Comparative proteome and serum analysis identified FSCN1 as a marker of abiraterone resistance in castration-resistant prostate cancer.

BACKGROUND: Abiraterone (Abi) is an androgen receptor signaling inhibitor that significantly improves patients' life expectancy in metastatic prostate cancer (PCa). Despite its beneficial effects, many patients have baseline or acquired resistance against Abi. The aim of this study was to identify predictive serum biomarkers for Abi treatment. METHODS: We performed a comparative proteome analysis on three Abi sensitive (LNCaPabl, LAPC4, DuCaP) and resistant (LNCaPabl-Abi, LAPC4-Abi, DuCaP-Abi) PCa cell lines using liquid chromatography tandem mass spectrometry (LC-MS/MS) technique. Two bioinformatic selection workflows were applied to select the most promising candidate serum markers. Serum levels of selected proteins were assessed in samples of 100 Abi-treated patients with metastatic castration-resistant disease (mCRPC) using ELISA. Moreover, FSCN1 serum concentrations were measured in samples of 69 Docetaxel (Doc) treated mCRPC patients. RESULTS: Our proteome analysis identified 68 significantly, at least two-fold upregulated proteins in Abi resistant cells. Using two filtering workflows four proteins (AMACR, KLK2, FSCN1 and CTAG1A) were selected for ELISA analyses. We found high baseline FSCN1 serum levels to be significantly associated with poor survival in Abi-treated mCRPC patients. Moreover, the multivariable analysis revealed that higher ECOG status (>1) and high baseline FSCN1 serum levels (>10.22 ng/ml by ROC cut-off) were independently associated with worse survival in Abi-treated patients (p < 0.001 and p = 0.021, respectively). In contrast, no association was found between serum FSCN1 concentrations and overall survival in Doc-treated patients. CONCLUSIONS: Our analysis identified baseline FSCN1 serum levels to be independently associated with poor survival of Abi-treated, but not Doc-treated mCRPC patients, suggesting a therapy specific prognostic value for FSCN1.

Proteome profiling of enzalutamide-resistant cell lines and serum analysis identified ALCAM as marker of resistance in castration-resistant prostate cancer.

Enzalutamide (ENZA) is a frequently used therapy in metastatic castration-resistant prostate cancer (mCRPC). Baseline or acquired resistance to ENZA have been observed, but the molecular mechanisms of resistance are poorly understood. We aimed to identify proteins involved in ENZA resistance and to find therapy-predictive serum markers. We performed comparative proteome analyses on ENZA-sensitive parental (LAPC4, DuCaP) and -resistant prostate cancer cell lines (LAPC4-ENZA, DuCaP-ENZA) using liquid chromatography tandem mass spectrometry (LC-MS/MS). The top four most promising candidate markers were selected using bioinformatic approaches. Serum concentrations of selected markers (ALCAM, AGR2, NDRG1, IDH1) were measured in pretreatment samples of 72 ENZA-treated mCRPC patients using ELISA. In addition, ALCAM serum levels were measured in 101 Abiraterone (ABI) and 100 Docetaxel (DOC)-treated mCRPC patients' baseline samples. Results were correlated with clinical and follow-up data. The functional role of ALCAM in ENZA resistance was assessed in vitro using siRNA. Our proteome analyses revealed 731 significantly differentially abundant proteins between ENZA-sensitive and -resistant cells and our filtering methods identified four biomarker candidates. Serum analyses of these proteins revealed only ALCAM to be associated with poor patient survival. Furthermore, higher baseline ALCAM levels were associated with poor survival in ABI- but not in DOC-treated patients. In LAPC4-ENZA resistant cells, ALCAM silencing by siRNA knockdown resulted in significantly enhanced ENZA sensitivity. Our analyses revealed that ALCAM serum levels may help to identify ENZA- and ABI-resistant patients and may thereby help to optimize future clinical decision-making. Our functional analyses suggest the possible involvement of ALCAM in ENZA resistance.

Comparative proteome analysis identified CD44 as a possible serum marker for docetaxel resistance in castration-resistant prostate cancer.

