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Staging Prostate Cancer with Dynamic Contrast-enhanced Endorectal MR Imaging prior to Radical Prostatectomy: Experienced versus Less Experienced Readers¹

¹ From the Departments of Radiology (J.J.F., M.R.E., H.J.H., G.J.J., J.O.B.), Pathology (C.A.H.), and Urology (J.A.W.), University Medical Center Nijmegen, Geert Grooteplein zuid 10, NL 6500 HB, Nijmegen, the Netherlands. Received October 7, 2004; revision requested December 13; revision received January 3, 2005; accepted February 2. Supported by a grant from the Dutch Cancer Society. Address correspondence to J.J.F. (e-mail: J.Futterer{at}rad.umcn.nl).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
PURPOSE: To prospectively determine the accuracy of experienced and less experienced readers in the interpretation of combined T2-weighted fast spin-echo (SE) magnetic resonance (MR) images and dynamic contrast material–enhanced MR images compared with T2-weighted fast SE alone, with respect to differentiation of stage T2 versus stage T3 prostate carcinoma, with histologic analysis serving as the reference standard.

MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained, and 124 consecutive men (age range, 42–74 years; median age, 63 years) with biopsy-proved prostate cancer underwent MR imaging and were candidates for radical prostatectomy. T2-weighted fast SE MR images and multisection dynamic contrast-enhanced MR images with a 2-second time resolution for the whole prostate were obtained. The T2-weighted and fused color-coded parametric dynamic contrast-enhanced MR images with T2-weighted images were evaluated prospectively and scored with regard to local extent by one experienced reader and evaluated retrospectively by two less experienced readers working in consensus by using a five-point scale; images with a score greater than or equal to four were considered indicative of T3 disease. Results were correlated with whole-mount section histopathologic findings, and receiver operating characteristics analysis was performed.

RESULTS: Twenty-five patients were excluded because of positive findings in the lymph nodes (n = 16), preoperative biopsy-proved seminal vesicle invasion (n = 5), and an absent dynamic dataset (n = 4). Ninety-nine patients were included in this study. The overall sensitivity, specificity, and accuracy of MR staging performance in prostate cancer with dynamic contrast-enhanced MR imaging was 69% (24 of 35 patients), 97% (62 of 64 patients), and 87% (86 of 99 patients), respectively, for the experienced reader. This difference was not significant (P = .48) when results were compared with results from the T2-weighted images. Staging performance for the less experienced readers with parametric dynamic contrast-enhanced MR imaging, however, resulted in significant improvement of the area under the receiver operating characteristics curve (A_z) compared with T2-weighted MR imaging alone (A_z = .66 and .82, respectively; P = .01).

CONCLUSION: The use of multisection dynamic contrast-enhanced MR imaging in staging prostate cancer showed significant improvement in staging performance for the less experienced readers but had no benefit for the experienced reader.

© RSNA, 2005

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
At present, there is controversy over the role of endorectal magnetic resonance (MR) imaging of the prostate in the detection of extraprostatic extension of cancer. Some authors have reported the poor performance of endorectal MR imaging in the staging of prostate cancer (1,2). Nonetheless, others have reported favorable results, with a large heterogeneity in local staging performance (2–7) and a limited ability to demonstrate microscopic capsular penetration (2).

An additional MR technique, such as dynamic contrast material–enhanced MR imaging, is reported to be effective in the depiction of prostate pharmacokinetics (8–10). Experience with this technique in patients with breast and bladder cancer indicates that because of neovascularization, malignant lesions demonstrate earlier and faster enhancement than do benign lesions (11,12). Engelbrecht et al (13) showed that prostate cancer demonstrated different enhancement patterns when evaluating onset time, time to peak, peak enhancement, and washout. The number of studies in which the use of contrast-enhanced MR imaging in staging and detection of prostate cancer is evaluated is small, with low numbers of patients (7,14–20) (Table 1). Results are conflicting and difficult to compare. Competing examination strategies have been used; these strategies include postcontrast high-spatial-resolution MR imaging or postcontrast high-temporal-resolution MR imaging and, subsequently, low spatial resolution and decreased anatomic coverage, respectively (7,14–20).

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
Study Design
Between March 1999 and February 2003, 124 consecutive patients with biopsy-proved prostate cancer underwent MR imaging of the prostate. Patients were included in this study if they were candidates for radical prostatectomy. The diagnosis of prostate cancer was confirmed with gross pathologic examination of tissue specimens obtained with systematic transrectal ultrasonography (US)-guided sextant biopsy. The urologist classified patients as having stage T2 disease on the basis of findings at clinical examination, transrectal US, and biopsy. Exclusion criteria were previous hormonal therapy, positive lymphadenectomy results, contraindications to MR imaging (eg, cardiac pacemakers and intracranial clips), and contraindications to endorectal coil insertion (eg, anorectal surgery and inflammatory bowel disease). The study was approved by the institutional review board, and informed consent was obtained from all patients.

