R A D I O L O G I CC L I N I C S

O F N O R T H A M E R I C A

Radiol Clin N Am 45 (2007) 207–222

207

Imaging of Prostate CancerOguz Akin, MDa,b,*, Hedvig Hricak, MD, PhDa,b

- Screening- Diagnosis- Tumor detection and staging

Transrectal ultrasonographyCTMR imaging and MR spectroscopic

imaging- Nuclear medicine studies

Capromab pendetideimmunoscintigraphy

Radionuclide bone scintigraphyPositron emission tomography

- Treatment planning- Post-treatment follow-up

Follow-up after radical prostatectomyFollow-up after radiation therapy

- Summary- Acknowledgments- References

Prostate cancer is the most common cancer andone of the leading causes of cancer death in Amer-ican men. The American Cancer Society estimatesthat in 2006, 234,460 new cases of prostate cancerwill be diagnosed and 27,350 men will die fromthis disease in the United States [1]. The manage-ment of prostate cancer is challenging because thedisease has variable clinical and pathologic behav-ior. The choice of treatment should be patient spe-cific and risk adjusted, aimed at improving cancercontrol while reducing the risks of treatment-relatedcomplications. There is a growing demand for fur-ther individualization of treatment plans, which re-quires the accurate characterization of the locationand extent of cancer. This characterization necessi-tates the optimal use of imaging methods that playan integral role in prostate cancer management.

Risk factors for developing prostate cancer are ad-vanced age, ethnicity, and family history of the dis-ease. More than 65% of all prostate cancers occur inmen older than 65 years. African American men

0033-8389/07/$ – see front matter ª 2006 Elsevier Inc. All rigradiologic.theclinics.com

have the highest incidence of prostate cancer inthe world. Familial predisposition is seen in 5%to 10% of prostate cancers. A diet high in saturatedfat may also play a role.

Measurement of prostate-specific antigen (PSA)in blood and digital rectal examination (DRE) areoffered for early detection of the disease for menat average risk beginning at age 50 years and formen at high risk beginning at age 45 years.

Treatment options for prostate cancer vary de-pending on age, disease stage, potential side effectsof the treatment, and other medical conditions ofthe patient. Surgery, external beam radiation ther-apy, and brachytherapy can be used for treatmentof early-stage prostate cancer. Hormonal therapy,chemotherapy, radiation therapy, or a combinationof these can be used to treat metastatic disease oras supplemental therapies in early-stage disease.Watchful waiting without immediate treatment canbe offered in some older patients who have limitedlife expectancy or less-aggressive tumors.

a Weill Medical College of Cornell University, New York, NY, USAb Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York,NY 10021, USA* Corresponding author. Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 YorkAvenue, New York, NY 10021.E-mail address: akino@mskcc.org (O. Akin).

hts reserved. doi:10.1016/j.rcl.2006.10.008

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Today, more than 90% of prostate cancers are di-agnosed during early stages. Over the past 20 years,the 5-year survival rate for all stages increased from67% to 100% [1]. This improvement in 5-year sur-vival rate is mainly due to early diagnosis.

This article reviews the role of imaging in the di-agnosis and management of prostate cancer. Trans-rectal ultrasonography (TRUS), which can be usedto guide biopsy, is the most frequently used imag-ing technique in cancer detection. For determiningthe extent of disease, CT and MR imaging are themost commonly used modalities; bone scintigra-phy and positron emission tomography (PET)have roles only in advanced disease. Currently, therole of imaging in prostate cancer is evolving to im-prove disease detection and staging, to determinethe aggressiveness of disease, and to predict out-comes in different patient populations.

Screening

Prostate cancer screening is performed with DREand measurement of serum PSA level. Since the ad-vent of PSA screening, the incidence of prostate can-cer has increased, but most prostate cancers are nowdiagnosed at an early stage.

There are certain limitations to PSA screening.PSA is not specific for prostate cancer and can beelevated in other conditions including benignprostatic hyperplasia, inflammation, trauma, andurinary retention. Although cancerous prostate tis-sue produces far more PSA in the serum than hyper-plastic tissue, benign prostatic hyperplasia is themost common cause of elevated serum PSA concen-tration [2].

Patients who have abnormal DRE findings or el-evated PSA levels are further evaluated with prostatebiopsy. Establishing a threshold at which prostatebiopsy should be performed in asymptomatic pa-tients is very difficult. Using a cutoff value that istoo low may cause unnecessary biopsies or detec-tion of clinically insignificant cancers, whereas us-ing a cutoff value that is too high may preventdetection of early-stage but aggressive tumors. APSA level of 4.0 ng/mL is generally accepted as thelower limit for biopsy consideration [3].

Although PSA screening is a valuable tool in theearly detection of prostate cancer, it is only one ofthe factors used to assess the likelihood that a pa-tient has prostate cancer. Evaluation of other riskfactors and DRE results may necessitate prostate bi-opsy in some patients who have normal PSA levels.