Baseline or acquired resistance to docetaxel (DOC) represents a significant risk for patients with metastatic prostate cancer (PC). In the last years, novel therapy regimens have been approved providing reasonable alternatives for DOC-resistant patients making prediction of DOC resistance of great clinical importance. We aimed to identify serum biomarkers, which are able to select patients who will not benefit from DOC treatment. DOC-resistant PC3-DR and DU145-DR sublines and their sensitive parental cell lines (DU145, PC3) were comparatively analyzed using liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS). Results were filtered using bioinformatics approaches to identify promising serum biomarkers. Serum levels of five proteins were determined in serum samples of 66 DOC-treated metastatic castration-resistant PC patients (mCRPC) using ELISA. Results were correlated with clinicopathological and survival data. CD44 was subjected to further functional cell culture analyses. We found at least 177 two-fold significantly overexpressed proteins in DOC-resistant cell lines. Our bioinformatics method suggested 11/177 proteins to be secreted into the serum. We determined serum levels of five (CD44, MET, GSN, IL13RA2 and LNPEP) proteins in serum samples of DOC-treated patients and found high CD44 serum levels to be independently associated with poor overall survival (p = 0.001). In accordance, silencing of CD44 in DU145-DR cells resulted in re-sensitization to DOC. In conclusion, high serum CD44 levels may help identify DOC-resistant patients and may thereby help optimize clinical decision-making regarding type and timing of therapy for mCRPC patients. In addition, our in vitro results imply the possible functional involvement of CD44 in DOC resistance.

Multiple Docetaxel Retreatments Without Prednisone for Metastatic Castration-Resistant Prostate Cancer in the Docetaxel-Only Era: Effects on PSA Kinetics and Survival.

INTRODUCTION: This study aimed to assess the effects of multiple docetaxel (DOC) treatments on prostate-specific antigen (PSA) kinetics and survival among patients with metastatic castration-resistant prostate cancer (mCRPC) who were sensitive to first-line DOC and received no other life-prolonging agents. To eliminate the effect of cortisone on serum PSA, only patients who were treated without prednisone were included. METHODS: This IRB-approved retrospective study evaluated 52 patients with mCRPC who were retreated using DOC after first-line DOC (without prednisone in both cases), based on a PSA response of > 50% and no radiographic progression. Twenty-three PSA-based factors, including static and kinetic PSA measures, were evaluate for their ability to predict overall survival (OS) RESULTS: The patients received 688 cycles of DOC in 143 series, including 91 courses of retreatments (1 cycle: 28 patients, 2 cycles: 14 patients, 3 cycles: 8 patients, 4 cycles: 1 patient, and 7 cycles: 1 patient). The median overall number of cycles per patient was 12 (range: 7-31). The median durations of the first, second, and third holidays were 18 weeks (6-60 weeks), 16 weeks (3-44 weeks), and 17 weeks (8-51 weeks), respectively. The median OSs were 22 months (10.5-70 months) after the first DOC treatment and 14 months (3-65 months) after the second DOC treatment. The > 50% PSA decline rate was 48% after retreatment. Short treatment holidays (< 3 months) were associated with shortened OS (p = 0.01). In the multivariate analysis, a 25% PSA increase over the nadir was the strongest predictor of survival (HR: 3.20, 95% CI: 1.47-6.99, p = 0.003). CONCLUSIONS: DOC retreatment without prednisone had anti-tumor activity in a considerable proportion of mCRPC cases that were initially sensitive to first-line DOC. A 25% PSA increase over the nadir might predict acquired DOC resistance.

The long-term outcome of urethrotomy for primary urethral strictures: a population-based analysis.