Patient ages ranged from 42 to 74 years (median age, 63 years). Median prostate specific antigen (PSA) levels and median Gleason score were 7.8 ng/mL (range, 3.7–78 ng/mL) and 6 (range, 3–9), respectively. The mean interval between transrectal US-guided sextant biopsy and MR imaging, which was performed after biopsy, was 33 days ± 18 (standard deviation). In all patients, prostatectomy was performed within 4 weeks (range, 1–28 days; median, 19 days) of MR imaging.

MR Imaging
MR images were obtained with a 1.5-T imager (Vision; Siemens Medical Systems, Erlangen, Germany) and the use of an integrated endorectal pelvic phased-array coil (MR Innerva; Medrad, Pittsburgh, Pa). The endorectal coil was inserted and inflated to a volume of approximately 80 mL. In all patients, peristalsis was suppressed by intramuscular injection of 1 mg glucagon (Glucagen; Nordisk, Gentofte, Denmark) before the examination. The imaging protocol included the following examinations: Multisection T2-weighted fast SE sequences were performed with an in-plane resolution of 0.55 x 0.55 mm (repetition time msec/echo time msec, 3500–4400/132; flip angle, 180°; 11–15 sections obtained; 4–5-mm section thickness, with a 0.5-mm gap; 280-mm field of view; 240 x 512 matrix; two signals acquired; echo train length, 15) in three orthogonal planes of the prostate and seminal vesicles after T1-weighted localizing images were obtained.

A multisection T1-weighted two-dimensional spoiled gradient-echo sequence (50/4.4; flip angle, 60°; seven sections; 7-mm section thickness, with a 0.5-mm gap; 280-mm field of view; 160 x 256 matrix; in-plane resolution, 1.07 x 1.07 mm) was acquired during intravenous bolus injection of a paramagnetic gadolinium chelate (0.1 mmol per kilogram of body weight gadopentetate dimeglumine [Magnevist; Schering, Berlin, Germany]) by means of a power injector (Medrad) with an injection rate of 2.5 mL/sec followed by a 15-mL saline flush. With this sequence, seven transverse sections were obtained every 2 seconds for 90–120 seconds, with the same positioning angle as that used for the transverse T2-weighted fast SE sequence covering the whole prostate. A multisection intermediate-weighted sequence was performed before injection of contrast material by using the similar transverse two-dimensional spoiled gradient-echo sequence (200/4.4; flip angle, 8°) and section positioning to allow calculation of relative gadopentetate dimeglumine concentration.

Images were obtained with the fast SE sequence in all 124 patients and with dynamic contrast-enhanced MR imaging in 120 patients; images were not obtained in four patients because of technical difficulties with the dynamic contrast-enhanced MR sequence. All dynamic data sets were transferred to an independent workstation. Analyzing software was used to display these dynamic datasets (9). Dynamic images were converted to four parameter images: start of enhancement, time to peak, peak enhancement, and washout. Contrast material–induced signal enhancement is converted to tracer concentration with the intermediate-weighted sequence data by solving a system of two low-angle gradient-echo signal equations with two unknowns (9,21). Time-concentration curves were fitted to an exponential model extended with a late washout term (9). The onset of the exponential curve is defined as the start of enhancement; the exponential constant characterizing the slope and height of the curve is defined as the time to peak. The peak enhancement is the concentration at which the exponential curve becomes level. Washout is defined as the negative slope of the late part of the exponential curve. The start of enhancement was calibrated by using the external iliac artery. The resulting parameter images depicted local flow differences in the feeding vascular system. Time to peak relates to permeability surface area (under low permeability conditions) and extracellular space. Peak enhancement correlates to differences in tracer-accessible extracellular volume.

Parametric maps were fused (three-dimensional rotation, translation, and linear interpolation) with T2-weighted MR images, such that the imager-provided position in any display mode matched exactly. The four-parameter images were displayed as transparent color-coded images, which were overlaid in semitransparent colors over the T2-weighted fast SE images. The postprocessing procedure (5 minutes per patient) was performed by an MR technologist.

Scoring and Evaluation of Data
First, the T2-weighted MR images were evaluated. The presence of extracapsular extension and seminal vesicle invasion was evaluated on the basis of specific features (Table 2) described in the literature as being highly indicative of extraprostatic disease. The readers (J.O.B., J.J.F., M.R.E.) subjectively expressed their findings of extracapsular extension and seminal vesicle invasion on a five-point confidence level scale (1, not present; 5, present). Precontrast T1-weighted images were additionally evaluated to rule out false-positive findings caused by postbiopsy hemorrhage (22). Evaluation of MR images was performed in all three planes. Criteria for extraprostatic extension were derived on the basis of the findings reported in the literature (23–26).

