E U R O P E A N U R O L O G Y 6 1 ( 2 0 1 2 ) 6 1 6 – 6 2 0

avai lable at www.sciencedirect .com

journal homepage: www.europeanurology.com

Case Study of the Month

Diffusion-Weighted Magnetic Resonance Imaging Detects Local

Recurrence After Radical Prostatectomy: Initial Experience

Gianluca Giannarini a, Daniel P. Nguyen a, George N. Thalmann a, Harriet C. Thoeny b,*

a Department of Urology, University of Bern, Inselspital, Bern, Switzerland; b Institute of Diagnostic, Interventional and Paediatric Radiology, University of

Bern, Inselspital, Bern, Switzerland

Article info

Article history:

Accepted November 15, 2011Published online ahead ofprint on November 24, 2011

Keywords:

Diffusion-weighted magnetic

resonance imaging

Prostate cancer

Radical prostatectomy

Prostate cancer recurrence,

Abstract

Current conventional cross-sectional imaging techniques, such as contrast-enhancedcomputed tomography and magnetic resonance imaging (MRI), are largely inaccurate indetecting local recurrence after radical prostatectomy. We report on five patients withbiochemical recurrence after radical retropubic prostatectomy and pelvic lymph nodedissection for whom local recurrence could only be detected with diffusion-weighted(DW) MRI. Prior to DW-MRI, all patients had negative digital rectal examinations,negative or equivocal conventional cross-sectional imaging, and negative bone scans.All suspicious lesions on DW-MRI imaging were histologically proved to be localrecurrences of prostate cancer after either transrectal ultrasound–guided or trans-urethral biopsy. These results should encourage other centres to test our findings.

# 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

local

* Corresponding author. Institute of Diagnostic, Interventional and Paediatric Radiology, Universityof Bern, Inselspital, Freiburgstrasse 10, CH-3010 Bern, Switzerland. Tel. +41 31 632 2939;

thoeny@insel.ch (H.C. Thoeny).

Fax: +41 31 632 4874.E-mail address: harriet.

1. Case report

Five asymptomatic patients aged 59–80 yr were diagnosed

with biochemical recurrence (defined as a serum prostate-

specific antigen [PSA] level>0.2 ng/ml and rising) 16–147 mo

after radical retropubic prostatectomy (RRP) and pelvic

lymph node dissection, with serum PSA levels ranging from

0.63 to 12.8 ng/ml (Table 1). All patients underwent a

standardised diagnostic work-up, including digital rectal

examination, computed tomography (CT) (n = 4), or as

an alternative to CT, F(18)-fluorodeoxyglucose positron

emission tomography (PET)/CT of the abdomen and pelvis

(n = 1), as well as a bone scan. All clinical and imaging

examinations were negative for local recurrence. We

0302-2838/$ – see back matter # 2011 European Association of Urology. Publis

therefore performed conventional magnetic resonance

imaging (MRI) of the pelvis with additional acquisition of a

diffusion-weighted (DW) sequence.

MRI of the entire pelvis from the aortic bifurcation to

the inferior border of the pubic symphysis was performed on

a 1.5-T MRI unit (Magnetom Sonata, Siemens Medical

Solutions, Erlangen, Germany) equipped with a surface

phased array coil using T2-weighted sequences in the

transverse, coronal, and sagittal planes, as well as transverse

T1-weighted sequences before and after intravenous gado-

linium administration without dynamic analysis of contrast

enhancement. In addition, a DW sequence with a slice

thickness of 4 mm covering the formerly periprostatic

area was performed (b values: 0–1000 s/mm2), and the

hed by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2011.11.030

Table 1 – Clinical and pathologic characteristics of our patients with biopsy-proven local recurrence after radical retropubic prostatectomyand pelvic lymph node dissection in whom the recurrence could only be detected by diffusion-weighted magnetic resonance imaging

Age attime

of RRP,yr

SerumPSA levelat timeof RRP,

ng/ml

Pathologicstage

Surgicalmarginstatus

(location)

Gleasonscore

at RRP

Age attime of

biochemicalrecurrence,

yr

Time fromRRP to

biochemicalrecurrence,

mo

SerumPSA levelat time of

biochemical

recurrence,ng/ml

Site oflocal

recurrence

Gleasonscore at

localrecurrence

Maximumdiameterof local

recurrence,

mm

ADCvalue of

localrecurrence

(� 10�3 mm2/s)