Diagnosis

Needle biopsy, which is often guided by TRUS, con-tinues to be the ‘‘gold standard’’ for the diagnosis of

prostate cancer. TRUS provides reasonably good–quality images of the prostate and adjacent struc-tures and facilitates needle placement and tissuesampling.

The fact that prostate cancer is often a multifocaland heterogeneous disease makes diagnosis by bi-opsy difficult. Only a small amount of tissue is ob-tained with needle biopsy. Thus, sampling errorsare common. Initial TRUS-guided biopsy detectsprostate cancer in only 22% to 34% of the cases[4–6]. Thus, many patients require repeat biopsy.In patients who have initial negative results fromTRUS-guided prostate biopsy, prostate cancer is de-tected in 10% to 19% on the second, in 5% to 14%on the third, and in 4% to 11% on the fourth repeatbiopsy [4–6]. The traditional sextant biopsyschema, in which six parallel core samples are ob-tained, is now considered inadequate. Newer pros-tate biopsy strategies include higher numbers ofbiopsy samples from different regions of the pros-tate to improve cancer detection and risk assess-ment [7,8].

Tumor detection and staging

The TNM staging system is widely used to stageprostate cancer (Table 1) [9]. Although imagingtechniques are sometimes useful in the detectionof prostate cancer, their main use is in the stagingof the disease. A combination of the currently avail-able imaging modalities is usually necessary to helpdetermine appropriate treatment strategies.

Transrectal ultrasonography

In addition to its role in biopsy guidance, TRUS isa commonly used imaging method for the detec-tion and local staging of prostate cancer becauseof its widespread availability and ease of use.

TRUS provides good-quality images of the pros-tate gland because a high-frequency (5- to 7.5-MHz) probe can be placed in the rectum close tothe prostate. Prostate cancer is most often seen asa hypoechoic area within the peripheral zone. Upto 40% of prostate cancers, however, are isoechoic,limiting their detection with TRUS [10,11]. Thefinding of a hypoechoic area within the peripheralzone is not specific for prostate carcinoma andcan also be seen in benign processes such as prosta-titis and focal atrophy [11]. Therefore, TRUS hasa limited role in the detection of prostate cancer[12].

Capsular bulging and irregularity and the obliter-ation of the fat plane posterior to the prostate andof the rectoprostatic angle are findings suggestiveof extracapsular extension on TRUS. In addition,seminal vesicle invasion by the tumor can be ob-served on TRUS. The accuracy of TRUS in the

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Table 1: TNM staging system for stagingprostate cancer

T – Primary tumorTX Primary tumor cannot be assessedT0 No evidence of primary tumorT1 Clinically inapparent tumor neither

palpable nor visible by imagingT1a Tumor incidental histologic finding in 5%

or less of tissue resectedT1b Tumor incidental histologic finding in

more than 5% of tissue resectedT1c Tumor identified by needle biopsy (eg,

because of elevated PSA)T2 Tumor confined within prostateT2a Tumor involves one half of one lobe or lessT2b Tumor involves more than one half of one

lobe but not both lobesT2c Tumor involves both lobesT3 Tumor extends through the prostate

capsuleT3a Extracapsular extension (unilateral or

bilateral)T3b Tumor invades seminal vesicle(s)T4 Tumor is fixed or invades adjacent

structures other than seminal vesicles:bladder neck, external sphincter, rectum,levator muscles, and/or pelvic wall

N – Regional lymph nodesNX Regional lymph nodes were not assessedN0 No regional lymph node metastasisN1 Metastasis in regional lymph node(s)

M – Distant metastasisMX Distant metastasis cannot be assessed (not

evaluated by any modality)M0 No distant metastasisM1 Distant metastasisM1aNonregional lymph node(s)M1bBone(s)M1c Other site(s) with or without bone disease

Adapted from Green FL, Page DL, Fleming ID, et al, edi-tors. AJCC cancer staging manual. 6th edition. NewYork: Springer-Verlag; 2002.

prediction of extracapsular extension of prostatecancer varies widely, with sensitivities rangingfrom 50% to 92% and specificities ranging from58% to 86% [13–15]. For the diagnosis of seminalvesicle invasion, reported sensitivities range from22% to 60%, and the specificity is about 88%[14,16].

The major limitation of TRUS is its limited softtissue resolution. Color Doppler and power Dopp-ler, which can show vascular changes in tissues, canbe added to improve the detection of prostate can-cer on TRUS [17,18]. Even with these techniques,however, accuracy of TRUS in the local staging ofprostate cancer remains limited. Contrast-enhancedTRUS is a new technique that is under investigationfor the assessment of prostate cancer [19]. A studyshowed that contrast-enhanced TRUS improvedthe sensitivity of TRUS in tumor detection from38% to 65%, with no significant change in its spec-ificity, which was about 80% [20].