OBJECTIVE: To determine the long-term outcome of endoscopic urethrotomy for primary urethral strictures based on a population-based approach. PATIENTS AND METHODS: We analysed a nationwide database of all patients with urethral stricture disease who underwent endoscopic urethrotomy as a primary intervention between January 2006 and December 2007. All patients were followed individually for 7-9 years. Frequencies and types of surgical re-interventions were documented. Repeat surgical interventions were stratified into three treatment types: urethrotomy, urethroplasty, and end-to-end urethral anastomosis. RESULTS: A total of 1203 men underwent urethrotomy during the index period. The median (SD, range) patient age was 63 (15.7, 20-85) years. A total of 136 patients (11%) died during follow-up. Within the follow-up period, 932 patients (78%) received no further surgical re-intervention for recurrent disease, and 176 patients (14.6%) required one, 53 (4.5%) two, and 41 (3.4%) three or more procedures. The mean number of re-interventions was 1.5/patient and the lowest re-intervention rate was in patients aged ≥80 years (13.9%). In 236 cases (68%) at least one repeat urethrotomy was performed. An open reconstruction was performed in 87 cases (32%), with urethroplasty in 21 patients (24%), and end-to-end anastomosis in 66 patients (76%). The mean interval until re-intervention was 29.5 months. CONCLUSIONS: This long-term population-based study suggests that the invasive re-treatment rate in men following initial urethrotomy is 22% within 8 years and lowest in the advanced age cohort.

Comprehensive analysis of serum chromogranin A and neuron-specific enolase levels in localized and castration-resistant prostate cancer.

OBJECTIVES: To assess chromogranin A (CGA) and neuron-specific enolase (NSE) levels and changes in these at different stages of prostatic adenocarcinoma (PCA). METHODS: Overall, 1095 serum samples from 395 patients, divided into three treatment groups, were analysed; the radical prostatectomy (RP) cohort (n = 157) included patients with clinically localized PCA, while the docetaxel (DOC) and the abiraterone (ABI)/enzalutamide (ENZA) cohorts included 95 and 143 patients, respectively, with metastatic castration-resistant prostate cancer. CGA, NSE and total PSA levels were measured using the KRYPTOR method. RESULTS: Baseline CGA and NSE levels were higher in castration-resistant (DOC and ABI/ENZA cohorts) than in hormone-naïve, clinically localized PCA (P < 0.001). High baseline CGA levels were independently associated with poor overall survival in both the DOC and the ABI/ENZA cohorts, with a stronger association in the ABI/ENZA cohort. In the ABI/ENZA cohort, a > 50% CGA increase at 3 months was associated with poor survival, especially in patients with high baseline CGA levels. CONCLUSIONS: The two- to threefold higher neuroendocrine marker levels in castration-resistant compared to hormone-naïve PCA support the presence of neuroendocrine transdifferentiation under androgen deprivation therapy. Our results showed patients with high baseline CGA levels who experienced a further CGA increase during ABI and ENZA treatment had the poorest prognosis. Serum CGA levels could help in tailoring and monitoring therapy in advanced PCA.

The Feasibility, Technique, and Medium-Term Follow-Up of Laparoscopic Transvesical Diverticulectomy.

BACKGROUND: To present our experience and results with the transvesical laparoscopic diverticulectomy, developed by Pansadoro et al. [BJU Int. 2009;103(3):412-24], as treatment of symptomatic bladder diverticula, with a medium-term follow-up. METHODS: Between June 2010 and July 2018, we successfully operated 15 patients (13 male/2 female), aged 32-85 years (mean age 61 years) in 2 centers in Austria, using the aforementioned technique. RESULTS: The median operative time was 297 min (range 83-488 min), and the blood loss was minimal. The median diameter of the diverticula was 94 mm (range 40-110 mm). The transurethral catheter was removed in most patients on day 7 (range 1-26 days), and cystography was performed before catheter removal. Patients were discharged on the ninth postoperative day (range 4-18 days). One case had a Clavien-Dindo grade IIIb complication (ureter injury), and 2 cases had a grade IIIa complication (nephrostomy drainage). After a median follow-up of 19 months, no recurrences were observed. CONCLUSION: The laparoscopic, transvesical diverticulectomy is a feasible and valuable procedure with good outcomes. To avoid complications, the ureter needs to be spared meticulously.

LithoVue™ for renal stone therapy - a perfect fit for high volume academic centers; a retrospective evaluation of 108 cases.

