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European Journal of Radiology 81 (2012) 700– 708

Contents lists available at ScienceDirect

European Journal of Radiology

journa l h o me pa ge: www.elsev ier .com/ locate /e j rad

rostate cancer: 1HMRS-DCEMR at 3 T versus [(18)F]choline PET/CT in theetection of local prostate cancer recurrence in men with biochemicalrogression after radical retropubic prostatectomy (RRP)

aleria Panebiancoa,∗, Alessandro Sciarrab, Danilo Lisi a, Francesca Galati a, Valeria Buonocorea,arlo Catalanoa, Vincenzo Gentileb, Andrea Laghia, Roberto Passarielloa

Dept. of Radiological Sciences, Sapienza University of Rome, v.le Regina Elena, 324 – 00161 Rome, ItalyDept. of Urological Sciences, Sapienza University of Rome, Italy

r t i c l e i n f o

rticle history:eceived 10 December 2010ccepted 24 January 2011

eywords:rostate canceradical prostatectomyR 3 T magnetR spectroscopy

8F-Choline-PET/CT

a b s t r a c t

Objectives: This study compares proton magnetic resonancespectroscopic imaging (1H-MRSI) anddynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined techniques at 3 T magnetversus [(18)F]choline PET/computed tomography (CT) in the detection of local prostate cancer recurrencein patients with biochemical progression after radical retropubic prostatectomy (RRP).Materials and methods: 84 consecutive patients at high risk of local recurrence underwent combined1HMRSI-DCEMR and 18-Fcholine- PET/CT. MR scan protocol included turbo spin echo (TSE) T2-weightedsequences in the axial, sagittal and coronal planes; three-dimensional (3D) chemical shift imaging(CSI) sequences with spectral/spatial pulses optimized for quantitative detection of choline and citrate;dynamic contrast enhanced gradient-echo (GRE) T1-weighted sequence.

The population was divided into two groups. Group A included 28 patients with a lesion size rang-ing between 5.00 mm and 7.2 mm and PSA reduction following radiation therapy. Group B included 56patients with a lesion size between 7.6 mm and 19.4 mm. Sensitivity, specificity, positive predictive value(PPV) and accuracy were evaluated and receiver operating characteristic (ROC) curves were performed.Results: In Group A combined 1H-MRSI and DCE-MRI showed a sensitivity of 92%, a specificity of 75%(PPV 96%) while PET–CT examination showed a sensitivity of 62% and a specificity of 50% (PPV 88%) inidentifying local recurrence. The accuracy of MRI was 89% while PET–CT showed an accuracy of 60%.Areas under the ROC curve (AUC) values for MR and PET–CT were 0.833 and 0.562, respectively. In Group

B combined 1H-MRSI and DCEMR showed a sensitivity of 94% and a specificity of 100% (PPV 100%) withaccuracy of 94%. PET–CT had a sensitivity of 92% and a specificity of 33% (PPV 98%) with accuracy of 91%.The AUCs for MR and PET–CT values were 0.971 and 0.837, respectively.Conclusion: The diagnostic accuracy of combined 1HMRSI-DCEMR was higher than PET/CT to identify localprostate cancer recurrence, mostly in patients with low biochemical progression after RRP (0.2–2 ng/mL).

. Introduction

Currently, new surgical techniques of radical retropubic prosta-ectomy (RRP) can ensure good functional results regardingncological radicality criteria. A rise of PSA level is the major indi-

ator for prostate cancer recurrence after RRP [1] and recurrencef cancer can be suspected at the earliest rise of PSA [2–4]. Accord-ng to the guidelines, a PSA increase over a threshold of 0.2 ng/mL

∗ Corresponding author. Tel.: +39 064455602; fax: +39 06490243.E-mail addresses: valeria.panebianco@uniroma1.it,

aleria.panebianco@gmail.com (V. Panebianco).

