Magnetic resonance imaging-guided transurethral ultrasound ablation in patients with localised prostate cancer: 3-year outcomes of a prospective Phase I study.

OBJECTIVES: To report the 3-year follow-up of a Phase I study of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) in 30 men with localised prostate cancer. Favourable 12-month safety and ablation precision were previously described. PATIENTS AND METHODS: As a mandated safety criterion, TULSA was delivered as near whole-gland ablation, applying 3-mm margins sparing 10% of peripheral prostate tissue in 30 men. After 12-month biopsy and MRI, biannual follow-up included prostate-specific antigen (PSA), adverse events (AEs), and functional quality-of-life assessment, with repeat systematic biopsy at 3 years. RESULTS: A 3-year follow-up was completed by 22 patients. Between 1 and 3 years, there were no new serious or severe AEs. Urinary and bowel function remained stable. Erectile function recovered by 1 year and was stable at 3 years. The PSA level decreased 95% to a median (interquartile range) nadir of 0.33 (0.1-0.4) ng/mL, stable to 0.8 (0.4-1.6) ng/mL at 3 years. Serial biopsies identified clinically significant disease in 10/29 men (34%) and any cancer in 17/29 (59%). By 3 years, seven men had recurrence (four histological, three biochemical) and had undergone salvage therapy without complications (including six prostatectomies). At 3 years, three of 22 men refused biopsy, and two of the 22 (9%) had clinically significant disease (one new, one persistent). Predictors of salvage therapy requirement included less extensive ablation coverage and higher PSA nadir. CONCLUSION: With 3-year Phase I follow-up, TULSA demonstrates safe and precise ablation for men with localised prostate cancer, providing predictable PSA and biopsy outcomes, without affecting functional abilities or precluding salvage therapy.

Combined Clinical Parameters and Multiparametric Magnetic Resonance Imaging for the Prediction of Extraprostatic Disease-A Risk Model for Patient-tailored Risk Stratification When Planning Radical Prostatectomy.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) facilitates the detection of significant prostate cancer. Therefore, addition of mpMRI to clinical parameters might improve the prediction of extraprostatic extension (EPE) in radical prostatectomy (RP) specimens. OBJECTIVE: To investigate the accuracy of a novel risk model (RM) combining clinical and mpMRI parameters to predict EPE in RP specimens. DESIGN, SETTING, AND PARTICIPANTS: We added prebiopsy mpMRI to clinical parameters and developed an RM to predict individual side-specific EPE (EPE-RM). Clinical parameters of 264 consecutive men with mpMRI prior to MRI/transrectal ultrasound fusion biopsy and subsequent RP between 2012 and 2015 were retrospectively analysed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariate regression analyses were used to determine significant EPE predictors for RM development. The prediction performance of the novel EPE-RM was compared with clinical T stage (cT), MR-European Society of Urogenital Radiology (ESUR) classification for EPE, two established nomograms (by Steuber et al and Ohori et al) and a clinical nomogram based on the coefficients of the established nomograms, and was constructed based on the data of the present cohort, using receiver operating characteristics (ROCs). For comparison, models' likelihood ratio (LR) tests and Vuong tests were used. Discrimination and calibration of the EPE-RM were validated based on resampling methods using bootstrapping. RESULTS AND LIMITATIONS: International society of Urogenital Pathology grade on biopsy, ESUR criteria, prostate-specific antigen, cT, prostate volume, and capsule contact length were included in the EPE-RM. Calibration of the EPE-RM was good (error 0.018). The ROC area under the curve for the EPE-RM was larger (0.87) compared with cT (0.66), Memorial Sloan Kettering Cancer Center nomogram (0.73), Steuber nomogram (0.70), novel clinical nomogram (0.79), and ESUR classification (0.81). Based on LR and Vuong tests, the EPE-RM's model fit was significantly better than that of cT, all clinical models, and ESUR classification alone (p<0.001). Limitations include monocentric design and expert reading of MRI. CONCLUSIONS: This novel EPE-RM, incorporating clinical and MRI parameters, performed better than contemporary clinical RMs and MRI predictors, therefore providing an accurate patient-tailored preoperative risk stratification of side-specific EPE. PATIENT SUMMARY: Extraprostatic extension of prostate cancer can be predicted accurately using a combination of magnetic resonance imaging and clinical parameters. This novel risk model outperforms magnetic resonance imaging and clinical predictors alone and can be useful when planning nerve-sparing radical prostatectomy.

