Twelve-month prostate volume reduction after MRI-guided transurethral ultrasound ablation of the prostate.

PURPOSE: To quantitatively assess 12-month prostate volume (PV) reduction based on T2-weighted MRI and immediate post-treatment contrast-enhanced MRI non-perfused volume (NPV), and to compare measurements with predictions of acute and delayed ablation volumes based on MR-thermometry (MR-t), in a central radiology review of the Phase I clinical trial of MRI-guided transurethral ultrasound ablation (TULSA) in patients with localized prostate cancer. MATERIALS AND METHODS: Treatment day MRI and 12-month follow-up MRI and biopsy were available for central radiology review in 29 of 30 patients from the published institutional review board-approved, prospective, multi-centre, single-arm Phase I clinical trial of TULSA. Viable PV at 12 months was measured as the remaining PV on T2-weighted MRI, less 12-month NPV, scaled by the fraction of fibrosis in 12-month biopsy cores. Reduction of viable PV was compared to predictions based on the fraction of the prostate covered by the MR-t derived acute thermal ablation volume (ATAV, 55°C isotherm), delayed thermal ablation volume (DTAV, 240 cumulative equivalent minutes at 43°C thermal dose isocontour) and treatment-day NPV. We also report linear and volumetric comparisons between metrics. RESULTS: After TULSA, the median 12-month reduction in viable PV was 88%. DTAV predicted a reduction of 90%. Treatment day NPV predicted only 53% volume reduction, and underestimated ATAV and DTAV by 36% and 51%. CONCLUSION: Quantitative volumetry of the TULSA phase I MR and biopsy data identifies DTAV (240 CEM43 thermal dose boundary) as a useful predictor of viable prostate tissue reduction at 12 months. Immediate post-treatment NPV underestimates tissue ablation. KEY POINTS: • MRI-guided transurethral ultrasound ablation (TULSA) achieved an 88% reduction of viable prostate tissue volume at 12 months, in excellent agreement with expectation from thermal dose calculations. • Non-perfused volume on immediate post-treatment contrast-enhanced MRI represents only 64% of the acute thermal ablation volume (ATAV), and reports only 60% (53% instead of 88% achieved) of the reduction in viable prostate tissue volume at 12 months. • MR-thermometry-based predictions of 12-month prostate volume reduction based on 240 cumulative equivalent minute thermal dose volume are in excellent agreement with reduction in viable prostate tissue volume measured on pre- and 12-month post-treatment T2w-MRI.

[Multiparametric MRI and MRI-TRUS fusion biopsy in patients with prior negative prostate biopsy]. / Wertigkeit der multiparametrischen MRT und der MRT-TRUS-Fusionsbiopsie bei primär negativ biopsierten Patienten.

BACKGROUND: Multiparametric MRI (mpMRI) plays an increasingly important role in prostate cancer (PCa) diagnostics and is recommended in men with previously negative TRUS biopsy. The optimal biopsy method after mpMRI is under discussion. OBJECTIVE: Prospective, PIRADS- and START-conform analysis of the relevance of mpMRI and MRI-TRUS fusion biopsy in patients with prior negative TRUS biopsy and comparison of the detection rates of fusion-targeted biopsies (tB) and systematic transperineal saturation biopsies (sB). MATERIALS AND METHODS: Between 10/2012 and 09/2015, 287 patients with prior negative TRUS biopsy underwent mpMRI and software-assisted, rigid MRI-TRUS fusion biopsy. In addition to and strictly separated from sB (median cores n = 24), tB (median cores per patient n = 4, per lesion n = 3) were performed in case of suspicious MRI lesions (PIRADS ≥ 2). Both biopsy methods were compared by using McNemar's test. RESULTS: Of the 287 patients, 148 (52 %) had positive biopsies. Of these, 108/287 (38 %) had significant PCa (Gleason Score [GS] = 3 + 3 and PSA ≥ 10 ng/ml or GS ≥ 3 + 4) and again 43/287 (15 %) had a GS ≥ 4 + 3 PCa. sB failed to diagnose 8/148 PCa (5.4 %) and 6/108 significant PCa (5.5 %), whereas tB failed to diagnose 48 (32.4 %) PCa (p < 0.0001) and 22 (20.4 %) significant PCa (p = 0.0046). Of the PCa missed by tB, 11  had a GS ≥ 3 + 4 and 5 of these a GS = 4 + 3. On a per patient basis, MRI failed to detect 5 significant PCa, whereby 17 of the significant PCa were missed by fusion-targeted cores alone. CONCLUSIONS: In men with unsuspicious MRI (PIRADS < 3), there is a 11 % risk of significant PCa. In case of suspicious MRI lesions, the combination of both biopsy approaches offers maximum tumor detection.