720-048X/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved.oi:10.1016/j.ejrad.2011.01.095

© 2011 Elsevier Ireland Ltd. All rights reserved.

later than 6–12 months after RRP suggests treatment failure witha high risk of local recurrence [5], whereas a PSA increase withina shorter period correlates with distant metastasis progression.Some diagnostic imaging techniques are useful to differentiate localcancer recurrence from systemic relapse and to direct patientsto the right therapeutic approach, such as radiotherapy for localrecurrence and hormone therapy for systemic disease [6,7]. 18-Fcholine (FCH) is a PET tracer that has been recently introducedto prostate cancer diagnosis [8–12] and its accuracy in detecting

the primary neoplasm, metastases and recurrences has been eval-uated by several preliminary studies [13–16]. Whole body (18)F-choline PET/computed tomography (CT) is justified for PSA valuemajor than 2 ng/mL. Recently, whole body PET is indicated only

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V. Panebianco et al. / European Jo

ith PSA values higher than 1.4 ng/mL [17]. It is assumed thathese PSA values indicate metabolically active disease. Transrectalltra sound (TRUS) – biopsy of the anastomosis is not recom-ended by EAU Guidelines (2010) in patients with PSA increase

1 ng/mL. In this wide range (0.2–1.4/2 ng/mL) of values the riskf locoregional recurrence is not to be neglected and hence theeed of a more accurate technique to examine the prostatic fossaost-RRP. A large number of studies have shown that magneticesonance (MR) is a powerful tool for early detection of local recur-ence after surgery [18–23], after external beam radiation therapyEBTR) [24–28], also for diagnosis of metastatic disease [29]. Sometudies have compared PET–CT and MR imaging in the preoper-tive detection of prostate cancer and have demonstrated thatR improves the detection of prostate cancer more than PET–CT

30,31]. We therefore conducted a comparative study of MRI andET/CT in early detection of local recurrence after RRP in a largeeries of patients. In particular, the aim of our study was to com-are proton MR spectroscopic imaging (1H-MRSI) and dynamicontrast-enhanced MRI (DCE-MRI) combined techniques, using a

T magnet, versus (18) F-choline PET/CT in 84 patients with rise ofSA value after RRP in early detection of local recurrence in prostaticossa.

. Materials and methods

.1. Patient population

This study was approved by the ethics review board of ournstitution, and informed consent was obtained. From November009 to March 2010, 84 consecutive male patients (age range6–72 years) were referred to our institution for routine surveil-

ance or for follow-up diagnostic imaging after RRP. Patients werencluded if they had (i) a surgical pathological local stage pT3a-

(high risk of local recurrence); (ii) negative surgical margins;iii) post-RP PSA increase >0.2 ng/mL; (iv) no adjuvant or neoadju-ant hormonal therapies; (v) negative regional lymph nodes (pN0);vi) no evidence of distant metastases at CT scan and bone scanerformed before RRP. Seventy-six patients were at high risk for

ocal cancer recurrence on the basis of the pathological stage andostoperative PSA increase and were candidates for external beamadiotherapy; 8 patients had no suspicion of recurrence or tumorrogression. Ten months after surgery, each patient underwentoth MR and PET–CT exam. The interval between the two proce-ures ranged from 1 to 20 days. We divided the patient population

nto two groups according to recurrent lesion size in prostaticossa, on MR examination. Group A included patients with PSAeduction following radiation therapy with a lesion average sizef 6 ± 0.5 mm (range 5.00–7.2 mm). According to the small recur-ence size, Group A patients did not undergo TRUS-biopsy and MRnd PET–CT results were validated by PSA level modification afteradiation therapy. Group B included patients with a lesion aver-ge size of 13.3 ± 4.5 mm (range 7.6–19.4 mm). Group B patientsnderwent TRUS-biopsy.

.2. MR equipment and image acquisition protocol

MR imaging of the prostate was performed using a 3 T MRcanner (Verio Magnetom, Siemens Medical Solutions, Erlangen,ermany); high performance gradient strength, 45 mT/m; slew

ate, (200 T/m/s), equipped with a surface phased array (Bodyatrix, Siemens Medical Solutions) and endorectal coil, filled with

0–90 mL of air on the basis of patient tolerance (e-Coil, Medrad,ittsburgh, PA, USA). The post-prostatectomy fossa MR imagingrotocol included the following sequences: T2-weighted turbo spincho (TSE) sequences were acquired (repetition time [TR]: 7200 ms;

of Radiology 81 (2012) 700– 708 701

echo time [TE]: 116 ms; flip angle: 130◦; average: 1; field of view(FOV) read: 251 mm; FOV phase: 75 mm; thickness: 3.00 mm;section gap: 0; matrix: 512 × 461; phase resolution: 100%; bandwidth: 130 kHz; scan time: 2.40 min) in axial, sagittal, and coro-nal planes. A 3-dimensional (3D) chemical shift imaging (CSI)with spectral/spatial pulses optimized for quantitative detection ofcholine, creatine and citrate was performed in patients with irreg-ular thickening of the anastomosis and the presence of solid tissue(acquisition time 7 min); the volume of interest (VOI) was focusedon suspect tissue. In the case of empty fossa, MR spectroscopy wasnot performed.