Combined Clinical Parameters and Multiparametric Magnetic Resonance Imaging for Advanced Risk Modeling of Prostate Cancer-Patient-tailored Risk Stratification Can Reduce Unnecessary Biopsies.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) is gaining widespread acceptance in prostate cancer (PC) diagnosis and improves significant PC (sPC; Gleason score≥3+4) detection. Decision making based on European Randomised Study of Screening for PC (ERSPC) risk-calculator (RC) parameters may overcome prostate-specific antigen (PSA) limitations. OBJECTIVE: We added pre-biopsy mpMRI to ERSPC-RC parameters and developed risk models (RMs) to predict individual sPC risk for biopsy-naïve men and men after previous biopsy. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed clinical parameters of 1159 men who underwent mpMRI prior to MRI/transrectal ultrasound fusion biopsy between 2012 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariate regression analyses were used to determine significant sPC predictors for RM development. The prediction performance was compared with ERSPC-RCs, RCs refitted on our cohort, Prostate Imaging Reporting and Data System (PI-RADS) v1.0, and ERSPC-RC plus PI-RADSv1.0 using receiver-operating characteristics (ROCs). Discrimination and calibration of the RM, as well as net decision and reduction curve analyses were evaluated based on resampling methods. RESULTS AND LIMITATIONS: PSA, prostate volume, digital-rectal examination, and PI-RADS were significant sPC predictors and included in the RMs together with age. The ROC area under the curve of the RM for biopsy-naïve men was comparable with ERSPC-RC3 plus PI-RADSv1.0 (0.83 vs 0.84) but larger compared with ERSPC-RC3 (0.81), refitted RC3 (0.80), and PI-RADS (0.76). For postbiopsy men, the novel RM's discrimination (0.81) was higher, compared with PI-RADS (0.78), ERSPC-RC4 (0.66), refitted RC4 (0.76), and ERSPC-RC4 plus PI-RADSv1.0 (0.78). Both RM benefits exceeded those of ERSPC-RCs and PI-RADS in the decision regarding which patient to receive biopsy and enabled the highest reduction rate of unnecessary biopsies. Limitations include a monocentric design and a lack of PI-RADSv2.0. CONCLUSIONS: The novel RMs, incorporating clinical parameters and PI-RADS, performed significantly better compared with RMs without PI-RADS and provided measurable benefit in making the decision to biopsy men at a suspicion of PC. For biopsy-naïve patients, both our RM and ERSPC-RC3 plus PI-RADSv1.0 exceeded the prediction performance compared with clinical parameters alone. PATIENT SUMMARY: Combined risk models including clinical and imaging parameters predict clinically relevant prostate cancer significantly better than clinical risk calculators and multiparametric magnetic resonance imaging alone. The risk models demonstrate a benefit in making a decision about which patient needs a biopsy and concurrently help avoid unnecessary biopsies.

Local recurrence of prostate cancer after radical prostatectomy is at risk to be missed in 68Ga-PSMA-11-PET of PET/CT and PET/MRI: comparison with mpMRI integrated in simultaneous PET/MRI.

PURPOSE: The positron emission tomography (PET) tracer 68Ga-PSMA-11, targeting the prostate-specific membrane antigen (PSMA), is rapidly excreted into the urinary tract. This leads to significant radioactivity in the bladder, which may limit the PET-detection of local recurrence (LR) of prostate cancer (PC) after radical prostatectomy (RP), developing in close proximity to the bladder. Here, we analyze if there is additional value of multi-parametric magnetic resonance imaging (mpMRI) compared to the 68Ga-PSMA-11-PET-component of PET/CT or PET/MRI to detect LR. METHODS: One hundred and nineteen patients with biochemical recurrence after prior RP underwent both hybrid 68Ga-PSMA-11-PET/CTlow-dose (1 h p.i.) and -PET/MRI (2-3 h p.i.) including a mpMRI protocol of the prostatic bed. The comparison of both methods was restricted to the abdomen with focus on LR (McNemar). Bladder-LR distance and recurrence size were measured in axial T2w-TSE. A logistic regression was performed to determine the influence of these variables on detectability in 68Ga-PSMA-11-PET. Standardized-uptake-value (SUVmean) quantification of LR was performed. RESULTS: There were 93/119 patients that had at least one pathologic finding. In addition, 18/119 Patients (15.1%) were diagnosed with a LR in mpMRI of PET/MRI but only nine were PET-positive in PET/CT and PET/MRI. This mismatch was statistically significant (p = 0.004). Detection of LR using the PET-component was significantly influenced by proximity to the bladder (p = 0.028). The PET-pattern of LR-uptake was classified into three types (1): separated from bladder; (2): fuses with bladder, and (3): obliterated by bladder). The size of LRs did not affect PET-detectability (p = 0.84), mean size was 1.7 ± 0.69 cm long axis, 1.2 ± 0.46 cm short-axis. SUVmean in nine men was 8.7 ± 3.7 (PET/CT) and 7.0 ± 4.2 (PET/MRI) but could not be quantified in the remaining nine cases (obliterated by bladder). CONCLUSION: The present study demonstrates additional value of hybrid 68Ga-PSMA-11-PET/MRI by gaining complementary diagnostic information compared to the 68Ga-PSMA-11-PET/CTlow-dose for patients with LR of PC.

Evaluation of an Automated Analysis Tool for Prostate Cancer Prediction Using Multiparametric Magnetic Resonance Imaging.