Reading with and without contrast enhancement was performed at a high specificity setting (27) for extraprostatic disease, and extraprostatic disease was rated only if the reader was certain of stage T3 disease. This was done to ensure that a patient with actual T2 disease received tailored curative therapy. The T2-weighted fast SE and the fused T2-weighted fast SE parametric MR images were prospectively evaluated and scored by an experienced radiologist (J.O.B.) and retrospectively scored by two less experienced radiologists (M.R.E. and J.J.F.) working in consensus. All readers were aware of the PSA level and Gleason score. The three radiologists had different levels of experience in the evaluation of prostate MR images. The radiologist who prospectively evaluated and scored images had 12 years of experience (approximately 750 studies) in MR imaging of prostate cancer at the beginning of this study. Of the radiologists who retrospectively evaluated and scored images, one (M.R.E.) had 1 year of experience with approximately 50 studies, and the other (J.J.F.) had 3 months of experience with 25 studies. For this reason, these readers evaluated the MR examinations in consensus.

Histologic Examination
The prostatectomy specimens were fixed overnight (10% neutral buffered formaldehyde) and coated with India ink. Seminal vesicles were separated from the prostate and examined separately. Transverse whole-mount step-section specimens were obtained at 4-mm intervals in a plane parallel to that in which transverse T2-weighted sequences were performed. All sections were routinely embedded in paraffin. Tissue sections of 5 µm were prepared and stained with hematoxylin-eosin. The presence and extent of cancer were outlined on the glass cover by one experienced pathologist (C.A.H., with 12 years of experience) who was blinded to the imaging results. For each tumor lesion, location and TNM stage (28) were determined and recorded.

Data Analysis
The extraprostatic extension that was predicted with MR imaging was correlated with the histopathologic analysis by one radiologist (J.J.F.) and one pathologist (C.A.H.) after scoring and evaluation of the data. The T2-weighted fast SE and the fused T2-weighted fast SE parametric MR images were aligned with the whole-mount sections. The morphology of the central gland, peripheral zone, cysts, calcifications, and urethra were used as landmarks. Aligning MR images and whole-mount specimens is considered difficult (14), and the section thickness used in the two MR imaging sequences is different. Although we are unaware of any literature on this subject, we were confident that our results were accurate within 10 mm (eg, two sections). If the detected extraprostatic extension in the whole-mount specimen was within 5 mm of the location seen on the aligned MR image and on the correct side, it was considered a match. Prostate cancer foci other than the tumors adjacent to the capsule were not evaluated separately.

Statistical Analysis
For statistical analysis, patient-by-patient evaluation was performed (ie, prostate-by-prostate analysis). A true-positive finding was considered in case of correlation of an imaging score of 4 or higher and histopathologic results with respect to the extraprostatic extension location. In the evaluation of a true-positive finding, there was stratification into extracapsular extension and seminal vesicle invasion at MR imaging and histologic analysis. For example, if a T3 tumor was diagnosed with MR imaging on the basis of seminal vesicle invasion but histologic analysis showed a T3 tumor on the basis of extracapsular extension, this was judged as a false-positive result. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy in the prediction of tumor stage, extracapsular extension, and seminal vesicle invasion were calculated by dichotomizing the readings. Scores of 4 and 5 were considered positive for extracapsular extension, seminal vesicle invasion, and stage T3 tumor. Statistical analysis included comparison of results from T2-weighted fast SE and the fused T2-weighted fast SE parametric MR images by using the McNemar test and evaluation of interobserver agreement (experienced reader vs less experienced readers) by using nonweighted statistics. The following qualitative terms were used to describe the strength of the various values of : 0.00–0.20, poor agreement; 0.21–0.40, fair agreement; 0.41–0.60, moderate agreement; 0.61–0.80, substantial agreement; and 0.81–1.00, almost perfect agreement (29). The area under the receiver operating characteristic curve (A_z) was calculated by using the scores of extracapsular extension, seminal vesicle invasion, and staging performance. All statistical analyses were performed with Rockit 0.9B (Department of Radiology, University of Chicago, Chicago, Ill) (30) and SPSS, version 9.0 (SPSS, Chicago, Ill) software. All reported P values are from two-sided tests; a P value of .05 or less was considered to indicate a statistically significant difference.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
Surgical Procedures
In 16 patients, prostatectomy was not performed because of positive findings in lymph nodes at frozen section analysis during the procedure. Five additional patients with positive findings at MR imaging were initially scheduled to undergo prostatectomy; however, they underwent US-guided seminal vesicle biopsy preoperatively, the results of which were positive in all patients. Subsequently, prostatectomy was cancelled. Of the remaining 103 patients, histopathologic analysis confirmed that 35 (34%) patients who underwent radical retropubic prostatectomy had non–organ-confined disease (stage T3a or higher) and 68 (66%) patients had organ-confined disease (stage T2b or lower). The group of patients with organ-confined disease comprised 28 patients with a stage T2a tumor and 40 patients with a stage T2b tumor. Thirty-four patients had extracapsular extension. Six of seven patients with seminal vesicle invasion also had extracapsular extension. In four MR examinations, no dynamic sequence was obtained because of technical difficulties; therefore, 99 patients were evaluated (age range, 42–72 years; median age, 61 years) with dynamic contrast-enhanced MR imaging. Although the T2-weighted MR images were degraded in 12 patients as a result of hemorrhage, the presence of capsular extension was assessable in all of these patients because these artifacts did not deform the prostate capsule. T1-weighted images were assessed to localize these artifacts. In Figure 1, examples of T2-weighted and fused T2-weighted fast SE parametric MR images are provided.

