-linedata processing (42).The assignment of suspicion level on multiparametric
MR imaging correlates with both the D’Amico riskstratification in visible lesions in the prostate and thecancer detection rate (Table) (39,43,40). In addition,multiparametric MR imaging can be used to detectclinically significant anterior tumors, which may bemissed on transrectal US biopsy (44). Compared withradical prostatectomy pathology, multiparametric MR
imaging has been shown to improve the classificationaccuracy when used with standard clinical criteria forpatient selection for active surveillance (45). MRimaging can be used to estimate tumor volumesaccurately (46), and in one study lesions localized onimaging had a 98% positive predictive value for prostatecancer compared with whole-gland histology, withgreater sensitivity for higher grade tumors (47). Scoresfor tumor visibility on T2-weighted MR imaging werealso predictive of upgrading of Gleason scores onconfirmatory biopsy compared with initial staging (48).
MR Imaging–Guided BiopsiesBecause regions suspicious for tumor may be visualizedon MR imaging, imaging can also be used to guideprostate biopsy (49). This guidance may be particularlyimportant in the setting of anterior or central lesionsbecause systematic biopsy targets only the lateral peri-pheral zone. MR imaging guidance has been perform-ed in both open and closed-bore MR imaging systems.Although open systems allow easy access to the patient,closed-bore systems offer much higher signal-to-noiseratios and clearer prostate cancer visualization (3). Mostin-gantry MR imaging–guided biopsy studies have useda transrectal approach with a closed-bore 3-tesla MRimaging system and an endorectal applicator (3).Diagnostic multiparametric MR imaging is performedbefore the biopsy for planning purposes (50). The needleguide may be filled with gadolinium-based contrastmaterial for visualization on MR imaging, and thereare commercial automated or robotic systems for trans-rectal and transperineal access. However, all devicesmust be MR-compatible, and the patient must be in theMR imaging gantry throughout the procedure, often inthe uncomfortable prone position. Because they mayoccupy four slots on an MR imaging schedule, these
devices are costly and burdensome on the limitedresource of MR imaging. Urologists may also havelimited access to an MR imaging suite reducing theirwillingness to refer patients for guided biopsy. MRimaging/US fusion has been developed to address theseissues (51).
MR Imaging/US Fusion BiopsiesMR imaging/US fusion superimposes diagnostic MRimages obtained before the biopsy procedure over a real-time US image obtained at a different time and place.This fusion allows targeting of suspicious lesions seen onMR imaging for biopsy under real-time US (Fig 7a, b).The goal is to combine the high soft tissue resolution ofthe MR image with the real-time visualization of trans-rectal US, in a more comfortable office setting withoutrequiring the physical presence of the MR imaginggantry. The operator can guide the biopsy needle tospecific locations after coregistering the imaging usingelectromagnetic sensors, which allow the system todetermine the spatial position of the US probe. Theregistration process requires a volumetric US image.Volumetric data can be obtained by performing a fan-shaped sweep (UroNav), by spinning an end-fire USprobe attached to a mechanical arm (Artemis), or byusing a three-dimensional US probe (Urostation). Cor-egistration with automatic motion compensation canreregister US and MR imaging if the patient moves orthe prostate deforms.Although some investigators have attempted to per-
form “cognitive fusion” (ie, use the human brain toestimate the location of a lesion on transrectal US),results are better with a standardized fusion approach.More recent studies have shown that MR imaging/USfusion significantly increases the per-core and per-patientcancer detection rates (12). In one cohort, the per-core
Figure 7. MR imaging registered with US visualized in the (a) axial plane and (b) sagittal plane. A biopsy target is located in the left
apical middle area of the prostate and visualized in red. The needle trajectory is shown by the red dots, and the orange line maps the
biopsy location for archiving and later use. (Available in color online at www.jvir.org.)
Figure 8. Cancer detection rates for biopsy cores were com-
pared between standard 12-core transrectal US biopsy alone
and MR imaging/US fusion–guided biopsy alone. TRUS ¼transrectal ultrasound. (Reproduced with permission from Pinto
PA, Chung PH, Rastinehad AR, et al. Magnetic resonance
cancer detection following transrectal ultrasound biopsy and
correlates with multiparametric magnetic resonance imaging.
J Urol 2011; 186:1281–1285.) (Available in color online at www.jvir.org.)
Hong et al ’ JVIR682 ’ Prostate Biopsy for the Interventional Radiologist
detection rate was 20.6% for MR imaging/US fusioncompared with 11.7% for transrectal US biopsy, andMR imaging/US fusion biopsy in conjunction withtransrectal US biopsy achieved an overall per-patientdetection rate of 54.4% (12). The fusion between the twomodalities is not exact; the error in one fusion systemwas 2.4 mm � 1.2 in phantoms and patients, implyingthat small lesions may still be missed (51). In aprospective study, cores obtained from MR imaging/US fusion had approximately twice the detection rate ofsystematic transrectal US biopsy overall and were higherrisk cancers (Fig 8) (12). In addition, MR imaging/USfusion prostate biopsy is capable of increasing detectionrates in patients with enlarged prostates (52) and patientswith a history of negative results of standard biopsies(53), where detection rates are lower. The addition oftargeted cores upgrades the Gleason score over standardbiopsy in 32% of cases (54). The targeted biopsiesdetected 67% more Gleason Z 4 þ 3 tumors butmissed 36% of the Gleason r 3 þ 4 tumors. Bytargeting the suspicious lesions with this platform, it ispossible to sample selectively areas more likely tocontain malignancy and detect preferentially highergrade tumors more likely to warrant intervention.However, because this is a newer technique, long-termoutcomes of MR imaging/US fusion biopsy are not wellstudied.