Further reduction of disqualification rates by additional MRI-targeted biopsy with transperineal saturation biopsy compared with standard 12-core systematic biopsies for the selection of prostate cancer patients for active surveillance.

BACKGROUND: Active surveillance (AS) is commonly based on standard 10-12-core prostate biopsies, which misclassify ~50% of cases compared with radical prostatectomy. We assessed the value of multiparametric magnetic resonance imaging (mpMRI)-targeted transperineal fusion-biopsies in men under AS. METHODS: In all, 149 low-risk prostate cancer (PC) patients were included in AS between 2010 and 2015. Forty-five patients were initially diagnosed by combined 24-core systematic transperineal saturation biopsy (SB) and MRI/transurethral ultrasound (TRUS)-fusion targeted lesion biopsy (TB). A total of 104 patients first underwent 12-core TRUS-biopsy. All patients were followed-up by combined SB and TB for restratification after 1 and 2 years. All mpMRI examinations were analyzed using PIRADS. AS was performed according to PRIAS-criteria and a NIH-nomogram for AS-disqualification was investigated. AS-disqualification rates for men initially diagnosed by standard or fusion biopsy were compared using Kaplan-Meier estimates and log-rank tests. Differences in detection rates of the SB and TB components were evaluated with a paired-sample analysis. Regression analyses were performed to predict AS-disqualification. RESULTS: A total of, 48.1% of patients diagnosed by 12-core TRUS-biopsy were disqualified from AS based on the MRI/TRUS-fusion biopsy results. In the initial fusion-biopsy cohort, upgrading occurred significantly less frequently during 2-year follow-up (20%, P<0.001). TBs alone were significantly superior compared with SBs alone to detect Gleason-score-upgrading. NPV for Gleason-upgrading was 93.5% for PIRADS⩽2. PSA level, PSA density, NIH-nomogram, initial PIRADS score (P<0.001 each) and PIRADS-progression on consecutive MRI (P=0.007) were significant predictors of AS-disqualification. CONCLUSIONS: Standard TRUS-biopsies lead to significant underestimation of PC under AS. MRI/TRUS-fusion biopsies, and especially the TB component allow more reliable risk classification, leading to a significantly decreased chance of subsequent AS-disqualification. Cancer detection with mpMRI alone is not yet sensitive enough to omit SB on follow-up after initial 12-core TRUS-biopsy. After MRI/TRUS-fusion biopsy confirmed AS, it may be appropriate to biopsy only those men with suspected progression on MRI.

[Value of MRI/ultrasound fusion in primary biopsy for the diagnosis of prostate cancer]. / Stellenwert der MRT/TRUS-Fusionsbiopsie im Rahmen der Primärbiopsie beim Prostatakarzinom.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) plays an emerging role in prostate cancer diagnosis. We compared the cancer detection rates of targeted biopsy (tB) of suspicious lesions in mpMRI versus systematic transperineal saturation biopsy (sB) in men with primary suspicion of prostate cancer (PCa). METHODS: A total of 437 consecutive primary biopsy patients, who underwent transperineal systematic and fusion-guided biopsy between 2012 and 2014, were enrolled. mpMRI was evaluated based on PI-RADS. Analysis of biopsy specimen was performed following START criteria. RESULTS: Of the 437 men, 334 harbored 426 MR lesions. Overall, 274 PCa and 203 significant PCa (Gleason score (GS) ≥ 3 + 4, GS = 3 + 3 and PSA values ≥ 10 ng/ml) were detected. There were 52 (26 %) significant PCa exclusively found by sB, whereas only 18 (9 %) were identified by tB (p < 0.001). Of 80 high-grade PCa with GS ≥ 4 + 3, 70 were diagnosed by sB, and 60 by tB (p = 0.007). In addition, 54 % of all insignificant PCa (GS < 7, PSA < 10 ng/ml) were detected by sB alone (p < 0.001). AUC of mpMRI was 0.76-0.78. CONCLUSION: The combination of tB + sB detects PCa most accurately. Ongoing prospective (multicenter) studies are evaluating the status of the 12 core TRUS-guided random biopsy.

