Peripheral Zone Cancer Research Articles

Detection of prostate cancer in peripheral zone: comparison of MR diffusion tensor imaging, quantitative dynamic contrast-enhanced MRI, and the two techniques combined at 3.0 T

Previous studies have shown that the diagnostic accuracy for prostate cancer improved with diffusion tensor imaging (DTI) or quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) only. However, the efficacy of combined DTI and quantitative DCE-MRI in detecting prostate cancer at 3.0 T is still indeterminate. To investigate the utility of diffusion tensor imaging (DTI), quantitative DCE-MRI, and the two techniques combined at 3.0 T in detecting prostate cancer of the peripheral zone (PZ). DTI and DCE-MRI of 33 patients was acquired prior to prostate biopsy. Regions of interest (ROIs) were drawn according to biopsy zones which were apex, mid-gland, and base on each side of the PZ. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), volume transfer constant (K(trans)), and rate constant (kep) values of cancerous sextants and non-cancerous sextants in PZ were calculated. Logistic regression models were generated for DTI, DCE-MRI, and DTI + DCE-MRI. Receiver-operating characteristic (ROC) curves were used to compare the ability of these models to differentiate cancerous sextants from non-cancerous sextants of PZ. There were significant differences in the ADC, FA, K(trans), and kep values between cancerous sextants and non-cancerous sextants in PZ (P < 0.0001, P < 0.0001, P < 0.0001, and P < 0.0001, respectively). The area under curve (AUC) for DTI + DCE-MRI was significantly greater than that for either DTI (0.93 vs. 0.86, P = 0.0017) or DCE-MRI (0.93 vs. 0.84, P = 0.0034) alone. The combination of DTI and quantitative DCE-MRI has better diagnostic performance in detecting prostate cancer of the PZ than either technique alone.

The prognostic role of ERG immunopositivity in prostatic acinar adenocarcinoma: a study including 454 cases and review of the literature

TMPRSS2/ERG fusion is among the most frequent genetic anomalies in prostate adenocarcinomas. Although positive immunostaining for ERG has been shown to tightly correlate with ERG fusion status, the clinical and prognostic significance of a positive ERG stain remains undetermined. The significance of ERG immunostaining in 454 consecutive prostate adenocarcinomas from radical prostatectomies (RPs) using tissue microarrays, herein, is evaluated. A separate set of 59 cases of incidental prostate adenocarcinoma detected on transurethral resection of prostate with a Gleason score of 6 was also included. ERG translocation was significantly more common in peripheral zone cancer in comparison with cancer of the transitional zone (33% in RP versus 5% in transurethral resection of prostate specimens). In the RP cohort, although ERG positivity was significantly associated with younger age at presentation and lower prostate-specific antigen values, it showed no association with Gleason score or with pathologic stage. In multivariate analysis, biochemical recurrence was only associated with the final RP Gleason score and elevated prostate-specific antigen levels and was unrelated to neither ERG positivity or to its staining intensity. In our hands, ERG positivity was unrelated to either aggressive local tumor characteristics or a worse outcome. Our results, as well as an extensive review of the related literature showing conflicting findings, seem to indicate that ERG immunopositivity cannot be considered as an important prognostic factor in prostate cancer.

Differentiation of central gland prostate cancer from benign prostatic hyperplasia using monoexponential and biexponential diffusion-weighted imaging