OBJECTIVE: To evaluate the diagnostic performance of an automated analysis tool for the assessment of prostate cancer based on multiparametric magnetic resonance imaging (mpMRI) of the prostate. METHODS: A fully automated analysis tool was used for a retrospective analysis of mpMRI sets (T2-weighted, T1-weighted dynamic contrast-enhanced, and diffusion-weighted sequences). The software provided a malignancy prediction value for each image pixel, defined as Malignancy Attention Index (MAI) that can be depicted as a colour map overlay on the original images. The malignancy maps were compared to histopathology derived from a combination of MRI-targeted and systematic transperineal MRI/TRUS-fusion biopsies. RESULTS: In total, mpMRI data of 45 patients were evaluated. With a sensitivity of 85.7% (with 95% CI of 65.4-95.0), a specificity of 87.5% (with 95% CI of 69.0-95.7) and a diagnostic accuracy of 86.7% (with 95% CI of 73.8-93.8) for detection of prostate cancer, the automated analysis results corresponded well with the reported diagnostic accuracies by human readers based on the PI-RADS system in the current literature. CONCLUSION: The study revealed comparable diagnostic accuracies for the detection of prostate cancer of a user-independent MAI-based automated analysis tool and PI-RADS-scoring-based human reader analysis of mpMRI. Thus, the analysis tool could serve as a detection support system for less experienced readers. The results of the study also suggest the potential of MAI-based analysis for advanced lesion assessments, such as cancer extent and staging prediction.

Multiparametric Magnetic Resonance Imaging (MRI) and MRI-Transrectal Ultrasound Fusion Biopsy for Index Tumor Detection: Correlation with Radical Prostatectomy Specimen.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) and MRI fusion targeted biopsy (FTB) detect significant prostate cancer (sPCa) more accurately than conventional biopsies alone. OBJECTIVE: To evaluate the detection accuracy of mpMRI and FTB on radical prostatectomy (RP) specimen. DESIGN, SETTING AND PARTICIPANTS: From a cohort of 755 men who underwent transperineal MRI and transrectal ultrasound fusion biopsy under general anesthesia between 2012 and 2014, we retrospectively analyzed 120 consecutive patients who had subsequent RP. All received saturation biopsy (SB) in addition to FTB of lesions with Prostate Imaging Reporting and Data System (PI-RADS) score ≥2. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The index lesion was defined as the lesion with extraprostatic extension, the highest Gleason score (GS), or the largest tumor volume (TV) if GS were the same, in order of priority. GS 3+3 and TV ≥1.3ml or GS ≥3+4 and TV ≥0.55ml were considered sPCa. We assessed the detection accuracy by mpMRI and different biopsy approaches and analyzed lesion agreement between mpMRI and RP specimen. RESULTS AND LIMITATIONS: Overall, 120 index and 71 nonindex lesions were detected. Overall, 107 (89%) index and 51 (72%) nonindex lesions harbored sPCa. MpMRI detected 110 of 120 (92%) index lesions, FTB (two cores per lesion) alone diagnosed 96 of 120 (80%) index lesions, and SB alone diagnosed 110 of 120 (92%) index lesions. Combined SB and FTB detected 115 of 120 (96%) index foci. FTB performed significantly less accurately compared with mpMRI (p=0.02) and the combination for index lesion detection (p=0.002). Combined FTB and SB detected 97% of all sPCa lesions and was superior to mpMRI (85%), FTB (79%), and SB (88%) alone (p<0.001 each). Spearman's rank correlation coefficient for index lesion agreement between mpMRI and RP was 0.87 (p<0.001). Limitations included the retrospective design, multiple operators, and nonblinding of radiologists. CONCLUSIONS: MpMRI identified 92% of index lesions compared with RP histopathology. The combination of FTB and SB was superior to both approaches alone, reliably detecting 97% of sPCa lesions. PATIENT SUMMARY: Multiparametric magnetic resonance imaging detects the index lesion accurately in 9 of 10 patients; however, the combined biopsy approach, while missing less significant cancer, comes at the cost of detecting more insignificant cancer.

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial.

BACKGROUND: Magnetic resonance imaging-guided transurethral ultrasound ablation (MRI-TULSA) is a novel minimally invasive technology for ablating prostate tissue, potentially offering good disease control of localized cancer and low morbidity. OBJECTIVE: To determine the clinical safety and feasibility of MRI-TULSA for whole-gland prostate ablation in a primary treatment setting of localized prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: A single-arm prospective phase 1 study was performed at three tertiary referral centers in Canada, Germany, and the United States. Thirty patients (median age: 69 yr; interquartile range [IQR]: 67-71 yr) with biopsy-proven low-risk (80%) and intermediate-risk (20%) PCa were treated and followed for 12 mo. INTERVENTION: MRI-TULSA treatment was delivered with the therapeutic intent of conservative whole-gland ablation including 3-mm safety margins and 10% residual viable prostate expected around the capsule. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end points were safety (adverse events) and feasibility (technical accuracy and precision of conformal thermal ablation). Exploratory outcomes included quality of life, prostate-specific antigen (PSA), and biopsy at 12 mo. RESULTS AND LIMITATIONS: Median treatment time was 36min (IQR: 26-44) and prostate volume was 44ml (IQR: 38-48). Spatial control of thermal ablation was ±1.3mm on MRI thermometry. Common Terminology Criteria for Adverse Events included hematuria (43% grade [G] 1; 6.7% G2), urinary tract infections (33% G2), acute urinary retention (10% G1; 17% G2), and epididymitis (3.3% G3). There were no rectal injuries. Median pretreatment International Prostate Symptom Score 8 (IQR: 5-13) returned to 6 (IQR: 4-10) at 3 mo (mean change: -2; 95% confidence interval [CI], -4 to 1). Median pretreatment International Index of Erectile Function 13 (IQR: 6-28) recovered to 13 (IQR: 5-25) at 12 mo (mean change: -1; 95% CI, -5 to 3). Median PSA decreased 87% at 1 mo and was stable at 0.8 ng/ml (IQR: 0.6-1.1) to 12 mo. Positive biopsies showed 61% reduction in total cancer length, clinically significant disease in 9 of 29 patients (31%; 95% CI, 15-51), and any disease in 16 of 29 patients (55%; 95% CI, 36-74). CONCLUSIONS: MRI-TULSA was feasible, safe, and technically precise for whole-gland prostate ablation in patients with localized PCa. Phase 1 data are sufficiently compelling to study MRI-TULSA further in a larger prospective trial with reduced safety margins. PATIENT SUMMARY: We used magnetic resonance imaging-guided transurethral ultrasound to heat and ablate the prostate in men with prostate cancer. We showed that the treatment can be targeted within a narrow range (1mm) and has a well-tolerated side effect profile. A larger study is under way. TRIAL REGISTRATION: NCT01686958, DRKS00005311.