CT

CT for local staging of prostate cancer is of littlevalue because even with contrast enhancement,CT lacks the soft tissue resolution necessary forthe detection of prostate cancer within normalprostate.

When there is marked extracapsular extension,soft tissue extending into the periprostatic fat andadjacent structures can be diagnosed with CT(Fig. 1). Unilateral enlargement of a seminal vesicleby soft tissue–density tumor with obliteration ofthe fat plane between the seminal vesicle and pros-tatic base is suggestive of seminal vesicle invasion.With its accuracy of about 65% to 67%, however,CT is of limited clinical use for the local staging ofprostate cancer [21,22]. CT may be helpful in theevaluation of patients who have advanced diseasewith adjacent organ invasion and distant lymph-adenopathy [23], although patients presenting

Fig. 1. Contrast-enhanced CT images of a 69-year-old man who had Gleason grade 4 1 5 prostate cancer. (A)Image shows a large prostatic mass (arrow) invading the bladder (B) and extending to the right pelvic wall.(B) Image shows hydronephrosis (arrow) in the right kidney due to obstruction of the right ureter by the mass.

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with advanced disease are becoming less and lesscommon.

Recently developed multidetector CT technologyallows estimation of prostate perfusion and locali-zation of prostate cancer. One report indicatedthat this technique was able to detect only local-ized, high-volume, poorly differentiated prostatecancers [24]. Further research is needed to definethe role of multidetector CT in the evaluation ofprostate cancer.

MR imaging and MR spectroscopic imaging

MR imaging and proton MR spectroscopic imagingare rapidly evolving as the most sensitive tools forthe noninvasive, anatomic, and metabolic evalua-tion of prostate cancer [25,26]. Therefore, this arti-cle places special emphasis on these techniques.

MR imaging demonstrates the zonal anatomy ofthe prostate with excellent soft tissue resolutionand allows assessment of local extent of disease.The addition of MR spectroscopy can improve pros-tate cancer detection and localization. Furthermore,MR spectroscopy provides metabolic informationcorrelating with pathologic Gleason grade andthus may offer a noninvasive means to better pre-dict prostate cancer aggressiveness [25,26].

A magnet strength of at least 1.5 T is required forhigh-quality MR imaging and MR spectroscopic im-aging study of the prostate. The combined use of anendorectal coil with a pelvic phased-array coilmarkedly improves image quality. In general,T1-weighted axial images of the entire pelvis areobtained for the detection of nodal disease. Thin-section (3-mm) T2-weighted images with a smallfield of view (w14 cm) in the transverse, sagittal,and coronal planes are used for tumor detection, lo-calization, and staging. The use of a dynamic

contrast-enhanced MR sequence is optional andmay aid in tumor detection. Postbiopsy hemor-rhage may cause under- or overestimation of the tu-mor presence and local extent. Therefore, MRimaging must be delayed for at least 4 to 8 weeks af-ter prostate biopsy.

The MR spectroscopic imaging techniques thatare commercially available include chemical shiftimaging with point resolved spectroscopy (PRESS)voxel excitation and band selective inversion withgradient dephasing for water and lipid suppression.The PRESS technique generates a cubic or rectangu-lar voxel by the acquisition of three orthogonal sliceselective pulses (ie, a 90� pulse followed by two180� pulses). Currently, three-dimensional protonMR spectroscopic mapping of the entire prostateis possible with a resolution of 0.24 mL or smaller,depending on the parameters used. The setup forspectroscopic imaging is the same as for morpho-logic imaging, and both datasets are usually ac-quired in the same examination to overlaymetabolic information directly on the correspond-ing anatomic display (Fig. 2).

On MR imaging, prostate cancer is most easilyseen on T2-weighted images as a focus of decreasedsignal intensity (Fig. 3). Low signal intensity canalso be seen in several other conditions such ashemorrhage, prostatitis, atrophy, benign prostatichyperplasia nodules, or sequelae resulting from ra-diation therapy or hormonal treatment.

MR spectroscopy provides metabolic informa-tion about prostatic tissue by displaying the relativeconcentrations of citrate, creatine, choline, andpolyamines within contiguous voxels. Normalprostate tissue contains high levels of citrate—high-er in the peripheral zone than in the central andtransition zones. Glandular hyperplastic nodules,

Fig. 2. Gleason grade 4 1 3 prostate cancer in a 65-year-old man. Transverse T2-weighted MR image (A) and cor-responding MR spectroscopic data (B) superimposed on the anatomic image show the tumor (arrow) on the leftside.