Dynamic contrast-enhanced MR (DCEMR) was obtained usinga Gradient-Echo (GRE) T1-weighted sequence (TR, 2.36 ms; TE,0.9 ms; flip angle, 19◦; average, 1; thickness, 3 mm; section gap,0; time resolution, 12 sections/3 s; matrix, 256 × 256; scan time,2.47 min) acquired during an intravenous bolus injection of aparamagnetic gadolinium chelate contrast agent, 1.0 mmol/mL ofGadobutrol (Gadovist, Bayer Shering Pharma AG) per kilogram ofbody weight, with a power injector (Spectris Medrad) at 3.0 mL/sand followed by a 15 mL saline flush. During contrast agent admin-istration, subtraction images were generated by an automatedalgorithm that uses the first 3 s of the sequence as baseline forthe following measurements. We used this technique to improveregions of interest (ROI) placing, in subsequent signal intensitytime (SI-T) curves analysis. The 3D volume was acquired with thesame positioning angle and center as the transverse T2-weightedsequence, covering the entire prostatic fossa. Relative gadoliniumchelate concentration curves were calculated.

2.3. Preparation of 18F-choline and PET study

All patients underwent whole-body FCH-PET–CT in 3 differentinstitutions, each exam acquired with the same PET–CT scan (16-slice computed tomography scanner) and the same equipment.PETCT studies were acquired using a Discovery ST unit (GeneralElectric Medical Systems, Waukesha, WI, USA). The acquisitionprotocol begins 60 min after i.v. injection of 185–259 MBq FCH(IASOcholine®, Graz-Seiersberg, Austria) and oral administrationof 10 mL of contrast medium in half a liter of water (Gastrografin,Schering SpA, Segrate, Italy). The acquisition protocol started witha scout view (a CT bidimensional projection of the patient), whichwas used to define the axial extension (start and end position) toacquire the CT and PET data. Once the scan range had been defined,usually from the proximal femur to the base of the skull, a low-dose CT scan was acquired (140 kV and 60 mAs). This scan lastedapproximately 1 min and was used for both anatomical whole-bodylocalization and attenuation correction of the PET emission data. Atthe end of the CT scan, the bed position was translated into the PETfield of view (FOV) for the PET study. A mean of seven FOVs wereacquired in a “standard” whole-body PET study. The image recon-struction was performed with the 3D FORE-Iterative reconstructionalgorithm, FOV 50 cm, image matrix 128 × 128.

2.4. PET–CT image interpretation

All viewing of co-registered images were performed with ded-icated software (Advantage Windows 4.2, GE Healthcare, ChafontSt. Giles, UK). Neoplastic disease on PET was diagnosed when one ormore areas of focal abnormal increase in tracer uptake were visu-ally evident. A radiologist, also expert in nuclear medicine with fiveyears of experience, retrospectively evaluated all exams.

2.5. Post-processing MR and image interpretation

The images were evaluated on an off-line dedicated workstation(Leonardo, Siemens). On T2-weighted images, suspect tissue with

702 V. Panebianco et al. / European Journal of Radiology 81 (2012) 700– 708

Table 1Patients group.

Group Patients number PSA serum level Maximal transverse dimension of local recurrence Features and standard validation

A 28 patients 0.8–1.4 ng/mL (mean 1.1 ng/mL) 5–7.2 mm (mean 6 ± 0.5 mm) Patients in which the PSA levelmodification after radiation therapywas used as validation of MR results