Repeat Biopsy after Initial Negative
BiopsyThe decision whether to accept a negative biopsy resultdepends on the probability of a positive result beforetesting as well as the effect of a positive biopsy result onclinical management. The presence of clinical symptoms,palpable lesions, increasing PSA levels, lesions visible onMR imaging, or a strong family history of prostatecancer should prompt further exploration of an initial
negative transrectal US biopsy result. In addition, thereis a greater chance of achieving a survival benefit bypursuing cancer detection and treatment in younger andhealthier patients.In a study of sequential systematic biopsies, the
detection rates of the first, second, third, and fourthbiopsy were 22%, 10%, 5%, and 4%; the third and fourthbiopsy attempts had slightly higher complication ratesand detected lower grade tumors (55). Saturation biopsymay be able to increase detection rates in patients withprior negative biopsy results (11). Most studies of MRimaging–guided fusion biopsy involve patients who haveundergone at least one negative conventional transrectalUS biopsy. In this population, detection rates rangefrom 38%–59% (3). In a cohort of 195 men with prior
negative biopsy results, 37% of subjects were found tohave cancer using a combination of transrectal US–guided and MR imaging/US fusion biopsy (53). High-grade (Gleason score Z 8) cancer was found in 11% ofsubjects; 55% of these high-grade cancers were missed onstandard biopsy. Pathologic upgrading occurred in 39%as a result of fusion biopsy.
DISCUSSION
Multimodality MR imaging, US, and image-guidedprocedures such as fusion biopsy are altering the stand-ard of care for prostate cancer. This review highlights theimportance of imaging and fusion approaches for accu-rate diagnosis and characterization of prostate cancer.Advanced imaging such as MR imaging has not yet beenbroadly applied to screen, diagnose, or target biopsy forprostate cancer. However, there is great interest in thesemethods because it is recognized that standard biopsiesmay create more problems than they solve. Specificindications and patient selection have not yet been welldefined for when to use MR imaging or fusion technol-ogy. Consensus on the ideal techniques should becomeclearer as data emerge on when to use which approach.Possible clinical indications include T1c lesions, priornegative transrectal US biopsy result with high clinicalsuspicion, or MR imaging–identified lesions.The standard method for “blind” transrectal US
biopsy has a low sensitivity and specificity for prostatecancer. “Blind” systematic transrectal US biopsy sup-posedly obtains specimens in an even distribution, butthe distribution of the biopsy needles is highly variableand operator-dependent. In one autopsy study, thesensitivity of detecting cancer by obtaining six coresfrom each of the medial and lateral peripheral zones wasestimated at 53% (56). The diagnostic yield when ob-taining 4 12 cores seems to depend more on the biopsysite than the number of cores obtained (56); this isconcordant with the observation that saturation biopsydoes not improve detection rates when used as an initialtechnique (11). A fundamental limitation to thesensitivity of “blind” techniques is imposed because theamount of unsampled tissue dwarfs the amount that isobtained.The fusion approach to prostate biopsy has not yet
been widely adopted but has become widely availablecommercially, with at least three companies offeringcompeting products. Cancer detection depends on malig-nancy being present in anatomic regions that wereselected a priori, which may explain why some patientswith high suspicion for prostate cancer can have repeat-edly negative biopsy results. In conclusion, the role ofimaging guidance with MR imaging, MR imaging/trans-rectal US fusion, and advanced US tools offers interven-tional and diagnostic radiologists new opportunities tocontribute to the field of prostate biopsy. In all
likelihood, the impact of MR imaging/transrectal USfusion technology will rely on multidisciplinary team-work, where radiologists interpret the MR images, whichare then used by urologists or interventional radiologiststo perform office-based fusion biopsy. The best proce-dures will leverage the skill sets of both urologists andradiologists in a collaborative team approach. The use ofreal-time navigation systems for spatial cancer mappingcould improve the diagnostic yield of biopsy and couldplay a major role in the screening, evaluation, diagnosis,surveillance, and management of patients with prostatecancer.
ACKNOWLEDGMENT
This work was supported by the Center for Interven-tional Oncology, the National Cancer Institute, and theIntramural Research Program of the National Institutesof Health (NIH). NIH and Philips Research NorthAmerica have a Cooperative Research and DevelopmentAgreement. This research was made possible through theNIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH andgenerous contributions to the Foundation for the NIHfrom Pfizer Inc, The Leona M. and Harry B. HelmsleyCharitable Trust, and the Howard Hughes MedicalInstitute as well as other private donors. For a completelist, please visit the Foundation website at http://www.fnih.org/work/programs-development/medical-research-scholars-program. The content of this publication doesnot reflect the views or policies of the Department ofHealth and Human Services, and mention of tradenames, commercial products, or organizations does notimply endorsement by the U.S. Government.
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