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Fig. 3. Gleason grade 4 1 3 prostate cancer in a 66-year-old man. Transverse (A), coronal (B), and sagittal (C) T2-weighted MR images show a low–signal intensity focus consistent with tumor (arrow) in the peripheral zone ofthe prostate extending from left midgland to apex.

however, can demonstrate citrate levels as high asthose observed in the peripheral zone. In the pres-ence of prostate cancer, the citrate level is dimin-ished or not detectable because of a conversionfrom citrate-producing to citrate-oxidating metabo-lism. The choline is elevated due to a high phos-pholipid cell membrane turnover in theproliferating malignant tissue. Therefore, voxelscontaining prostate cancer depict an increased cho-line-to-citrate ratio (Fig. 4). Because the creatinepeak is very close to the choline peak in the spectraltrace, the two may be inseparable; therefore, forpractical purposes, the ratio of choline plus creatineto citrate ([Cho 1 Cr]/Cit) is used for the spectralanalysis in the clinical setting. With the latest spec-troscopic sequences, polyamine peaks can also beresolved. The polyamine peak decreases in the pres-ence of prostate cancer.

The classification system described by Kurhane-wicz and colleagues [27] is often used for spectralinterpretation. A voxel is classified as normal, assuspicious for cancer, or as very suspicious for can-cer. Furthermore, a voxel may contain nondiagnos-tic levels of metabolites or artifacts that obscure themetabolite frequency range. Voxels are consideredsuspicious for cancer when (Cho 1 Cr)/Cit is atleast 2 SD above the average ratio for the normal pe-ripheral zone, and voxels are considered very suspi-cious for cancer when (Cho 1 Cr)/Cit is more than

3 SD above the average ratio [28]. Voxels considerednondiagnostic contain no metabolites with signal-to-noise ratios greater than 5. In voxels in whichonly one metabolite is detectable, the other metab-olites are assigned a value equivalent to the noiseSD.

It has been shown that the (Cho 1 Cr)/Cit ratioin a lesion correlates with the Gleason grade [29].Thus, a potential advantage of MR spectroscopy isthat it may allow noninvasive assessment of pros-tate cancer aggressiveness.

One study found that in prostate cancer detectionand tumor localization, MR imaging had 61% and77% sensitivity, respectively, and 46% and 81%specificity, respectively, with moderate inter-readeragreement; MR spectroscopy had significantly high-er specificity (75%, P<.05) but lower sensitivity(63%, P<.05). The investigators reported high spec-ificity (91%) when combined MR imaging and MRspectroscopy indicated a positive result, and highsensitivity (95%) when either test alone did so[30]. A recent study comparing DRE, TRUS-guidedbiopsy, and MR imaging in the detection and local-ization of prostate cancer showed that MR imagingsignificantly increased the accuracy of prostate can-cer localization compared with DRE or TRUS-guided biopsy (P<.0001 for each). The area underthe receiver operating characteristic (ROC) curvefor tumor localization was higher for MR imaging

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than for DRE at the prostatic apex (0.72 versus0.66), the midgland (0.80 versus 0.69), and thebase (0.83 versus 0.69); it was also higher for MRimaging than for TRUS-biopsy at the midgland(0.75 versus 0.68) and the base (0.81 versus 0.61)but not the apex (0.67 versus 0.70) [31].

Most MR imaging studies focus on tumor detec-tion in the peripheral zone of the prostate, wheremost cancers originate. The transition zone, how-ever, harbors cancer in up to 25% of radical prosta-tectomy specimens [32]. A recent study showed thatMR imaging can be used to assess transition zoneprostate cancers. In detecting the location of transi-tion zone cancer, the areas under the ROC curves oftwo readers were 0.75 and 0.73. Both readers’ accu-racy in detecting transition zone cancer foci in-creased significantly (P 5 .001) as tumor volumeincreased [33].

Dynamic contrast-enhanced MR imaging hasbeen proposed as a means of achieving higher accu-racy in prostate cancer localization and staging thancan be obtained with conventional T2-weighted MRimaging [34]. It has been postulated that on dy-namic contrast-enhanced imaging, increased mi-crovascular density in prostate cancer results indifferent contrast enhancement than that seen innormal prostate. Numerous contrast enhancementparameters can be used to differentiate cancerousfrom benign tissue, including onset time, time to

Fig. 4. Gleason grade 5 1 4 prostate cancer in a 59-year-old man. MR spectroscopy shows normal spectrain the healthy (H) right peripheral zone and suspi-cious spectra with elevated choline and reducedcitrate in the left peripheral zone tumor (T).

peak enhancement, peak enhancement, relativepeak enhancement, and washout time. A recentstudy suggested that the peak enhancement of can-cer relative to that of surrounding benign tissue isthe most accurate parameter for cancer localization[35]. Another suggested approach to cancer detec-tion is the identification of areas of enhancementon early postcontrast images (within the first 30–60 seconds after contrast material injection) [36].The challenge in dynamic contrast-enhanced MRimaging is to provide an optimal balance betweentemporal and spatial resolution. More studies arenecessary to optimize the technology and definethe clinical value of this technique.