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B 56 patients 1.3–2.5 ng/mL (mean 1.9 ng/mL) 7.6–19.4

ntermediate signal (fat and muscle) was evaluated. An operator-ndependent standard post-processing protocol, using dedicatedoftware (SyngoSpectroscopy Evaluation) for spectroscopic anal-sis, was applied to the 1H-MRSI data. Data sets were acquireds a 16 × 8 × 8 phase-encoded matrix before Fourier transforma-ion into the spatial dimensions. This transformation resulted inpectroscopic measurements of all voxels for patients with a nomi-al spectral and spatial resolution of 0.25 cm3 (interpolated voxel).verage post-processing duration was 25–30 min for each data set.he software (Syngo Spectroscopy Evaluation) analyzed resonancereas using an automatic Gaussian curve and revealed regions ofnterest (ROIs) value. A single ROI including three voxel (0.75 cm3)

as positioned on the suspect local recurrence tissue. The dynamicR post-processing procedure took approximately 10 min per

atient. Each MR signal enhancement-time curve was comparedith a pelvic muscle before contrast material injection for eachatient; consequently, the enhancement curve was modeled withour parameters in a semi-quantitative manner: onset time of sig-

ig. 1. A 56-years-old men with PSA value of 1 ng/mL. (A) The 6 mm nodule was detectedith perianastomotic mucosa. (B) Spectroscopic analysis showed alteration of ratio val

nhancement and the method of positioning the respective ROI. In particular, the ROI nuegion with none enhancing evidence and the ROI number 3 on the pelvic muscle as bahows a higher peak enhancement on 1 ROI than other curves. (E) Coregistered positroecurrence.

ean 13.3 ± 4.5 mm) Patients in which a TRUS-biopsy of thepost-prostatectomy prostatic fossa wasperformed as control

nal enhancement (OT); time to peak (TTP); peak enhancement (PE);washout (WSH).

Two radiologists (blinded to the initial PSA serum levels, TRUSbiopsy results, or PSA level after radiation therapy) evaluatedindependently and blindly MR imaging set on off-line dedi-cated workstation (Leonardo, Siemens Medical Solutions, Erlangen,Germany) during three reading session. During the first session,each radiologist interpreted T2-weighted images without formu-lating a definitive judgment of cancer recurrence. Abnormal tissuelocalization was determined as follows: periurethral and peri-anastomotic sites, around the bladder neck, and or retro-trigone,according to the localizations where perform TRUS biopsies [32,33].Evaluation was performed if the tissue was considered a recurrenceor a scar. The major diameter of the suspected tissue was measured

and described as semi-circumferential (i.e., around the urethra),nodular-like, or plaque-like.

In the first interpreting session with a different case order, all MRspectra data were overlaid in the three planes (axial, coronal and

on axial T2-w image on the basis of increased signal region (red arrow) comparedue for increased of choline rate. (C) Dynamic subtracted image shows an area ofmber 1 was placed on enhancing nodule, the ROI number 2 on opposed peripheralseline. (D) The resulting signal-intensity time curve in which the curve number 1n emission tomography CT image with any pathological uptake as a local disease

V. Panebianco et al. / European Journal of Radiology 81 (2012) 700– 708 703

Fig. 2. The same patient of Fig. 1 after 9 months. At this control, patient present PSA value of 2.1 ng/mL. (A) The 11 mm nodule on anterior side of perianastomotic mucosawas detected on axial T2-w image on the basis of increased signal region (red arrow) compared with peri-anastomotic mucosa. (B) Spectroscopic analysis showed increasedof choline value. (D) Dynamic subtracted image shows an area of enhancement and the method of positioning the respective ROI. In particular, the ROI number 1 was placedon enhancing nodule, the ROI number 2 on opposed peripheral region with none enhancing evidence and the ROI number 3 on the pelvic muscle as baseline. (E) The resultingsignal-intensity time curve in which the curve number 1 shows a high peak enhancement, short OT, early TTP and wash-out. (C–F) Positron emission tomography (PET)m oline

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aximum intensity projection image shows multiple areas of pathological 18F-chathological uptake at the level of the prostate lodge, corresponding on morpholog

agittal) on the corresponding turbo spin echo (TSE) T2-weightedmages, and the following constraints observed: suspected recur-ence tissue was included; urethra, seminal vesicles, ejaculatoryucts, and bladder and rectal wall were excluded; signal-to-noiseatio had to be greater than 3:1; and water/fat suppression had to bedequate. Voxels that did not fit these criteria were considered notseable, as described previously. For each available voxel, the ratiof choline (Cho) plus creatine (Cr) to citrate (Ci) was calculated.

