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Usefulness of Diffusion-weighted Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer

Rationale and Objectives

The aim of this study was to evaluate the diagnostic accuracy of diffusion-weighted magnetic resonance imaging (DWI) in prostate cancer.

Materials and Methods

The MEDLINE, Embase, CANCERLIT, and Cochrane Library databases were searched for studies published from January 2001 to August 2011 evaluating the diagnostic performance of DWI in detecting prostate carcinoma. Sensitivities and specificities were determined across studies, and summary receiver-operating characteristic curves were constructed using hierarchical regression models.

Results

Sixteen studies (18 subsets) with a total of 852 patients were included. Six studies (seven subsets) examining men with pathologically confirmed prostate cancer (260 patients) had pooled sensitivity and specificity of 0.88 (95% confidence interval [CI], 0.76–0.95) and 0.84 (95% CI, 0.76–0.90), respectively. Compared to patients at high risk for clinically relevant cancer, sensitivity was higher in low-risk patients (0.94 [95% CI, 0.89–0.97] vs 0.62 [95% CI, 0.54–0.70], P < .05), but specificity was lower (0.86 [95% CI, 0.72–0.94] vs 0.89 [95% CI, 0.83–0.93], P < .05). Ten studies (11 subsets) examining patients with suspected prostate cancer (592 patients) had pooled sensitivity and specificity of 0.76 (95% CI, 0.68–0.84) and 0.86 (95% CI, 0.79–0.91). Sensitivity was lower in high-risk patients (0.74 [95% CI, 0.57–0.87] vs 0.78 [95% CI, 0.70–0.84], P > .05), but specificity was higher (0.92 [95% CI, 0.89–0.94] vs 0.78 [95% CI, 0.70–0.84], P < .05).

Conclusions

A limited number of small studies suggest that DWI could be a rule-in test for high-risk patients. Further prospective studies including larger populations are necessary to confirm the actual value of DWI in this field.

The early detection of prostate cancer is essential to decrease mortality rates. Several diagnostic methods have been applied in recent years to detect the malignant changes within the prostate. As a result of widespread screening with prostate-specific antigen (PSA), prostate cancer is increasingly being detected at an early stage . However, the specificity of PSA level for prostate cancer screening is limited, and even if PSA levels are between 2.5 and 4 ng/mL, cancer is detected in 25% to 30% of biopsies .

Transrectal ultrasound (TRUS) of the prostate is the primary method worldwide. It is used not only to gain a first impression of the organ but also to guide prostate biopsies, if necessary . But TRUS has limitations in diagnostic performance of randomized sextant biopsies, as first illustrated by Levine et al , who analyzed the results of 137 men subjected to two consecutive sets of biopsies in a single office visit and showed that 30% of the cancers were detected exclusively in the second biopsy set. This was then confirmed in the European Prostate Cancer Detection Study, in which in 820 of 1051 patients with negative results on first TRUS-guided biopsies, cancer was detected in 10% ( n = 83) on repeat biopsy .

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Materials and methods

Search Strategy

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Study Selection

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Table 1

Evaluation of Quality of Included Studies Using the Quality Assessment of Studies of Diagnostic Accuracy Tool

Number Quality Item Positive Score 1 Was the spectrum of patients representative of the patients who will receive the test in practice? Only patients with primary cancer were included 2 Were selection criteria clearly described? It was clear how patients were selected to undergo DWI 3 Is the reference standard likely to enable correct classification of the target condition? Only histopathologic analysis after surgery was used as the reference standard 4 Is the time period between reference standard and index test short enough to be reasonably sure that the target condition did not change between the two tests? <30 days 5 Did the whole sample or a random selection of the sample receive verification with a reference standard? All patients or a random selection of the patients received verification with histopathologic analysis after surgery 6 Did patients receive the same reference standard regardless of the index test result? All patients received the same reference standard regardless of response at therapy 7 Was the reference standard independent of the index test (the index test did not form part of the reference standard)? The DWI findings did not form part of the reference test 8 Was the execution of the index test described in sufficient detail to permit replication of the test? The DWI protocol was described 9 Was the execution of the reference standard described in sufficient detail to permit its replication? Sufficient details or citations were reported to permit replication of the reference standard 10 Were the index test results interpreted without knowledge of the results of the reference standard? Interpretation of DWI was performed without knowledge of histopathologic findings 11 Were the reference standard results interpreted without knowledge of the results of the index test? Interpretation of the reference test results was performed without knowledge of DWI findings 12 Were the same clinical data available when test results were interpreted as would be available when the test is used in practice? Clinical data such as age, sex, and clinical stage were available when DWI was interpreted 13 Were uninterpretable/intermediate test results reported? All DWI results, including uninterpretable and/or intermediate results, were reported 14 Were withdrawals from the study explained? It was clear what happened to all patients who entered the study

DWI, diffusion-weighted imagine.