BACKGROUND: Over the last few years the number of flexible ureterorenoscopies, used for renal stone treatment, has risen steadily. This was associated with an increase in costs for maintenance and repair of the fragile ureterorenoscopes used. To overcome this problem single-use devices have been introduced to the market. The aim of this study was to assess surgical outcome and workability for LithoVue™, a single-use flexible ureterorenoscope. METHODS: We retrospectively analyzed all flexible ureterorenoscopies performed at our department between January and October 2017. We included a total of 108 interventions for renal stone therapy, all performed using the single-use device LithoVue™. We assessed patients' characteristics including stone size, count and location. We evaluated the surgical outcome, analyzing stone-free rates, reintervention rates, complication rates, as well as surgery time. Learning curve for single-use ureterorenoscopes was evaluated by comparing the surgical outcome between residents and consultants. RESULTS: The average time needed per intervention was 52,31 min ± 28,11. In 77 out of 108 (71,30%) patients we were able to remove all stones by a single intervention. In 8 patients (7,41%) intra- or postoperative complications occurred, none of which was graded higher than Clavien-Dindo III B. We did not find any statistical differences comparing the surgical outcome between residents and consultants. No technical difficulties occurred during surgery. CONCLUSION: Single-use flexible ureterorenoscopes provide decent working properties resulting in good surgical outcome. Furthermore, they are proven to be easy to handle even for unexperienced surgeons, making them a feasible choice for high volume academic centers.

Bone Scintigraphy in Staging of Newly Diagnosed Prostate Cancer in Regard of Different Risk Groups.

OBJECTIVES: Prostate cancer (PC) is the most common cancer in men over 50 years of age. Bone scintigraphy is still performed in many institutions at the time of primary diagnosis. We aimed to evaluate the role of bone scan in the primary staging of PC in regard of different risk groups. METHODS: A retrospective analysis of bone scans in 296 patients (mean age 64±6 y) acquired at the time of primary diagnosis was performed in our institution. The median prostate specific antigen (PSA) was 6.73 ng/ml, all patients had a Gleason score of >5. RESULTS: Only 11/296 patients had a positive bone scan, 1 being in the intermediate risk group, 10 in the high-risk group and none in the low-risk group according to D'Amico classification. CONCLUSION: Our results support the few published studies that less than 10% of patients with newly diagnosed PC by biopsy would develop bone metastasis, all in the intermediate or high-risk groups. Therefore, a staging by bone scan can only be recommended in patients with intermediate or high-risk, or symptomatic patients only.

Claros System: A Rapid Microfluidics-Based Point-of-Care System for Quantitative Prostate Specific Antigen Analysis from Finger-Stick Blood.

INTRODUCTION: Determination of circulating prostate specific antigen (PSA) is commonly used in the diagnosis and treatment monitoring of prostate cancer [1]. Presently, PSA testing is performed in centralized laboratories, which is associated with prolonged time between venipuncture and the PSA value being available. In this prospective study, we present a new and rapid test system for the quantitative determination of PSA levels from finger-stick blood. METHODS: The Claros1® analyzer is a rapid microfluidics-based point-of-care system for quantitative PSA analysis from 10-µl finger-stick blood that requires only 10 min for testing. Total PSA concentrations by the Claros system in 100 consecutive asymptomatic men (median age 57 years, range 44-81 years) were compared with two commercially available, commonly used PSA assays (Abbott and Elecsys by Roche) performed by a reference laboratory. RESULTS: Eighty-six percent of finger-stick blood-borne probes from 100 men were evaluable for PSA testing by the Claros1® analyzer system. In 13/14 cases the expiry date of the microfluid cassettes of the Claros system was exceeded and one blood puncture was performed inadequately. The correlations between the Claros results and OPKO-Abbott and OPKO-Roche assay results were high, with R2 values of 0.982 and 0.985, respectively. The R2 value for the Roche-Abbott correlation was 0.991 with a slope value of 1.160. Prostate cancer was diagnosed in seven cases, with a median PSA of 1.8 ng/ml in the Claros group compared to 1.75 ng/ml and 2.1 ng/ml in the Abbott and Roche groups, respectively. CONCLUSION: The Claros1® PSA assay combines the advantages of rapid, accurate detection with a low required sample volume, allowing the analysis to be performed using finger-stick blood. Provided that further analysis proves the reproducibility of the test, it may help to reduce the number of office visits, thus decreasing costs to the health care system.

