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Original Research |
1 All authors: Department of Radiology, University of California, San Francisco, 505 Parnassus Ave., Rm. M-372, Box 0628, San Francisco, CA 94143-0628.
Received January 31, 2006;
accepted after revision August 1, 2006.
Address correspondence to F. V. Coakley
(fergus.coakley{at}radiology.ucsf.edu).
Abstract
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MATERIALS AND METHODS. We retrospectively identified 40 patients with an elevated serum PSA level and without a histologic diagnosis of prostate cancer who underwent endorectal MRI and MRSI at our institution. On the basis of MRI findings alone and then combined MRI and MRSI findings, a single experienced observer rated the presence or absence of prostate cancer in each side of the prostate on a 5-point scale (1 = definitely absent, 5 = definitely present). Areas under the receiver operating characteristic (ROC) curve were calculated using the hemiprostate as the unit of analysis. The presence or absence of cancer on subsequent endorectal sonographically guided sextant biopsy was used as the standard of reference.
RESULTS. Biopsy revealed no cancer in 24 patients, bilateral cancer in 11, and unilateral cancer in five. The areas under the ROC curve for the diagnosis of prostate cancer by hemigland was 0.70 for MRI alone and 0.63 for combined MRI and MRSI (no significant difference, p =0.32).
CONCLUSION. Endorectal MRI and MRSI are reasonably accurate for the diagnosis of prostate cancer in patients with an elevated serum PSA level, but the remaining limitations suggest that MRI and MRSI should be used as a supplement rather than a replacement for biopsy using the current technology and diagnostic criteria.
Keywords: MRI • MR spectroscopic imaging • oncologic imaging • prostate • prostate cancer
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Forty-five patients met these criteria. Five patients were excluded because of saw palmetto use (saw palmetto is a plant extract with some apparent hormonal activity that may be used as an alternative therapy) or hormone deprivation therapy during the study period because of the possible confounding effects of hormonal modulation. The final study population consisted of 40 men with a mean age of 63 years (range, 48-80 years) and a mean serum PSA level of 10.6 ng/mL (range, 5.2-24.1 ng/mL). Thirty-six had a prior negative biopsy at the time of MRI and MRSI, and four had not undergone a biopsy. The mean interval between the MR study and subsequent biopsy was 95 days (range, 0-537 days), with only six patients having biopsy performed at an interval greater than 6 months. Subsequent biopsies were performed at our institution (n = 22) using a previously described technique [21]. Biopsy was performed in a standard sextant fashion and was not affected or targeted by MRI findings. Eighteen patients had their subsequent biopsy performed at other institutions.
MRI and MRSI Technique
MRI was performed on a 1.5-T whole-body scanner (Signa, GE Healthcare).
Patients were scanned in a supine position using the body coil for excitation
and a pelvic phased-array coil in combination with a commercially available
balloon-covered expandable endorectal coil for signal reception. Sequences
acquired included thin-section high-spatial-resolution axial and coronal
T2-weighted fast spin-echo images of the prostate and seminal vesicles with
the following parameters: TR/effective TE, 5,000/96; echotrain length, 16;
slice thickness, 3 mm; interslice gap, 0 mm; field of view, 14 cm; matrix, 256
x 192; frequency direction, anteroposterior; and 3 excitations. All MR
images were routinely postprocessed to compensate for the reception profile of
the endorectal and pelvic phased-array coils.
After review of the axial T2-weighted images, an MRSI volume was selected by the technologist performing the examination to maximize coverage of the prostate while minimizing the inclusion of periprostatic fat and rectal air; technologists who perform MRSI studies of the prostate at our institution have had extensive training and experience, with more than 4,000 such studies performed in the last decade before the study. Three-dimensional MRSI data were acquired using a water- and lipid-suppressed double spin-echo point-resolved spectroscopy (PRESS) sequence that used spectral-spatial pulses for the two 180° excitation pulses. The spectral-spatial pulses allowed both sharp volume selection and frequency selection to reduce the water resonance and suppress lipid resonances [22, 23]. The influence of chemical shift on the apparent location of the selected volume was also reduced by the higher spectral bandwidth of the spectral-spatial pulses [22, 23]. Outer voxel saturation pulses were also used to further sharpen volume selection and conform the selected volume to the shape of the prostate to eliminate susceptibility artifacts from periprostatic fat and rectal air [24]. Data sets were acquired as 16 x 8 x 8 phase-encoded spectral arrays (1,024 voxels with a spatial resolution of 0.24-0.34 cm3), with a TR/TE of 1,000/130 and a 17-minute acquisition time. The spectroscopic imaging data were zero-filled from 8 to 16 in both the anteroposterior and craniocaudal directions to increase the likelihood of optimal alignment between spectroscopic voxels and the peripheral zone. The total examination time was 1 hour, including coil placement and patient positioning.
