Faculty Bibliography

OBJECTIVE: The purpose of this study was to evaluate the utility of multiparametric MRI in localization of the index lesion of prostate cancer. MATERIALS AND METHODS: Fifty-one patients who underwent 3-T MRI of the prostate with a pelvic phased-array coil that included T2-weighted, diffusion-weighted, and dynamic contrast-enhanced sequences before prostatectomy were included. Six radiologists assessed all images to identify the lesion most suspicious of being the index lesion, which was localized to one of 18 regions. A uropathologist using the same 18-region scheme reviewed the prostatectomy slides to localize the index lesion. MRI performance was assessed by requiring either an exact match or an approximate match (discrepancy of up to one region) between the MRI and pathologic findings in terms of assigned region. RESULTS: The pathologist identified an index lesion in 49 of 51 patients. In exact-match analysis, the average sensitivity was 60.2% (range, 51.0-63.3%), and the average positive predictive value (PPV) was 65.3% (range, 61.2-69.4%). In approximate-match analysis, the average sensitivity was 75.9% (range, 65.3-69.6%), and the average PPV was 82.6% (range, 79.2-91.4%). The sensitivity was higher for index lesions with a Gleason score greater than 6 in exact-match (74.8% vs 15.3%, p < 0.001) and approximate-match (88.7% vs 36.1%, p = < 0.001) analyses and for index lesions measuring at least 1 cm in approximate-match analysis (80.3% vs 58.3%, p = 0.016). In exact-match analysis, 30.0%, 44.9%, and 79.1% of abnormalities found with one, two, and three MRI parameters represented the index lesion (p < 0.001). CONCLUSION: The sensitivity and PPV of multiparametric MRI for index lesion localization were moderate, although they improved in the setting of more aggressive pathologic features and a greater number of abnormal MRI parameters, respectively.

PURPOSE: The GR gene produces GRalpha and GRbeta isoforms by alternative splicing of a C-terminal exon. GRalpha binds glucocorticoids, modulates transcription in a glucocorticoid dependent manner and has a growth inhibitory role in prostate cells. Due to this role glucocorticoids are often used to treat androgen independent prostate cancer. In contrast, GRbeta has intrinsic transcriptional activity and binds mifepristone (RU486) but not glucocorticoids to control gene expression. To our knowledge the role of GRbeta in prostate cell proliferation is unknown. MATERIALS AND METHODS: We determined GRbeta levels in various prostate cancer cell lines by reverse transcriptase-polymerase chain reaction and Western blot. The effect of GRbeta on the kinetics of prostate cancer cell growth was determined by cell counting and flow cytometry upon mifepristone and dexamethasone treatment. Cell proliferation was also examined after siRNA mediated knockdown and over expression of GRbeta. RESULTS: GRbeta mRNA and protein were up-regulated in LNCaP cells that over expressed the androgen receptor co-factor ARA70beta. Treatment of LNCaP-ARA70beta with mifepristone or siRNA targeting GRbeta inhibited proliferation compared to that of parental LNCaP cells. The immortal but nontumorigenic RC165 prostate cell line and the tumorigenic DU145 prostate cell line with endogenous GRbeta also showed partial growth reduction upon GRbeta depletion but to a lesser extent than LNCaP-ARA70beta cells. The growth stimulatory effect of ARA70beta on LNCaP cells was partly GRbeta dependent, as was the proliferation of RC165 cells and to a lesser extent of DU145 cells. CONCLUSIONS: Results suggest that patients with a primary tumor that expresses GRbeta and ARA70beta may benefit from mifepristone.

OBJECTIVE: The purpose of this study is to retrospectively compare 1D, 2D, and 3D measurements on CT for detection of growth of solid renal masses on active surveillance. MATERIALS AND METHODS: Forty solid renal masses measuring at least 1 cm in patients who underwent two CT studies at least 3 months apart were included. Two radiologists independently assessed the studies for interval growth using gestalt visual assessment and 1D, 2D, and 3D measurements. Prospective reports were also evaluated for indications of growth. The summation-of-areas technique was used to calculate volumes of lesions, which served as reference standard in determination of growth. Logistic regression analysis for correlated data was used to compare accuracy of methodologies for detection of lesion growth. Interreader agreement was assessed using kappa coefficients and intraclass correlation coefficients. RESULTS: The accuracy of gestalt visual, 1D, 2D, and 3D assessments for detection of interval growth was 72.5%, 70.0%, 82.5%, and 85% for reader 1 and 77.5%, 70.0%, 90.0%, and 95.0% for reader 2. These differences were significant or nearly significant (p = 0.003-0.054) for the greater accuracy of 2D or 3D measurements than for 1D measurements for reader 1 as well as the greater accuracy of 2D measurements than 1D measurements and 3D measurements than gestalt visual assessment or 1D measurements for reader 2. The accuracy of prospective reports for detection of growth was 65.0%. Reader agreement was fair for gestalt visual assessment (kappa = 0.31) and nearly perfect for 1D, 2D, and 3D measurements (intraclass correlation coefficient = 0.97-0.99). CONCLUSION: Our results show that 2D or 3D measurements may be preferable to 1D measurements on CT in assessment for growth of solid renal masses on active surveillance.