Comparison of hybrid (68)Ga-PSMA PET/MRI and (68)Ga-PSMA PET/CT in the evaluation of lymph node and bone metastases of prostate cancer.

PURPOSE: To evaluate the reproducibility of the combination of hybrid PET/MRI and the (68)Ga-PSMA-11 tracer in depicting lymph node (LN) and bone metastases of prostate cancer (PC) in comparison with that of PET/CT. MATERIALS AND METHODS: A retrospective analysis of 26 patients who were subjected to (68)Ga-PSMA PET/CTlow-dose (1 h after injection) followed by PET/MRI (3 h after injection) was performed. MRI sequences included T1-w native, T1-w contrast-enhanced, T2-w fat-saturated and diffusion-weighted sequences (DWIb800). Discordant PET-positive and morphological findings were evaluated. Standardized uptake values (SUV) of PET-positive LNs and bone lesions were quantified and their morphological size and conspicuity determined. RESULTS: Comparing the PET components, the proportion of discordant PSMA-positive suspicious findings was very low (98.5 % of 64 LNs concordant, 100 % of 28 bone lesions concordant). Two PET-positive bone metastases could not be confirmed morphologically using CTlow-dose, but could be confirmed using MRI. In 12 of 20 patients, 47 PET-positive LNs (71.9 %) were smaller than 1 cm in short axis diameter. There were significant linear correlations between PET/MRI SUVs and PET/CT SUVs in the 64 LN metastases (p < 0.0001) and in the 28 osseous metastases (p < 0.0001) for SUVmean and SUVmax, respectively. The LN SUVs were significantly higher on PET/MRI than on PET/CT (p SUVmax < 0.0001; p SUVmean < 0.0001) but there was no significant difference between the bone lesion SUVs (p SUVmax = 0.495; p SUVmean = 0.381). Visibility of LNs was significantly higher on MRI using the T1-w contrast-enhanced fat-saturated sequence (p = 0.013), the T2-w fat-saturated sequence (p < 0.0001) and the DWI sequence (p < 0.0001) compared with CTlow-dose. For bone lesions, only the overall conspicuity was higher on MRI compared with CTlow-dose (p < 0.006). CONCLUSION: Nodal and osseous metastases of PC are accurately and reliably depicted by hybrid PET/MRI using (68)Ga-PSMA-11 with very low discordance compared with PET/CT including PET-positive LNs of normal size. The correlation between PET/MRI SUVs and PET/CT SUVs was linear in LN and bone metastases but was significantly lower in control (non-metastatic) tissue.

The Impact of Magnetic Resonance Imaging on Prediction of Extraprostatic Extension and Prostatectomy Outcome in Patients with Low-, Intermediate- and High-Risk Prostate Cancer: Try to Find a Standard.

PURPOSE: To investigate the value of multiparametric magnetic resonance imaging (mpMRI) and to predict extracapsular extension (ECE), seminal vesicle (SV) infiltration, and a negative surgical margin (SM) status at radical prostatectomy (RP) for different prostate cancer (PC) risk groups. PATIENTS AND METHODS: In the study, 805 men underwent 3 tesla mpMRI without endorectal coil before MRI/transrectal ultrasonography-fusion guided prostate biopsy. MRIs were analyzed using the prostate imaging reporting and data system. The cohort was classified into risk groups according to National Comprehensive Cancer Network (NCCN) criteria. Of 132 men who subsequently underwent RP, pathologic stage and SM status at RP were used as reference. Retrospectively, we investigated a European Society of Urogenital Radiology (ESUR) score for ECE and SV-infiltration. Statistical analyses included regression analyses, receiver operating characteristics (ROC), and Youden Index to assess an ESUR-score cutoff. RESULTS: Area under the curve in ROC curve analyses was 0.82 for ESUR-ECE score to detect pT(3a)-disease and 0.77 for ESUR-SV score for pT(3b). Using a cutoff of 4 for ECE and of 2 for SV, the positive predictive value of the ECE-score for harboring pT(3) was 50.0%, 90.0%, and 88.8% for the low-, intermediate- and high-risk cohort. Retrospectively, the use of the ESUR-ECE score preoperatively would have changed the initial surgical plan, according to NCCN criteria, in 31.1% of patients. In the high-risk subgroup, 9/35 (25.7%) patients were correctly assessed as not harboring pT(3) by imaging (ECE score <4), and would have allowed secure robot-assisted radical prostatectomy and nerve-sparing surgery (NSS). When T3 suspicion on preoperative MRI would be taken into account, intraoperative frozen-sections (IFS) might avoid positive SM in 12/18 high-risk patients and an oncologic secure NSS in 8/20 intermediate-risk patients. CONCLUSION: Prediction of pT(3) disease is crucial to plan NSS and to achieve negative SM in RP. Standardized ECE scoring on mpMRI is an independent predictor of pT(3) and may help to plan RP with oncologic security, even in high-risk patients. In addition, it allows more accurate selection of a subgroup of patients for systematic and MRI-guided IFS.

