Transition Zone Prostate Cancer Research Articles

Diagnosis of typical and atypical transition zone prostate cancer and its mimics at multiparametric prostate MRI.

Many of the current clinical screening methods for prostate cancer (PCa) such as prostate-specific antigen (PSA) testing or transrectal ultrasound-guided prostate biopsy lack sensitivity and specificity for diagnosis of PCa of the transition zone (TZ). Recent technical advances in multiparametric-MRI have markedly improved detection of PCa of the TZ. However, there are many diagnostic challenges that we still encounter in our daily practice that compromise the accuracy of the diagnosis. By performing both MRI-guided and ultrasound/MRI fusion-guided biopsies, we have gained extensive experience in the diagnosis of PCa of the TZ. Biopsy-proven examples including but not limited to typical and atypical PCa of the TZ as well as a wide variety of its mimics will be presented. Recognition of the MR features of typical and atypical PCa of the TZ and its mimics on multiparametric-MRI along with findings that help to differentiate these mimics from PCa is important in establishing an accurate diagnosis and in guiding clinical management.

The value of ADC, T2 signal intensity, and a combination of both parameters to assess Gleason score and primary Gleason grades in patients with known prostate cancer.

The ability to non-invasively analyze tumor aggressiveness is an important predictor for individual treatment stratification and patient outcome in prostate cancer (PCA). To evaluate: (i) whether apparent diffusion coefficient (ADC), the T2 signal intensity (SI), and a combination of both parameters allow for an improved discrimination of Gleason Score (GS) ≥7 (intermediate and high risk) and GS <7 (low risk) in PCA; and (ii) whether ADC may distinguish between 3 + 4 and 4 + 3 PCA (primary Gleason grades [pGG]). Prostatectomy specimens of 66 patients (mean age, 63 ± 5.6 years; 104 PCA foci) with a preceding multiparametric 1.5 T endorectal coil magnetic resonance imaging (MRI) were included. ADC (b values = 0, 100, 400, 800 s/mm(2)), standardized T2 (T2s), and the ADC/T2s ratio were tested for correlation with GS applying multivariate analysis. ADC cutoff values were calculated for prediction of GS and pGG, and logarithm of the odds (LOGIT) was used to express the probability for GS and pGG. Diagnostic accuracy was assessed by ROC analysis. We found an almost linear negative relationship of ADC for GS ≥7 (P = 0.002). The effect of ADC for GS ≥7 (adjusted odds ratio = 0.995) was almost identical for peripheral and transition zone PCA (P = 0.013 and P < 0.001, respectively). ADC showed an AUC of 78.9% for discrimination between GS <7 and GS ≥7. An ADC cutoff of <1.005 × 10(-3 )mm(2)/s indicated a GS ≥7 (90.5% sensitivity, 62.5% specificity). Within the group of GS = 7 PCA, an ADC > 0.762 × 10(-3 )mm(2)/s indicated a pGG of3 (AUC = 69.6%). T2s and the ADC/T2s ratio do not provide additional information regarding prediction of GS. ADC values have a good discriminatory power to distinguish tumors with GS ≥7 from GS <7 and to predict pGG in GS = 7 PCA.

Logistic regression model for diagnosis of transition zone prostate cancer on multi-parametric MRI.

ObjectivesWe aimed to develop logistic regression (LR) models for classifying prostate cancer within the transition zone on multi-parametric magnetic resonance imaging (mp-MRI).MethodsOne hundred and fifty-five patients (training cohort, 70 patients; temporal validation cohort, 85 patients) underwent mp-MRI and transperineal-template-prostate-mapping (TPM) biopsy. Positive cores were classified by cancer definitions: (1) any-cancer; (2) definition-1 [≥Gleason 4 + 3 or ≥ 6 mm cancer core length (CCL)] [high risk significant]; and (3) definition-2 (≥Gleason 3 + 4 or ≥ 4 mm CCL) cancer [intermediate–high risk significant]. For each, logistic-regression mp-MRI models were derived from the training cohort and validated internally and with the temporal cohort. Sensitivity/specificity and the area under the receiver operating characteristic (ROC-AUC) curve were calculated. LR model performance was compared to radiologists’ performance.ResultsTwenty-eight of 70 patients from the training cohort, and 25/85 patients from the temporal validation cohort had significant cancer on TPM. The ROC-AUC of the LR model for classification of cancer was 0.73/0.67 at internal/temporal validation. The radiologist A/B ROC-AUC was 0.65/0.74 (temporal cohort). For patients scored by radiologists as Prostate Imaging Reporting and Data System (Pi-RADS) score 3, sensitivity/specificity of radiologist A ‘best guess’ and LR model was 0.14/0.54 and 0.71/0.61, respectively; and radiologist B ‘best guess’ and LR model was 0.40/0.34 and 0.50/0.76, respectively.ConclusionsLR models can improve classification of Pi-RADS score 3 lesions similar to experienced radiologists.Key Points• MRI helps find prostate cancer in the anterior of the gland • Logistic regression models based on mp-MRI can classify prostate cancer • Computers can help confirm cancer in areas doctors are uncertain about