Improved detection of anterior fibromuscular stroma and transition zone prostate cancer using biparametric and multiparametric MRI with MRI-targeted biopsy and MRI-US fusion guidance.

BACKGROUND: The objective of this study was to analyze the potential of prostate magnetic resonance imaging (MRI) and MRI/transrectal ultrasound-fusion biopsies to detect and to characterize significant prostate cancer (sPC) in the anterior fibromuscular stroma (AFMS) and in the transition zone (TZ) of the prostate and to assess the accuracy of multiparametric MRI (mpMRI) and biparametric MRI (bpMRI) (T2w and diffusion-weighted imaging (DWI)). METHODS: Seven hundred and fifty-five consecutive patients underwent prebiopsy 3 T mpMRI and transperineal biopsy between October 2012 and September 2014. MRI images were analyzed using PIRADS (Prostate Imaging-Reporting and Data System). All patients had systematic biopsies (SBs, median n=24) as reference test and targeted biopsies (TBs) with rigid software registration in case of MRI-suspicious lesions. Detection rates of SBs and TBs were assessed for all PC and sPC patients defined by Gleason score (GS)⩾3+4 and GS⩾4+3. For PC, which were not concordantly detected by TBs and SBs, prostatectomy specimens were assessed. We further compared bpMRI with mpMRI. RESULTS: One hundred and ninety-one patients harbored 194 lesions in AFMS and TZ on mpMRI. Patient-based analysis detected no difference in the detection of all PC for SBs vs TBs in the overall cohort, but in the repeat-biopsy population TBs performed significantly better compared with SBs (P=0.004 for GS⩾3+4 and P=0.022 for GS⩾4+3, respectively). Nine GS⩾4+3 sPCs were overlooked by SBs, whereas TBs missed two sPC in men undergoing primary biopsy. The combination of SBs and TBs provided optimal local staging. Non-inferiority analysis showed no relevant difference of bpMRI to mpMRI in sPC detection. CONCLUSIONS: MRI-targeted biopsies detected significantly more anteriorly located sPC compared with SBs in the repeat-biopsy setting. The more cost-efficient bpMRI was statistically not inferior to mpMRI in sPC detection in TZ/AFMS.

Evaluation of microvascular permeability with dynamic contrast-enhanced MRI for the differentiation of primary CNS lymphoma and glioblastoma: radiologic-pathologic correlation.

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced MR imaging can provide in vivo assessment of the microvasculature in intracranial tumors. The aim of the present study was to evaluate the diagnostic performance of dynamic contrast-enhanced MR imaging derived vascular permeability parameters, including the volume transfer constant, the volume of extravascular extracellular space, and the flux rate constant between the extravascular extracellular space and plasma, for the differentiation of primary CNS lymphoma and glioblastoma. MATERIALS AND METHODS: Sixty glioblastomas and 11 primary central nervous system lymphomas were included. Pretreatment T1-weighted dynamic contrast-enhanced MR imaging with a 3D T1-weighted spoiled gradient-echo sequence was performed on a 3T MR imaging scanner. Perfusion parameters (volume transfer constant, the volume of extravascular extracellular space, and the flux rate constant) were measured on the basis of the Tofts-Kernmode model. The Mann-Whitney U test and receiver operating characteristic analysis were used to compare those parameters between primary central nervous system lymphoma and glioblastoma. Histopathologic correlation of dynamic contrast-enhanced MR imaging findings was performed by using reticulin staining and CD31 immunohistochemistry. RESULTS: Median volume transfer constant and flux rate constant values were significantly higher in primary central nervous system lymphoma (0.145 ± 0.057 and 0.396 ± 0.088) than in glioblastoma (0.064 ± 0.021 and 0.230 ± 0.058) (P < .001, respectively). Median volume of extravascular extracellular space values did not differ significantly between primary central nervous system lymphoma (0.434 ± 0.165) and glioblastoma (0.319 ± 0.107). On receiver operating characteristic analysis, volume transfer constant had the best discriminative value for differentiating primary central nervous system lymphoma and glioblastoma (threshold, 0.093; sensitivity, 90.9%; specificity, 95.0%). Histopathologic evaluation revealed intact vascular integrity in glioblastoma despite endothelial proliferation, whereas primary central nervous system lymphoma demonstrated destroyed vessel architecture, thereby promoting vascular disintegrity. CONCLUSIONS: Primary central nervous system lymphoma demonstrated significantly higher volume transfer constant and flux rate constant values compared with glioblastoma, implying a higher vascular permeability in primary central nervous system lymphoma. These findings confirm initial observations from perfusion CT and dynamic contrast-enhanced MR imaging studies, correlating with underlying histopathologic features, and may be useful in distinguishing primary central nervous system lymphoma from glioblastoma.