On the basis of the literature for 1H-MRSI [18], each voxel wasategorized as follows: no solid tissue/empty prostatic fossa whenho + Cr/Ci was undetectable; fibrotic/scar tissue when Cho + Cr/Ci0.2; residual healthy prostatic gland tissue when Cho + Cr/Ci0.2 and <0.5; probably recurrent prostate cancer tissue whenho + Cr/Ci >0.5 and <1; and definitively recurrent prostate cancerissue when Cho + Cr/Ci >1. During the second session each radi-logist formulated an opinion of cancer recurrence. In the secondeading session, cases were evaluated at least 1 week after the read-ng of the 1H-MRSI data sets in a different random order, and curvesf the following dynamic MR parameters were assessed: onset timeOT); time to peak (TTP); peak enhancement (PE); washout (WSH).ach reader blindly evaluated the dynamic imaging parameters inandom order, on the basis of the presence, asymmetry, and degreef enhancement. On the basis of prior studies, we considered earlyodular enhancement (prior to enhancement of the rest of therostatic fossa and pelvic muscles) and early washout to be fea-ures that were highly indicative of prostate cancer [34]. Individualssessments of 1H-MRSI and DCEMR were evaluated in conjunction

ith the T2-weighted images.

To minimize recall bias the third session was separated by oneeek. In that analysis the same radiologists interpreted the cases

ncluding all available data (morphological, 1H-MRSI, and dynamic

uptake. Fused axial, sagittal and coronal planes views and whole-body PET shows.

MRI findings) and formulated a definitive diagnosis. Where amethod has reported a borderline or dubious result, the final assess-ment has been worked out on the correlation of both techniques.

2.6. Histological examination

TRUS-guided biopsies were performed in 56 patients, withrecurrence size ranging between 7.6 mm and 19.4 mm, 5–6 weekafter MR and PET–CT imaging of the post-prostatectomy fossa,using a biplanar 7.5-MHz frequency probe. In each patient thebiopsy was performed following standard biopsy scheme, takingone core from each side of the bladder neck, one from each sideof the anastomosis and two cores from the retro-trigone region(six cores biopsy) [35,36]. In patients in whom biochemical relapseemerged, the biopsy specimens were taken under TRUS with theuse of an 18-G needle loaded in a spring action automatic biopsydevice and were fixed overnight in a solution of 10% neutralbuffered formalin. TRUS was considered positive if any hypoechoiclesion was identified at the bladder neck, on the anastomosis or inthe retro-trigone area. Where no hypoechoic lesion was detectedon TRUS, biopsy specimens were taken random following standardbiopsy scheme.

2.7. Statistical analysis and clinical validation

Statistical data analysis was applied using the statisticalsoftware MedCalc Software Demo for Windows, version 9.3

(Mariakerke, Belgium). Sensitivity (Se), specificity (Spe), positivepredictive value (PPV), negative predictive value (NPV) of detectingprostate cancer were calculated for all data sets, and receiver oper-ating characteristic (ROC) curves were generated to summarize the

704 V. Panebianco et al. / European Journal of Radiology 81 (2012) 700– 708

Table 2MR and PET results for localization of cancer recurrence.

Imaging modality Sensitivity Specificity PPV NPV Accuracy

MRGroup A 92%(22/24) 75%(3/4) 96%(22/23) 60%(3/5) 89%(25/28)Group B 94%(49/52) 100%(4/4) 100%(49/49) 57%(4/7) 94%(53/56)

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tion (Table 2). The AUCs for MR and PET–CT values were 0.971 and0.837, respectively, (SE 0.0163 and 0.126; CI 95% 0.887–0.998 and0.714–0.922) (Table 3). The pairwise comparison of ROC curves forGroup A and Group B (Graph 1Graphs 1 and 2) values were 0.271

PET–CTGroup A 62%(15/24) 50%(2/4Group B 92%(48/52) 33%(1/3

ata. For the analysis of 1H-MRSI data, a standardized uptake ratioaximum cut-off value of Cho + Cr/Ci >0.5 was employed, and an

rea under the curve (AUC) was calculated to assess which cut-offalue for each dynamic curve parameter (OT, TTP, PE, WSH) coulde optimal for cancer detection.