Clinical results of a dorsally positioned hydraulic ID-sling in male patients with post-prostatectomy-incontinence.

PURPOSE: To prospectively evaluate the effectiveness and safety of and the long-term experience with a re-adjustable hydraulic sling (ID-sling) device positioned dorsally to the urethra for the treatment of male post-prostatectomy incontinence (PPI). MATERIALS AND METHODS: Between September 2007 and November 2009 13 patients with persisting SUI were treated consecutively with an ID-sling™ in two European tertiary centers by a single surgeon. Physical examinations and standardized questionnaires (ICIQ-SF + VAS), pad tests, and 24-h pad number counts were performed at baseline and during follow-up. RESULTS: The implantation of the hydraulic cuff was uncomplicated in all cases. The ICIQ-SF score diminished from a preoperative mean value of 18 to a mean of five postoperatively. One patient remained completely dry with normal micturition. All patients demonstrated a mild improvement at primary filling but did not show any significant improvement after the second or any subsequent filling. In total, 1/13 (7.7%) patients were completely dry and 5/13 (38.4%) showed improved continence. In 6/13 (46.2%) patients, satisfactory continence results according to subjective criteria, were not achieved. Subsequently, artificial urinary sphincter (AUS) implantation was offered to one patient (7.7%) after 12 months and to ten patients (76,9%) after 24 months. CONCLUSIONS: The implantation of a dorsally placed hydraulic sling is a not yet standardized and complex procedure, even for the experienced surgeon. To date, this implantation method is not an alternative to other devices. An improved sling design is necessary to simplify the surgical procedure and to improve long-term stability.

The Role of YKL-40 in Predicting Resistance to Docetaxel Chemotherapy in Prostate Cancer.

INTRODUCTION: High baseline YKL-40 serum levels are associated with drug resistance in several solid tumours. However, their role in predicting docetaxel (DOC) resistance in prostate cancer (PCa) is unknown. METHODS: Pre-treatment serum levels of YKL-40 and prostate-specific antigen (PSA) were analyzed in 109 castration-resistant prostate cancer patients who underwent DOC-therapy. Responsive patients were retreated by repeated series of DOC. Results were compared with the clinical parameters as well as overall (OS) and disease-specific survival (DSS). RESULTS: YKL-40 but not PSA serum levels were significantly higher in patients with baseline resistance to DOC (p = 0.035). Higher YKL-40 and PSA levels were detected in patients with bone metastasis (p = 0.032; p = 0.010) and in those who were not pre-treated with radical prostatectomy (p = 0.011, p = 0.008). High YKL-40 levels were associated with shorter OS (p = 0.037) and DSS (p = 0.017) in patients who received DOC in the first-line setting. In multivariable analysis, ECOG performance status (p = 0.009), presence of any metastases (p = 0.016) and high PSA levels (p = 0.005) remained independent predictors for DSS. CONCLUSIONS: YKL-40 may help to identify patients with baseline resistance to DOC and therefore may help to optimize treatment decisions. In accordance, high pre-treatment YKL-40 serum levels were associated with shorter OS and DSS in patients who received DOC as first-line therapy.

Matrix metalloproteinase 7, soluble Fas and Fas ligand serum levels for predicting docetaxel resistance and survival in castration-resistant prostate cancer.