PurposeTo investigate biexponential apparent diffusion parameters of prostate central gland (CG) cancer, stromal hyperplasia (SH), and glandular hyperplasia (GH) and compare with monoexponential apparent diffusion coefficient (ADC) value for discriminating prostate cancer from benign hyperplasia. Materials and MethodsTwenty-one CG cancer foci, 23 SH and 26 GH nodules in the CG were analyzed in 39 patients (19 with CG cancer, 20 with peripheral zone cancer but no CG cancer) who underwent preoperative conventional DWI (b-value 0, 1000s/mm2) and a 10 b-value (range 0 to 3000s/mm2) DWI. All of the cancer and hyperplastic foci on MR images were localized on the basis of histopathologic correlation. The ADC value of the monoexponential DWI, and the fast apparent diffusion coefficient (ADCf), slow apparent diffusion coefficient (ADCs) value and the fraction of ADCf (f) of the biexponential DWI were calculated for all of the lesions. Receiver operating characteristic (ROC) analysis was performed for the differentiation of CG cancer from SH and GH. ResultsThe ADC values (×10−3mm2/s) were 0.87±0.11, 1.06±0.15, and 1.61±0.27 in CG cancer, SH and GH foci, respectively, and differed significantly, yielding areas under the ROC curve (AUCs) of 1.00 and 0.80 for the differentiation of carcinoma from GH and SH, respectively. The ADCf (×10−3mm2/s), ADCs (×10−3mm2/s) and f for cancer were 1.92±0.38, 0.53±0.17, and 47.7±6.1%, respectively, which were lower than the same values for GH (3.43 ±0.65, 1.12±0.21, 61.1±8.7%) (all p<0.01). The ADCf and ADCs for cancer were also lower than those for SH (3.11±0.30, 0.79±0.21) (all p<0.01). The ADCf yielded AUCs (1.00, p>0.01) that were comparable to those from ADC for the differentiation of cancer from GH, while ADCf yielded higher AUCs (0.92) compared with ADC (p<0.01) for the differentiation of cancer from SH. ADCs and f revealed AUCs of 0.97 and 0.90, respectively, for the differentiation of cancer from GH, and the ADCs offered relatively lower AUCs (0.68) for differentiating cancer from SH. ConclusionBiexponential DWI could potentially improve the differentiation of prostate cancer in CG, and the ADCf of the biexponential model offers better accuracy than ADC.

TMPRSS2–ERG rearrangement in dominant anterior prostatic tumours: incidence and correlation with ERG immunohistochemistry

To study prostate cancer zonal differences in TMPRSS2-ERG gene rearrangement. We examined 136 well-characterized dominant anterior prostatic tumours, including 61 transition zone (TZ) and 75 anterior peripheral zone (PZ) lesions, defined using strict anatomical considerations. TMPRSS2-ERG FISH and ERG protein immunohistochemistry were performed on tissue microarrays. FISH results, available for 56 TZ and 71 anterior PZ samples, were correlated with ERG staining and TZ-associated 'clear cell' histology. Fewer TZ cancers (four of 56; 7%) were rearranged than anterior PZ cancers (18 of 71; 25%) (P = 0.009); deletion was the sole mechanism of TZ cancer rearrangement. ERG protein overexpression was present in 4% (two of 56; both FISH+) and 30% (21 of 71; 17 FISH+) of TZ and anterior PZ tumours, respectively. 'Clear cell' histology was present in 21 of 56 (38%) TZ and eight of 71 (11%) anterior PZ tumours. Seven per cent of cancers with and 21% without this histology had rearrangement, regardless of zonal origin. TMPRSS2-ERG rearrangement occurs in dominant TZ and anterior PZ prostate cancers, with all rearranged TZ cancers in this cohort showing deletion. ERG immunohistochemistry demonstrated excellent sensitivity (86%) and specificity (96%) for TMPRSS2-ERG rearrangement. TMPRSS2-ERG fusion is rare in TZ tumours and present at a low frequency in tumours displaying 'clear cell' histology.

Prostate Cancer: Feasibility and Preliminary Experience of a Diffusional Kurtosis Model for Detection and Assessment of Aggressiveness of Peripheral Zone Cancer

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. 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/mm2). 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. 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). Preliminary findings suggest increased value for DK imaging compared with standard DW imaging in prostate cancer assessment.

Clinical utility of apparent diffusion coefficient values obtained using high b‐value when diagnosing prostate cancer using 3 tesla MRI: Comparison between ultra‐high b‐value (2000 s/mm2) and standard high b‐value (1000 s/mm2)

To determine whether the apparent diffusion coefficient (ADC) obtained using b = 2000 s/mm(2) upon 3 Tesla (T) diffusion-weighted MRI is superior to b = 1000 s/mm(2) for discriminating malignant from normal prostate tissue and predicting the aggressiveness of prostate cancer, using histopathological findings of radical prostatectomy as a reference. Eighty prostate cancer patients underwent preoperative 3T MRI including diffusion weighted imaging with b-values of 0, 1000, and 2000 s/mm(2) . ADCs were measured for malignant lesions and normal sites on three sets of ADC maps calculated with monoexponential fitting between b = 0 and 1000, 0 and 2000, and 1000 and 2000, respectively. The relationship between the ADC and Gleason score was evaluated. The areas under the ROC curves for b = 0,1000, b = 0,2000, and b = 1000,2000 were 0.896, 0.937, and 0.857, respectively, in the peripheral zone (PZ) and 0.877, 0.889, and 0.731, respectively, in the transition zone (TZ). The difference between b = 0,1000 and b = 0,2000 was significant in PZ (P = 0.033), but not in TZ (P = 0.84). Weak but significant negative correlations were identified between ADCs and Gleason score in both PZ and TZ cancer at b = 0,1000 and b = 0,2000 (r = -0.323 to -0.341). For 3T MRI, ADCs using b = 0,2000 are more accurate than b = 0,1000 for diagnosing PZ cancer, and as accurate for TZ cancer.