As mentioned before, biopsy remains the goldstandard for the diagnosis of prostate cancer. In pa-tients who have elevated PSA levels or clinical find-ings suggestive of prostate cancer and negativeTRUS-guided biopsy results, MR imaging and MRspectroscopy can be used to localize areas thatmay harbor prostate cancer and can help direct tar-geted biopsies and limit multiple repeat biopsies[37,38]. MR imaging-guided transrectal prostate bi-opsy is technically possible; however, the uses ofand indications for MR imaging in prostate biopsyand other types of prostate interventions such asbrachytherapy seed placement are under investiga-tion [39–41].

MR imaging criteria for extracapsular extensioninclude a contour deformity with a step-off or angu-lated margin, an irregular capsular bulge or retrac-tion, a breach of the capsule with evidence ofdirect tumor extension, obliteration of the rectopro-static angle, and asymmetry of the neurovascularbundles. MR imaging criteria for seminal vesicle in-vasion include contiguous low–signal intensity tu-mor extension from the base of the gland into theseminal vesicles, disruption or loss of the normalarchitecture of the seminal vesicle and decreasedconspicuity of the seminal vesicle wall, tumor ex-tension along the ejaculatory duct (nonvisualiza-tion of the ejaculatory duct), asymmetric decreasein the signal intensity of the seminal vesicles withmass effect, and obliteration of the angle betweenthe prostate and the seminal vesicle on sagittal im-ages. MR imaging is also helpful for diagnosing theinvasion of adjacent organs (eg, the urinary bladderand rectum). Combined transverse, coronal, andsagittal planes of section facilitate evaluation of ex-tracapsular extension, seminal vesicle invasion, andadjacent organ invasion [25,26] (Figs. 5–8).

The accuracy of MR imaging in the local stagingof prostate cancer varies widely (from 50% to92%) [34]. MR imaging has been reported to have13% to 95% sensitivity and 49% to 97% specificityfor the detection of extracapsular extension and23% to 80% sensitivity and 81% to 99% specificity

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for the detection of seminal vesicle invasion [42–50]. A recent study showed that for two readers,the areas under the ROC curves were 0.93 and0.81 for the detection of seminal vesicle invasionat MR imaging; the features that had the highestsensitivity and specificity were low signal intensitywithin the seminal vesicle and lack of preservationof seminal vesicle architecture. Tumor at the

Fig. 5. Gleason grade 4 1 4 prostate cancer in a 54-year-old man. This tumor was clinically staged asT1c; however, a transverse T2-weighted MR imageshowed a small tumor (T) with gross extracapsular ex-tension (arrows) and the tumor was staged as T3a,which was confirmed at pathologic examination afterprostatectomy.

prostate base that extended beyond the capsuleand low signal intensity within a seminal vesiclethat had lost its normal architecture were highlypredictive of seminal vesicle invasion [51].

MR spectroscopy may have a role in reducing thewide variation in the accuracy of MR imaging for lo-cal staging of prostate cancer, which may be attrib-uted to the lack of standardized diagnostic criteriaand interobserver variability in image interpreta-tion. In a study on the detection of extracapsular ex-tension by two independent readers, the addition ofMR spectroscopy to MR imaging reduced interob-server variability and significantly improved accu-racy for the less experienced reader, whose areaunder the ROC curve increased from 0.62 to 0.75(P<.05); for the more experienced reader, the addi-tion of MR spectroscopy also improved accuracy,but not significantly (the area under the ROC curveincreased from 0.78 to 0.86) [52].

A study has shown that for the prediction of ex-tracapsular extension, MR imaging findings con-tribute significant incremental value to clinicalvariables (areas under the ROC curves for detectionof extracapsular extension with and without endor-ectal MR imaging findings were 0.838 and 0.772,respectively, P 5 .022) [53]. A related study that an-alyzed the same data demonstrated that the incre-mental value of MR imaging in predictingextracapsular extension was only significant wheninterpretation was performed by genitourinary

Fig. 6. Gleason grade 5 1 4 prostate cancer in a 58-year-old man. Transverse (A, B) and coronal (C) T2-weightedMR images show a large tumor (T) predominantly involving the right side of the prostate and seminal vesicles(SV). Note that disruption of the capsule and gross extracapsular extension of tumor (arrows) (A, C) and bilateralseminal vesicle (SV) invasion (asterisk) (B, C) are seen.

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Fig. 7. Gleason grade 4 1 5 prostate cancer in a 69-year-old man. Transverse T2-weighted MR images (A, B) showa large tumor (T) that invades the urinary bladder (B) anteriorly and abuts the rectum (R) posteriorly. Bilateralobturator lymphadenopathy (arrows) and bilateral seminal vesicle (SV) invasion are also seen (B).

radiologists with experience in endorectal MR im-aging [54]. In another study, MR imaging and com-bined MR imaging and MR spectroscopic imagingcontributed significant incremental value (P%.02)to the staging nomograms in predicting organ-con-fined prostate cancer; the contribution of MR find-ings was significant in all risk groups but wasgreatest in the intermediate- and high-risk groups(P<.01 for both) [55].