Patients were divided into two groups on the basis of the clinicalalidation used for MR and PET CT results (Table 1). Moreover theetection rate [37] was calculated. The “gold standard” for localisease presence was ascertained on the basis of a TRUS-biopsyesult from the prostate fossa (Group B), or a reduction in PSA level>50%) following radiation therapy (Group A). A patient suspectedf local recurrence detected with MR imaging and with PET–CT,as considered to be true-positive when the imaging results corre-

ated with the conclusive histopathological findings in Group B andith PSA reduction after external beam radiation therapy in Group. To allow for reasonable differences in morphology between thevaluated imaging and histopathological findings, we consideredhe histopathologically and imaging-detected tumors to be of com-arable size, localization, and number. When this condition wasot respected, a patient was considered to be false-positive. Com-arisons of these parameters at per-ROI analysis versus those ater-patient analysis revealed only minor insignificant differences.oc curve analysis was performed in order to compare each tech-iques diagnostic accuracy level. Statistical analysis was performed

ndependently on each group.

. Results

In Group A, MR results were validated by PSA level modificationfter radiation therapy. This group included 28 patients with meanSA 1.1 ng/mL (range 0.8–1.4 ng/mL), Figs. 1 and 2. PSA provenocal recurrences were identified in 24 of 28 (86%) patients eval-ated, whereas 4 (14%) had no biochemical evidence for cancer.he maximal transverse dimension of a lesion representing localecurrence averaged 5.00 mm and 7.2 mm (mean 6 ± 0.5), Fig. 3.ombined 1H-MRSI and DCEMR shows a Se and Spe of 92% and5%, respectively, (PPV 96% and NPV 60%) while PET–CT exami-ation shows Se of 62% and Spe of 50% (PPV 88% and NPV 18%)

n identifying local recurrence. The accuracy of MRI in detectionf cancer recurrence in this group was 89% while PET–CT showsn accuracy of 60% (Table 2). The AUCs for MR and PET–CT values

ere 0.833 and 0.562, respectively, (standard error [SE], 0.0904 and

.153; 95% confidential integral [CI] 0.645–0.946 and 0.363–0.748)Table 3).

able 3esults of receiver operating characteristic (ROC) curve analysis in both groups.

Imaging modality AUC SE 95% CI

MRGroup A 0.833 0.0904 0.645–0.946Group B 0.971 0.0163 0.887–0.998

PET–CTGroup A 0.562 0.153 0.363–0.748Group B 0.837 0.126 0.714–0.922

UC, area under curve; SE, statistical error; CI, confidential interval.

88%(15/17) 18%(2/11) 60%(17/28)98%(48/49) 43%(3/7) 91%(51/56)

In Group B biopsy-proven local recurrences were identified in52 of 56 (93%) patients evaluated, whereas 4 (7%) had no biopsyevidence for cancer. PSA ranged from 1.3 ng/mL to 2.5 ng/mL (mean1.9 ng/mL) and tumor size local recurrence ranged between 7.6 mmand 19.4 mm (mean 13.3 ± 4.5), Fig. 4. Combined 1H-MRSI andDCEMR shows a Se of 94% and Spe of 100% (PPV 100% and NPV57%) with accuracy of 94% in identifying local recurrence. PET–CTrevealed local recurrence in 48 patients (Se = 92%) and has a Spe of33% (PPV 98% and NPV 43%) with accuracy of 91% in cancer detec-

Graphs 1 and 2. Graphs show receiver operating characteristic (ROC) curves com-parison for each technique in first (A) and in second (B) patient group. ROC showarea under the curve (AUC) values for combined 1H-MRSI and DCE-MRI and AUCvalue for PET–CT examination. The area under the curve related to combined1H-MRSI and DCE-MRI is greater compared with those PETCT, reflecting the supe-riority of the combined approach in detection of local recurrence in both patientgroup. In Group A (PSA value ranged between 0.8 and 1.4 ng/mL), AUC combined1HMRSI–DCEMR = 0.833; 95% CI = 0.645–0.946. AUC of PET–CT exam = 0.562; 95%CI = 0.363–0.748. In Group B (PSA value ranged between 1.3 and 2.5 ng/mL) AUCcombined 1HMRSI–DCEMR = 0.971; 95% CI = 0.887–0.998. AUC of PET–CT = 0.837;95% CI = 0.714–0.922. Pairwise comparison of ROC curves shows in the first groupdifference between areas of 0.271; SE 0.141; CI 0.00569–0.547; Z statistic 1.92;P = 0.055. In the second group difference between areas of 0.135; SE 0.125; CI0.111–0.380; Z statistic 1.074; P = 0.238.