Diffusionsgewichtete MRT der Prostata

Diffusion-weighted magnetic resonance imaging (DWI) can complement MRI of the prostate in the detection and localization of prostate cancer, particularly after previous negative biopsy. A total of 13 original reports and 2 reviews published in 2010 demonstrate that prostate cancer can be detected by DWI due to its increased cell density and decreased diffusiveness, either qualitatively in DWI images or quantitatively by means of the apparent diffusion coefficient (ADC). In the prostate, the ADC is influenced by the strength of diffusion weighting, localization (peripheral or transitional zone), presence of prostatitis or hemorrhage and density and differentiation of prostate cancer cells. Mean differences between healthy tissue of the peripheral zone and prostate cancer appear to be smaller for ADC than for the (choline + creatine)/citrate ratio in MR spectroscopy. Test quality parameters vary greatly between different studies but appear to be slightly better for combined MRI and DWI than for MRI of the prostate alone. Clinical validation of DWI of the prostate requires both increased technical conformity and increased numbers of patients in clinical studies.

Evaluation of Diffusion-Weighted Magnetic Resonance Imaging and Contrast-Enhanced Harmonic Ultrasonography in Detection and Location of Prostate Transition-Zone Cancer

This retrospective study was designed to evaluate the value of contrast-enhanced harmonic ultrasonography (CEHU), diffusion-weighted magnetic resonance imaging (DW-MRI) and CEHU plus DW-MRI for the diagnosis of prostate transition-zone (TZ) cancer. In total, 31 TZ cancers in 28 patients and 25 peripheral zone (PZ) cancers in 21 patients without a TZ cancer were evaluated. All patients underwent DW-MRI and CEHU followed by radical prostatectomy. Predictors for the diagnosis of prostate cancer were evaluated in three protocols (CEHU, DW-MRI, CEHU plus DW-MRI). Statistical analysis of the differences between these protocols and receiver operating characteristic (ROC) curve analysis were carried out. CEHU plus DW-MRI had a significantly higher sensitivity, accuracy and negative-predictive value (90.3%, 73.2% and 81.3%, respectively) for TZ cancer than either method alone. The area under the ROC curve values were 0.659, 0.679 and 0.712 for CEHU, DW-MRI, and CEHU plus DW-MRI, respectively. In conclusion, CEHU plus DW-MRI might be a useful protocol for the detection and location of TZ cancer.

Assessment of Aggressiveness of Prostate Cancer: Correlation of Apparent Diffusion Coefficient With Histologic Grade After Radical Prostatectomy

The purpose of this article is to evaluate the relationship between apparent diffusion coefficient (ADC) values, tumor volume, and total Gleason grade in patients with prostate cancer before radical prostatectomy. A total of 110 patients with prostate cancer who had undergone endorectal prostate MRI at 1.5 T before radical prostatectomy were included. ADC values were derived by drawing a region of interest on the histologically confirmed tumors. Tumor volume was obtained by manual segmentation on T2-weighted images (T2WIs) and ADC maps. The relationship between the ADC value or tumor volume and the Gleason grade was assessed by using multivariate mixed linear and effect models. Multivariate analysis was performed to evaluate the accuracy of ADC and tumor volume in determining the aggressiveness of prostate cancer. A total of 197 tumors were studied; 128 (65%) tumors were found in the peripheral zone and 69 (35%) were found in the central gland. The ADC value was found to be negatively correlated with the Gleason grade (r = -0.39 for peripheral zone cancer). Higher ADC values were found to be associated with lower Gleason grades in the peripheral zone prostate cancers. No association was found in the central zone prostate cancers. Both ADC values and tumor volumes were found to significantly predict tumor aggressiveness, specifically in the peripheral zone (area under the curve, 0.78). ADC values were found to be negatively correlated with the postsurgical Gleason grade in patients with prostate cancer. Our results show that ADC values might help to predict prostate cancer, especially for tumors in the peripheral zone. Given the substantial overlap in the ADC values, the addition of other MR parameters, such as volumetry, and technical improvements in diffusion-weighted imaging might improve accuracy in the stratification of patients.