Case 1 59 28.5 pT3b pN1 Positive

(apex)

3 + 3 69 120 9.5 Vesicourethral

anastomosis

3 + 3 13 1.05

Case 2 58 3.8 pT2c pN0 Negative 4 + 3 59 16 0.63 Retrovesical

area

4 + 4 15 0.92

Case 3 68 23.8 pT3a pN0 Negative 3 + 2 80 147 4.1 Vesicourethral

anastomosis

3 + 3 13 0.93

Case 4 66 18.1 pT3b pN1 Positive

(apex)

5 + 4 69 35 4 Posterior

bladder wall

4 + 4 15 1.18

Case 5 61 48 pT2c pN0 Negative 4 + 3 65 55 12.8 Vesicourethral

anastomosis

3 + 3 10 1.08

RRP = radical retropubic prostatectomy; PSA = prostate-specific antigen; ADC = apparent diffusion coefficient.

E U R O P E A N U R O L O G Y 6 1 ( 2 0 1 2 ) 6 1 6 – 6 2 0 617

corresponding apparent diffusion coefficient map was

automatically generated. Reporting of MRI findings was

binary, that is, positive or negative/equivocal.

The conventional MRI could not convincingly detect

the recurrent prostate cancer (PCa). None of the patients

showed enlarged (>8-mm short axis) pelvic lymph nodes.

In four patients a small hyperintense (bright) lesion on[(Fig._1)TD$FIG]

Fig. 1 – Magnetic resonance imaging (MRI) of a 59-yr-old man with a serum proprostatectomy. (a) Axial T2-weighted MRI at the level of the formerly periprossaturated image, no enhancing mass is visible. (c) On axial diffusion-weighted Mmass (arrow) is evident in the retrovesical area. (d) On the corresponding appalesion (arrow) highly suspicious for tumour. Histology confirmed recurrent pr

the high-b-value images corresponding to a hypointense

lesion on the apparent diffusion coefficient map was

detected in the formerly periprostatic area, and a similar

lesion was observed in the posterior bladder wall in

one patient. All lesions were diagnosed as highly

suspicious for local recurrence by the referring radiologist

(Figs. 1–3).

state-specific antigen level of 0.63 ng/ml at 16 mo after radical retropubictatic area shows no focal mass. (b) On the axial contrast-enhanced fat-

RI at a b value of 900 s/mm2 at the same level, a small focal hyperintenserent diffusion coefficient map, the focal mass is seen as a hypointense

ostate cancer. Asterisk identifies the bladder.

[(Fig._2)TD$FIG]

Fig. 2 – Magnetic resonance imaging (MRI) of an 80-yr-old man with a serum prostate-specific antigen level of 4.1 ng/ml at 147 mo after radicalretropubic prostatectomy. (a) Axial T2-weighted MRI at the level of the formerly periprostatic area shows no obvious focal mass. (b) On the axial contrast-enhanced fat-saturated image, no enhancing mass is visible. (c) On axial diffusion-weighted MRI at a b value of 900 s/mm2 at the same level, a small focalhyperintense mass (arrow) is evident on the left side of the vesicourethral anastomotic area. (d) On the corresponding apparent diffusion coefficient map, thefocal mass is seen as a hypointense lesion (arrow) highly suspicious for tumour. Histology confirmed recurrent prostate cancer.

E U R O P E A N U R O L O G Y 6 1 ( 2 0 1 2 ) 6 1 6 – 6 2 0618

The four patients with suspected tumour in the formerly

periprostatic area underwent a transrectal ultrasound

(TRUS)–guided biopsy using an 18-gauge needle. For the

purpose of the study, a total of four to six biopsy cores

were taken. Three to four cores were directed to the area

where the DW sequence noted the suspicious lesions, and

two to three cores were directed elsewhere in the formerly

periprostatic area. All cores directed to the lesion noted on

DW sequence were positive for malignant prostatic tissue,

whereas all cores directed elsewhere in the formerly

periprostatic area were negative. In the patient with a

suspicious lesion in the posterior bladder wall, transurethral

biopsy confirmed recurrence of PCa.

All patients were, or currently are, being treated with

external-beam radiation therapy.