View larger version (113K): [in this window] [in a new window] [Download PPT slide]   Figure 1a. Fusion of a T2-weighted fast SE transverse image in gray value with partly opaque rendered color overlay of four contrast enhancement parameters (see text for detailed explanation of parameters). (a) Transverse T2-weighted fast SE image obtained through the prostate demonstrates a low-signal-intensity lesion (T) in the left peripheral zone with bulging (arrows) and obliteration (arrowheads) of the rectoprostatic angle. (b) The start-of-enhancement parameter demonstrates an earlier enhancement in part of the low-signal-intensity lesion (arrows) compared with the right peripheral zone (red vs green). (c) Fast time to peak (red) is present in the left peripheral zone (arrows) and right central gland (arrowheads). (d) Peak enhancement is increased markedly in the center of the lesion in the left peripheral zone (arrows) and right central gland (arrowheads). (e) A negative washout area (red) is seen in the left peripheral zone (arrows) and right central gland (arrowheads). (f) Photomicrograph shows stage T3a disease with prostate capsule penetration in the left peripheral zone (arrows) and a prostate tumor lesion (red) in the right central gland (arrowheads).

View larger version (110K): [in this window] [in a new window] [Download PPT slide]   Figure 1b. Fusion of a T2-weighted fast SE transverse image in gray value with partly opaque rendered color overlay of four contrast enhancement parameters (see text for detailed explanation of parameters). (a) Transverse T2-weighted fast SE image obtained through the prostate demonstrates a low-signal-intensity lesion (T) in the left peripheral zone with bulging (arrows) and obliteration (arrowheads) of the rectoprostatic angle. (b) The start-of-enhancement parameter demonstrates an earlier enhancement in part of the low-signal-intensity lesion (arrows) compared with the right peripheral zone (red vs green). (c) Fast time to peak (red) is present in the left peripheral zone (arrows) and right central gland (arrowheads). (d) Peak enhancement is increased markedly in the center of the lesion in the left peripheral zone (arrows) and right central gland (arrowheads). (e) A negative washout area (red) is seen in the left peripheral zone (arrows) and right central gland (arrowheads). (f) Photomicrograph shows stage T3a disease with prostate capsule penetration in the left peripheral zone (arrows) and a prostate tumor lesion (red) in the right central gland (arrowheads).

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 1c. Fusion of a T2-weighted fast SE transverse image in gray value with partly opaque rendered color overlay of four contrast enhancement parameters (see text for detailed explanation of parameters). (a) Transverse T2-weighted fast SE image obtained through the prostate demonstrates a low-signal-intensity lesion (T) in the left peripheral zone with bulging (arrows) and obliteration (arrowheads) of the rectoprostatic angle. (b) The start-of-enhancement parameter demonstrates an earlier enhancement in part of the low-signal-intensity lesion (arrows) compared with the right peripheral zone (red vs green). (c) Fast time to peak (red) is present in the left peripheral zone (arrows) and right central gland (arrowheads). (d) Peak enhancement is increased markedly in the center of the lesion in the left peripheral zone (arrows) and right central gland (arrowheads). (e) A negative washout area (red) is seen in the left peripheral zone (arrows) and right central gland (arrowheads). (f) Photomicrograph shows stage T3a disease with prostate capsule penetration in the left peripheral zone (arrows) and a prostate tumor lesion (red) in the right central gland (arrowheads).

View larger version (106K): [in this window] [in a new window] [Download PPT slide]   Figure 1d. Fusion of a T2-weighted fast SE transverse image in gray value with partly opaque rendered color overlay of four contrast enhancement parameters (see text for detailed explanation of parameters). (a) Transverse T2-weighted fast SE image obtained through the prostate demonstrates a low-signal-intensity lesion (T) in the left peripheral zone with bulging (arrows) and obliteration (arrowheads) of the rectoprostatic angle. (b) The start-of-enhancement parameter demonstrates an earlier enhancement in part of the low-signal-intensity lesion (arrows) compared with the right peripheral zone (red vs green). (c) Fast time to peak (red) is present in the left peripheral zone (arrows) and right central gland (arrowheads). (d) Peak enhancement is increased markedly in the center of the lesion in the left peripheral zone (arrows) and right central gland (arrowheads). (e) A negative washout area (red) is seen in the left peripheral zone (arrows) and right central gland (arrowheads). (f) Photomicrograph shows stage T3a disease with prostate capsule penetration in the left peripheral zone (arrows) and a prostate tumor lesion (red) in the right central gland (arrowheads).