For the assessment of lymph node metastases,MR imaging, like CT, has low sensitivity (0%–69%) [47,56–61]. The low sensitivity of MRimaging and CT is mainly due to the inability ofcross-sectional imaging to detect metastases innormal-sized nodes. High-resolution MR imagingwith lymphotropic superparamagnetic nanopar-ticles, however, is a promising technique in thedetection of occult lymph node metastases becauseit allows detection of metastases in normal-sizedlymph nodes. In one study, MR imaging with lym-photropic superparamagnetic nanoparticles hada significantly higher sensitivity than conventionalMR imaging in the detection of metastasis ona node by node basis (90.5% versus 35.4%,P<.001); the new technique also had a sensitivityof 100% and a specificity of 95.7 in detecting nodalmetastasis on a per patient basis [62].

Although these results are promising, the low in-cidence of lymph node metastasis in patients whohave prostate cancer does not warrant the routineuse of lymphotropic superparamagnetic nanopar-ticles. A recent study showed that incorporation ofthe Partin nomogram results and standard MR im-aging findings regarding extracapsular extensionand seminal vesicle invasion improves the predic-tion of lymph node metastasis on MR imaging inpatients who have prostate cancer [63]. Only 22(5%) of 411 patients in the study had lymph nodemetastases at surgical pathology, and MR imagingwas an independent, statistically significant

predictor of lymph node metastasis (P 5 .002),with positive and negative predictive values of50% and 96.36%, respectively. On multivariateanalysis, prediction of lymph node status usinga model that included all MR imaging variables (ex-tracapsular extension, seminal vesicle invasion, andlymph node metastases) along with the Partin no-mogram results had a significantly greater area un-der the ROC curve than the univariate model thatincluded only MR imaging lymph node metastasisfindings (areas under the ROC curves were 0.892and 0.633, respectively, P<.01). The investigatorssuggested that because MR imaging offers high neg-ative predictive value for lymph node metastasis inaddition to anatomic information useful for

Fig. 8. Gleason grade 4 1 5 prostate cancer in thetransition zone in a 68-year-old man. This anterior tu-mor involving the entire transition zone was clinicallystaged as T1c; however, a transverse T2-weighted MRimage showed a large transition zone tumor (T) withgross anterior extraprostatic extension (arrows) andthe tumor was staged as T3a, which was confirmedat pathologic examination after prostatectomy. Al-though the tumor was large, its anterior locationfar from the rectum made clinical evaluation difficult.PZ, peripheral zone.

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treatment planning, MR imaging and the Partin no-mogram could be used together to determinewhether imaging with lymphotropic superpara-magnetic nanoparticles is warranted.

Nuclear medicine studies

Capromab pendetide immunoscintigraphy

Capromab pendetide immunoscintigraphy is a mu-rine monoclonal antibody that reacts with prostatemembrane–specific antigen, which is highly ex-pressed in prostate cancer. Immunoscintigraphy isaccomplished by labeling the antibody with indium111. After infusion of the antibody, whole-body pla-nar and single-photon emission CT images are ob-tained. Capromab pendetide immunoscintigraphycan be used for the detecting lymph node metasta-ses, the site of relapse in a patient who has a detect-able PSA after prostatectomy, and occult metastasisbefore primary therapy [64]. One study found thatcapromab pendetide immunoscintigraphy scan-ning had 67% to 94% sensitivity and 42% to 80%specificity for the detection of lymph node metasta-ses [65,66]. Another study on the use of capromabpendetide immunoscintigraphy scanning to evalu-ate patients who had recurrent prostate cancershowed that the technique had a sensitivity of89%, a specificity of 67%, and an overall accuracyof 89% [67]. Coregistration of capromab pendetideimmunoscintigraphy images with MR imaging orCT could improve the specificity of the examination[68]; however, there are many reasons for false-pos-itive uptake of this antibody, and the image qualityis often suboptimal. In the era of PET, the imagingof prostate cancer with capromab pendetide immu-noscintigraphy should no longer be encouraged.

Radionuclide bone scintigraphy

Radionuclide bone scan is a sensitive imagingmethod used to detect bone metastases in patientswho have prostate cancer (Fig. 9) [69]. Bone scansare commonly obtained even for patients in low-and intermediate-risk categories [70]; however,studies have shown that patients who have PSAlevels of 20 ng/mL or less and a Gleason score lowerthan 8 have a 1% to 13% rate of positive bone scans[71,72]. Other studies have confirmed that in pa-tients who have low PSA levels (<10 ng/mL) andno skeletal symptoms, the yield of bone scanningis too low to warrant its routine use unless the pa-tient has stage T3 or T4 disease or a high Gleasonscore [73–75]. Therefore, a PSA level of greaterthan 15 to 20 ng/mL is usually used as the cutoffpoint for obtaining a bone scan, but patients whohave skeletal symptoms and those who havea high Gleason score or advanced stage shouldalso be assessed with bone scans.

