Detecting and Locating the Site of Local Relapse Using 18F-PSMA-1007 Imaging After Primary Treatment of 135 Prostate Cancer Patients-Potential Impact on PSMA-Guided Radiation Therapy.

PURPOSE: Due to limited imaging options, the visualization of a local relapse of prostate cancer used to pose a considerable challenge. However, since the integration of 18F-PSMA-1007-PET/CT into the clinic, a relapsed tumor can now easily be detected by hybrid imaging. The present study aimed to evaluate and map the allocate relapse in a large cohort of prostate cancer patients focusing on individual patient management conclusions for radiation therapy. PROCEDURES: The current study included 135 men with prostate cancer after primary treatment who underwent 18F-PSMA-1007-PET/CT due to biochemical relapse detecting a local relapse. Imaging data were reassessed and analyzed with regard to relapse locations. For the correlation of tumor foci with clinical data, we used binary logistic regression models as well as the Kruskal-Wallis test and Mann-Whitney test. RESULTS: In total, 69.6% of all patients (mean age: 65 years) underwent prostatectomy while 30.4% underwent radiation therapy. PET imaging detected most frequently a unifocal relapse (72.6%). There was a statistically significantly higher rate of ipsilateral cases among the relapsed tumors. Comparing both treatment approaches, tumors relapsed most commonly within the posterior region after surgery and transition/peripheral zone after radiation therapy, respectively. CONCLUSIONS: The present study confirms that 18F-PSMA-1007-PET/CT is highly suitable for the localization and allocation of a local relapse in patients with prostate cancer. The data enable further optimizing dose prescriptions and target volume delineations of radiation therapy in the future.

Magnetic resonance imaging-guided transurethral ultrasound ablation of prostate tissue in patients with localized prostate cancer: single-center evaluation of 6-month treatment safety and functional outcomes of intensified treatment parameters.

OBJECTIVES: To evaluate the effect of intensified treatment parameters on safety, functional outcomes, and PSA after MR-Guided Transurethral Ultrasound Ablation (TULSA) of prostatic tissue. PATIENTS AND METHODS: Baseline and 6-month follow-up data were collected for a single-center cohort of the multicenter Phase I (n = 14/30 at 3 sites) and Pivotal (n = 15/115 at 13 sites) trials of TULSA in men with localized prostate cancer. The Pivotal study used intensified treatment parameters (increased temperature and spatial extent of ablation coverage). The reporting site recruited the most patients to both trials, minimizing the influence of physician experience on this comparison of adverse events, urinary symptoms, continence, and erectile function between subgroups of both studies. RESULTS: For Phase I and TACT patients, median age was 71.0 and 67.0 years, prostate volume 41.0 and 44.5 ml, and PSA 6.7 and 6.7 ng/ml, respectively. All 14 Phase I patients had low-risk prostate cancer, whereas 7 of 15 TACT patients had intermediate-risk disease. Baseline IIEF, IPSS, quality of life, and pad use were similar between groups. Pad use at 1 month and quality of life at 3 months favored Phase I patients. At 6 months, there were no significant differences in functional outcomes or adverse events. CONCLUSION: TULSA demonstrated acceptable clinical safety in Phase I trial. Intensified treatment parameters in the TACT Pivotal trial increased ablation coverage from 90 to 98% of the prostate without affecting 6-month adverse events or functional outcomes. Long-term follow-up and 12-month biopsies are needed to evaluate oncological safety.

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

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

68Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer.