View larger version (108K): [in this window] [in a new window] [Download PPT slide]   Figure 1e. Fusion of a T2-weighted fast SE transverse image in gray value with partly opaque rendered color overlay of four contrast enhancement parameters (see text for detailed explanation of parameters). (a) Transverse T2-weighted fast SE image obtained through the prostate demonstrates a low-signal-intensity lesion (T) in the left peripheral zone with bulging (arrows) and obliteration (arrowheads) of the rectoprostatic angle. (b) The start-of-enhancement parameter demonstrates an earlier enhancement in part of the low-signal-intensity lesion (arrows) compared with the right peripheral zone (red vs green). (c) Fast time to peak (red) is present in the left peripheral zone (arrows) and right central gland (arrowheads). (d) Peak enhancement is increased markedly in the center of the lesion in the left peripheral zone (arrows) and right central gland (arrowheads). (e) A negative washout area (red) is seen in the left peripheral zone (arrows) and right central gland (arrowheads). (f) Photomicrograph shows stage T3a disease with prostate capsule penetration in the left peripheral zone (arrows) and a prostate tumor lesion (red) in the right central gland (arrowheads).

View larger version (105K): [in this window] [in a new window] [Download PPT slide]   Figure 1f. Fusion of a T2-weighted fast SE transverse image in gray value with partly opaque rendered color overlay of four contrast enhancement parameters (see text for detailed explanation of parameters). (a) Transverse T2-weighted fast SE image obtained through the prostate demonstrates a low-signal-intensity lesion (T) in the left peripheral zone with bulging (arrows) and obliteration (arrowheads) of the rectoprostatic angle. (b) The start-of-enhancement parameter demonstrates an earlier enhancement in part of the low-signal-intensity lesion (arrows) compared with the right peripheral zone (red vs green). (c) Fast time to peak (red) is present in the left peripheral zone (arrows) and right central gland (arrowheads). (d) Peak enhancement is increased markedly in the center of the lesion in the left peripheral zone (arrows) and right central gland (arrowheads). (e) A negative washout area (red) is seen in the left peripheral zone (arrows) and right central gland (arrowheads). (f) Photomicrograph shows stage T3a disease with prostate capsule penetration in the left peripheral zone (arrows) and a prostate tumor lesion (red) in the right central gland (arrowheads).

View larger version (112K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. Histologically confirmed stage T2 prostate carcinoma in a 66-year-old patient with a PSA level of 11.4 ng/mL and a Gleason score of 6. (a) Transverse T2-weighted fast SE MR image shows a suspicious low-signal-intensity lesion (T) in the left peripheral zone. The experienced radiologist classified this as bulging (arrows) and obliteration (arrowheads) of the rectoprostatic angle and scored this as stage T3a disease. (b) After injection of contrast material, the time-to-peak parameter showed fast enhancement (arrows) in the left peripheral zone within the location of the low-signal-intensity lesion within the border of the capsule. (c) Peak enhancement parameter showed a high level of contrast enhancement in the left peripheral zone (arrows) within the contours of the prostate. The combination of T2-weighted fast SE and fused parametric MR images resulted in this tumor being correctly downstaged to stage T2a disease, which was confirmed with (d) whole-mount section histopathologic analysis. The red outline in this photograph of the specimen represents a tumor in the left peripheral zone.

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. Histologically confirmed stage T2 prostate carcinoma in a 66-year-old patient with a PSA level of 11.4 ng/mL and a Gleason score of 6. (a) Transverse T2-weighted fast SE MR image shows a suspicious low-signal-intensity lesion (T) in the left peripheral zone. The experienced radiologist classified this as bulging (arrows) and obliteration (arrowheads) of the rectoprostatic angle and scored this as stage T3a disease. (b) After injection of contrast material, the time-to-peak parameter showed fast enhancement (arrows) in the left peripheral zone within the location of the low-signal-intensity lesion within the border of the capsule. (c) Peak enhancement parameter showed a high level of contrast enhancement in the left peripheral zone (arrows) within the contours of the prostate. The combination of T2-weighted fast SE and fused parametric MR images resulted in this tumor being correctly downstaged to stage T2a disease, which was confirmed with (d) whole-mount section histopathologic analysis. The red outline in this photograph of the specimen represents a tumor in the left peripheral zone.