OBJECTIVE: To assess the predictive value of pre-chemotherapy matrix metalloproteinase 7 (MMP-7), soluble Fas (sFas) and Fas ligand (FasL) serum levels, as well as their changes during therapy. PATIENTS AND METHODS: Serum levels of MMP-7, Fas and FasL were determined by ELISA in 96 patients with castration-resistant prostate cancer (CRPC): 21 docetaxel-resistant patients who received one single series and 75 docetaxel-sensitive patients who received repeated series of docetaxel. In addition to the 96 pretreatment serum samples, 987 sera collected during chemotherapy were also analysed. RESULTS: Higher pretreatment serum MMP-7, sFas and prostate-specific antigen (PSA) levels were significantly associated with both docetaxel resistance (P = 0.007, P = 0.001, P < 0.001, respectively) and shorter cancer-specific survival (P < 0.001, P = 0.041, P < 0.001, respectively). High MMP-7 level remained an independent predictor of both docetaxel resistance (hazard ratio [HR] 2.298, 95% confidence interval [CI]: 1.354-3.899; P = 0.002) and poor cancer-specific survival (HR 2.11, 95% CI: 1.36-3.30; P = 0.001) in multivariable analyses. Greater increase in MMP-7 levels in the second treatment holiday and greater increase in PSA levels in the first and second treatment holidays were predictive of survival. CONCLUSIONS: Pretreatment serum MMP-7 levels may help to select patients with CRPC who are likely to benefit from docetaxel chemotherapy. Furthermore, MMP-7 levels alone or in combination with PSA levels could be used for therapy monitoring. Correlative studies embedded in clinical trials are necessary to validate these biomarkers for clinical decision-making.

Application of Cu-64 NODAGA-PSMA PET in Prostate Cancer.

INTRODUCTION: The high diagnostic potential of 64Cu-PSMA PET-CT imaging was clinically investigated in prostate cancer patients with recurrent disease and in the primary staging of selected patients with advanced local disease. The aim of our study is to assess the uptake behavior in the clinical setting of 64Copper Prostate-Specific Membrane Antigen (64Cu PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) in prostate cancer. METHODS: A retrospective study was performed in 23 patients with intermediate, high risk and progressive disease at primary staging of prostate cancer. All patients underwent 64Cu-PSMA PET. Overall, 250 MBq (4 MBq per kg bodyweight, range 230-290 MBq) of 64Cu-NODAGA PSMA was intravenously applied. PET images were performed 30 min (pelvis and abdomen) and 1-2 h post-injection (skull base to mid-thigh). Maximum standardized uptake values (SUVmax) were measured in the organs with high physiological uptake such as liver and kidney, and, additionally, background activity was measured in the gluteal area and in suspected tumor lesions using a HERMES workstation. RESULTS: PSMA uptake was detected in prostate bed in nine patients, in six patients in distant metastases (bone, lung and liver) and in nine patients in lymph nodes. Of 23 patients, 5 (20.8%) did not show any focal pathological uptake in the whole body. The number of sites (prostate bed, lymph nodes, distant metastases) with positive PSMA uptake was significantly associated with PSA values before imaging (P = 0.0032). The 64Cu PSMA uptake increased significantly from 30 min to 1-3 h post-injection (Wilcoxon signed rank test, P = 0.002). CONCLUSIONS: 64Cu NODAGA-PSMA PET is a promising imaging tool in the detection of residual disease in patients with recurrent or primary progressive prostate cancer. Furthermore, the increased tracer uptake over time indicates in vivo stability of the diagnostic radiopharmaceutical.

Circulating syndecan-1 is associated with chemotherapy-resistance in castration-resistant prostate cancer.