Positron emission tomography

The role of PET is still under investigation in thestaging workup of patients who have prostate can-cer (see Fig. 9) [76–80]. Fluorodeoxyglucose(FDG), the most commonly used PET tracer, was re-ported to be ineffective for the initial staging ofprostate cancer because most primary prostate can-cer lesions were not detected by FDG-PET [81].FDG-PET, however, could have a role in the detec-tion of local recurrence or distant metastases withincreasing PSA after initial treatment failure[55,76,80,82].

Other radiotracers are being studied for their usein prostate cancer, including C 11 or F 18 cholineand acetate, methionine C 11, fluorine 18, fluorodi-hydrotestosterone, and gallium 68–labeled pep-tides [77,79,80,83–86]. These agents, however, arenot widely available and their use remainsexperimental.

Treatment planning

The therapeutic options for patients who have pros-tate cancer vary widely and include watchful wait-ing, androgen ablation (chemical or surgicalcastration), hormone therapy, radical surgery, andvarious forms of radiation therapy (brachytherapy,external beam irradiation). The choice of optimaltreatment strategy in patients who have prostatecancer is patient specific and risk adjusted. The ther-apeutic goal is to maximize cancer control whileminimizing the risks of complications. The optimaltreatment option for prostate cancer is chosenbased on clinical TNM stage, Gleason grade, andthe level of PSA. Other factors such as patient age,associated medical illnesses, and the patient’s per-sonal preferences also have an effect on the treat-ment planning process. The findings fromimaging studies assist in this patient-specific treat-ment planning approach. Imaging may also havea role in the guidance and assessment of emerginglocal prostate cancer therapies.

Post-treatment follow-up

After treatment, patients who have prostate cancerare followed with periodic measurement of PSAlevels and DRE. Imaging is necessary after treatmentfor clinically localized prostate cancer only if thereare suspicious findings on DRE, PSA is elevated,or the patient has symptoms such as bone pain.

Follow-up after radical prostatectomy

Radical prostatectomy includes resection of theprostate, the seminal vesicles, and the pelvic lymphnodes. After radical prostatectomy, PSA decreases toundetectable levels (<0.1 ng/mL) within a few

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Fig. 9. Gleason grade 5 1 4prostate cancer in a 76-year-oldman. Bone scan (A) and PET (B)show a metastatic focus in theleft femur (large arrows). Meta-static lymph nodes (small ar-rows) are also seen on PET (B).

weeks of surgery and should remain undetectablethereafter [87,88]. Detectable levels of PSA in pa-tients who have undergone radical prostatectomyindicate that there is residual prostate tissue becausePSA is specific to the prostate. A rise in a previouslyundetectable or stable PSA level after surgery is sug-gestive of residual, recurrent, or metastatic disease.In these cases, the role of imaging is to help distin-guish locally recurrent disease (which can be man-aged with local therapy) from distant metastaticdisease (which requires systemic therapy). Thetype of recurrence is difficult to determine clinicallybecause an increasing PSA level is rarely associatedwith symptoms or findings at physical examination.

Radionuclide bone scintigraphyRadionuclide bone scan is often the first examina-tion obtained. If the bone scan is negative or incon-clusive, then further imaging studies are performed.The probability of a positive bone scan in patientswho have biochemical failure following radicalprostatectomy is very low until PSA levels increaseabove 30 to 40 ng/mL [89]. Therefore, bone scansare recommended only when the patient has symp-toms of bone pain, a rapid rise in PSA, or markedlyelevated PSA [90].

Transrectal ultrasonographyTRUS is the most commonly used imaging mo-dality in the detection of local recurrence follow-ing prostatectomy. TRUS is also used for biopsy

guidance of the vesicourethral anastomosis andprostatic fossa to document local recurrence. Anegative result on TRUS-guided biopsy, however,does not definitely rule out recurrent diseasedue to possible sampling errors. Only about25% of men who have prostatectomy and PSAlevels lower than 1 ng/mL have positive biopsyresults [91]. The yield for detection of locally re-current tumor with TRUS-guided biopsy, however,rises significantly with increasing PSA levels[91,92].

CTCT is not effective for detecting early recurrent tu-mor in the surgical bed. A study showed that CT de-tected only 36% of recurrences, and all of thesewere larger than 2 cm [93]. CT can be useful inthe evaluation of nodal recurrence (Fig. 10); how-ever, CT relies only on size criteria for the detectionof positive lymph nodes. CT can also be useful indetecting bone and visceral metastases, althoughbone scan and MR imaging are superior in the diag-nosis and follow-up of bone metastases [94].