Evaluation of Diffusion Kurtosis Imaging Versus Standard Diffusion Imaging for Detection and Grading of Peripheral Zone Prostate Cancer.

OBJECTIVES: The purpose of the study was to evaluate and validate diffusion kurtosis imaging (DKI) for detection grading of peripheral zone prostate cancer (PCa) compared with standard diffusion-weighted imaging (DWI) in a cohort of patients with biopsy-proven PCa. MATERIALS AND METHODS: In this retrospective, single-institutional study, 55 patients (age, 67.5 ± 6.9 years; range, 52-84 years) who underwent multiparametric magnetic resonance imaging (MRI) before transperineal magnetic resonance/transrectal ultrasound-guided fusion biopsy were included. Suspicious lesions identified in multiparametric MRI underwent image-guided targeted biopsy procedure using a hybrid magnetic resonance/transrectal ultrasound-guided fusion biopsy system. Multiparametric MRI examinations were performed at 3.0 T using a 16-channel phased array coil. Diffusion kurtosis imaging has been acquired with 9 b values (0, 50, 250, 500, 750, 1000, 1250, 1500, and 2000 s/mm). In patients with histologically proven PCa, a representative tumor region was determined as region of interest (ROI) on axial T2-weighted images in consensus by 2 board-certified radiologists. For quantitative evaluation, ROIs located in malignant and contralateral tumor-free regions were transferred to diffusion-weighted images. Diffusion kurtosis imaging parameters (Dapp and Kapp) and apparent diffusion coefficient (ADC) values of the ROIs in tumor and contralateral remote areas were calculated. Estimation of the kurtosis-derived parameters was performed using a voxel-by-voxel fit followed by an ROI-based averaging and a second fit to ROI-averaged signal values. A subgroup analysis was performed to determine the influence of aggressiveness of PCa using ADC, Dapp, and Kapp. The receiver operating characteristic (ROC) curves were calculated for DKI parameters and ADC values. RESULTS: In the 55 patients, the average prostate-specific antigen level was 12.4 ± 12.6 ng/mL (range, 2.7­75.0 ng/mL), and the median Gleason score was 7 (range, 6­10). Dapp (units, 10(-3) mm(2)/s) was significantly lower in tumor compared with control regions (1.48 ± 0.35 vs 2.00 ± 0.32, P < 0.05), and Kapp was significantly higher (1.01 ± 0.21 vs 0.76 ± 0.14, P < 0.05). Dapp was significantly higher than standard ADC (units, 10(-3) mm(2)/s) both in tumor regions and in controls (1.48 ± 0.35 vs 1.10 ± 0.25 and 2.00 ± 0.32 vs 1.43 ± 0.25, P < 0.05). Neither the ROI-based calculation of the kurtosis parameters nor the application of the noise correction significantly changed the DKI parameter estimation. There was no significant difference for the applied fitting method for DKI-derived parameters considering the differentiation between tumor and control tissue. Subsequent ROC analyses did not reveal a significant difference between DKI and ADC for detection of PCa. Sensitivities derived by Youden J statistics cutoff values ranged from 69% to 91% for DKI parameters; specificities ranged from 71% to 89%. Subgroup analysis for DKI (Dapp, Kapp) and ADC for assessing aggressiveness of PCa found significant difference (P < 0.05) for discrimination between high- and low-grade findings. However, no significant difference could be obtained between standard DWI- and DKI-derived parameters. CONCLUSIONS: The results of this study demonstrated no significant benefit of DKI for detection and grading of PCa as compared with standard ADC in the peripheral zone determined from b values of 0 and 800 s/mm. For clinical routine application, ADC derived from monoexponential fitting of DWI data remains the standard for characterizing peripheral zone cancer of the prostate.

Comparative analysis of transperineal template saturation prostate biopsy versus magnetic resonance imaging targeted biopsy with magnetic resonance imaging-ultrasound fusion guidance.