View larger version (96K): [in this window] [in a new window] [Download PPT slide]   Figure 2c. Histologically confirmed stage T2 prostate carcinoma in a 66-year-old patient with a PSA level of 11.4 ng/mL and a Gleason score of 6. (a) Transverse T2-weighted fast SE MR image shows a suspicious low-signal-intensity lesion (T) in the left peripheral zone. The experienced radiologist classified this as bulging (arrows) and obliteration (arrowheads) of the rectoprostatic angle and scored this as stage T3a disease. (b) After injection of contrast material, the time-to-peak parameter showed fast enhancement (arrows) in the left peripheral zone within the location of the low-signal-intensity lesion within the border of the capsule. (c) Peak enhancement parameter showed a high level of contrast enhancement in the left peripheral zone (arrows) within the contours of the prostate. The combination of T2-weighted fast SE and fused parametric MR images resulted in this tumor being correctly downstaged to stage T2a disease, which was confirmed with (d) whole-mount section histopathologic analysis. The red outline in this photograph of the specimen represents a tumor in the left peripheral zone.

View larger version (95K): [in this window] [in a new window] [Download PPT slide]   Figure 2d. Histologically confirmed stage T2 prostate carcinoma in a 66-year-old patient with a PSA level of 11.4 ng/mL and a Gleason score of 6. (a) Transverse T2-weighted fast SE MR image shows a suspicious low-signal-intensity lesion (T) in the left peripheral zone. The experienced radiologist classified this as bulging (arrows) and obliteration (arrowheads) of the rectoprostatic angle and scored this as stage T3a disease. (b) After injection of contrast material, the time-to-peak parameter showed fast enhancement (arrows) in the left peripheral zone within the location of the low-signal-intensity lesion within the border of the capsule. (c) Peak enhancement parameter showed a high level of contrast enhancement in the left peripheral zone (arrows) within the contours of the prostate. The combination of T2-weighted fast SE and fused parametric MR images resulted in this tumor being correctly downstaged to stage T2a disease, which was confirmed with (d) whole-mount section histopathologic analysis. The red outline in this photograph of the specimen represents a tumor in the left peripheral zone.

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 3a. Stage T3a disease in a 72-year-old patient with a PSA level of 10.2 ng/mL and a Gleason score of 5. (a) Transverse T2-weighted fast SE MR image shows a low-signal-intensity lesion (arrows) in the left peripheral zone, which was scored as stage T2a disease. (b) After contrast material injection, early start of enhancement was present in the right peripheral zone (oval). (c) In the right peripheral zone, faster time-to-peak enhancement was demonstrated with contrast enhancement (arrows) outside the capsule compared with the left peripheral zone. (d) Peak enhancement is displayed, which also showed an asymmetric lesion (arrows). Symmetric enhancement in the central gland was present, which turned out to be benign prostate hyperplasia. (e) No substantial washout was present. (f) The combination of the T2-weighted fast SE and fused parametric MR images resulted in this tumor being correctly upstaged to stage T3a disease, which was confirmed with whole-mount section histopathologic analysis. The red outline represents prostate cancer with capsular extension (arrow) in the right peripheral zone.

View larger version (89K): [in this window] [in a new window] [Download PPT slide]   Figure 3b. Stage T3a disease in a 72-year-old patient with a PSA level of 10.2 ng/mL and a Gleason score of 5. (a) Transverse T2-weighted fast SE MR image shows a low-signal-intensity lesion (arrows) in the left peripheral zone, which was scored as stage T2a disease. (b) After contrast material injection, early start of enhancement was present in the right peripheral zone (oval). (c) In the right peripheral zone, faster time-to-peak enhancement was demonstrated with contrast enhancement (arrows) outside the capsule compared with the left peripheral zone. (d) Peak enhancement is displayed, which also showed an asymmetric lesion (arrows). Symmetric enhancement in the central gland was present, which turned out to be benign prostate hyperplasia. (e) No substantial washout was present. (f) The combination of the T2-weighted fast SE and fused parametric MR images resulted in this tumor being correctly upstaged to stage T3a disease, which was confirmed with whole-mount section histopathologic analysis. The red outline represents prostate cancer with capsular extension (arrow) in the right peripheral zone.

View larger version (87K): [in this window] [in a new window] [Download PPT slide]   Figure 3c. Stage T3a disease in a 72-year-old patient with a PSA level of 10.2 ng/mL and a Gleason score of 5. (a) Transverse T2-weighted fast SE MR image shows a low-signal-intensity lesion (arrows) in the left peripheral zone, which was scored as stage T2a disease. (b) After contrast material injection, early start of enhancement was present in the right peripheral zone (oval). (c) In the right peripheral zone, faster time-to-peak enhancement was demonstrated with contrast enhancement (arrows) outside the capsule compared with the left peripheral zone. (d) Peak enhancement is displayed, which also showed an asymmetric lesion (arrows). Symmetric enhancement in the central gland was present, which turned out to be benign prostate hyperplasia. (e) No substantial washout was present. (f) The combination of the T2-weighted fast SE and fused parametric MR images resulted in this tumor being correctly upstaged to stage T3a disease, which was confirmed with whole-mount section histopathologic analysis. The red outline represents prostate cancer with capsular extension (arrow) in the right peripheral zone.