Comparison of qualitative and quantitative approach to prostate MR spectroscopy in peripheral zone cancer detection

To compare the diagnostic performance of a qualitative (pattern recognition) and a quantitative (numerical assessment) approach to magnetic resonance spectroscopy (MRS) in the diagnosis of peripheral zone prostate cancer. 185 patients (131 with histopathologically proven cancer, 54 normal/benign after at least 12 months follow-up) were prospectively evaluated with qualitative MRS using a 4-point scale between 3/2004 and 1/2008, and retrospectively reassessed using a prototype quantitative postprocessing software in April 2008. Based on pathology and follow-up data, diagnostic performance parameters were calculated. The qualitative and quantitative approaches were concordant in 78.9% (146/185) of cases. The difference between the areas under the ROC curve (0.791 versus 0.772, respectively) was not statistically significant. The sensitivity, specificity and accuracy were 55.7%, 94.4% and 67.0% for the qualitative approach, and 55.0%, 83.3% and 63.2% for the quantitative approach. The sensitivity for high grade tumours (Gleason 4+3 or higher) was 85.2% (23/27) for both approaches. All cancers missed on either one approach separately (31/31) and 91% of cancers missed on both approaches together (23/27) were of lower grade (Gleason 3+4 or lower). Qualitative and quantitative approaches to MRS yield similar diagnostic results. Discordances in tumour detection only occurred in lower grade cancers.

Contrast-enhanced Ultrasonography of the Prostate with Sonazoid

The diagnosis of prostate cancer is based on the results of ultrasonography-guided needle biopsy of the prostate, but cancer foci are often not visible in conventional transrectal ultrasonography. Sonazoid is a new microbubble contrast agent. The purpose of our study was to compare areas of contrast material enhancement in the prostate at ultrasonography with whole-mount radical prostatectomy specimens to determine if the use of Sonazoid improves the detection rate of prostate cancer. Fifty patients with biopsy-proven cancer of the prostate who were scheduled to undergo radical prostatectomy were recruited for this study. The day before the operation, each patient was evaluated with ultrasonography at baseline and again during intravenous infusion of Sonazoid. A map of ultrasonography findings was created prospectively at the time of imaging. Following radical prostatectomy, independent mapping of the pathologic results was performed and the maps were compared. Ultrasonography evaluation at baseline demonstrated that at least one focus of cancer was identified in 20 of the 50 subjects (40.0%). Meanwhile at least one cancer focus was enhanced in 31 of the 50 patients (62.0%) when Sonazoid was used. The combination of baseline grayscale imaging and contrast-enhanced imaging allowed identification of at least one focus of cancer in 40 patients (80.0%). Contrast-enhanced ultrasonography can improve sensitivity, especially for the detection of large cancer, peripheral zone cancer and highly malignant cancer. Our study has demonstrated significantly improved detection of prostate cancer with the combination of baseline grayscale imaging and contrast-enhanced imaging compared with conventional ultrasonography techniques only, and this technique may be applicable to targeted biopsy.

Characterization of the anatomical extension pattern of localized prostate cancer arising in the peripheral zone

To characterize the anatomical extension pattern of prostate cancer arising in the peripheral zone (PZ) in radical prostatectomy (RP) specimens and to evaluate its prognostic significance. Of 174 consecutive patients undergoing RP, 128 diagnosed as having PZ cancer (PZC) were enrolled. The maximum tumour area (MTA) and maximum tumour volume (MTV) in RP specimens were measured using digital planimetry. A circle with an area equal to the MTA, in which the central point was the intersection of the longest line of the MTA and the line perpendicularly bisecting the first line, was defined as a hypothetical extension area, regardless of anatomical structure. The area within this circle that did not overlap the MTA was defined as DeltaTA. There was a significant correlation between the MTV and DeltaTA/MTA, introduced as a variable representing the degree of PZC extension along the anatomical shape of the PZ. The DeltaTA/MTA in patients with a MTV of >5 mL was significantly greater than that in those with a MTV of < or = 5 mL. Furthermore, DeltaTA/MTA was significantly associated with several prognostic indicators, including extracapsular extension, surgical margin status and perineural invasion. Multivariate analysis identified DeltaTA/MTA in addition to preoperative serum prostate-specific antigen level, extracapsular extension and surgical margin status as independent predictors of biochemical recurrence after RP. PZC tends to extend along the anatomical shape of the PZ during progression, resulting in higher DeltaTA/MTA value in advanced PZC than that in early PZC.