PURPOSE: Multiparametric magnetic resonance imaging and magnetic resonance imaging targeted biopsy may improve the detection of clinically significant prostate cancer. However, standardized prospective evaluation is limited. MATERIALS AND METHODS: A total of 294 consecutive men with suspicion of prostate cancer (186 primary, 108 repeat biopsies) enrolled in 2013 underwent 3T multiparametric magnetic resonance imaging (T2-weighted, diffusion weighted, dynamic contrast enhanced) without endorectal coil and systematic transperineal cores (median 24) independently of magnetic resonance imaging suspicion and magnetic resonance imaging targeted cores with software registration (median 4). The highest Gleason score from each biopsy method was compared. McNemar's tests were used to evaluate detection rates. Predictors of Gleason score 7 or greater disease were assessed using logistic regression. RESULTS: Overall 150 cancers and 86 Gleason score 7 or greater cancers were diagnosed. Systematic, transperineal biopsy missed 18 Gleason score 7 or greater tumors (20.9%) while targeted biopsy did not detect 11 (12.8%). Targeted biopsy of PI-RADS 2-5 alone overlooked 43.8% of Gleason score 6 tumors. McNemar's tests for detection of Gleason score 7 or greater cancers in both modalities were not statistically significant but showed a trend of superiority for targeted primary biopsies (p=0.08). Sampling efficiency was in favor of magnetic resonance imaging targeted prostate biopsy with 46.0% of targeted biopsy vs 7.5% of systematic, transperineal biopsy cores detecting Gleason score 7 or greater cancers. To diagnose 1 Gleason score 7 or greater cancer, 3.4 targeted and 7.4 systematic biopsies were needed. Limiting biopsy to men with PI-RADS 3-5 would have missed 17 Gleason score 7 or greater tumors (19.8%), demonstrating limited magnetic resonance imaging sensitivity. PI-RADS scores, digital rectal examination findings and prostate specific antigen greater than 20 ng/ml were predictors of Gleason score 7 or greater disease. CONCLUSIONS: Compared to systematic, transperineal biopsy as a reference test, magnetic resonance imaging targeted biopsy alone detected as many Gleason score 7 or greater tumors while simultaneously mitigating the detection of lower grade disease. The gold standard for cancer detection in primary biopsy is a combination of systematic and targeted cores.

Direct comparison of targeted MRI-guided biopsy with systematic transrectal ultrasound-guided biopsy in patients with previous negative prostate biopsies.

OBJECTIVE: To directly compare the diagnostic performance of targeted MRI-guided biopsy (MR-GB) and systematic transrectal ultrasound-guided biopsy (TRUS-GB). METHODS: Thirty-five patients with at least one negative TRUS-GB, persistently elevated or rising prostate-specific antigen and a lesion suspicious for prostate cancer (PC) on multiparametric MRI (mpMRI) scored by using the Prostate Imaging Reporting and Data System (PI-RADS) were included. A median of three targeted biopsies per lesion were obtained and systematic TRUS-GB was performed subsequently by an independent urologist without knowledge of the MRI findings. Definite pathology reports were analyzed for anatomical location and criteria of clinical significance. RESULTS: The tumor detection rate was significantly higher with MR-GB compared with TRUS-GB (16/35, 46% and 8/35, 23%, respectively, p < 0.05). MR-GB detected PC in all patients with positive TRUS-GB. All tumors detected by MR-GB exhibited at least one criterion of clinical significance. PC lesions showed a significantly higher PI-RADS sum score compared with benign lesions. CONCLUSIONS: MR-GB is more effective compared with TRUS-GB in detecting clinically significant PC in men after previous negative TRUS-GB. PI-RADS scores give additional information and could be part of the decision-making process when considering retrial biopsy. Additional systematic biopsy can be omitted in patients undergoing targeted MR-GB.

Comparison of 68Ga-DOTATOC-PET/CT and PET/MRI hybrid systems in patients with cranial meningioma: Initial results.

BACKGROUND: (68)Ga-DOTATOC-PET/CT is a well-established method for detecting and targeting the volume definition of meningiomas prior to radiotherapy. Moreover, there is evidence that this method is able to detect meningiomas with higher sensitivity than the goldstandard MRI. Since the hybrid PET/MRI scanner became available in the past few years, the next stage of development could consequently evolve by evaluating the feasibility of a hybrid PET/MRI scanner using (68)Ga-DOTATOC for detecting meningiomas. METHODS: Fifteen patients received (68)Ga-DOTATOC-PET/CT (0.5 h post injection [p.i.]) followed by PET/MRI 2 hours p.i. Both investigations were analyzed separately and then compared with respect to image quality, detection of intracranial meningiomas, and radiotracer uptake values (RUVs). In addition, ratios between radiotracer uptake in meningiomas and pituitary glands were compared between both PET/CT and PET/MRI. RESULTS: Overall, 33 intracranial meningiomas were detected. All were visible with high contrast in both PET/CT and PET/MRI. (68)Ga-DOTATOC-PET/MRI provided flawless image quality without artefacts. Calculated RUV in meningiomas, as well as the ratios of RUVs in meningiomas to those of pituitary glands, were higher in PET/CT. As a result, meningiomas can be distinguished from pituitary glands better in early images. CONCLUSIONS: (68)Ga-DOTATOC-PET/MRI provided flawless image quality and presented an ideal combination of high sensitivity/specificity (PET) and the best possible morphological visualization of meningiomas (MRI). In addition, excellent detection of meningiomas is already possible at 0.5 hours p.i. Later images do not improve the distinction between pituitary gland and adjacent meningiomas. However, RUVs need to be carefully compared between both imaging modalities.