View larger version (95K): [in this window] [in a new window] [Download PPT slide]   Figure 3d. Stage T3a disease in a 72-year-old patient with a PSA level of 10.2 ng/mL and a Gleason score of 5. (a) Transverse T2-weighted fast SE MR image shows a low-signal-intensity lesion (arrows) in the left peripheral zone, which was scored as stage T2a disease. (b) After contrast material injection, early start of enhancement was present in the right peripheral zone (oval). (c) In the right peripheral zone, faster time-to-peak enhancement was demonstrated with contrast enhancement (arrows) outside the capsule compared with the left peripheral zone. (d) Peak enhancement is displayed, which also showed an asymmetric lesion (arrows). Symmetric enhancement in the central gland was present, which turned out to be benign prostate hyperplasia. (e) No substantial washout was present. (f) The combination of the T2-weighted fast SE and fused parametric MR images resulted in this tumor being correctly upstaged to stage T3a disease, which was confirmed with whole-mount section histopathologic analysis. The red outline represents prostate cancer with capsular extension (arrow) in the right peripheral zone.

View larger version (106K): [in this window] [in a new window] [Download PPT slide]   Figure 3e. Stage T3a disease in a 72-year-old patient with a PSA level of 10.2 ng/mL and a Gleason score of 5. (a) Transverse T2-weighted fast SE MR image shows a low-signal-intensity lesion (arrows) in the left peripheral zone, which was scored as stage T2a disease. (b) After contrast material injection, early start of enhancement was present in the right peripheral zone (oval). (c) In the right peripheral zone, faster time-to-peak enhancement was demonstrated with contrast enhancement (arrows) outside the capsule compared with the left peripheral zone. (d) Peak enhancement is displayed, which also showed an asymmetric lesion (arrows). Symmetric enhancement in the central gland was present, which turned out to be benign prostate hyperplasia. (e) No substantial washout was present. (f) The combination of the T2-weighted fast SE and fused parametric MR images resulted in this tumor being correctly upstaged to stage T3a disease, which was confirmed with whole-mount section histopathologic analysis. The red outline represents prostate cancer with capsular extension (arrow) in the right peripheral zone.

View larger version (109K): [in this window] [in a new window] [Download PPT slide]   Figure 3f. Stage T3a disease in a 72-year-old patient with a PSA level of 10.2 ng/mL and a Gleason score of 5. (a) Transverse T2-weighted fast SE MR image shows a low-signal-intensity lesion (arrows) in the left peripheral zone, which was scored as stage T2a disease. (b) After contrast material injection, early start of enhancement was present in the right peripheral zone (oval). (c) In the right peripheral zone, faster time-to-peak enhancement was demonstrated with contrast enhancement (arrows) outside the capsule compared with the left peripheral zone. (d) Peak enhancement is displayed, which also showed an asymmetric lesion (arrows). Symmetric enhancement in the central gland was present, which turned out to be benign prostate hyperplasia. (e) No substantial washout was present. (f) The combination of the T2-weighted fast SE and fused parametric MR images resulted in this tumor being correctly upstaged to stage T3a disease, which was confirmed with whole-mount section histopathologic analysis. The red outline represents prostate cancer with capsular extension (arrow) in the right peripheral zone.

The various A_z values were used as indicators of diagnostic accuracy. The receiver operator characteristic curves describing the results of MR staging (stage T2 vs stage T3 disease) performance by the radiologists are presented in Figure 4. The receiver operating characteristic curves that describe the results of the interpretation of T2-weighted fast SE (A_z = 0.66) and fused T2-weighted fast SE parametric MR datasets (A_z = 0.82) by consensus of the less experienced radiologists showed a significantly greater A_z value with dynamic contrast-enhanced MR imaging (P = .01) (Fig 4). There was no significant difference in the A_z value between the experienced radiologist and the less experienced radiologists working in consensus (Fig 4). No significant difference was present for the experienced radiologist when comparing the fused T2-weighted fast SE parametric MR images (A_z = 0.84) with the T2-weighted fast SE images (A_z = 0.77).

View larger version (42K): [in this window] [in a new window] [Download PPT slide]   Figure 4. Receiver operating characteristic curves show the results of the interpretation of T1- and T2-weighted dynamic contrast-enhanced MR imaging by an experienced radiologist and two less experienced radiologists. A significantly greater Az was present with contrast-enhanced MR imaging (Az = 0.82, P = .01) compared with unenhanced T2-weighted MR imaging for the less experienced readers.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

Jager et al (14) reported no significant improvement in staging with use of a single-section dynamic fast low-angle shot subtraction technique. The limitations of the study of Jager et al were the use of a 10-mm-thick section, a single-section technique, and only an endorectal coil. The method used in our study is comparable to that of Jager et al; however, to overcome the aforementioned limitations, integrated endorectal phased-array coil, multisection technique, and parametric images were used in our study. This resulted in a significant (P = .01) improvement of the A_z value for staging accuracy for the less experienced radiologists.