OBJECTIVES: Docetaxel chemotherapy is a standard treatment for castration-resistant prostate cancer (CRPC). Rapidly expanding treatment options for CRPC provide reasonable alternatives for those who are resistant to docetaxel. Therefore, prediction of docetaxel resistance has become of great clinical importance. Syndecan-1 (SDC1) has been currently shown to be involved in chemotherapy resistance in various malignancies including prostate cancer. The predicting value of serum SDC1 level has not been evaluated yet. PATIENTS AND METHODS: We assessed the baseline levels of SDC1 in serum samples of 75 patients with CRPC who received docetaxel therapy until the appearance of therapy resistance. In one patient who was treated with three treatment series, we assessed also 6 additional serum samples collected during a 1-year treatment period. Serum SDC1 levels were correlated with clinical outcomes as well as with serum levels of MMP7. RESULTS: Pretreatment SDC1 serum levels were not associated with patients' age, the presence of bone or visceral metastases. In univariable analyses, patients' performance status, the presence of bone or visceral metastases, high pretreatment prostate specific antigen and SDC1 levels were significantly associated with cancer-specific survival. In multivariable analysis patients' performance status (P = 0.005), presence of bone or visceral metastases (P = 0.013) and high SDC1 level (P = 0.045) remained independent predictors of patients' survival. In the patient with available follow-up samples serum SDC1 level increased from 50 to 300ng/ml at radiographic progression. Serum concentrations of SDC1 were correlated with those of MMP7 (r = 0.420, P = 0.006). CONCLUSIONS: Our present results together with currently published data suggest a role for SDC1 shedding in chemotherapy resistance. Determination of serum SDC1 may contribute to the prediction of docetaxel resistance and therefore may help to facilitate clinical decision-making regarding the type and timing of therapy for patients with CRPC.

In-bore 3.0-T Magnetic Resonance Imaging-guided Transrectal Targeted Prostate Biopsy in a Repeat Biopsy Population: Diagnostic Performance, Complications, and Learning Curve.

OBJECTIVE: To evaluate the diagnostic performance and complication rate of the in-bore magnetic resonance imaging-guided transrectal targeted prostate biopsy (MRGB) in a repeat biopsy population on the basis of a nearly 4-year learning curve (2014-2017). MATERIALS AND METHODS: A total of 142 consecutive males with previous biopsies and persistent suspicion of prostate cancer (PCa) due to high prostate-specific antigen level initially underwent MRGB in the case of prostate imaging reporting and data system (PI-RADS) 3-5 lesions. Cancer detection rate (CDR), number and length of cores, biopsy time, operator experience, complications, and prediction of clinically significant (cs) PCa (Gleason score ≥7) were investigated. RESULTS: PCa was found in 57% of patients. CDR in PI-RADS 3, 4, and 5 lesions were 46%, 52%, and 74%, respectively. csPCa was found in 9%, 25%, and 48% of patients. In univariate analysis the PI-RADS score (P = .0067) was a significant predictor of csPCa. In the multivariate logistic regression, age (P = .0007), number of previous biopsies (P = .0236), and prostate-specific antigen density (P = .0250) were significant predictors of csPCa. Location and size of the index lesion, number and length of cores obtained, and operator experience did not affect CDR. Concerning learning curve, biopsy time and number of cores obtained improved significantly after 10 procedures. Complications requiring medical intervention were seen in 6% (infections 2%). CONCLUSION: In a re-biopsy setting the MRGB showed sufficient diagnostic performance in detecting csPCa in PI-RADS 3-5 lesions, with low complication rate. The skill of performing biopsy is quickly acquired, and location of index lesion did not have an impact on CDR.

Malignancy rates and diagnostic performance of the Bosniak classification for the diagnosis of cystic renal lesions in computed tomography - a systematic review and meta-analysis.

OBJECTIVE: To systematically review the literature on the Bosniak classification system in CT to determine its diagnostic performance to diagnose malignant cystic lesions and the prevalence of malignancy in Bosniak categories. METHODS: A predefined database search was performed from 1 January 1986 to 18 January 2016. Two independent reviewers extracted data on malignancy rates in Bosniak categories and several covariates using predefined criteria. Study quality was assessed using QUADAS-2. Meta-analysis included data pooling, subgroup analyses, meta-regression and investigation of publication bias. RESULTS: A total of 35 studies, which included 2,578 lesions, were investigated. Data on observer experience, inter-observer variation and technical CT standards were insufficiently reported. The pooled rate of malignancy increased from Bosniak I (3.2 %, 95 % CI 0-6.8, I2 = 5 %) to Bosniak II (6 %, 95 % CI 2.7-9.3, I2 = 32 %), IIF (6.7 %, 95 % CI 5-8.4, I2 = 0 %), III (55.1 %, 95 % CI 45.7-64.5, I2 = 89 %) and IV (91 %, 95 % CI 87.7-94.2, I2 = 36). Several study design-related influences on malignancy rates and subsequent diagnostic performance indices were identified. CONCLUSION: The Bosniak classification is an accurate tool with which to stratify the risk of malignancy in renal cystic lesions. KEY POINTS: • The Bosniak classification can accurately rule out malignancy. • Specificity remains moderate at 74 % (95 % CI 64-82). • Follow-up examinations should be considered in Bosniak IIF and Bosniak II cysts. • Data on the influence of reader experience and inter-reader variability are insufficient. • Technical CT standards and publication year did not influence diagnostic performance.