Volumetry may predict early renal function after nephron sparing surgery in solitary kidney patients.

We investigate the impact of the residual kidney volume measured by tumor volumetry on preoperative imaging in predicting post-operative renal function. Nephron sparing surgery (NSS) in renal cell carcinoma (RCC) is the standard treatment for T1 kidney tumors. Resection of kidney tumors in solidary kidneys needs precise preoperative counseling of patients regarding post-operative renal function. Patients planned for renal tumor surgery who underwent prior nephrectomy on the contralateral side were included. We identified 35 patients in our database that underwent NSS in solitary kidneys and met the inclusion criteria. Tumor volumetry was performed on computer tomography (CT) or magnetic resonance imaging (MRI) with the Medical Imaging Interaction Toolkit (MITK). Clinical and pathological data were assessed. Follow-up data included renal function over 3 years. Mean age was 64 ± 8.1 years. Mean tumor volume on imaging was 27.5 ± 48.6 cc. Mean kidney volume was 195.2 ± 62.8 cc and mean residual kidney volume was 173.4 ± 65.3 cc. We found a correlation between renal function (MDRD) and residual kidney volume on imaging 1-week post-surgery (p = 0.038). Mid- and long-term renal function was not associated with residual kidney volume. In conclusion, renal volumetry may predict early renal function after NSS.

Evolution of repeat prostate biopsy strategies incorporating transperineal and MRI-TRUS fusion techniques.

PURPOSE: To test the hypothesis that MRI-TRUS fusion technique can increase the detection rate of prostate cancer (PC) in patients with previously negative biopsy. METHODS: Patient records of men with persisting suspicion for PC after previous negative biopsy having undergone either extensive transrectal prostate biopsies (MD Anderson protocol; MDA), transperineal saturation (STP) or magnetic resonance imaging (MRI)/transrectal ultrasound (TRUS) fusion transperineal biopsies (MTTP) in three consecutive time intervals were reviewed retrospectively. The respective approach was the standard for the above indication at these episodes. In Cambridge, 70 patients underwent MDA biopsies, 75 STP underwent biopsies and 74 patients underwent MTTP biopsies. In total, 164 MTTP patients with the same indication from Heidelberg were analysed as reference standard. In total, 383 men were included into analysis. Low-grade PC was defined as Gleason score 7 (3 + 4) or lower. RESULTS: Even though MTTP patients had significantly larger prostates, the overall cancer detection rate for PC was the highest in MTTP (24.2 % MDA, 41.3 % STP, 44.5 % MTTP, p = 0.027, Kruskal-Wallis test). The detection rate for clinically relevant high-grade PC was highest in MTTP; however, this did not reach statistical significance compared with MDA (23.5 % MDA, 12.9 % STP, 27.2 % MTTP, p = 0.25, Fischer's exact test). Comparing MTTP between Cambridge and Heidelberg, detection rates did not differ significantly (44.5 vs. 48 %, p = 0.58). There was a higher detection rate of high-grade cancer in Heidelberg. (36.3 vs. 27.2 %, p = 0.04). CONCLUSION: Patients whom are considered for repeat biopsies may benefit from undergoing MRI-targeted TRUS fusion technique due to higher cancer detection rate of significant PC.

Trocar-sharpened needles for image-guided prostate biopsy improve sample quality and performance: first clinical results.

OBJECTIVE: To show the benefit of trocar-sharpened needles for image-guided prostate biopsy compared with standard bevelled needles in patients. MATERIALS AND METHODS: Twenty-four men underwent magnetic resonance imaging-targeted fusion-guided transperineal saturation prostate biopsy, each with half standard bevelled and half trocar-sharpened needles. All taken biopsies were scored (1=worse to 5=best) by one urologist for the following criteria. (1) Accuracy of matching between planned and performed biopsy. (2) Histologic quality of the sample. (3) Elegance, which is the easiness to take the biopsy in proper time, planned position, and best histologic quality. Afterward, the histologic sample quality was evaluated by a blinded pathologist. To show a possible training effect, blinded untrained junior residents performed biopsies in four men (103 cores). RESULTS: Overall, 600 single biopsies were analyzed. The trocar-sharpened needles demonstrated a significantly (p<0.05) better scoring for accuracy and elegance rated by the urologist. The histologic quality scored by the pathologist was superior. Moreover, significantly lower target errors with trocar-sharpened needles were achieved by untrained residents, but not by the experienced user. CONCLUSION: Using trocar-sharpened needles helps urologists to perform targeted prostate biopsy more elegantly and accurately. In addition, the histopathologic sample quality was superior, which may directly improve diagnostic certainty. There is an undeniable training effect in image-guided biopsy and unexperienced users can significantly reduce target errors with trocar-sharpened needles.

Primary central nervous system lymphoma and atypical glioblastoma: multiparametric differentiation by using diffusion-, perfusion-, and susceptibility-weighted MR imaging.