PURPOSE: The aims of this retrospective analysis were to compare 68Ga-PSMA PET findings and low-dose CT findings (120 kV, 30 mA), and to obtain semiquantitative and quantitative 68Ga-PSMA PET data in patients with prostate cancer (PC) bone metastases. METHODS: In total, 152 PET/CT scans from 140 patients were evaluated. Of these patients, 30 had previously untreated primary PC, and 110 had biochemical relapse after treatment of primary PC. All patients underwent dynamic PET/CT scanning of the pelvis and lower abdomen as well as whole-body PET/CT with 68Ga-PSMA-11. The PET/CT scans were analysed qualitatively (visually), semiquantitatively (SUV), and quantitatively based on a two-tissue compartment model and a noncompartmental approach leading to the extraction of the fractal dimension. Differences were considered significant for p values <0.05. RESULTS: In total, 168 68Ga-PSMA-positive and 113 CT-positive skeletal lesions were detected in 37 patients (8 with primary PC, 29 with biochemical recurrence). Of these 168 lesions, 103 were both 68Ga-PSMA PET-positive and CT-positive, 65 were only 68Ga-PSMA-positive, and 10 were only CT-positive. The Yang test showed that there were significantly more 68Ga-PSMA PET-positive lesions than CT-positive lesions. Association analysis showed that PSA plasma levels were significantly correlated with several 68Ga-PSMA-11-associated parameters in bone metastases, including the degree of tracer uptake (SUVaverage and SUVmax), its transport rate from plasma to the interstitial/intracellular compartment (K1), its rate of binding to the PSMA receptor and its internalization (k3), its influx rate (Ki), and its distribution heterogeneity. CONCLUSION: 68Ga-PSMA PET/CT is a useful diagnostic tool in the detection of bone metastases in PC. 68Ga-PSMA PET visualizes more bone metastases than low-dose CT. PSA plasma levels are significantly correlated with several 68Ga-PSMA PET parameters.

Incidental appendectomy during robotic laparoscopic prostatectomy-safe and worth to perform?

PURPOSE: The purpose of this study is to investigate the safety and patients' benefit of incidental appendectomy during robot-assisted laparoscopic radical prostatectomy (RALRP). METHODS: Fifty-three patients, who had incidental appendectomy during RALRP between January 2012 and March 2014, were enrolled to this study. To evaluate the safety of the procedure, following parameters were evaluated: patient age, duration of surgery, perioperative complications (classified by Clavien-Dindo), time to bowel movement, and length of hospital stay. Furthermore, intraoperative visual appearance, location, and histopathological evaluation of the appendix were evaluated. Data was analyzed by descriptive statistics. RESULTS: Mean age of patients was 61 years, the average hospital stay 5 days. No perioperative complications occurred. The appendix was unsuspicious in 39 patients (73.6%); 14 patients (26.4%) had macroscopically signs of inflammation. Of the 53 resected appendixes, the histopathological evaluation showed 33 (62.2%) inconspicuous appendices, 11 (20.8%) post-inflammatory changes, 4 (7.5%) with chronical signs of inflammation and 3 (5.7%) with signs of acute inflammation. In 2 patients (3.8%), low-grade mucinous neoplasms were found in the specimens. CONCLUSIONS: Incidental appendectomy during RALRP is a feasible procedure. With regard to inflammation and neoplastic changes, incidental appendectomy can be considered for patients scheduled for robot-assisted prostate surgery.

Post-prostatectomy radiotherapy adversely affects urinary continence irrespective of radiotherapy regime.

PURPOSE: To investigate the influence of different postoperative radiotherapy (RT) regimes on post-prostatectomy continence and QoL. METHODS: Men after prostatectomy (RP) and RT were assigned in adjuvant (ART), early salvage (ESRT) and salvage radiotherapy (SRT) groups depending on time of initiation, indication and pre-RT-PSA (≤/>0.5 ng/ml). Continence and QoL outcomes were evaluated by validated questionnaire. Statistical analysis included students t test, Chi square, Fisher's test, ROC- and McNemar-Bowker-Analyses. RESULTS: The mean follow-up was 5.1 years. 33.5, 38.2 and 28.3% received ART, ESRT and SRT, respectively. Mean time to RT was 0.3 (±0.4), 1.8 (±2.5) and 3.3 (±3.6) years respectively. Differences in age at RP (p = 0.54) and RT (p = 0.47) between groups were not significant. Mean-RT-dose was similar (p = 0.70). Differences in continence distribution between groups before (p = 0.56) and after RT (p = 0.38) were not significant. No significant differences were observed for frequency (p = 0.58) or amount (p = 0.88) of urine loss, impact on QoL (p = 0.13) and ICIQ-SF scores (p = 0.69) between groups. Even though no significant difference in post-RT-continence (p = 0.89) was observed in the direct comparison between groups, a significant worsening of long-term continence was observed in all groups (p < 0.001). We found no cutoff and no time-point after RP at which this negative effect of RT on continence became insignificant (AUC = 0.474). A subgroup with apparent local recurrence showed no differences for ICIQ-SF-score (p = 0.155), QoL (0.077), incontinence grade (p = 0.387), frequency (p = 0.182) and amount (p = 0.415) of urine loss. Proportionally more men in this subgroup remembered deterioration of continence after RT (p = 0.029). CONCLUSION: Postoperative RT adversely affects long-term continence; this negative effect is irrespective of time of initiation or indication for RT. These results suggest a need for innovative strategies of prostate cancer therapy with lasting oncological, functional and QoL outcomes.