MP53-09 TRANSITIONAL ZONE AND ANTERIOR ZONE PROSTATE CANCER– DETECTION USING MULTIPARAMETRIC MR-IMAGING AND FUSION-GUIDED TRANSPERINEAL BIOPSY

You have accessJournal of UrologyProstate Cancer: Detection & Screening II1 Apr 2014MP53-09 TRANSITIONAL ZONE AND ANTERIOR ZONE PROSTATE CANCER– DETECTION USING MULTIPARAMETRIC MR-IMAGING AND FUSION-GUIDED TRANSPERINEAL BIOPSY Jan Philipp Radtke, Silvan Boxler, Yesilda Belavarca, Timur Hasan Kuru, Matthias Röthke, Heinz-Peter Schlemmer, Markus Hohenfellner, and Boris Hadaschik Jan Philipp RadtkeJan Philipp Radtke More articles by this author , Silvan BoxlerSilvan Boxler More articles by this author , Yesilda BelavarcaYesilda Belavarca More articles by this author , Timur Hasan KuruTimur Hasan Kuru More articles by this author , Matthias RöthkeMatthias Röthke More articles by this author , Heinz-Peter SchlemmerHeinz-Peter Schlemmer More articles by this author , Markus HohenfellnerMarkus Hohenfellner More articles by this author , and Boris HadaschikBoris Hadaschik More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1640AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives To evaluate the incidence of anterior zone (AZ) and transitional zone (TZ) prostate cancer (PCA) in MRI-navigated, TRUS-fusion-guided perineal biopsies and to determine the detection accuracy of multiparametric (mp) 3T MRI and PI-RADS scoring. Methods In 200 consecutive patients undergoing stereotactic biopsy from june 2010 to december 2011, 62 patients had biopsy proven AZ and TZ PCA and were retrospectively analyzed. Every patient underwent mp 3T MRI before biopsy, which was scored according to PI-RADS. In addition to targeted cores, systematic transperineal biopsies were taken as gold standard (median 24 cores). Cancerous lesions were stratified to that prostate zone, where the main volume of the index lesion was localized. Statistical analysis was performed using Fisher's test. Results 20 out of 62 patients had PCA ventral to the urethra in the AZ (median PSA-level 12.01 ng/ml), and 42 out of 62 were positive predominantly in the TZ (median PSA-level 11.78 ng/ml). Overall, incidence was 10% in the AZ and 21% in the TZ. Gleason-score (GS) of AZ PCA was 6, 7a, and 7b in 30%, 50%, and 20%, respectively. In TZ PCA, GS was 6, 7a, 7b, 8, and 9 in 31%, 43%, 19%, 2%, and 5%, respectively. Coincidental small cancer lesions in the peripheral zone (PZ) were GS 6 in 39%, 7a in 48%, 7b in 10 % and 9 in 3 %. Accuracy, sensitivity, specificity, PPV and NPV of PI-RADS Likert scores ≥3 for AZ cancers was 79%, 60%, 88%, 71% and 82%. For TZ cancers, it was 63%, 59%, 75%, 87% and 73%, and for coincidental cancers in the PZ it was 74%, 67%, 77%, 75% and 73%, respectively. Distribution of Gleason grades 4 and 5 showed no significant difference between TZ and PZ (p = 0.231), but were significantly lower in AZ (p < 0.05). The correlation of high Gleason grades (4,5) to high PI-RADS scores (3-5) was significant for AZ (p = 0.006), TZ (p = 0.003) and PZ (p = 0.009). Conclusions 31% of PCA index lesions were detected outside the PZ. As expected, PCA was more frequent in the TZ than in the AZ. In our cohort, accuracy of mp MRI was highest in the AZ. GS distribution was not statistically significant different between PZ and TZ, but high gleason patterns were more frequent in both as compared to the AZ. A cancer suspicious PI-RADS score correlated significantly with the appearance of gleason patterns 4 and 5 in all prostate zones. The combination of mp MRI and fusion-guided transperineal biopsy shows promising results in PCAs of the TZ and AZ. However, targeted biopsy alone cannot be recommended since the NPV of MRI as compared to systematic transperineal saturation biopsy is still not optimal. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e592 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Jan Philipp Radtke More articles by this author Silvan Boxler More articles by this author Yesilda Belavarca More articles by this author Timur Hasan Kuru More articles by this author Matthias Röthke More articles by this author Heinz-Peter Schlemmer More articles by this author Markus Hohenfellner More articles by this author Boris Hadaschik More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Transition Zone Prostate Cancer: Incremental Value of Diffusion-weighted Endorectal MR Imaging in Tumor Detection and Assessment of Aggressiveness