PURPOSE: To compare multiparametric diagnostic performance with diffusion-weighted, dynamic susceptibility-weighted contrast material-enhanced perfusion-weighted, and susceptibility-weighted magnetic resonance (MR) imaging for differentiating primary central nervous system lymphoma (PCNSL) and atypical glioblastoma. MATERIALS AND METHODS: This retrospective study was institutional review board-approved and informed consent was waived. Pretreatment MR imaging was performed in 314 patients with glioblastoma, and a subset of 28 patients with glioblastoma of atypical appearance (solid enhancement with no visible necrosis) was selected. Parameters of diffusion-weighted (apparent diffusion coefficient [ADC]), susceptibility-weighted (intratumoral susceptibility signals [ITSS]), and dynamic susceptibility-weighted contrast-enhanced perfusion-weighted (relative cerebral blood volume [rCBV]) imaging were evaluated in these 28 patients with glioblastoma and 19 immunocompetent patients with PCNSL. A two-sample t test and χ(2) test were used to compare parameters.The diagnostic performance for differentiating PCNSL from glioblastoma was evaluated by using logistic regression analyses with leave-one-out cross validation. RESULTS: Minimum, maximum, and mean ADCs and maximum and mean rCBVs were significantly lower in patients with PCNSL than in those with glioblastoma (P < .01, respectively), whereas mean ADCs and mean rCBVs allowed the best diagnostic performance. Presence of ITSS was significantly lower in patients with PCNSL (32% [six of 19]) than in those with glioblastoma (82% [23 of 28]) (P < .01). Multiparametric assessment of mean ADC, mean rCBV, and presence of ITSS significantly increased the probability for differentiating PCNSL and atypical glioblastoma compared with the evaluation of one or two imaging parameters (P < .01), thereby correctly predicting histologic results in 95% (18 of 19) of patients with PCNSL and 96% (27 of 28) of patients with atypical glioblastoma. CONCLUSION: Combined evaluation of mean ADC, mean rCBV, and presence of ITSS allowed reliable differentiation of PCNSL and atypical glioblastoma in most patients, and these results support an integration of advanced MR imaging techniques for the routine diagnostic workup of patients with these tumors.

Intravoxel incoherent motion (IVIM) diffusion imaging in prostate cancer - what does it add?

OBJECTIVE: To compare 2 previously presented algorithms for extracting parameters from intravoxel incoherent motion (IVIM) studies and investigate them in the context of tissue differentiation. METHODS: Magnetic resonance imaging (MRI) was performed in 23 patients without histologically proven prostate carcinoma (PCa) and 27 patients with histologically proven PCa. Two methods were used to determine IVIM parameters (f, D, D*). Receiver operating characteristic analysis was performed for IVIM parameters and apparent diffusion coefficient for discrimination of prostate tissue. RESULTS: The IVIM parameters showed no significant difference between patients without PCa and normal areas in patients with PCa (r = 0.46-0.99). Results for D were not significantly different for both methods (P = 0.22), whereas f from method 1 was significantly higher than the f from method 2 (P < 0.05). The diffusion parameters D (both methods) and apparent diffusion coefficient could discriminate between tumor and normal areas (receiver operating characteristic analysis, area under the curve, ≥0.90). Additionally, in subgroup analysis, only D was able to discriminate between low- and high-grade PCa. CONCLUSIONS: For tumor detection, IVIM diffusion does not yield a clear added value, but the perfusion-free diffusion constant D may hold potential for improved image-based tumor grading.

Ion Prostate Irradiation (IPI) - a pilot study to establish the safety and feasibility of primary hypofractionated irradiation of the prostate with protons and carbon ions in a raster scan technique.

BACKGROUND: Due to physical characteristics, ions like protons or carbon ions can administer the dose to the target volume more efficiently than photons since the dose can be lowered at the surrounding normal tissue. Radiation biological considerations are based on the assumption that the α/ß value for prostate cancer cells is 1.5 Gy, so that a biologically more effective dose could be administered due to hypofractionation without increasing risks of late effects of bladder (α/ß = 4.0) and rectum (α/ß = 3.9). METHODS/DESIGN: The IPI study is a prospective randomized phase II study exploring the safety and feasibility of primary hypofractionated irradiation of the prostate with protons and carbon ions in a raster scan technique. The study is designed to enroll 92 patients with localized prostate cancer. Primary aim is the assessment of the safety and feasibility of the study treatment on the basis of incidence grade III and IV NCI-CTC-AE (v. 4.02) toxicity and/or the dropout of the patient from the planned therapy due to any reason. Secondary endpoints are PSA-progression free survival (PSA-PFS), overall survival (OS) and quality-of-life (QoL). DISCUSSION: This pilot study aims at the evaluation of the safety and feasibility of hypofractionated irradiation of the prostate with protons and carbon ions in prostate cancer patients in an active beam technique. Additionally, the safety results will be compared with Japanese results recently published for carbon ion irradiation. Due to the missing data of protons in this hypofractionated scheme, an in depth evaluation of the toxicity will be created to gain basic data for a following comparison study with carbon ion irradiation. TRIAL REGISTRATION: Clinical Trial Identifier: NCT01641185 (clinicaltrials.gov).