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Data Extraction and Quality Assessment

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Risk Stratification

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Data Synthesis and Analysis

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Results

Literature Search and Selection of Studies

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Study Description

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Table 2

Technical Characteristics

Study Year Model Field Strength (T) Coil MRI Protocol DWI b Value (s/mm 2 ) SENSE Additional Techniques Yamamura et al 2011 Siemens 1.5 Integrated endorectal pelvic phased-array coil T1WI, T2WI Echo-planar sequence 50, 400, 800 No — Vilanova et al 2011 Signa Horizon HDx (GE) 1.5 Integrated endorectal pelvic phased-array coil T1WI, T2WI Single-shot echo-planar image 0, 1000 Yes DCE MRI, MRS Nagayama et al 2011 Gyroscan ACS-Intera (Philips) 1.5 Five-channel cardiac phased-array coil T1WI, T2WI Single-shot spin-echo echo-planar imaging sequence 0 Yes — Iwazawa et al 2011 Magnetom Symphony (Siemens) 1.5 Eight-channel phased-array coils T1WI, T2WI Echo-planar sequence 0, 1000 Yes DCE MRI Yağci et al 2010 Signa Excite HD (GE) 1.5 Endorectal coil T1WI, T2WI Echo-planar sequence 800 No — Rosenkrantz et al 2010 Magnetom Avanto (Siemens) 1.5 Pelvic surface phased-array coil T1WI, T2WI Single-shot echo-planar image 50, 500, 1000 No — Portalez et al 2010 Achieva (Philips) 1.5 Integrated endorectal pelvic phased-array coil T1WI, T2WI Echo-planar sequence 0, 600 Yes DCE MRI, MRS Kim et al 2010 Intera Achieva (Philips) 3 Body coil T1WI, T2WI Single-shot echo-planar image 0, 1000, 2000 Yes — Tamada et al 2008 Signa Excite HighSpeed (GE) 1.5 Body coil T1WI, T2WI Single-shot echo-planar sequence 0, 800 No DCE MRI Chen et al 2008 Magnetom Espree (Siemens) 1.5 Endorectal coil T1WI, T2WI Single-shot echo-planar imaging 0, 1000 No MRS Reinsberg et al 2007 Intera Achieva (Philips) 1.5 Phased-array coil T1WI, T2WI Echo-planar sequence 0, 300, 500, 800 Yes MRS Kim et al 2007 Intera Achieva (Philips) 3 Body coil T1WI, T2WI Single-shot echo-planar imaging 0, 1000 No — deSouza et al 2007 Intera Achieva (Philips) 1.5 Endorectal coil T1WI, T2WI Echo-planar sequence 0, 300, 500, 800 No — Miao et al 2006 Magnetom Avanto (Siemens) 3 Phased-array coil T1WI, T2WI Single-shot echo-planar imaging 0, 300, 600 No — Kozlowski et al 2006 GE 1.5 Integrated endorectal pelvic phased-array coil T1WI, T2WI Single-shot fast spin-echo sequence 600 No — Gibbs et al 2006 GE 3 Torso phased-array coil T1WI, T2WI Spin-echo echo-planar imaging 0, 500 No —

DCE, dynamic contrast-enhanced; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; SENSE, sensitivity encoding; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Table 3

Study Quality Characteristics

Study Year Study Design Patient Enrollment Blinding Region of Investigation Single Pathologic Correlative Reference Test Yamamura et al 2011 Retrospective ND ND Peripheral zone Sextant Biopsy Vilanova et al 2011 Retrospective ND ND Whole prostate Patient Biopsy, prostatectomy Nagayama et al 2011 Retrospective Consecutive ND Whole prostate Sextant Prostatectomy Iwazawa et al 2011 Retrospective Consecutive Blind Whole prostate Sextant Biopsy Yağci et al 2010 Prospective Consecutive ND Peripheral zone Sextant Biopsies Rosenkrantz et al 2010 Retrospective Consecutive Not blind Peripheral zone Sextant Prostatectomy Portalez et al 2010 Prospective Consecutive Blind Whole prostate Sextant Biopsy Kim et al 2010 Retrospective ND Blind Whole prostate Sextant Prostatectomy Tamada et al 2008 Retrospective ND Blind Whole prostate Sextant Biopsy Chen et al 2008 Retrospective ND ND Whole prostate Sextant Biopsy Reinsberg et al 2007 Prospective Consecutive ND Whole prostate Voxels Biopsy Kim et al 2007 Prospective Consecutive ND Whole prostate Sextant Prostatectomy deSouza et al 2007 Prospective Consecutive ND Peripheral zone Voxels Biopsy Miao et al 2006 Retrospective ND Blind Whole prostate Sextant Biopsy Kozlowski et al 2006 Prospective ND ND Peripheral zone Sextant Biopsy Gibbs et al 2006 Retrospective ND ND Peripheral zone Sextant Biopsy

ND, not documented.