To evaluate the incremental value of using diffusion-weighted magnetic resonance (MR) imaging in addition to T2-weighted imaging for the detection of prostate cancer in the transition zone and the assessment of tumor aggressiveness. This retrospective HIPAA-compliant institutional review board-approved study included 156 consecutive patients (median age, 59.2 years) who underwent MR imaging before radical prostatectomy. Two readers who were blinded to patient data independently recorded their levels of suspicion on a five-point scale of the presence of transition zone tumors on the basis of T2-weighted imaging alone and then, 4 weeks later, diffusion-weighted imaging and T2-weighted imaging together. Apparent diffusion coefficients (ADCs) were measured in transition zone cancers and glandular and stromal benign prostatic hyperplasia. Areas under the receiver operating characteristic curves were used to evaluate detection accuracy, and generalized linear models were used to test ADC differences between benign and malignant prostate regions. Whole-mount step-section histopathologic examination was the reference standard. In overall tumor detection, addition of diffusion-weighted imaging to T2-weighted imaging improved the areas under the receiver operating characteristic curves for readers 1 and 2 from 0.60 and 0.60 to 0.75 and 0.71, respectively, at the patient level (P = .004 for reader 1 and P = .027 for reader 2) and from 0.64 and 0.63 to 0.73 and 0.68, respectively, at the sextant level (P = .001 for reader 1 and P = .100 for reader 2). Least squares mean ADCs (× 10(-3) mm(2)/sec) in glandular and stromal benign prostatic hyperplasia were 1.44 and 1.09, respectively. Mean ADCs were inversely associated with tumor Gleason scores (1.10, 0.98, 0.87, and 0.75 for Gleason scores of 3 + 3, 3 + 4, 4 + 3, and ≥ 4 + 4, respectively). Use of diffusion-weighted imaging in addition to T2-weighted imaging improved detection of prostate cancer in the transition zone, and tumor ADCs were inversely associated with tumor Gleason scores in the transition zone.

Transition Zone Prostate Cancer: Incremental Value of Diffusion-weighted Endorectal MR Imaging in Tumor Detection and Assessment of Aggressiveness

To evaluate the incremental value of using diffusion-weighted magnetic resonance (MR) imaging in addition to T2-weighted imaging for the detection of prostate cancer in the transition zone and the assessment of tumor aggressiveness. This retrospective HIPAA-compliant institutional review board-approved study included 156 consecutive patients (median age, 59.2 years) who underwent MR imaging before radical prostatectomy. Two readers who were blinded to patient data independently recorded their levels of suspicion on a five-point scale of the presence of transition zone tumors on the basis of T2-weighted imaging alone and then, 4 weeks later, diffusion-weighted imaging and T2-weighted imaging together. Apparent diffusion coefficients (ADCs) were measured in transition zone cancers and glandular and stromal benign prostatic hyperplasia. Areas under the receiver operating characteristic curves were used to evaluate detection accuracy, and generalized linear models were used to test ADC differences between benign and malignant prostate regions. Whole-mount step-section histopathologic examination was the reference standard. In overall tumor detection, addition of diffusion-weighted imaging to T2-weighted imaging improved the areas under the receiver operating characteristic curves for readers 1 and 2 from 0.60 and 0.60 to 0.75 and 0.71, respectively, at the patient level (P = .004 for reader 1 and P = .027 for reader 2) and from 0.64 and 0.63 to 0.73 and 0.68, respectively, at the sextant level (P = .001 for reader 1 and P = .100 for reader 2). Least squares mean ADCs (× 10(-3) mm(2)/sec) in glandular and stromal benign prostatic hyperplasia were 1.44 and 1.09, respectively. Mean ADCs were inversely associated with tumor Gleason scores (1.10, 0.98, 0.87, and 0.75 for Gleason scores of 3 + 3, 3 + 4, 4 + 3, and ≥ 4 + 4, respectively). Use of diffusion-weighted imaging in addition to T2-weighted imaging improved detection of prostate cancer in the transition zone, and tumor ADCs were inversely associated with tumor Gleason scores in the transition zone.