MRSI data were overlaid on the corresponding axial T2-weighted images and evaluated by a spectroscopist with more than 15 years of experience in MRSI of the prostate to determine which voxels were suitable for analysis. Individual voxels were considered suitable if they consisted of at least 75% peripheral zone tissue, did not include tissue surrounding the urethra or ejaculatory ducts, had a signal-to-noise ratio of greater than 5:1, and were not spectroscopically contaminated by insufficient water or fat suppression. A score from 1 to 5 was assigned to each usable voxel. A score of 1 is considered probably benign; 2, possibly benign; 3, equivocal; 4, possibly malignant; and 5, probably malignant. The details of this scoring system have been previously described [25]; the system has shown both high accuracy and interobserver agreement, with kappa values of 0.79-0.80 [25]. The final combined images consisted of axial T2-weighted images with an overlaid grid showing both the corresponding spectra and the spectral score on the 1-5 scale.
Image Interpretation
MR images alone and then MR and MRSI images in combination were
independently evaluated by an attending radiologist with more than 9 years of
experience in interpreting MRI and MRSI of the prostate. MRSI scoring by voxel
was overlaid on the corresponding MR images to be interpreted by the
radiologist. This observer was unaware of PSA level or biopsy results and
rated the presence or absence of prostate cancer in each side of the prostate
on a 5-point scale (1 = definitely absent, 2 = probably absent, 3 =
intermediate or indeterminate, 4 = probably present, 5 = definitely
present).
Statistical Analysis
Due to the known limitations of tumor localization and registration when
using sextant biopsy results
[26-28],
we used the hemiprostate (i.e., left and right sides of the gland) as the unit
of analysis. The limitation of the prostatic sextant as a unit of analysis was
illustrated in a study investigating tumor localization by MRI and MRSI
[14]; the accuracy of imaging
for sextant localization was only 67% (157/234) to 74% (173/234),
respectively, but rose to 75% (80/106) to 88% (93/106) for tumor
lateralization [14].
Cancer was determined to be present or absent in each hemiprostate on the basis of the presence or absence of an ipsilateral positive biopsy result, respectively, on a subsequent endorectal sonographically guided biopsy. We generated nonparametric receiver operating characteristic (ROC) curves for cancer detection on MRI and MRSI at different thresholds based on the score assigned by the expert observer. Areas under the ROC curve (AUCs) were calculated and compared between MRI alone and combined MRI and MRSI using nonparametric methods [29]. In addition, we dichotomized the 5-point scale into cancer absent (ratings 1-2) and cancer present (ratings 3-5) and calculated the associated sensitivity and specificity for MRI alone and combined MRI and MRSI, again using the hemiprostate as the unit of analysis. The sensitivities and specificities of MRI alone and combined MRI and MRSI were compared using the McNemar test.
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MRI and MRSI
The AUC by prostate hemigland was 0.70 (95% CI = 0.60-0.81) for MRI alone
and 0.63 (95% CI = 0.51-0.77) for MRI and MRSI in combination
(Fig. 1). These findings were
not statistically significant (p = 0.32). Using dichotomized ratings
(1-2 = cancer absent and 3-5 = cancer present) for each hemigland, the
sensitivity and specificity of MRI alone were 43% (95% CI = 27-60%) and 81%
(95% CI = 65-90%), respectively. For MRI and MRSI in combination, the
sensitivity and specificity were 35% (95% CI = 17-59%) and 79% (95% CI =
64-88%), respectively. There was no significant differ- ence in sensitivity
(p = 0.56) or specificity (p = 0.78) between MRI alone and
combined MRI and MRSI (Fig. 2).
The number of patients with acute or chronic inflammation was insufficient to
perform a meaningful analysis about the possible effect of prostatitis on MRSI
findings (Fig. 3).
