Diffusion-Weighted Magnetic Resonance Imaging Detects Local Recurrence After Radical Prostatectomy: Initial Experience

Transcription

1 EUROPEAN UROLOGY 61 (2012) available at journal homepage: 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, 2011 Published online ahead of print on November 24, 2011 Keywords: Diffusion-weighted magnetic resonance imaging Prostate cancer Radical prostatectomy Prostate cancer Abstract Current conventional cross-sectional imaging techniques, such as contrast-enhanced computed tomography and magnetic resonance imaging (MRI), are largely inaccurate in detecting after radical prostatectomy. We report on five patients with after radical retropubic prostatectomy and pelvic lymph node dissection for whom 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 s of prostate cancer after either transrectal ultrasound guided or transurethral biopsy. These results should encourage other centres to test our findings. # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Institute of Diagnostic, Interventional and Paediatric Radiology, University of Bern, Inselspital, Freiburgstrasse 10, CH-3010 Bern, Switzerland. Tel ; Fax: address: harriet.thoeny@insel.ch (H.C. Thoeny). 1. Case report Five asymptomatic patients aged yr were diagnosed with (defined as a serum prostatespecific antigen [PSA] level >0.2 ng/ml and rising) 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. We 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 gadolinium 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: s/mm 2 ), and the /$ see back matter # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 EUROPEAN UROLOGY 61 (2012) Table 1 Clinical and pathologic characteristics of our patients with biopsy-proven after radical retropubic prostatectomy and pelvic lymph node dissection in whom the could only be detected by diffusion-weighted magnetic resonance imaging Age at time of RRP, yr Serum PSA level at time of RRP, ng/ml Pathologic stage Surgical margin status (location) Gleason score at RRP Age at time of yr Time from RRP to mo Serum PSA level at time of ng/ml Site of Gleason score at Maximum diameter of mm ADC value of ( 10 3 mm 2 /s) Case pt3b pn1 Positive (apex) Vesicourethral Case pt2c pn0 Negative Retrovesical area Case pt3a pn0 Negative Vesicourethral Case pt3b pn1 Positive (apex) Posterior bladder wall Case pt2c pn0 Negative Vesicourethral RRP = radical retropubic prostatectomy; PSA = prostate-specific antigen; ADC = apparent diffusion coefficient 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] 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 by the referring radiologist (Figs. 1 3). Fig. 1 Magnetic resonance imaging (MRI) of a 59-yr-old man with a serum prostate-specific antigen level of 0.63 ng/ml at 16 mo after radical retropubic prostatectomy. (a) Axial T2-weighted MRI at the level of the formerly periprostatic area shows no focal mass. (b) On the axial contrast-enhanced fatsaturated image, no enhancing mass is visible. (c) On axial diffusion-weighted MRI at a b value of 900 s/mm 2 at the same level, a small focal hyperintense mass (arrow) is evident in the retrovesical area. (d) On the corresponding apparent diffusion coefficient map, the focal mass is seen as a hypointense lesion (arrow) highly suspicious for tumour. Histology confirmed recurrent prostate cancer. Asterisk identifies the bladder.

3 618 [(Fig._2)TD$FIG] EUROPEAN UROLOGY 61 (2012) 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 radical retropubic prostatectomy. (a) Axial T2-weighted MRI at the level of the formerly periprostatic area shows no obvious focal mass. (b) On the axial contrastenhanced fat-saturated image, no enhancing mass is visible. (c) On axial diffusion-weighted MRI at a b value of 900 s/mm 2 at the same level, a small focal hyperintense mass (arrow) is evident on the left side of the vesicourethral anastomotic area. (d) On the corresponding apparent diffusion coefficient map, the focal mass is seen as a hypointense lesion (arrow) highly suspicious for tumour. Histology confirmed recurrent prostate cancer. 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 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 in five men with 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 s of PCa. Thus, DW-MRI appears to be a useful instrument for detecting PCa s that cannot be detected with conventional cross-sectional imaging. In patients with after RRP, the ability to distinguish between and distant has critical therapeutic consequences. If is detected, salvage radiation therapy can be offered [1]. Moreover, accurate anatomic isation 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 imaging 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. Thus, more accurate, and preferably noninvasive, 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 importance 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].

4 [(Fig._3)TD$FIG] EUROPEAN UROLOGY 61 (2012) 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 retropubic 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, a small enhancing structure not suspicious for recurrent tumour is visible. (c) On axial diffusion-weighted MRI at a b value of 900 s/mm 2 at the same level, a small hyperintense focal mass (arrow) is evident on the right side of the vesicourethral anastomotic area. (d) On the corresponding apparent diffusion coefficient map, the focal mass is seen as a hypointense lesion (arrow) highly suspicious for tumour. Histology confirmed recurrent prostate cancer. 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 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 multiparametric 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 at low serum PSA levels. Other promising imaging modalities were recently investigated for their ability to detect after RRP. In one study of 70 patients with 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

5 620 EUROPEAN UROLOGY 61 (2012) (mean serum PSA level at : 1.26 ng/ml) and serum PSA response after salvage radiation therapy in the remaining 20 patients (mean serum PSA level at : 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 morphologic and functional information, it was concluded that this modality cannot be currently recommended for the detection and definition of radiation target volume in mainly because of its limited sensitivity at the level, especially for serum PSA levels <1 ng/ml [7]. In fact, while distant metastases may be accurately identified, ly 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 visualisation of 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 of the Swiss National Science Foundation and by CARIGEST SA Switzerland, advisor of a generous grantor. EU-ACME question Please visit 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. References [1] Mottet N, Bellmunt J, Bolla M, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castrationresistant prostate cancer. Eur Urol 2011;59: [2] Thoeny HC, De Keyzer F. Extracranial applications of diffusionweighted magnetic resonance imaging. Eur Radiol 2007;17: [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: [5] Sciarra A, Panebianco V, Salciccia S, et al. Role of dynamic contrastenhanced magnetic resonance (MR) imaging and proton MR spectroscopic imaging in the detection of after radical prostatectomy for prostate cancer. Eur Urol 2008;54: [6] Seitz M, Shukla-Dave A, Bjartell A, et al. Functional magnetic resonance imaging in prostate cancer. Eur Urol 2009;55: [7] Picchio M, Briganti A, Fanti S, et al. The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer. Eur Urol 2011;59:51 60.