T 2 -Weighted Combined with Diffusion-Weighted Images for Evaluating Prostatic Transition Zone Tumors at 3 Tesla

We hypothesize that the combination of T(2)-weighted (T(2)W) MRI with diffusion-weighted imaging (DWI) methods provides a powerful clinical application for the differential diagnosis of prostate cancer and benign lesion in the prostatic transition zone (TZ). This retrospective study included 113 patients who were diagnosed with TZ lesions by MRI. The apparent diffusion coefficient values were compared between biopsy-proven benign and malignant lesions. The apparent diffusion coefficient values for the malignant nodules were significantly lower than those of the benign nodules. The area under the curve values for T(2)W imaging combined with DWI and T(2)W imaging alone were 0.991 and 0.884, respectively. T(2)W combined with DWI provides a powerful tool for noninvasive differentiation between malignant and benign prostatic hyperplasia nodules in the prostatic TZ.

Differentiation of transitional zone prostate cancer from benign hyperplasia nodules: Evaluation of discriminant criteria at multiparametric MRI

To assess topographical and magnetic resonance imaging (MRI) features in characterizing prostate transitional zone (TZ) nodules. Two radiologists evaluated all TZ nodules visible at multiparametric MRI in 52 consecutive patients who underwent radical prostatectomy. The radiologists assessed topographical (anteroposterior and superior-inferior location, crossing of the sagittal midline) and T2-weighted (shape, presence and distinctness of capsule, distinctness of contours, presence of cysts) features, the apparent diffusion coefficient (ADC), and eight semi-quantitative and quantitative enhancement parameters derived from dynamic contrast-enhanced (DCE) imaging. The nature of the nodules was assessed using prostatectomy specimens. Five statistical methods taking into account multiple testing were used. One hundred and thirty-seven nodules (117 benign, 20 malignant) were evaluated. Mean ADC, all topographical, and all T2-weighted features were significant predictors of malignancy according to at least four out of the five statistical methods. Particularly, 20/20 and 18/20 cancers involved the anterior and apical third of the TZ, respectively. None of the enhancement parameters was significantly different between cancers and benign nodules. By assessing the presence of cysts, the nodules' capsule, and their anteroposterior and superior-inferior location, 111/117 benign nodules were correctly diagnosed, without misclassifying any cancer. Topographical, T2-weighted, and diffusion-weighted features can be used to characterize TZ nodules. DCE imaging does not seem to provide additional information.

Transition Zone Prostate Cancer: Detection and Localization with 3-T Multiparametric MR Imaging

Transition Zone Prostate Cancer: Detection and Localization with 3-T Multiparametric MR Imaging

Low incidence of prostate cancer identified in the transition and anterior zones with transperineal biopsy

PurposeDetermine the incidence of anterior (AZ) and transition (TZ) zone prostate cancers using a transperineal mapping approach.MethodsA retrospective review of 137 patients with history of previous negative biopsy undergoing transperineal saturation biopsy for an elevated prostate-specific antigen (PSA), high-grade prostate intraepithelial neoplasia, atypical small acinar proliferation history, or abnormal digital rectal exam. The number of biopsy cores was determined by prostate volume and obtained using a predefined template. The electronic medical records were reviewed for patients’ clinical and pathological characteristics.ResultsForty-one of 137 patients (31.4%) had positive biopsy for prostate adenocarcinoma; 11 were from 24-core, 19 from 36-core, and 11 from 48-core sampling. Glands > 45 mL had a mean of 1.7 previous biopsies and a PSA of 9.1 ng/mL. Glands < 30 mL were 1.3 and 6.3 ng/mL and glands 30–45 mL were 1.4 and 6.5 ng/mL. Glands < 45 mL had a higher number of positive biopsies per total cores. Seven patients chose active surveillance while 34 chose treatment. Of the 36- and 48-cores biopsies, 2.2% and 1.5%, respectively, were positive in the TZ. One patient was AZ-positive, 1 was TZ-positive, and 18 were peripheral zone (PZ)-positive alone. Twelve patients had cancer detected in PZ and TZ. Two patients developed urinary retention and one had a urine infection.ConclusionTransperineal saturation biopsy is a safe and efficacious method of prostate cancer detection in patients with previous negative biopsy and high suspicion for cancer. Few cancers were found to originate in the TZ or AZ alone. We recommend that initial biopsy templates should sample PZ with less focus on the TZ.