Evaluation of the ESUR PI-RADS scoring system for multiparametric MRI of the prostate with targeted MR/TRUS fusion-guided biopsy at 3.0 Tesla.

OBJECTIVES: To evaluate the Prostate Imaging Reporting and Data System (PI-RADS) proposed by the European Society of Urogenital Radiology (ESUR) for detection of prostate cancer (PCa) by multiparametric magnetic resonance imaging (mpMRI) in a consecutive cohort of patients with magnetic resonance/transrectal ultrasound (MR/TRUS) fusion-guided biopsy. METHODS: Suspicious lesions on mpMRI at 3.0 T were scored according to the PI-RADS system before MR/TRUS fusion-guided biopsy and correlated to histopathology results. Statistical correlation was obtained by a Mann-Whitney U test. Receiver operating characteristics (ROC) and optimal thresholds were calculated. RESULTS: In 64 patients, 128/445 positive biopsy cores were obtained out of 95 suspicious regions of interest (ROIs). PCa was present in 27/64 (42%) of the patients. ROC results for the aggregated PI-RADS scores exhibited higher areas under the curve compared to those of the Likert score. Sensitivity/Specificity for the following thresholds were calculated: 85 %/73 % and 67 %/92 % for PI-RADS scores of 9 and 10, respectively; 85 %/60 % and 56 %/97 % for Likert scores of 3 and 4, respectively [corrected. CONCLUSIONS: The standardised ESUR PI-RADS system is beneficial to indicate the likelihood of PCa of suspicious lesions on mpMRI. It is also valuable to identify locations to be targeted with biopsy. The aggregated PI-RADS score achieved better results compared to the single five-point Likert score. KEY POINTS: • The ESUR PI-RADS scoring system was evaluated using multiparametric 3.0-T MRI. • To investigate suspicious findings, transperineal MR/TRUS fusion-guided biopsy was used. • PI-RADS can guide biopsy locations and improve detection of clinically significant cancer. • Biopsy procedures can be optimised, reducing unnecessary negative biopsies for patients. • The PI-RADS scoring system may contribute to more effective prostate MRI.

Seminal vesicle invasion: accuracy and analysis of infiltration patterns with high-spatial resolution T2-weighted sequences on endorectal magnetic resonance imaging.

OBJECTIVE: To evaluate the accuracy of high-spatial resolution T2-weighted endorectal magnetic resonance imaging (eMRI) for detection and pattern depiction of seminal vesicle invasion (SVI) in patients with prostate cancer (PCa). METHODS: 376 patients were included who underwent eMRI for staging before radical open prostatectomy at 1.5 T with an endorectal coil. Statistical accuracy for detection of SVI was calculated. MR images of patients with SVI were further evaluated by two radiologists according to the classification by Wheeler and Ohori. RESULTS: In the cohort, 35 patients had SVI after histopathological evaluation of the prostatectomy specimen (stage pT3b). Sensitivity and specificity for detection of SVI were 48.6 and 97.7%, respectively. Negative and positive predictive values and overall accuracy were 94.9, 68.0, and 93.1%, respectively. Infiltration pattern analysis showed that type I invasion was most common with 48.6 followed by type IIa (31.4%) and IIb (20%). Type III was not present. There was no statistical significant difference between the three groups regarding Gleason score, age, and prostate-specific antigen level. CONCLUSIONS: eMRI with high-spatial resolution T2-weighted imaging is accurate for assessment of SVI. Depiction of different infiltration types of SVI is feasible. By adding information about the extent of SVI, diagnostic reporting and risk stratification could be improved.

MRI-guided prostate biopsy detects clinically significant cancer: analysis of a cohort of 100 patients after previous negative TRUS biopsy.