V473 TARGETED PARTIAL PROSTATECTOMY FOR ISOLATED, ANTERIOR CANCER: A NOVEL LAPAROSCOPIC/ROBOTIC TECHNIQUE

You have accessJournal of UrologyProstate Oncology1 Apr 2010V473 TARGETED PARTIAL PROSTATECTOMY FOR ISOLATED, ANTERIOR CANCER: A NOVEL LAPAROSCOPIC/ROBOTIC TECHNIQUE Georges-Pascal Haber, Sebastien Crouzet, Philippe Puech, Laurent Lemaitre, Xavier Leroy, Jean-Francois Biset, Mihir M. Desai, Inderbir S. Gill, and Arnauld Villers Georges-Pascal HaberGeorges-Pascal Haber Cleveland, OH More articles by this author , Sebastien CrouzetSebastien Crouzet Lyon, France More articles by this author , Philippe PuechPhilippe Puech Lille, France More articles by this author , Laurent LemaitreLaurent Lemaitre Lille, France More articles by this author , Xavier LeroyXavier Leroy Lille, France More articles by this author , Jean-Francois BisetJean-Francois Biset Noumea, France More articles by this author , Mihir M. DesaiMihir M. Desai Los Angeles, CA More articles by this author , Inderbir S. GillInderbir S. Gill Los Angeles, CA More articles by this author , and Arnauld VillersArnauld Villers Lille, France More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.547AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Localized prostate cancer (PCa) located in the anterior fibromuscular stroma (AFMS) or transition zone (TZ) represents upto 25% of diagnosed PCa. Such PCa can be well-depicted by magnetic resonance imaging (MRI) and sampled by targeted needle biopsies. We hypothesized that if well-selected patients with isolated anterior PCa underwent partial prostatectomy, adequate oncologic control could accrue while eliminating the undesirable side effects of radical prostatectomy METHODS Over a 2-year period we identified 5 selected patients with an isolated, anterior, low-intermediate risk PCa who were potential candidates for targeted partial prostatectomy. IRB approval was obtained. The virgin, isolated PCa lesion was identified on multi-parametric MRI, and subsequently confirmed by targeted ultrasound-guided biopsies. Robotic or laparoscopic partial prostatectomy was performed for en-bloc template excision of AFMS, TZ, anterior horns of peripheral zone (PZ), bladder neck, and anterior aspect of prostatic urethra distal to verumontanum. Preserved intact were the rest of the prostate gland and the entire peri-prostatic neurovascular & musculo-fascial anatomy. Follow-up included PSA, MRI, prostate biopsy and QOL questionnaires RESULTS Mean age was 68.5 years, preoperative PSA was 14.3ng/ml (9.5-19.6) and Gleason score was 6 or 7 (3+4). Template anterior partial prostatectomy was technically feasible en-bloc in all 5 cases. There were no peri-operative complications and minimal morbidity. Positive margins occurred in 3 cases, focal anterior in 2 (therefore adjuvant therapy not offered), and residual PZ cancer in 1 (secondary radical prostatectomy with resultant undetectable PSA & normal continence). Of the other 4 cases, 2 maintained uninterrupted potency postoperatively. Continence remained uninterrupted in all patients. Mean PSA at 3 months and 1 y decreased to 0.49 ng/ml (0.28-0.64) and 0.40 ng/ml (0.25-0.53), respectively. One year follow-up multi-core needle biopsy showed no residual cancer in 2 patients, and a 1mm focus of new Gleason 6 PZ cancer in 1 patient. Mean follow-up was 11 months (3-15) CONCLUSIONS Targeted partial prostatectomy for isolated, anteriorly-located, low-intermediate risk PCa is feasible. Early clinical, histological, biological and MRI responses appear favorable, with moderate adverse effects. In these carefully selected patients, partial prostatectomy could represent an alternative to standard radical surgery. Further experience is necessary to determine the oncologic validity of this treatment concept © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e186-e187 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Georges-Pascal Haber Cleveland, OH More articles by this author Sebastien Crouzet Lyon, France More articles by this author Philippe Puech Lille, France More articles by this author Laurent Lemaitre Lille, France More articles by this author Xavier Leroy Lille, France More articles by this author Jean-Francois Biset Noumea, France More articles by this author Mihir M. Desai Los Angeles, CA More articles by this author Inderbir S. Gill Los Angeles, CA More articles by this author Arnauld Villers Lille, France More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prostate Cancer: Comparison of 3D T2-Weighted With Conventional 2D T2-Weighted Imaging for Image Quality and Tumor Detection