Transition Zone Prostate Cancer: Detection and Localization with 3-T Multiparametric MR Imaging

To retrospectively compare transition zone (TZ) cancer detection and localization accuracy of 3-T T2-weighted magnetic resonance (MR) imaging with that of multiparametric (MP) MR imaging, with radical prostatectomy specimens as the reference standard. The informed consent requirement was waived by the institutional review board. Inclusion criteria were radical prostatectomy specimen TZ cancer larger than 0.5 cm(3) and 3-T endorectal presurgery MP MR imaging (T2-weighted imaging, diffusion-weighted [DW] imaging apparent diffusion coefficient [ADC] maps [b < 1000 sec/mm(2)], and dynamic contrast material-enhanced [DCE] MR imaging). From 197 patients with radical prostatectomy specimens, 28 patients with TZ cancer were included. Thirty-five patients without TZ cancer were randomly selected as a control group. Four radiologists randomly scored T2-weighted and DW ADC images, T2-weighted and DCE MR images, and T2-weighted, DW ADC, and DCE MR images. TZ cancer suspicion was rated on a five-point scale in six TZ regions of interest (ROIs). A score of 4-5 was considered a positive finding. A score of 4 or higher for any ROI containing TZ cancer was considered a positive detection result at the patient level. Generalized estimating equations were used to analyze detection and localization accuracy by using ROI-receiver operating characteristics (ROC) curve analyses for the latter. Gleason grade (GG) 4-5 and GG 2-3 cancers were analyzed separately. Detection accuracy did not differ between T2-weighted and MP MR imaging for all TZ cancers (68% vs 66%, P = .85), GG 4-5 TZ cancers (79% vs 72%-75%, P = .13), and GG 2-3 TZ cancers (66% vs 62%-65%, P = .47). MP MR imaging (area under the ROC curve, 0.70-0.77) did not improve T2-weighted imaging localization accuracy (AUC = 0.72) (P > .05). Use of 3-T MP MR imaging, consisting of T2-weighted imaging, DW imaging ADC maps (b values, 50, 500, and 800 sec/mm(2)), and DCE MR imaging may not improve TZ cancer detection and localization accuracy compared with T2-weighted imaging. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120281/-/DC1.

PAGE4 Positivity Is Associated with Attenuated AR Signaling and Predicts Patient Survival in Hormone-Naive Prostate Cancer

Aberrant activation of the androgen receptor (AR) plays a key role during prostate cancer (PCa) development and progression to castration-resistant prostate cancer (CR-PCa) after androgen deprivation therapy, the mainstay systemic treatment for PCa. New strategies to abrogate AR activity and biomarkers that predict aggressive tumor behavior are essential for improved therapeutic intervention. PCa tissue microarrays herein reveal that prostate-associated gene 4 (PAGE4), an X-linked cancer/testis antigen, is highly up-regulated in the epithelium of preneoplastic lesions compared with benign epithelium, but subsequently decreases with tumor progression. We show that AR signaling is attenuated in PAGE4-expressing cells both in vitro and in vivo, most likely via impaired androgen-induced AR nuclear translocation and subsequently reduced AR protein stabilization and phosphorylation at serines 81 and 213. Consistently, epithelial PAGE4 protein levels inversely correlated with AR activation status in hormone-naive and CR-PCa clinical specimens. Moreover, PAGE4 impaired the development of CR-PCa xenografts, and strong PAGE4 immunoreactivity independently predicted favorable patient survival in hormone-naive PCa. Collectively, these data suggest that dysregulation of epithelial PAGE4 modulates AR signaling, thereby promoting progression to advanced lethal PCa and highlight the potential value of PAGE4 as a prognostic and therapeutic target.