Table 4

Patient Characteristics

Study Year Patients Mean Age (y) Age Range (y) Mean PSA (ng/mL) PSA Range (ng/mL) Mean ADC of Normal (×10 −3 mm 2 /s) Mean ADC of Malignant (×10 −3 mm 2 /s) ADC Cutoff Value and Level (×10 −3 mm 2 /s) Mean Gleason Score Gleason Score (Range) Previous Negative Biopsy Results Cancer Status Yamamura et al 2011 50 61.8 41–78 7.19 ±5.12 1.65 ± 0.32 0.96 ± 0.24 1.21 ND ND Yes Suspected Vilanova et al 2011 70 63.5 43–87 7.4 (median) 4–17.20 ND ND ND 7 5–8 No Suspected Nagayama et al 2011 45 67 53–74 8.7 4.1–22.8 1.94 ± 0.31 1.07 ± 0.35 1.35 ND ND No Diagnosed Iwazawa et al 2011 178 68.8 41–86 20.51 4.04–568.50 ND ND ND ND ND No Suspected Yağci et al 2010 43 66 49–79 9.1 (median) 1.4–120 1.58 ± 0.36 0.94 ± 0.32 1.2 7 6–10 No Suspected Rosenkrantz et al 2010 45 60 46–80 7.4 0.6–69.4 1.02 ± 0.22 1.52 ± 0.30 1.39 6.8 6–9 No Diagnosed Portalez et al 2010 68 62.4 49–76 9.16 1.6–25 ND ND 1.24 ND ND Yes Suspected Kim et al 2010 48 66 45–80 7.21 2.3–23.2 2.04 ± 0.34 (b = 1000 s/mm 2 ), 2.61 ± 0.36 (b = 2000 s/mm 2 ) 1.19 ± 0.33 (b = 1000 s/mm 2 ), 1.58 ± 0.41 (b = 2000 s/mm 2 ) ND 7 6–9 No Suspected Tamada et al 2008 40 71 62–84 16.9 2.98–125.0 ND ND ND 7 5–10 No Diagnosed Chen et al 2008 42 63 45–82 11.93 4.7–38.00 ND ND 1.3 ND ND No Suspected Reinsberg et al 2007 42 69.3 60–78 10.2 (median) 0.45–45 1.51 ± 0.27 1.03 ± 0.18 1.26 7 6–8 No Suspected Kim et al 2007 35 64.3 44–76 7.94 1.32–35.3 1.97 ± 0.25 (PZ), 1.79 ± 0.19 (TZ) 1.32 ± 0.24 (PZ), 11.37 ± 0.29 (TZ) 1.67, 1.61 7 6–8 No Diagnosed deSouza et al 2007 33 68.7 52–78 14.1 2.9–72.3 1.71 ± 0.16 1.30 ± 0.30 1.6 7 6–8 No Diagnosed Miao et al 2006 37 63.7 43–82 22.4 4.07–136 ND ND ND ND ND No Suspected Kozlowski et al 2006 14 60.3 48–71 9.4 4.3–46 1.57 ± 0.27 0.99 ± 0.16 ND ND ND No Suspected Gibbs et al 2006 62 65 49–80 9.2 1.6–130.0 1.86 ± 0.47 1.33 ± 0.32 1.45 7 2–10 No Diagnosed

ADC, apparent diffusion coefficient; ND, not documented; PSA, prostate-specific antigen; PZ, peripheral zone; TZ, transition zone.

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Assessment of Study Quality and Publication Bias

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Figure 1, Results of Deeks' funnel-plot asymmetry test for publication bias. The nonsignificant slope indicates that no significant bias was found ( P = .55). ESS, effective sample size.

Figure 2, Bar graph of study assessment with Quality Assessment of Studies of Diagnostic Accuracy (QUADAS) checklist. Data are the numbers of responses from the QUADAS tool. The numbers indicate how many articles were assigned a score of “yes” (for the QUADAS tool) and how many articles were assigned a score of “no.” The responses of “no” and “unclear” were summarized together.

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Diagnostic Accuracy of DWI

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Figure 3, Hierarchical summary receiver-operating characteristic (HSROC) curve for the diagnostic performance of diffusion-weighted imaging for suspected prostate cancer. The size of the circle indicates the weight of each study.

Figure 4, Hierarchical summary receiver-operating characteristic (HSROC) curve for the diagnostic performance of diffusion-weighted imaging for diagnosed prostate cancer. The size of the circle indicates the weight of each study.

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Risk Stratification in the Suspected Cancer Group

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Table 5

Diagnostic Accuracy of Diffusion-weighted Imaging (Risk Stratification)

Group References Summary Sensitivity (95% CI) Summary Specificity (95% CI) Suspected prostate cancer 0.76 (0.68–0.84) 0.86 (0.79–0.91) High-risk group 0.74 (0.62–0.85) 0.92 (0.88–0.95) ∗ Low-risk group 0.78 (0.70–0.84) 0.78 (0.70–0.84) ∗ Pathologically confirmed prostate cancer 0.88 (0.76–0.95) 0.84 (0.76–0.90) High-risk group 0.62 (0.54–0.70) ∗ 0.89 (0.83–0.93) ∗ Low-risk group 0.94 (0.89–0.97) ∗ 0.86 (0.72–0.94) ∗

CI, confidence interval.

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Risk Stratification in the Confirmed Cancer Group

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Discussion

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Conclusions

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