V. Panebianco et al. / European Journal of Radiology 81 (2012) 700– 708 705

Fig. 3. A 66-years old man with PSA value of 0.4 ng/mL. In (A) morphologic axial T2-w image showed a 5 mm nodule on posterior side of peri-anastomotic mucosa. In (B)spectroscopic analysis showed alteration of ratio value with increased of choline rate. (C) Dynamic subtracted image shows an area of enhancement corresponding to 5 mmnodule and the method of positioning the respective ROI. The resulting signal-intensity time curve shows a high, strong and progressive enhancement (D), corresponding toROI 1. In this patient, 18F-choline PET–CT does not detect further areas of pathological uptake.

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nd 0.135, respectively, (SE 0.141 and 0.125; CI 95% 0.00569–0.547nd 0.111–0.380; Z statistic 1.92 and 1.074; P value 0.045 and 0.283)Table 4). We obtained a Detection rate of 72% PSA < 0.8 ng/mL;6% PSA > 0.8 ng/mL; 87% PSA > 0.9 ng/mL; 92% PSA = 14 ng/mL; 93%SA > 14 ng/mL.

The location of recurrence within the post-prostatectomy fossaas peri-anastomotic in 24 of 84 patients (20%), around the bladdereck in 20 of 84 (16%), Fig. 5, within a retained seminal vesicle in9 of 84 (16%), and at the anterior or lateral surgical margin in 21 of4 (18%). Morphology was semi-circumferential in 24 of 84 cases,laque-like in 26 of 84 cases, and nodular in 34 of 84 cases. PET–CTevealed systemic disease in 30 patients, 5 from Group A and 25rom Group B. Both bone and lymph node metastasis were found in7 patients; in particular, PET–CT shows involvement of externalnd internal iliac and lumbar lymph node (DM 8 mm). In 8 patients,

ETCT shows only bone metastasis (5 of lumbar vertebra and 3 ofacrum), while in 5 patients it revealed only pelvic lymph nodeetastasis.

able 4alue of pairwise comparison of ROC curves.

Group Differencebetween areas

SE 95% CI Z statistic P value

Group A 0.271 0.141 0.00569–0.547 1.92 0.055Group B 0.135 0.125 0.111–0.380 1.074 0.283

4. Discussion

Compared with choline PET/CT, combined 1HMRSI-DCEMRimaging results showed higher sensitivity, specificity and accuracy.Prior published data regarding the diagnostic value of 1HMRSI-DCEMR for detection of local recurrence of prostate cancer afterRRP are limited. Other previous studies demonstrated the role ofMR in the detection of prostate cancer recurrence after radicalprostatectomy [18–23], but not in comparison with PET/CT. Thisstudy includes higher number of patients (84) than the other stud-ies reported in literature concerning diagnosis of prostate cancerrecurrence. In our results MR showed both good sensitivity andspecificity (92% and 75% in Group A, 94% and 100% in Group B,respectively). In particular specificity was higher than PET/CT bothin Group A and B. PET/CT demonstrated relatively low sensitivity(62%) and specificity (50%) especially in Group A, group includ-ing smaller lesions and lower PSA values. Also the overall MRaccuracy was higher (89% in Group A and 94% in Group B) thanPET/CT (60% in Group A and 91% in Group B) especially in GroupA. Otherwise (18)F-choline uptake is often low in organ confinedprostate cancer and excretion of FDG in the bladder may interferewith the visualization of prostate cancer. Moreover, MR imaging

due to its high-contrast and spatial resolution, may represent apromising technique for accurate evaluation of prostatic fossa post-RRP [18,21]. According to our previous experience [20], where weused a 1.5 T magnet, in this study, using a 3 T magnet, sensitivity

706 V. Panebianco et al. / European Journal of Radiology 81 (2012) 700– 708

Fig. 4. A 72-years old men with PSA value of 0.8 ng/mL. (A and B) morphologic axial T2-w image showed a 17 mm nodule on anterior-right side of peri-anastomotic mucosa(red arrow), compatible with residual gland tissue post-prostatectomy (A) and a 8 mm nodule on posterior-left side of perianastomotic mucosa, compatible with localrecurrence (B) (yellow arrow). (D and E) Spectroscopic analysis showed alteration of ratio value for increased of citrate rate (prostate specific marker) in residual tissue(D) and for increased of choline value in recurrence tissue (E). (C and F) Dynamic subtracted image shows an area of enhancement corresponding to 8 mm nodule and them rve inC lanesl