2. Discussion

In this small series of well-selected patients, DW-MRI was

able to detect local recurrence in five men with biochemical

recurrence following RRP for whom CT and conventional

MRI findings were negative or equivocal and the bone scan

was negative. All suspicious lesions were biopsy-proven

local recurrences of PCa. Thus, DW-MRI appears to be a

useful instrument for detecting PCa recurrences that cannot

be detected with conventional cross-sectional imaging.

In patients with biochemical recurrence after RRP, the

ability to distinguish between local and distant recurrence

has critical therapeutic consequences. If local recurrence is

detected, salvage radiation therapy can be offered [1].

Moreover, accurate anatomic localisation of tumour deposits

within the formerly periprostatic area may allow for an

individualised field of irradiation in an image-guided fashion,

thereby maximising efficacy and minimising toxicity.

Unfortunately, especially in patients with low serum PSA

levels for whom the tumour burden is lowest, neither

established clinicopathologic parameters nor current imag-

ing techniques (ie, TRUS and conventional cross-sectional

imaging) nor needle biopsy of the formerly periprostatic

area is sufficiently sensitive or specific to identify the site of

recurrence. Thus, more accurate, and preferably noninva-

sive, imaging techniques are needed.

DW-MRI is a noninvasive imaging technique capable of

detecting microstructural and functional changes preceding

morphologic changes in several pathologies of various

organs with no need to administer contrast medium [2].

DW-MRI is the current gold standard for diagnosis of acute

cerebral vascular injury and has gained increasing impor-

tance as an imaging biomarker for tissue characterisation

(eg, liver, breast) and functional evaluation (eg, kidney), as

well as prediction and monitoring of cancer treatment

response (eg, liver metastases, head and neck tumours) [3].

[(Fig._3)TD$FIG]

Fig. 3 – Magnetic resonance imaging (MRI) of a 65-yr-old man with a serum prostate-specific antigen level of 12.8 ng/ml at 55 mo after radical retropubicprostatectomy. (a) Axial T2-weighted MRI at the level of the formerly periprostatic area shows no obvious focal mass. (b) On the axial contrast-enhancedfat-saturated image, a small enhancing structure not suspicious for recurrent tumour is visible. (c) On axial diffusion-weighted MRI at a b value of900 s/mm2 at the same level, a small hyperintense focal mass (arrow) is evident on the right side of the vesicourethral anastomotic area. (d) On thecorresponding apparent diffusion coefficient map, the focal mass is seen as a hypointense lesion (arrow) highly suspicious for tumour. Histologyconfirmed recurrent prostate cancer.

E U R O P E A N U R O L O G Y 6 1 ( 2 0 1 2 ) 6 1 6 – 6 2 0 619

Use of DW-MRI has recently expanded to the field of urologic

oncology with various applications, mainly characterisation

of focal renal masses and the detection, assessment of

aggressiveness, and pelvic lymph node staging of PCa and

bladder cancer [4].

Preliminary results have shown the ability of DW-MRI to

detect local recurrence in PCa patients treated with external

and interstitial radiation therapy or with high-intensity

focussed ultrasound ablation [4]. In these studies, however,

the highest diagnostic performance of DW-MRI was found

when this technique was combined with either T2-weighted

or dynamic contrast-enhanced (DCE) MRI, with the multi-

parametric approach giving the best results. A plausible

reason for the insufficient accuracy of DW-MRI alone could

be that the prostate was left in situ in these studies. This

situation would hinder identification of residual/recurrent

tumour because of the coexisting radiation-induced

changes in, coagulation necrosis of, or cavitation effects of

prostate tissue that result in diffuse low-signal intensity in

T2-weighted MRI sequences and possibly artefacts also in

DW sequences. Conversely, the postprostatectomy setting is

apparently more favourable thanks to higher contrast. In fact,

because of the low signal intensity of the bladder and

formerly periprostatic area on high-b-value images, only

recurrent PCa tissue would appear bright because of impeded

diffusion and would thus be more easily detectable. A major

challenge for future studies is to explore whether DW-MRI is

able to consistently detect local recurrence at low serum PSA

levels.