A prospective randomized controlled trial for assessment of perineal hydrodissection technique for nervesparing robot assisted radical prostatectomy.

BACKGROUND: This study prospectively evaluated the safety and efficacy of perineal hydrodissection in robot assisted nervesparing prostatectomy. METHODS: Patients were randomized for perineal, ultrasound guided hydrodissection (HD) before radical prostatectomy and compared with standard treatment (ST). Follow-up was done every 3 months, including erectile function (IIEF5-score), reported grade of erection, ability for sexual intercourse, continence, PSA. RESULTS: 21 patients were enrolled to this prospective study, 10 for ST and 11 for HD. No significant differences in demographic and preoperative oncological data between both groups were identified. Blood loss and time for surgery did not differ significantly. HD resulted in 66% (4/6) rate of positive surgical margins (PSM) in pT3 tumors vs 50% in ST (1/2; P = 0.67). Follow-up revealed higher IIEF scores, better ability for sexual intercourse and early continence in HD. CONCLUSIONS: Erectile function after radical prostatectomy was improved by perineal hydrodissection in this proof of principal study. However, careful patient selection and further studies are needed as perineal hydrodissection could result in increased positive surgical margins in pT3a tumors.

[Level IV inferior vena cava tumor thrombus : A rare diagnosis in patients with renal cell carcinoma]. / Level-IV-Cavathrombus : Eine seltene Diagnose bei Patienten mit Nierenzellkarzinom.

Renal cell carcinoma in combination with a supradiaphragmatic tumor thrombus is a rare tumor entity. Radical surgery including nephrectomy and thrombectomy is still considered standard treatment. The extent of the tumor thrombus should be preoperatively evaluated by MRI and TEE. An interdisciplinary team is important for surgery planning and realization. Despite the known risks of an operation, a longer overall survival is achieved.

Quality of life and functional outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer.

BACKGROUND: To evaluate quality of life, functional and oncological outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer. METHODS: One hundred thirty-one patients, treated with TURP and HIFU in a single institution were followed up for oncological and functional outcome. Oncological outcome was quantified by biochemical recurrence free survival using the Stuttgart and Phoenix criteria. Quality of life was assessed by usage of standardized QLQ-C30 and QLQ-PR25 questionnaires. In addition, functional questionnaires such as IPSS and IIEF-5 were used. Complications were assessed by the Clavien-Dindo classification. RESULTS: One hundred thirty-one patients with a mean age of 72.8 years (SD: 6.0) underwent HIFU for prostate cancer (29.0% low risk, 58.8% intermediate risk, 12.2% high risk). PSA nadir was 0.6 ng/ml (SD: 1.2) after a mean of 4.6 months (SD: 5.7). Biochemical recurrence free survival defined by Stuttgart criteria was 73.7%, 84.4% and 62.5% for low-, intermediate- and high-risk patients after 22.2 months. Complications were grouped according to Clavien-Dindo and occurred in 10.7% (grade II) and 11.5% (grade IIIa) of cases. 35.1% of patients needed further treatment for bladder neck stricture. Regarding incontinence, 14.3%, 2.9% and 0% of patients had de novo urinary incontinence grade I°, II° and III° and 3.8% urge incontinence due to HIFU treatment. Patients were asked for the ability to have intercourse: 15.8%, 58.6% and 66.7% of patients after non-, onesided and bothsided nervesparing procedure were able to obtain sufficient erection for intercourse, respectively. Regarding quality of life, mean global health score according to QLQ-C30 was 69.4%. CONCLUSION: HIFU treatment for localized prostate cancer shows acceptable oncological safety. Quality of life after HIFU is better than in the general population and ranges within those of standard treatment options compared to literature. HIFU seems a safe valuable treatment alternative for patients not suitable for standard treatment.