PURPOSE: To investigate the positive biopsy rate of MRI-guided biopsy (MR-GB) in a routine clinical setting, identify factors predictive for positive biopsy findings and to report about the clinical significance of the diagnosed tumors. METHODS: Patients with at least one negative trans-rectal-ultrasound-guided biopsy (TRUS-GB), persistently elevated or rising serum prostate specific antigen (PSA) and at least one lesion suspicious for PCa on diagnostic 1.5 Tesla endorectal coil MRI (eMR) were included. Biopsies were carried out using a 1.5 Tesla MRI and an 18 G biopsy gun. Clinical information and biopsy results were collected; logistic regression analysis was carried out. Definite pathology reports of patients with diagnosis of PCa and subsequent radical prostatectomy (RP) were analyzed for criteria of clinical significance. RESULTS: One hundred patients were included, mean number of previous biopsies was 2 (range 1-9), mean PSA at time of biopsy was 11.7 ng/ml (1.0-65.0), and mean prostate volume was 46.7 ccm (range 13-183). In 52/100 (52.0%) patients, PCa was detected. Out of 52 patients, 27 patients with a positive biopsy underwent RP, 20 patients radiation therapy, and 5 patients active surveillance. In total, 80.8% of the patients revealed a clinically significant PCa. In univariate regression analysis, only serum PSA levels were predictive for a positive biopsy result. Number of preceding negative biopsies was not associated with the likelihood of a positive biopsy result. CONCLUSIONS: MR-GB shows a high detection rate of clinically significant PCa in patients with previous negative TRUS-GB and persisting suspicion for PCa.

[MRI navigated stereotactic prostate biopsy: fusion of MRI and real-time transrectal ultrasound images for perineal prostate biopsies]. / MRT-navigierte stereotaktische Prostatabiopsie : Echtzeitfusion von MRT und transrektalem Ultraschall zu perinealen Prostatastanzbiopsien.

BACKGROUND: A key challenge for prostate cancer (PC) therapy is to exactly diagnose tumor lesions. In this context we describe a new stereotactic prostate biopsy system, which integrates pre-interventional MRI with peri-interventional ultrasound for targeted perineal prostate biopsies. Furthermore, the novel system allows exact documentation of biopsies in three dimensions. PATIENTS AND METHODS: Stereotactic biopsy was performed in 50 consecutive men with suspicion of PC [median age 67 years (42-77), mean PSA 8.9±6.8 ng/ml, and mean prostate volume 51±23.7 ml]. Twenty-five of these patients (50%) had already had a negative transrectal ultrasound (TRUS)-guided biopsy. All men underwent multiparametric, contrast-enhanced 3T MRI without endorectal coil. Suspicious lesions were marked before the obtained data were transferred to a novel stereotactic biopsy system. Using a custom-made biplane TRUS probe mounted on a stepper, 3-D ultrasound data were generated and fused with the MRI. As a result, suspicious MRI lesions were superimposed onto the TRUS data. Next, 3-D biopsy planning was performed including systematic biopsies from the peripheral zone of the prostate. According to local standards patients were treated with perioperative quinolone antibiotics and applied a rectal enema the evening before the procedure. Perineal biopsies were taken under live US imaging, and the location of each biopsy was documented in an individual 3-D model. Feasibility, safety, target registration error, and cancer detection were evaluated. RESULTS: The median number of biopsies taken per patient was 24 (12-36). In 27 men of the initial cohort of 50 consecutive patients presented here, biopsy samples showed PC (54%). In patients undergoing their first biopsy, cancerous lesions were diagnosed in 13 of 19 patients (68%). The result was positive in 36% of men undergoing a re-biopsy without previous cancer diagnosis (9/25). A positive correlation between MRI findings and histopathology was found in 72%. In MRI lesions marked as highly suspicious, the tumor detection rate was 100% (13/13). Looking at single cores from highly suspicious lesions, 40 of 75 (53%) biopsies were positive. The target registration error of the first 1,159 biopsy cores was 1.7 mm. Regarding adverse effects, one patient experienced urinary retention and one patient a perineal hematoma. Urinary tract infections did not occur. CONCLUSION: Perineal stereotactic prostate biopsies guided by the combination of MRI and ultrasound allow effective examination of suspicious MRI lesions. Each biopsy core taken is documented accurately for its location in 3-D enabling MRI validation and tailored treatment planning. The morbidity of the procedure was minimal.