Three dimensional proton MR spectroscopic imaging in transition zone prostate cancer

Objective To discuss the clinical value of three dimensional proton MR spectroscopic imaging( 3D 1HMRSI) in the detection of transition zone(TZ) prorate cancer and evaluate the feasibility of 3D 1HMRSI for determining the aggressiveness of TZ cancer by analyzing its metabolic characteristics.Methods The 3D 1HMRSI data of sixty patients suspected TZ cancer in conventional MR examinations were retrospectively analyzed.The values of (Cho + Cre)/Cit of TZ cancer and benign prostatic hyperplasia (BPH) voxels were recorded and compared using independent sample t' test,and the area under the ROC curve was used to evaluate the diagnostic accuracy.Based on Gleason scores,TZ cancer voxels were divided into three groups,including low-risk ( Gleason score ＜ 7 ),intermediate-risk ( Gleason score =7 ) and highrisk (Gleason score ＞ 7).The values of (Cho + Cre)/Cit were compared among the three groups using Kruskal-Wallis test.The correlation of the value of (Cho + Cre)/Cit and Gleason score was analyzed using rank correlation analysis.Results Among the 60 patients,histopathology confirmed TZ cancer in 25 patients and BPH in 35 patients.The inversion of Cho and Cit peak value with increased ( Cho + Cre)/Cit was detected in 160 out of 177 TZ cancer voxels.Most spectral curves of the 517 BPH voxels were similar with that of normal peripheral zone on 1HMRSI.The mean values of ( Cho + Cre)/Cit of TZ cancer and BPH voxels were 2.17 ± 1.29 and 0.77 ± 0.20,respectively,with significant difference between them( t' =14.38,P ＜ 0.01).Using (Cho + Cre)/Cit for distinguishing TZ cancer,the area under ROC curve was 0.985 (P ＜ 0.01).With the cut-off point 1.08,the sensitivity,specificity and accuracy of TZ cancer diagnosis was 92.7％,94.2％ and 93.8％,respectively.The number of low-risk,intermediate-risk and high-risk TZ cancer voxels were 57,64 and 56 respectively,and the mean values of ( Cho + Cre)/Cit of the three groups were 1.43 ( 1.16-1.87 ),1.66 ( 1.43-2.36 ) and 2.32 ( 1.86-3.30 ) respectively,with significant difference among them ( x2 =36.282,P ＜ 0.01).The value of ( Cho + Cre )/Cit of TZ cancer increased with the increasing of Gleason score with positive correlation ( r =0.555,P ＜ 0.01).Conclusions TZ caner has a different metabolic profile from BPH.The value of ( Cho + Cre)/Cit on 3D 1HMRSI could provide useful information for early detection and differentiation TZ cancer from BPH.Besides these,( Cho +Cre)/Cit is also a valuable imaging marker to evaluate the aggressiveness of TZ cancer. Key words: Prostatic neoplasms; Prostatic hyperplasia; Magnetic resonance spectroscopy

Prostate Cancer Foci Detected on Multiparametric Magnetic Resonance Imaging are Histologically Distinct From Those Not Detected

We identified histological differences between prostate cancer foci that are detected and missed using multiparametric magnetic resonance imaging. A total of 49 patients who underwent multiparametric magnetic resonance imaging, including T2-weighted imaging, including diffusion weighted imaging and dynamic contrast enhanced imaging, before prostatectomy were enrolled in the study. One radiologist identified areas highly suspicious for tumor. One pathologist identified and categorized tumors in terms of size, Gleason score, solid tumor growth, intermixed benign glands, loose stroma, desmoplastic stroma and a high malignant epithelium-to-stroma ratio. Differences between detected and missed tumors were assessed using logistic regression analyses based on generalized estimating equations for correlated data. All histological features showed significant differences between detected and missed tumors on multiparametric magnetic resonance imaging (p<0.0001). Independent predictors of detection on multivariate analysis were size (OR 5.38, p=0.0077), Gleason score (OR 5.12, p=0.0094) and solid growth (OR 17.83, p<0.0001). Size, Gleason score and loose stroma were significant predictors of identification with diffusion weighted imaging on univariate analysis (p≤0.0245), while Gleason score (OR 17.05, p=0.0212) and solid growth (OR 34.90, p=0.0103) were independent predictors of identification with diffusion weighted imaging on multivariate analysis. Identification with T2-weighted imaging was associated with size and Gleason score (p≤0.01876). Identification with dynamic contrast enhanced imaging was associated with intermixed benign epithelium, loose stroma and a high malignant epithelium-to-stroma ratio (p≤0.0499). No combination of features served as independent predictors on multivariate analysis for T2-weighted imaging or dynamic contrast enhanced imaging. There are fundamental histological differences between detected and missed prostate tumors using magnetic resonance imaging. Insights into these differences may facilitate the prospective role of magnetic resonance imaging in counseling and treatment selection for patients with prostate cancer.

