Timur H. Kuru

Histology core‐specific evaluation of the European Society of Urogenital Radiology (ESUR) standardised scoring system of multiparametric magnetic resonance imaging (mpMRI) of the prostate

To evaluate the Prostate Imaging Reporting and Data System (PIRADS) in multiparametric magnetic resonance imaging (mpMRI) based on single cores and single‐core histology. To calculate positive (PPV) and negative predictive values (NPV) of different modalities of mpMRI.

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

ObjectivesThe 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 MethodsIn 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/mm2). 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. ResultsIn the 55 patients, the average prostate-specific antigen level was 12.4 ± 12.6 ng/mL (range, 2.7–75.0 ng/mL), and the median Gleason score was 7 (range, 6–10). Dapp (units, 10−3 mm2/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 mm2/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. ConclusionsThe 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/mm2. For clinical routine application, ADC derived from monoexponential fitting of DWI data remains the standard for characterizing peripheral zone cancer of the prostate.

Definitions of terms, processes and a minimum dataset for transperineal prostate biopsies: a standardization approach of the Ginsburg Study Group for Enhanced Prostate Diagnostics.

To define terms and processes and agree on a minimum dataset in relation to transperineal prostate biopsy procedures and enhanced prostate diagnostics. To identify the need for further evaluation and establish a collaborative research practice.

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.

Phantom study of a novel stereotactic prostate biopsy system integrating preinterventional magnetic resonance imaging and live ultrasonography fusion.

PURPOSE To determine the targeting error of a novel stereotactic prostate biopsy system that integrates preinterventional MRI with peri-interventional ultrasonography (US) for perineal navigated prostate biopsies. MATERIALS AND METHODS We performed stereotactic biopsies on five prostate phantoms (one CIRS 053-MM and four CIRS 066). Phantom 053-MM incorporates three MRI- and transrectal ultrasonography (TRUS)-visible lesions, while lesions within phantom 066 are only detectable on MRI. In both phantoms, the 0.5 cc volume lesions are placed randomly. The phantoms were examined by 3T-MRI preinterventionally. Then three stereotactic biopsies from one lesion in phantom 053-MM and from all US-invisible lesions in the 066 phantoms were taken under live-fusion imaging guidance. During intervention, a mix of blue ink and gadobutrol was injected into each biopsy channel. Afterward, another 3T-MRI was obtained. These MRI images were then fused again with the intraoperative TRUS data. Thus, the targeting error (TE) between the planned and performed biopsy cores could be measured. In addition, the procedural targeting error (PTE) between the virtually planned biopsy trajectory and the manually registered three-dimensional needle position of every single biopsy core taken was calculated. RESULTS The overall TE of the 39 biopsy cores taken was 0.83 mm (standard deviation [SD]: 0.48 mm) with the highest TE in the sagittal plane (1.09 ± 0.54 mm), followed by the coronal (0.72 ± 0.43 mm) and axial (0.69 ± 0.34 mm) planes. The procedural TE, which is provided intraoperatively, was 0.26 mm on average (SD: 0.46 mm). Comparing PTE and TE, there was no statistically significant difference (P=0.39). CONCLUSION The TE of stereotactic biopsies using our novel perineal prostate biopsy system is below 1 mm and can be estimated in vivo by the automatically calculated procedural TE. Thus, stereotactic prostate biopsies guided by the combination of MRI and US allow effective and precise examination of MRI lesions.

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.

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.

The role of salvage extended lymph node dissection in patients with rising PSA and PET/CT scan detected nodal recurrence of prostate cancer