Reader experience is important in the staging of prostate cancer (2,27,33,34). In our study, the less experienced radiologists improved their results (from an A_z value of 0.66 to an A_z value of 0.82, P = .01) by using dynamic contrast-enhanced MR imaging. The parametric maps helped draw the attention of the less experienced readers to areas of prostate cancer. These areas of prostate cancer were examined for extraprostatic spread by using the parametric maps and established signs on unenhanced T2-weighted MR images. As presented in the Results section, the less experienced readers downstaged five cases and upstaged eight by using dynamic contrast-enhanced MR imaging findings, whereas the experienced reader only up- or downstaged six cases. This suggests dynamic contrast-enhanced MR imaging should be used by less experienced radiologists as an additional tool in case of local staging of prostate cancer.

In our local situation, prostate MR images are interpreted by one experienced radiologist. Radiologists in training have the opportunity to learn MR imaging of the prostate; thus, less experienced radiologists interpreted the MR findings in consensus and retrospectively. In addition, one radiologist had only 3 months of experience in the interpretation of endorectal MR images of the prostate. This is a limitation of the current study; however, there is always a considerable learning curve in the interpretation of prostate MR images (33).

The experienced radiologist did not improve his staging performance by using fused T2-weighted fast SE parametric MR images; this could be explained by his extensive experience in reading T2-weighted images. An experienced reader learns to distinguish tumorous areas of low T2 signal intensity from nontumorous areas in difficult cases.

In the evaluation of MR images in this study, the PSA level and Gleason score were known to the readers. It would have been interesting to determine the effect of knowledge of PSA and Gleason score on reading performance; however, that was not the purpose of our study. Sixty-six percent of the study population consisted of patients that had tumors with a stage of T2b or less at histopathologic analysis. According to Partin et al (32), the population in this study is at low to intermediate risk for having extraprostatic disease; one-third of these patients had extracapsular extension. Considering the five patients with seminal vesicle invasion, this number will be increased. An explanation for the number of patients with positive capsular extension could be that the Partin et al tables (32) underestimate the risk of local disease in our patient populations; however, this possibility was not explored in our study.

Evaluation and scoring of the images were performed at the prostate level. The analysis could be improved by scoring the prostate at the octant level (35); however, as described in the meta-analysis of Engelbrecht et al (6), most current examinations are performed at the prostate level. We evaluated patients at the prostate level, as this is the most important data from a clinical point of view. In case of stage T3 disease, the urologist will not perform radical prostatectomy. Thus, the results of our study can be compared with results of other studies.

Tempany (36) and Seltzer et al (37) have reported that radiologists can improve their diagnostic accuracy after being trained on computers afforded with examples of confined and nonconfined disease. As we do not have this facility in our hospital, we were not able to compare these techniques.

Our study is limited by the use of a relatively large (ie, 7-mm) section thickness for the dynamic sequence. This can be improved by using faster gradients and new MR software, should these be available. For this investigation, the attainable optimal parameters with the MR system were used. In general practice, this situation is not uncommon, and the obtained images are sufficient for the evaluation of MR images. The low number of radiologists who participated in this study is another limitation. It is difficult to generalize our results with only one experienced radiologist.

Jager et al (38) developed a decision analysis model that indicated MR staging in the preoperative work-up of prostate cancer is cost-effective and should be performed with a high specificity reading. The need for high specificity was also emphasized by Langlotz et al (27) to ensure that as few patients as possible are unnecessarily denied potentially curative therapy because of false-positive findings. Our prospective study has demonstrated that it is possible to achieve high specificity and accuracy in a large group of patients. Even for less experienced readers, it appeared possible to achieve these results in staging of prostate cancer with the additional use of contrast-enhanced MR imaging.

In conclusion, use of multisection dynamic contrast-enhanced MR imaging in the staging of prostate cancer resulted in significant improvement in the staging performance of the less experienced readers; however, it had no benefit to the experienced reader. Studies with more readers are needed to confirm our results.

	ACKNOWLEDGMENTS

 
The authors gratefully acknowledge Yvonne Hoogeveen, PhD (Department of Radiology, University Medical Center, Nijmegen, the Netherlands), and Anja d'Houw, MD (Department of Pathology, University Medical Center, Nijmegen, the Netherlands), for their support.

	FOOTNOTES

 

Abbreviations: A_z = area under the receiver operating characteristic curve • PSA = prostate specific antigen • SE = spin echo

Authors stated no financial relationship to disclose.

Author contributions: Guarantors of integrity of entire study, J.J.F., J.O.B.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, J.J.F., M.R.E., J.O.B.; clinical studies, J.J.F., M.R.E., C.A.H., J.A.W., J.O.B.; experimental studies, J.J.F., H.J.H., J.O.B.; statistical analysis, J.J.F., J.O.B.; and manuscript editing, all authors

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