The purpose of this study was to compare a 3D T2-weighted imaging sequence with a conventional multiplanar 2D turbo spin-echo T2-weighted sequence in terms of tumor detection and staging of prostate cancer, as well as image quality. Before prostatectomy, 38 men (mean age, 60 years) with prostate cancer underwent MRI of the prostate with multiplanar 2D turbo spin-echo T2-weighted sequences (total acquisition time, approximately 11 minutes 4 seconds) and a 3D T2-weighted sampling perfection with application optimized contrasts sequence with different flip angle evolutions (SPACE) (acquisition time, approximately 3 minutes 52 seconds). Two blinded observers in consensus reviewed 2D turbo spin-echo T2-weighted images and SPACE images for detection of peripheral zone cancer, extracapsular extension, and seminal vesicle invasion. The observers also assessed subjective image quality and measured the signal-to-noise ratio (SNR) of normal peripheral zone and tumor-to-peripheral zone contrast. Prostatectomy was used as the reference standard. The diagnostic accuracy of the two sequences was assessed with generalized estimating equations and McNemar tests. The agreement between sequences was assessed with kappa coefficients. A paired Wilcoxon signed rank test was used to compare the subjective image quality, SNR, and tumor-to-peripheral zone contrast of the two sequences. For tumor detection and diagnosis of extracapsular extension, there was substantial agreement between the two sequences (kappa = 0.79, kappa = 0.76) with no difference in sensitivity, specificity, positive predictive value, negative predictive value, accuracy (p = 0.25-1), or image quality (p = 0.937). Images obtained with the 2D turbo spin-echo sequence had a significantly higher SNR ratio for normal peripheral zone (p = 0.0010), but SPACE images had significantly greater tumor-to-peripheral zone contrast (p < 0.0001). In comparison with conventional multiplanar 2D turbo spin-echo MRI of the prostate, 3D T2-weighted SPACE MRI was associated with substantial time saving (nearly 8 minutes), had similar image quality and accuracy in the diagnosis of tumor and extracapsular extension, and had better tumor conspicuity.

Characterization and Functional Role of the Stroma Compartment in Prostate Tumors

Evaluation of: Dakhova O, Ozen M, Creighton CJ et al.: Global gene expression analysis of reactive stroma in prostate cancer. Clin. Cancer Res. 15, 3979–3989 (2009). Prostate tumors are composed of many cell types, yet the biological significances of the different nonepithelial cells have been largely overlooked. According to recent studies, however, the stroma, which constitutes a substantial part of the tumor volume, plays an important role during the initiation, progression, metastasis and metastatic growth of prostate cancers. To explore this further, Dakhova and co-workers compared gene expression in laser microdissected normal peripheral zone stroma with stroma in peripheral zone cancers (only those with reactive stroma grade 3). A total of 544 genes were upregulated and 606 genes downregulated in tumor stroma. The cancer stroma showed signs of formation of nerves, increased number of stem cells, and responses to DNA damage. Further studies are needed to explore the functional consequences of this, particularly the role of nerves. If these stroma changes can be used as prognostic markers, as targets for therapy, and if similar changes occur in metastases also need to be explored.

Prostate Tumor Volume Measurement with Combined T2-weighted Imaging and Diffusion-weighted MR: Correlation with Pathologic Tumor Volume