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In studies of similar cohorts, researchers have reported an accuracy of 70-77% using MRI for prostate cancer detection [16, 30], which is similar to our findings of a 70% accuracy using MRI alone. The addition of MRSI was recently shown to yield a diagnostic accuracy of 88% [18]. This result is higher than our reported accuracy of 63% for combined MRI and MRSI. This disparity might be explained by differences in analysis: They used a 2 x 2 table with dichotomous calculation, whereas we constructed ROC curves and used the calculation of the AUC to determine accuracy. In fact, when grouping normal MRI and MRSI images versus equivocal and suspicious, their accuracy was reported as 47.6%. Thus, perhaps the true accuracy of combined MRI and MRSI may lie in-between their reported values of 47.6% and 88% and closer to our reported value of 63%.
In another recent study of 42 prostate cancer patients with a rising PSA
level and negative findings on prior biopsies, in which MRI and MRSI results
were used to target an endorectal sonographically guided biopsy, a similar
overall accuracy of cancer detection was reported
[19]. Cancer was detected in
17 (55%) of 31 men with positive MRSI findings (voxels with scores 
4)
with a sensitivity of 100%, specificity of 44%, positive predictive value of
55%, negative predictive value of 100%, and accuracy of 67%. In men with a
more clear-cut metabolic abnormality—that is, at least one spectroscopic
voxel with a score of 5 (12 of 17 men)—the sensitivity, specificity,
positive and negative predictive values, and accuracy were 71%, 84%, 75%, 81%,
and 79%, respectively.
Despite our inability to show improved accuracy with the addition of MRSI, continued improvements in MRSI technology may eventually provide a significant improvement in the diagnostic accuracy of MRI and MRSI. For instance, current spectroscopic voxel volume is limited, which poses a challenge in this diagnostically difficult population who are more likely to have a small cancer volume if cancer is present. In fact, seven of our patients had a Gleason score of 6. Thus, MRI and MRSI may be less accurate in those with small-volume, low-risk, or both small-volume and low-risk disease. Continued improvement in spectroscopic voxel size to limit the effects of partial voluming and the identification of additional prostate cancer markers may eventually make combined MRI and MRSI a more feasible secondary screening and primary diagnostic technique in this patient population.
MRI and MRSI have their own current intrinsic confounding variables, such as postbiopsy hemorrhage, inflammation from prostatitis, and therapeutic effects, that reduce imaging specificity [31, 32]. This study did not include patients with recent prostate biopsy results and excluded patients on concurrent androgen-deprivation medication or saw palmetto in an attempt to limit these confounding effects. However, histologic evidence of acute or chronic inflammation was present in 35 of 80 hemiglands. Because of the limited number of cases in this study, it was not statistically feasible to incorporate these data as a possible confounder that was limiting the accuracy of MRI and MRSI (Fig. 3). Another limitation of this study involves the intrinsic nature of combining the MRSI scoring system with MRI information, which is ultimately subjective and based on expert judgment.
Although endorectal sonographically guided biopsy targets lesions that show differences in echogenicity, approximately one third of prostate cancers have been reported as isoechoic [33]. Also, in patients with negative findings on a prior biopsy, the sensitivity and positive predictive value of endorectal sonography has been reported as 33% and 57%, respectively [17]. Few patients with negative biopsy results proceed to radical prostatectomy, a more robust gold standard for determining the presence of prostate cancer, which possibly resulted in an overestimate of false-negative cases in this study. Therefore, more long-term follow-up is needed to correctly identify such cases not correctly identified on postimaging endorectal sonographically guided biopsy. Also, only the peripheral zone was evaluated in our study, and MRSI scores were not assigned to central gland voxels. Because our study used biopsy data as a measure for the presence of cancer, we cannot be certain that a biopsy sample with positive results was taken from the peripheral zone. However, our experience suggests that central gland tumors account for only approximately 10% of all cancer foci [13].
Endorectal MRI and MRSI are reasonably accurate in the diagnosis of prostate cancer in patients with an elevated serum PSA level, but current limitations suggest MRI and MRSI should be used as a supplement rather than as a replacement for biopsy using current technology and diagnostic criteria; the appropriate role of imaging in this problematic population requires further research.
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