Other promising imaging modalities were recently

investigated for their ability to detect local recurrence after

RRP. In one study of 70 patients with biochemical recurrence

after RRP and no adjuvant androgen deprivation therapy,

magnetic resonance (MR) spectroscopy, DCE-MRI, and their

combination were compared for diagnostic accuracy [5]. The

reference standard was TRUS-guided biopsy in 50 patients

EU-ACME question

Please visit www.eu-acme.org/europeanurology to

answer the following EU-ACME question online (the

EU-ACME credits will be attributed automatically).

Question:

Diffusion-weighted magnetic resonance imaging is a

radiologic modality that:

A. Can only be performed on 3-T magnetic resonance

units.

B. Needs intravenous contrast medium administration.

C. Needs special software for image analysis.

D. Provides noninvasive information on cellular density

and integrity of cell membranes.

E U R O P E A N U R O L O G Y 6 1 ( 2 0 1 2 ) 6 1 6 – 6 2 0620

(mean serum PSA level at recurrence: 1.26 ng/ml) and serum

PSA response after salvage radiation therapy in the remaining

20 patients (mean serum PSA level at recurrence: 0.8 ng/ml).

The combination of MR spectroscopy and DCE-MRI resulted

in the highest diagnostic accuracy compared with either

modality alone. Although these results are very promising,

MR spectroscopy is at present limited by low spatial

resolution and high sensitivity to field inhomogeneities.

Moreover, MR spectroscopy is not widely available, and

proficient image interpretation requires ample experience.

DCE-MRI also has lower spatial resolution compared with

DW-MRI; moreover, the modality requires contrast medium

administration and dedicated software for image analysis

and has limited reproducibility [6].

In a recent review of the possible postprostatectomy

applications of choline PET/CT, which also provides morpho-

logic and functional information, it was concluded that this

modality cannot be currently recommended for the detection

and definition of radiation target volume in local recurrence,

mainly because of its limited sensitivity at the local level,

especially for serum PSA levels <1 ng/ml [7]. In fact, while

distant metastases may be accurately identified, locally

recurrent PCa tissue, at least for the time being, is scarcely or

not at all detectable because of interference from the isotope

accumulating in the bladder, which masks the contiguous

formerly periprostatic area.

In contrast to all these new imaging techniques, DW-MRI

has the advantages of being widely available and requiring

no contrast medium administration, no ionizing radiation

exposure, no special software for image analysis, and no

particular experience in image interpretation, since visual-

isation of local recurrence is straightforward. A current

limitation of this technique is the lack of standardisation

across multiple centres.

Large and well-designed prospective multi-institutional

trials comparing these modern imaging techniques are

warranted to establish the clinical usefulness of DW-MRI.

Conflicts of interest: The authors have nothing to disclose.

Funding support: This work was supported by research grant number

320000–113512 of the Swiss National Science Foundation and by

CARIGEST SA Switzerland, advisor of a generous grantor.

References

[1] Mottet N, Bellmunt J, Bolla M, et al. EAU guidelines on prostate

cancer. Part II: treatment of advanced, relapsing, and castration-

resistant prostate cancer. Eur Urol 2011;59:572–83.

[2] Thoeny HC, De Keyzer F. Extracranial applications of diffusion-

weighted magnetic resonance imaging. Eur Radiol 2007;17:1385–93.

[3] Thoeny HC, Ross BD. Predicting and monitoring cancer treatment

response with diffusion-weighted MRI. J Magn Reson Imaging 2010;

32:2–16.

[4] Giannarini G, Petralia G, Thoeny HC. Potential and limitations of

diffusion-weighted magnetic resonance imaging in kidney, prostate

and bladder cancer including pelvic lymph node staging: a critical

analysis of the literature. Eur Urol 2012;61:326–40.

[5] Sciarra A, Panebianco V, Salciccia S, et al. Role of dynamic contrast-

enhanced magnetic resonance (MR) imaging and proton MR spec-

troscopic imaging in the detection of local recurrence after radical

prostatectomy for prostate cancer. Eur Urol 2008;54:589–600.

[6] Seitz M, Shukla-Dave A, Bjartell A, et al. Functional magnetic reso-

nance imaging in prostate cancer. Eur Urol 2009;55:801–14.

[7] Picchio M, Briganti A, Fanti S, et al. The role of choline positron

emission tomography/computed tomography in the manage-

ment of patients with prostate-specific antigen progression after

radical treatment of prostate cancer. Eur Urol 2011;59:51–60.