MR imagingDue to its excellent soft tissue resolution, MR imag-ing is superior to TRUS and CT in the detection ofclinically evident locally recurrent disease after rad-ical prostatectomy (Fig. 11). Two studies reportedthat MR imaging had 95% to 100% sensitivity and100% specificity for detecting local recurrence

Prostate Cancer Imaging 217

Fig. 10. Recurrent prostate cancer in a 76-year-old man. (A, B) Transverse contrast-enhanced CT images show dis-tal para-aortic and left common iliac lymphadenopathy (arrows).

[95,96]. In one of these studies, local recurrencesseen on MR imaging were perianastomotic in29% of patients and retrovesical in 40%, within re-tained seminal vesicles in 22%, and at anterior orlateral surgical margins in 9%; the mean diameterof tumors was 1.4 cm (range, 0.8–4.5 cm), andPSA levels ranged from undetectable to 10 ng/mL(mean, 2.18 ng/mL) [95].

MR imaging can also be used in the detection ofnodal disease; however, the accuracy of MR imagingfor staging pelvic lymph nodes by size criteria issimilar to that of CT.

MR imaging is more sensitive and specific in thediagnosis of bone metastases compared with bonescan; however, it is more feasible to use bone scanto cover the entire skeleton. In addition, bonescan is more cost-effective than MR imaging. There-fore, MR imaging should be used when other imag-ing modality findings are indeterminate.

Positron emission tomographyThe role of PET in detecting recurrence, assessingprognosis, monitoring therapy, and studying the bi-ology of prostate cancer is still under investigation.

Fig. 11. Recurrent prostate cancer after radical prostatectomy in a 76-year-old man. Transverse (A), sagittal (B),and coronal (C) T2-weighted MR images demonstrate nodular intermediate–signal intensity tumor (arrows) con-sistent with local recurrence in the bladder neck.

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Fig. 12. Gleason grade 4 1 5 prostate cancer in a 66-year-old man. Transverse T2-weighted MR image (A) showsa large tumor (T) with gross extracapsular extension (arrows). After radiation treatment, transverse T2-weightedimage (B) shows that the tumor (T) and extracapsular extension markedly decreased (arrows). Note that the restof the prostate demonstrates diffuse low signal intensity consistent with radiation changes (B).

FDG-PET could have a role in the detection of localrecurrence or distant metastases with increasingPSA after initial treatment failure [76,80,82]. Astudy showed that FDG-PET detected local or sys-temic disease in 31% of 91 patients who had PSA re-lapse following prostatectomy. In this study, theprobability for disease detection increased withPSA level [82].

Follow-up after radiation therapy

Following radiation therapy, the PSA level decreasesin most patients during the first year. Recurrencefollowing radiation therapy is defined as three con-secutive rises in PSA after a postradiation PSA nadir[97]. Detection of local recurrence after failed radi-ation therapy is a clinical challenge because an in-crease in the PSA level is not a reliable variable fordifferentiating local from distant recurrence. Afterradiation therapy, the prostate becomes atrophicand fibrotic, making detection of local recurrentdisease within the irradiated prostate difficult byDRE. If bone scan is positive, then further imagingis not necessary. If the bone scan is negative, thenTRUS-directed biopsy of the prostate can be per-formed. Lymph nodes can be evaluated by CT orby MR imaging.

It is commonly believed that assessment of loca-tion and extent of prostate cancer on MR imaging ishindered by tissue changes related to radiation ther-apy (Fig. 12). A recent study showed, however, thatMR imaging and MR spectroscopy could be moresensitive than sextant biopsy and DRE for sextantlocalization of cancer recurrence after externalbeam radiation therapy [98]. In this study, MR im-aging and MR spectroscopy had sensitivities of 68%and 77%, respectively, whereas the sensitivities ofbiopsy and DRE were 48% and 16%, respectively.MR spectroscopy appears to be less specific (78%)

than the other three tests, which each had a specific-ity higher than 90%. Another recent study alsoshowed that in patients who underwent salvageprostatectomy after failed radiation therapy, MR im-aging could help identify tumor sites and depict lo-cal extent of disease. In this study, areas under theROC curves for two readers were 0.61 and 0.75for tumor detection, 0.76 and 0.87 for predictionof extracapsular extension, and 0.70 and 0.76 forprediction of seminal vesicle invasion [99].

Summary

Imaging modalities are rapidly evolving to provideimproved evaluation of prostate cancer. Our under-standing of imaging criteria and experience in im-age interpretation are also growing. In addition tothe traditional roles of imaging in prostate cancer(ie, localization and staging), extensive research isbeing done on metabolic imaging to predict canceraggressiveness. Future directions in prostate cancerimaging include more precise patient stratificationfor different management options and newmethods for guidance and assessment of emerginglocal prostate cancer therapies.

Acknowledgments

The authors thank Ada Muellner, BA, for her assis-tance in editing the manuscript.

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