Relevance of cohort design for studying the frequency of the ERG rearrangement in prostate cancer

ERG rearrangements, mostly resulting in TMPRSS2-ERG fusions, are frequent alterations in prostate cancer (PCa), with a frequency ranging from 15% to 78%. As the reason for this variability is unknown, our aim was to investigate the ERG rearrangement frequency with a cohort design. We assessed three well-defined cohorts for ERG rearrangements, using fluorescence in situ hybridization (FISH). The first cohort comprised 119 prostatectomy specimens. The second and third cohorts included incidentally diagnosed PCa [71 cystoprostatectomy specimens, and 105 transurethral resection of the prostate (TURP) specimens]. Seventy of 119 (59%) cases of the prostatectomy cohort harboured ERG rearrangements. Regarding zonal origin, 2/11 (18%) transition zone (TZ) foci and 75/145 (52%) peripheral zone (PZ) foci harboured ERG rearrangements. Within the cystoprostatectomies, 24/71 (34%) cases harboured ERG rearrangements. Regarding zonal origin, 2/9 (22%) TZ foci and 26/86 (30%) PZ foci harboured ERG rearrangements. PCa incidentally identified by TURP harboured ERG rearrangements in 31/105 (29%) cases. ERG rearrangements occur in TZ PCa, although at a lower frequency than in PZ PCa. We confirmed that approximately half of all prostatectomies harbour ERG rearrangements. However, the frequency in incidentally diagnosed PCa cohorts was significantly lower, even if multifocality was considered. Consequently, zonal origin and cohort design are key for studying the clinical implications of ERG rearrangements.

Editorial Comment

The authors report the largest to date series of transperineal template-guided mapping biopsies (TTMB) in the setting of a previous negative biopsy, atypical small acinar proliferation or high grade prostatic intraepithelial neoplasia, and persistently elevated prostate-specific antigen. In this study, the authors emphasize the importance of TTMB for accurate sampling of the prostate and specifically the transition zone (TZ) that is largely inaccessible to conventional transrectal diagnostic methods. The Incidence of Transition Zone Prostate Cancer Diagnosed by Transperineal Template-guided Mapping Biopsy: Implications for Treatment PlanningUrologyVol. 77Issue 5PreviewTo report the incidence of transition zone (TZ) cancer in patients undergoing transperineal template-guided mapping biopsy (TTMB) of the prostate gland. Full-Text PDF ReplyUrologyVol. 77Issue 5PreviewIn our practice, transperineal template-guided mapping biopsy (TTMB) has proven to be of great use in the diagnosis and intraprostatic staging of prostate cancer. TTMB results in the accurate and complete three-dimensional sampling of the gland, especially the periurethral and apical regions, which are not readily accessible via transrectal ultrasound (TRUS) approaches (especially in obese patients and/or those with large prostates). In our series, patients with 1, 2, and ≥3 prior negative TRUS biopsies have been diagnosed with prostate cancer after TTMB in 55.5%, 41.7%, and 34.4% of cases, respectively. Full-Text PDF

The Incidence of Transition Zone Prostate Cancer Diagnosed by Transperineal Template-guided Mapping Biopsy: Implications for Treatment Planning

To report the incidence of transition zone (TZ) cancer in patients undergoing transperineal template-guided mapping biopsy (TTMB) of the prostate gland. Five hundred thirty-nine consecutive patients underwent TTMB by means of an anatomic technique with sampling of 24 defined prostate regions. The position of each biopsy core was recorded in 3 dimensions. For every patient, the location of each positive biopsy core, the number of positive cores, the Gleason score, the percentage involvement of each core, and the presence/absence of perineural invasion was documented. The median volumetric prostate volume was 56.0 cm(3) with an ellipsoid TZ volume of 20.1 cm(3). The median number of TTMB cores was 58 with a median of 11 TZ cores. Two hundred eighty-seven (53.2%) were diagnosed with prostate cancer. TZ cancer was detected in 130 (45.3%) of patients with prostate cancer but only 6 (4.6%) were confined to the TZ. Overall, 38.9% of TZ cores were positive for malignancy. Of the TZ cancers, 37 (28.5%), 64 (49.2%), and 29 (22.3%) were assigned Gleason scores 6, 7, and 8-10. Compared with a standard 12-core biopsy approach, the results of the TZ biopsy upgraded the Gleason score in 24.6% of patients. Only 4 cancers (3.1%) involving the TZ were classified as clinically insignificant. Although only 4.6% of cancers were confined to the TZ, 45.3% of all prostate cancer patients had TZ involvement.