BACKGROUND:Non-prostatic bed recurrence of prostate cancer (PCa) is usually treated with androgen deprivation therapy (ADT). We analyzed the impact of salvage extended lymph node dissection (sLND) on cancer control in patients with rising PSA and lymph node (LN) metastases.METHODS:Between 2009 and 2016 we performed sLND in 87 patients with biochemical recurrence (BCR) and positive LNs on 18FEC and 68Ga-PSMA positron emission tomography/X-ray computer tomography (PET/CT) after primary treatment (PT) of PCa. Intra- and postoperative complications according to Clavien-Dindo were assessed and the rates of biochemical response (BR), BCR-free and clinical recurrence (CR)-free survival, as well as time to initiation of systemic treatment were evaluated.RESULTS:Mean age of patients and mean PSA at sLND was 66.7 years (46–80 years) and 2.63 ng ml−1 (1.27–3.75 ng ml−1), respectively. With 87.4% radical prostatectomy (RP) was the most common PT. In all, 57.9% of patients additionally underwent adjuvant/salvage radiation therapy (RT) and 18.4% received ADT before sLND. Complete BR (cBR) was diagnosed in 27.5% of patients and incomplete BR in 40.6%. In total, 62.2% of patients remained without ADT at follow-up. With a median follow-up of 21 months (1–75 months), the cancer-specific mortality rate was 3.7%. The 3-year BCR-free, systemic therapy-free and CR-free survival rates for patients with cBR were 69.3%, 77.0% and 75%, respectively.CONCLUSIONS:sLND can be performed without significant complications and achieves an immediate BR, thus allowing a significant postponement of systemic therapy in selected patients with BCR and nodal recurrence of PCa. Therefore, sLND following 68Ga-PSMA PET/CT should be considered as part of a multimodal diagnostic and treatment concept for selective patients.

Prospective Multicenter Phase II Study on Focal Therapy (Hemiablation) of the Prostate with High Intensity Focused Ultrasound

Purpose: We evaluated focal therapy with high intensity focused ultrasound hemiablation in a prospective trial. Materials and Methods: We performed a prospective, multicenter, single arm study in patients with unilateral low/intermediate risk prostate cancer who were treated from April 2013 through March 2016 in Germany in AUO (Arbeitsgemeinschaft Urologische Onkologie) Study Protocol AP 68/11. Unilateral prostate cancer was assessed by transrectal ultrasound guided biopsy and multiparametric magnetic resonance imaging. Hemiablation was done using the Ablatherm® or the Focal One® device. The oncologic outcome was assessed by the salvage treatment rate, multiparametric magnetic resonance imaging and rebiopsy at 12 months. Functional outcome, quality of life, anxiety and depression were measured by validated questionnaires at baseline and every 3 months. Results: Of the 54 recruited patients 51 completed 12‐month or greater visits. Mean ± SD followup was 17.4 ± 4.5 months. Mean prostate specific antigen decreased from 6.2 ± 2.0 to 2.9 ± 1.9 ng/ml at 12 months (p <0.001). Biopsy at 12 months was positive for any prostate cancer and for clinically significant prostate cancer in 13 (26.5%) and 4 (8.2%) of the 49 patients, respectively. Posttreatment multiparametric magnetic resonance imaging had limited 25% sensitivity for clinically significant prostate cancer. Ten patients (19.6%) underwent salvage treatment. Potency was maintained in 21 of the 30 men who were potent preoperatively. There was no increase in incontinence. Quality of life, anxiety and depression did not change postoperatively. The study was limited by a short followup and the lack of a control arm. Conclusions: Focal therapy hemiablation is safe with little alteration of functional outcome. The oncologic outcome is acceptable on short‐term followup. Followup multiparametric magnetic resonance imaging performed poorly and should not replace repeat biopsy. Focal therapy has no impact on posttreatment anxiety and depression.

Initial Experience with Temsirolimus in 2nd-, 3rd- and 4th-Line Therapy for Metastatic Renal Cell Cancer: Good Clinical Response

Purpose: To report our experience with temsirolimus in 2nd-, 3rd- and 4th-line therapy for patients with metastatic renal cell carcinoma (mRCC). Patients and Methods: In our prospectively maintained tumor registry, we identified 6 mRCC patients with temsirolimus in >1st-line systemic therapy. Patients were followed by weekly clinical and laboratory examination during admission of temsirolimus. Re-staging with chest CT and abdominal MRI was performed every 3 months. Results: We observed excellent response rates. Progression-free survival (PFS) ranged from 6 to 40 months with a median of 15 months. Treatment was generally well tolerated. However, pneumonitis was observed in 4 of 6 patients. Drug-related pneumonitis led to severe dyspnea, with the result that treatment with temsirolimus had to be interrupted for a short period of time in 2 patients and discontinued in 1 patient. Conclusions: Temsirolimus proved to be a very good treatment option in 2nd- to 4th-line therapy with excellent response rates and manageable side effects. The incidence of pneumonitis must not be underestimated.