[Recurrence-free survival after radical prostatectomy and PDE-5 inhibitor intake]. / Rezidivfreies Überleben nach radikaler Prostatektomie und PDE-5-Hemmer-Einnahme.

BACKGROUND: Phosphodiesterase type 5 (PDE-5) inhibitors are widely used for penile rehabilitation and treatment of erectile dysfunction after radical prostatectomy. Recently, Michl et al. showed in a monocentric, retrospective and non-randomized analysis that PDE-5 inhibitors may cause higher biochemical recurrence rates after radical prostatectomy. This unexpected and serious adverse side effect of PDE-5 inhibitors was scrutinized on the basis of patients in our prospective tumor database. MATERIALS AND METHODS: We included 358 patients after radical prostatectomy with bilateral nerve-sparing and without neo- or adjuvant therapy during 2004 and 2015. In all, 65.9% of the patients regularly took PDE-5 inhibitors postoperatively, 34.1% did not. Patients with sporadic use were excluded from the primary analysis. We used Kaplan-Mayer analysis to compare biochemical recurrence rates in both groups (endpoint: PSA > 0.2 ng/ml or salvage therapy). RESULTS: Both groups showed comparable clinical parameters. There was no significant difference in recurrence-free survival (p = 0.9334): 60 months postoperatively 90.4% of men with PDE-5 intake vs. 90.8% of men without intake of PDE-5 inhibitors were recurrence-free. CONCLUSION: Although our analysis was constructed similar to the analysis of Michl et al., we could not confirm their results. Taken together with recent cohort study from Scandinavia, postoperative prescription of PDE-5 inhibitors seems to be safe and should be discussed with patients.

[Self-concept and erectile dysfunction in 45-year-old men : Results of a corollary study of the PROBASE trial]. / Selbstbild und erektile Dysfunktion 45-jähriger Männer : Ergebnisse eines Begleitprojekts der PROBASE-Studie.

BACKGROUND: Self-concept consists of self-perceptions and is influenced by the life course of the person. OBJECTIVES: This study investigated associations between self-concept and erectile dysfunction (ED) in 45-year-old German men. MATERIALS AND METHODS: Forty-five-year-old, heterosexual men who had participated in the PROBASE-study were included. Erectile Function was evaluated using the International Index of Erectile Function (IIEF-6). The presence of ED was defined by IIEF-6 score ≤ 25. Self-concept was assessed using the facets "body image" (three items from the Dresden Body Image Inventory, DKB-35), "perception of masculinity" (three items from the Male Role Norms Scale, MRNS), "perceived social pressure with regard to sexual performance" (four newly constructed items), and "sexual self-esteem" (three newly constructed items). Scores for these facets of self-concept can range from 1 to 5. Higher scores indicate a more positive body image, higher sexual self-esteem, a more modern understanding of masculinity, and greater perceived social pressure. Differences in self-concept between men with ED and without ED were analyzed using the Mann-Whitney-U-test. Furthermore, Cohen's d effect sizes (ES d) were calculated. RESULTS: The responses of 3143 men were analyzed. Men with ED (16.2 %) have significantly lower scores regarding body image (mean 3.6 ± 0.6 vs 3.8 ± 0.5; p < 0.001; ES d = -0.5), perception of masculinity (mean 3.4 ± 0.7 vs 3.7 ± 0.6; p < 0.001; ES d = -0.4), and sexual self-esteem (mean 3.6 ± 0.6 vs 3.9 ± 0.5; p < 0.001, ES d = -0.4) than men without ED. Furthermore, they had significantly higher scores for perceived social pressure (mean 2.1 ± 0.7 vs 1.5 ± 0.5; p < 0.001; ES d = 1.2). CONCLUSIONS: Self-concept and ED are associated in 45-year-old men. Men with ED have a more negative body image, a more traditional understanding of masculinity, more negative sexual self-esteem, and greater perceived social pressure with regard to sexual performance than men without ED.