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ethod of positioning the respective ROI (C). The resulting signal-intensity time cuoregistered positron emission tomography CT image in axial, sagittal and coronal p

ocal recurrence.

alue improved from 86% to 92% for Group A (lesion size rangeetween 5.00 mm and 7.2 mm) and from 87% to 94% for Group Blesion size range between 7.6 mm and 19.4 mm), respectively; weid not observe any improvement for specificity value of Group; specificity was improved for Group B from 94% to 100%. Theccuracy of MR exam increased thanks to metabolic examination;ccording to literature ratio Cho + Cr/Ci <0.2 indicates fibrotic/scarissue; ratio value >0.2 and <0.5 is present in residual healthy pro-tatic gland tissue and definitively recurrent prostate cancer tissuehen Cho + Cr/Ci >1; metabolic analysis, instead of PET–CT, distin-

uished between recurrence, in which increased choline value, androstate residual after prostatectomy, were characterized by highitrate value [18]. As additional value MR is a no invasive modalityapable in the diagnosis of prostate cancer recurrence. In fact MRIechnique is safe to repeat because doesn’t involve radiation riskss PETCT modality and tracers labeled with radioactive isotopessed in PET–CT. The presence of pathological tissue in the prostate

fter radical prostatectomy has direct correlation with low valuesf PSA (0.2–2). In this range of values, PET does not show loco-egional disease, while MRI shows high diagnostic accuracy. So, theain role of PET–CT is to investigate metastates, because of its low

which the curve number 1 shows a high and progressive enhancement (F). (G–I) shows pathological uptake on posterior-left side of anastomosis, corresponding to

detection rate in local recurrence for PSA value < 1 ng/mL (detectionrate is 36% PSA < 1 ng/mL; 43% PSA < 2 ng/mL; 62% PSA < 3 ng/mL;73% PSA > 3 ng/mL). As described in our results we improved thedetection rate value, (72% PSA < 0.8 ng/mL; 86% PSA > 0.8 ng/mL;87% PSA > 0.9 ng/mL; 92% PSA = 14 ng/mL; 93% PSA > 14 ng/mL). Inthis contest, PET–CT shows low sensitivity in detection of localrecurrence in patients with PSA value lower than 2 ng/mL, in whichhowever, 1HMRS-DCEMR can detect local recurrence. Despite a PSAvalue >0.2 ng/mL being indicative of biochemical recurrence, wholebody [(18)F]choline PET/CT is justified only with PSA values higherthan 2 ng/mL. Recently, whole body PET/CT is indicated only withPSA values higher than 1.4 ng/mL [17] and biopsy TRUS-guided ofthe anastomosis is not recommended by EAU Guidelines (2009) inpatients with PSA increase <1 ng/mL.

In this wide range of values (0.2–1.4/2 ng/mL) the risk of loco-regional recurrence is not to be neglected and hence the need of amore accurate technique to examine the prostatic fossa post-RRP.

In conclusion, MRI can be considered a high diagnostic accuracytool to evaluate the prostatic fossa in patients with low PSA value,(ranged between 0.2 ng/mL and 2 ng/mL) where according to theguidelines other techniques (PET, TRUS biopsy) are not recom-

V. Panebianco et al. / European Journal of Radiology 81 (2012) 700– 708 707

Fig. 5. A 63-years old patient with PSA value of 1.3 ng/mL. (A and B) morphologic T2-w image showed and a 8 mm nodule on left side of bladder neck in axial (A) andcoronal planes (B) (red arrow). In C spectroscopic analysis showed alteration of ratio value with increased of choline rate. Dynamic subtracted image (D) shows an areaof enhancement corresponding to lesion on bladder neck. The ROI number 1 was placed on enhancing nodule, the ROI number 2 on opposed peripheral region with nonee sultini issios

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nhancing evidence and the ROI number 3 on the pelvic muscle as baseline. The renitial wash-out, corresponding to ROI of enhancing nodule. Coregistered Positron emhows pathological uptake on pelvic lymph node on the left side.

ended. In this contest the main clinical implication is to define correct therapeutical planning: patients with loco-regional dis-ase can be treated with radiation therapy while patients with theetastatic disease can be direct to hormonal therapy.In conclusion 1HMRS-DCEMR combined techniques is a valid

ool to detect prostate cancer recurrence and it is more accuratehan PET/CT in the identification of smaller lesions in patients withow biochemical alterations after RRP (0.2–2 ng/mL).

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