Inter-observer variation and diagnostic efficacy of apparent diffusion coefficient (ADC) measurements obtained by diffusion-weighted imaging (DWI) in small renal masses.

BACKGROUND: Diffusion-weighted imaging (DWI) is increasingly used to diagnose renal lesion subtypes. Especially in small renal masses, identification of less aggressive tumor types is of clinical interest, as active surveillance strategies can be applied. PURPOSE: To evaluate the inter-observer variation and diagnostic efficacy of apparent diffusion coefficient (ADC) measurements obtained by DWI in small renal masses ≤4 cm (SRM). MATERIAL AND METHODS: This retrospective IRB-approved study included 39 patients (46 SRM: 12 benign, 34 malignant). All underwent a 3 T DWI of SRM prior to surgery. Two radiologists independently analyzed all imaging data by three measurements. Limits of agreement, intraclass correlation coefficients (ICC), group comparisons by t-tests, and ROC analysis were performed. RESULTS: Reliability of ADC measurements was very high with an ICC of >0.9 for both observers. Inter-rater reliability was high with an ICC of 0.82. Limits of agreement for average ADC values between both observers were -23.5% to 38.3% with a mean difference of 7.5% between both observers. No significant differences were found between benign and malignant lesions (P value Observer 1: 0.362, Observer 2: 0.622). Papillary carcinoma showed lower ADC values compared to non-papillary carcinoma (P value Observer 1: 0.008, Observer 2: 0.012). Consequently, ROC analysis revealed a significant (P < 0.001, respectively) area under the ROC curve of 0.853 (Observer 1) and 0.837 (Observer 2) without significant differences between both readers (P = 0.772). CONCLUSION: ADC measurements of SRM at 3 T show a high reproducibility and differentiate papillary from non-papillary carcinoma subtypes. However, measurement variability may limit the application of fixed ADC thresholds for lesion diagnosis.

Focused Dual-energy CT Maintains Diagnostic and Compositional Accuracy for Urolithiasis Using Ultralow-dose Noncontrast CT.

OBJECTIVE: To evaluate the diagnostic accuracy of a new energy and radiation dose-reduced protocol for noncontrast computed tomography (NCCT) with dual-energy CT (DECT) analysis and its potential for the compositional analysis of uric acid (UA)- or non-uric acid (N-UA)-containing calculi. METHODS: A retrospective evaluation was carried out in 61 patients who underwent dose-reduced DECT (tube A: 140 kV/55 mAs; tube B: 80 kV/303 mAs) with a tube current 38.8% lower than that set by the manufacturer. A protocol combining low-dose CT and targeted DE scans was used. Urinary stones were detected and classified as UA- or N-UA-containing or mixed based on DE software results. The accuracy of the compositional analysis was controlled by correlation with conventional infrared-based analysis. RESULTS: The compositional stone differentiation was correct in 58 of 61 (95.1%) patients. The sensitivity of detecting pure UA-containing and pure N-UA-containing stones was 100%. The specificity of detecting UA- and pure N-UA-containing stones was 100% and 78.57%, respectively, as 3 of 7 mixed urinary stones (small fragments <4 mm) were classified as N-UA calculi. The total radiation dose in patients with body mass index <25 and >25 kg/m(2) was 1.2 and 2.5 mSv, respectively. CONCLUSION: Lowering the DECT tube current by up to 38% of the manufacturer's recommendations allows a reduced radiation dose without impairing detection accuracy and stone compositional analysis. Compared with previous studies, this protocol might significantly decrease patient radiation exposure without affecting the quality of results.