Background The presence of muscularis propria invasion by bladder cancer is a key factor in prognosis and treatment decisions, although may be missed by biopsy due to sampling error. MRI has shown potential for detection of muscle invasion but has not specifically been evaluated for this purpose in the setting of bladder cancer patients without evidence of muscle invasion on initial biopsy. Purpose To evaluate the role of MRI in detection of muscularis propria invasion by bladder cancer following a pathologic diagnosis of non-invasive tumor. Material and Methods This retrospective study included 23 patients who underwent pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis propria invasion and in whom additional histologic evaluation was performed following MRI. Two radiologists in consensus reviewed T2-weighted images to identify those cases suspicious for muscle invasion on MRI. The radiologists identified whether cases suspicious for invasion demonstrated disruption of the T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding, and peri-vesical soft tissue nodularity. Findings were compared with pathologic results obtained after MRI. Results Suspicion was raised for muscle invasion in eight of 23 cases, four of which exhibited invasion on follow-up pathology. No case without suspicion on MRI exhibited invasion on follow-up pathology. Therefore, sensitivity and specificity were 100% and 79%, respectively. Among individual findings, muscularis disruption on T2WI exhibited sensitivity of 100% and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited sensitivity and specificity of 25% and 100%. Conclusion MRI demonstrated high sensitivity for detection of muscle invasion in cases of bladder cancer without invasion on initial histologic assessment. Muscularis disruption on T2WI appeared to exhibit a better combination of sensitivity and specificity than did peri-vesical changes.

Purpose: To assess the feasibility of diffusional kurtosis (DK) imaging for distinguishing benign from malignant regions, as well as low- from high-grade malignant regions, within the peripheral zone (PZ) of the prostate in comparison with standard diffusion-weighted (DW) imaging. Materials and Methods: The institutional review board approved this retrospective HIPAA-compliant study and waived informed consent. Forty-seven patients with prostate cancer underwent 3-T magnetic resonance imaging by using a pelvic phased-array coil and DW imaging (maximum b value, 2000 sec/mm(2)). Parametric maps were obtained for apparent diffusion coefficient (ADC); the metric DK (K), which represents non-Gaussian diffusion behavior; and corrected diffusion (D) that accounts for this non-Gaussianity. Two radiologists reviewed these maps and measured ADC, D, and K in sextants positive for cancer at biopsy. Data were analyzed by using mixed-model analysis of variance and receiver operating characteristic curves. Results: Seventy sextants exhibited a Gleason score of 6; 51 exhibited a Gleason score of 7 or 8. K was significantly greater in cancerous sextants than in benign PZ (0.96 ± 0.24 vs 0.57 ± 0.07, P < .001), as well as in cancerous sextants with higher rather than lower Gleason score (1.05 ± 0.26 vs 0.89 ± 0.20, P < .001). K showed significantly greater sensitivity for differentiating cancerous sextants from benign PZ than ADC or D (93.3% vs 78.5% and 83.5%, respectively; P < .001), with equal specificity (95.7%, P > .99). K exhibited significantly greater sensitivity for differentiating sextants with low- and high-grade cancer than ADC or D (68.6% vs 51.0% and 49.0%, respectively; P ≤ .004) but with decreased specificity (70.0% vs 81.4% and 82.9%, respectively; P ≤ .023). K had significantly greater area under the curve for differentiating sextants with low- and high-grade cancer than ADC (0.70 vs 0.62, P = .010). Relative contrast between cancerous sextants and benign PZ was significantly greater for D or K than ADC (0.25 ± 0.14 and 0.24 ± 0.13, respectively, vs 0.18 ± 0.10; P < .001). Conclusion: Preliminary findings suggest increased value for DK imaging compared with standard DW imaging in prostate cancer assessment. Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112290/-/DC1