To retrospectively determine the accuracy of diffusion-weighted (DW) magnetic resonance (MR) imaging for identifying cancer in the prostate peripheral zone (PZ) and to assess the accuracy of tumor volume measurements made with T2-weighted imaging and combined T2-weighted and DW MR imaging by using surgical pathologic examination as the reference standard. The institutional review board issued a waiver of informed consent for this HIPAA-compliant study. Forty-two patients underwent endorectal MR at 1.5 T before undergoing radical prostatectomy for prostate cancer and had at least one PZ tumor larger than 0.1 cm(3) at surgical pathologic examination. On T2-weighted images, an experienced radiologist outlined suspected PZ tumors. Two apparent diffusion coefficient (ADC) cutoff values were identified by using the Youden index and published literature. Image cluster analysis was performed on voxels within the suspected tumor regions. Associations between volume measurements from imaging and from pathologic examination were assessed by using concordance correlation coefficients (CCCs). The sensitivity and specificity of ADCs for identifying malignant PZ voxels were calculated. In identifying malignant voxels, respective ADC cutoff values of 0.0014 and 0.0016 mm(2)/sec yielded sensitivity of 82% and 95% and specificity of 85% and 65%, respectively. Sixty PZ cancer lesions larger than 0.1 cm(3) were found at pathologic examination; 43 were detected by the radiologist. CCCs between imaging and pathologic tumor volume measurements were 0.36 for T2-weighted imaging, and 0.46 and 0.60 for combined T2-weighted and DW MR imaging with ADC cutoffs of 0.0014 and 0.0016 mm(2)/sec, respectively; the CCC of combined T2-weighted and DW MR imaging (ADC cutoff, 0.0016 mm(2)/sec) was significantly higher (P = .006) than that of T2-weighted imaging alone. Adding DW MR to T2-weighted imaging can significantly improve the accuracy of prostate PZ tumor volume measurement. http://radiology.rsnajnls.org/cgi/content/full/252/2/449/DC1.

Prostate cancer detection with multi‐parametric MRI: Logistic regression analysis of quantitative T2, diffusion‐weighted imaging, and dynamic contrast‐enhanced MRI

To develop a multi-parametric model suitable for prospectively identifying prostate cancer in peripheral zone (PZ) using magnetic resonance imaging (MRI). Twenty-five radical prostatectomy patients (median age, 63 years; range, 44-72 years) had T2-weighted, diffusion-weighted imaging (DWI), T2-mapping, and dynamic contrast-enhanced (DCE) MRI at 1.5 Tesla (T) with endorectal coil to yield parameters apparent diffusion coefficient (ADC), T2, volume transfer constant (K(trans)) and extravascular extracellular volume fraction (v(e)). Whole-mount histology was generated from surgical specimens and PZ tumors delineated. Thirty-eight tumor outlines, one per tumor, and pathologically normal PZ regions were transferred to MR images. Receiver operating characteristic (ROC) curves were generated using all identified normal and tumor voxels. Step-wise logistic-regression modeling was performed, testing changes in deviance for significance. Areas under the ROC curves (A(z)) were used to evaluate and compare performance. The best-performing single-parameter was ADC (mean A(z) [95% confidence interval]: A(z,ADC): 0.689 [0.675, 0.702]; A(z,T2): 0.673 [0.659, 0.687]; A(z,Ktrans): 0.592 [0.578, 0.606]; A(z,ve): 0.543 [0.528, 0.557]). The optimal multi-parametric model, LR-3p, consisted of combining ADC, T2 and K(trans). Mean A(z,LR-3p) was 0.706 [0.692, 0.719], which was significantly higher than A(z,T2), A(z,Ktrans), and A(z,ve) (P < 0.002). A(z,LR-3p) tended to be greater than A(z,ADC), however, this result was not statistically significant (P = 0.090). Using logistic regression, an objective model capable of mapping PZ tumor with reasonable performance can be constructed.

Prostate Cancer: Sextant Localization at MR Imaging and MR Spectroscopic Imaging before Prostatectomy—Results of ACRIN Prospective Multi-institutional Clinicopathologic Study

To determine the incremental benefit of combined endorectal magnetic resonance (MR) imaging and MR spectroscopic imaging, as compared with endorectal MR imaging alone, for sextant localization of peripheral zone (PZ) prostate cancer. This prospective multicenter study, conducted by the American College of Radiology Imaging Network (ACRIN) from February 2004 to June 2005, was institutional review board approved and HIPAA compliant. Research associates were required to follow consent guidelines approved by the Office for Human Research Protection and established by the institutional review boards. One hundred thirty-four patients with biopsy-proved prostate adenocarcinoma and scheduled to undergo radical prostatectomy were recruited at seven institutions. T1-weighted, T2-weighted, and spectroscopic MR sequences were performed at 1.5 T by using a pelvic phased-array coil in combination with an endorectal coil. Eight readers independently rated the likelihood of the presence of PZ cancer in each sextant by using a five-point scale-first on MR images alone and later on combined MR-MR spectroscopic images. Areas under the receiver operating characteristic curve (AUCs) were calculated with sextant as the unit of analysis. The presence or absence of cancer at centralized histopathologic evaluation of prostate specimens was the reference standard. Reader-specific receiver operating characteristic curves for values obtained with MR imaging alone and with combined MR imaging-MR spectroscopic imaging were developed. The AUCs were estimated by using Mann-Whitney statistics and appropriate 95% confidence intervals. Complete data were available for 110 patients (mean age, 58 years; range, 45-72 years). MR imaging alone and combined MR imaging-MR spectroscopic imaging had similar accuracy in PZ cancer localization (AUC, 0.60 vs 0.58, respectively; P > .05). AUCs for individual readers were 0.57-0.63 for MR imaging alone and 0.54-0.61 for combined MR imaging-MR spectroscopic imaging. In patients who undergo radical prostatectomy, the accuracy of combined 1.5-T endorectal MR imaging-MR spectroscopic imaging for sextant localization of PZ prostate cancer is equal to that of MR imaging alone.