ERG rearrangement is present in a subset of transition zone prostatic tumors

A majority of prostate cancers exhibit a recurrent gene rearrangement involving chromosome 21. In approximately 90% of cases, the rearrangement is characterized by fusion of the androgen-regulated gene TMPRSS2 with the oncogene ERG. A recent study suggested that TMPRSS2–ERG gene fusion is lacking in cancers arising from the transition zone of the prostate. A dominant transition zone cancer was detected in 62/397 (16%) patients who underwent radical prostatectomy at our institution and were reviewed and mapped by a single pathologist. In 46/62 specimens, a secondary tumor was identified in the peripheral zone of the prostate. A tissue microarray containing both transition and peripheral zone tumors was constructed and evaluated for gene fusion analysis. TMPRSS2–ERG fusion status was determined using a multicolor interphase fluorescence in situ hybridization assay for ERG break-apart. The median age of the patients was 59 years. Prostatectomy Gleason score was 6 in 21, 7 in 34, and ≥8 in 7 cases. Median tumor volume was 200 mm2. TMPRSS2–ERG gene fusion was present in 7/59 (12%) transition zone, and in 12/35 (34%) peripheral zone tumors. Transition zone fusion-positive cases were larger than their negative counterparts. No significant correlation was found between fusion status and Gleason score or pathologic stage. Gene fusion through deletion occurred in 4/7 transition zone and 7/12 peripheral zone tumors. Transition zone prostate cancers are considered biologically and genetically different from peripheral zone tumors. Although ERG rearrangement is more common in peripheral zone tumors, we have detected TMPRSS2–ERG fusion in a subset of transition zone cancers (12%). The lower frequency of gene fusion in transition zone prostate cancer may suggest distinct molecular alterations from peripheral zone tumors and the association with a high tumor volume may indicate a growth advantage for transition zone tumors harboring the gene fusion. Further studies are necessary to confirm this hypothesis.

The Incidence of Transition Zone Prostate Cancer Diagnosed by Transperineal Template Guided Mapping Biopsy: Implications for Treatment Planning

The Incidence of Transition Zone Prostate Cancer Diagnosed by Transperineal Template Guided Mapping Biopsy: Implications for Treatment Planning

The Role of TURP in the Detection of Prostate Cancer in BPH Patients with Previously Negative Prostate Biopsy

PurposeWe aimed to investigate the significance of early detection of transition zone prostate cancer by transurethral resection of prostate (TURP) in benign prostatic hyperplasia (BPH) patients with lower urinary tract symptoms (LUTS) in whom prostate cancer was suspected despite a negative transrectal ultrasonography (TRUS) biopsy result.Materials and MethodsFrom January 2006 to January 2009, a total of 165 patients who underwent TURP were evaluated. The prostate cancer detection rate was compared between patients who underwent TRUS biopsy before TURP (group A) and those who did not (group B). All charts were evaluated retrospectively, including prostate-specific antigen (PSA), digital rectal examination (DRE), TURP results (including resection volume and pathology report), TRUS, and TRUS biopsy results. Group A was subdivided into group A1, who were diagnosed with prostate cancer after TURP, and group A2, who were diagnosed with BPH after TURP.ResultsThe cancer detection rate showed no significant difference between groups A and B (8.9% vs. 7.5%, p>0.05). The mean PSA levels in groups A1 and A2 were 15.5±14.0 ng/ml and 9.1±5.1 ng/ml, respectively (p>0.05). In group A1, 40% had an abnormal DRE, compared with 6.7% in group A2 (p<0.05). After TURP, the mean percentage of resected prostatic chips of the prostate cancer group and BPH group were 33.9% and 18.6%, respectively (p=0.001). A positive correlation was found between the detection rate of prostate cancer and PSA (p=0.01).ConclusionsBPH patients in whom prostate cancer is suspected and who have lower urinary tract symptoms (LUTS) with a previously negative TRUS biopsy result can undergo TURP, which results in immediate improvement in bladder outlet obstruction and early diagnosis of clinically significant transition zone prostate cancer.