Usefulness of diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging in the diagnosis of prostate transition-zone cancer

Conventional T2-weighted (T2-WI) magnetic resonance imaging (MRI) has poor sensitivity for prostate transition-zone (TZ) cancer detection. To retrospectively evaluate the clinical value of diffusion-weighted MRI (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) in combination with T2-WI for the diagnosis of TZ cancer. Twenty-six TZ cancers in 23 patients with at least one tumor (tumor size >10 mm) located predominantly in the TZ were included in the study. Sixteen peripheral-zone (PZ) cancers in 12 patients with PZ cancer but without TZ cancer (control group) were selected by step-section pathologic maps. All patients underwent MRI and radical prostatectomy. MRI was obtained by a 1.5T superconducting system with a phased-array coil. Imaging sequences were T2-WI with fat saturation (FST2-WI), DW-MRI (single-shot echoplanar image, b=0 and 1000 s/mm(2), apparent diffusion coefficient [ADC] map findings), and DCE-MRI (3D fast spoiled gradient recalled [SPGR], contrast medium [0.2 mmol/kg], total injection time 5 s, image acquisition 30, 60, and 90 s). Sensitivity, specificity, accuracy, and positive predictive value (PPV) for the diagnosis of TZ cancer were evaluated in four protocols: A) FST2-WI alone, B) FST2-WI plus DW-MRI, C) FST2-WI plus DCE-MRI, D) FST2-WI plus DW-MRI plus DCE-MRI. Sensitivity, specificity, accuracy, and PPV in protocol A (FST2-WI alone) were 61.5%, 68.8%, 64.3%, and 76.2%, respectively. FST2-WI plus DW-MRI (protocol B) improved the sensitivity, specificity, accuracy, and PPV. In FST2-WI plus DW-MRI plus DCE-MRI (protocol D), the number of true-negative lesions increased and false-positive lesions decreased, and the sensitivity, specificity, accuracy, and PPV were 69.2%, 93.8%, 78.6%, and 94.7%, respectively. There was a significant difference between protocols A and D (P<0.05). Adding DW-MRI to FST2-WI in the diagnosis of prostate TZ cancer increased the diagnostic accuracy. The addition of DCE-MRI may be an option to improve the specificity and PPV of diagnosing TZ cancer with FST2-WI and DW-MRI.

Peripheral zone prostate cancers: Location and intraprostatic patterns of spread at histopathology

To describe the precise location of peripheral zone (PZ) prostate cancers at various stages of development and to demonstrate their pattern of intraprostatic spread from their site of origin. PZ cancers defined as cancers located in peripheral zone (PZ) including the anterolateral part of PZ, were identified from radical prostatectomy specimens. PZ cancers morphometric histopathological study included largest surface area, volume and spatial distribution. Out of 188 PZ cancers, 179 were <4 cm(3) and 168 <2 cm(3). PZ cancers were still confined to their zone of origin for volumes <2 cm(3). Between 2 and 4 cm(3), some cancers partially spread into the transition zone or anterior fibromuscular stroma. Sixty-four and 90% of PZ cancers <4 cm(3) were located in the lower and posterior half of the gland respectively. Ten percent were located in the anterior horn of PZ. Overall, non-index (second) cancers were located in the ipsi and contolateral side of the index cancer (largest) in 31% and 69% of cases, respectively. Cancers <2 cm(3) were confined to one lobe in 164 of 168 (98%) cases and not confined in 3 out of 11 (27%) cancers 2-4 cm(3). On vertical axis, only cancers >or=2 cm(3) involved both apex and base. PZ cancers contours and locations are predictable and conform to histological zone boundaries if <2 cm(3) in volume. Knowledge of PZ cancers origin and pattern of spread in PZ are of importance for imaging diagnosis, guidance for biopsy and focal therapy.