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

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

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

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

Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? Results of a comprehensive analysis based on the multicenter CORONA database.

BACKGROUND: Since there is still an unmet need for potent adjuvant strategies for renal cancer patients with high progression risk after surgery, several targeted therapies are currently evaluated in this setting. We analyzed whether inclusion criteria of contemporary trials (ARISER, ASSURE, SORCE, EVEREST, PROTECT, S-TRAC, ATLAS) correctly identify high-risk patients. METHODS: The study group comprised 8873 patients of the international CORONA-database after surgery for non-metastatic renal cancer without any adjuvant treatment. Patients were divided into potentially eligible high-risk and assumable low-risk patients who didn't meet inclusion criteria of contemporary adjuvant clinical trials. The ability of various inclusion criteria for disease-free survival (DFS) prediction was evaluated by Harrell's c-index. RESULTS: During a median follow-up of 53 months 15.2% of patients experienced recurrence (5-year-DFS 84%). By application of trial inclusion criteria, 24% (S-TRAC) to 47% (SORCE) of patients would have been eligible for enrollment. Actual recurrence rates of eligible patients ranged between 29% (SORCE) and 37% (S-TRAC) opposed to <10% in excluded patients. Highest Hazard Ratio for selection criteria was proven for the SORCE-trial (HR 6.42; p < 0.001), while ASSURE and EVEREST reached the highest c-index for DFS prediction (both 0.73). In a separate multivariate Cox-model, two risk-groups were identified with a maximum difference in 5-year-DFS (94% vs. 61%). CONCLUSION: Results of contemporary adjuvant clinical trials will not be comparable as inclusion criteria differ significantly. Risk assessment according to our model might improve patient selection in clinical trials by defining a high-risk group (28% of all patients) with a 5-year-recurrence rate of almost 40%.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

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

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

Predictive factors for immediate continence after radical prostatectomy.

PURPOSE: To identify predictive factors for immediate continence after radical prostatectomy. PATIENTS AND METHODS: A total of 1553 patients underwent radical prostatectomy in a single institution (670 RRP, 883 RARP), had complete perioperative data and follow-up for urinary continence and were included in this prospective analysis. Immediate continence was defined as no pad usage after catheter removal. Evaluated parameters included age, body mass index, ECOG performance status, erectile function, prostate volume, PSA, Gleason score, tumor stage and D'Amico risk groups, as well as surgical approach (RRP, RARP), surgeon volume, nerve-sparing, lymphadenectomy, blood transfusions and duration of catheterization. RESULTS: A total of 240 men (15.5 %) did not require any pads 1 day or later after removal of the transurethral catheter. Correlation of parameters with immediate continence revealed significance for age (p < 0.001), ECOG-score (p = 0.025), erectile function (p = 0.001), nerve-sparing (p = 0.022), Gleason score (p = 0.002) and surgeon volume (p ≤ 0.022). Multivariate analyses identified IIEF-score >21 (p = 0.031), ECOG (p < 0.05), bilateral nerve-sparing (p = 0.049), Gleason score <3 + 4 (p ≤ 0.028), less blood transfusion (p ≤ 0.044) and surgeon volume (p ≤ 0.042) as the remaining prognostic parameters for immediate continence after radical prostatectomy. The type of surgical approach (robotic vs. open radical prostatectomy) did not yield significant influence. CONCLUSION: Evaluating continence in a contemporary prospective cohort revealed 15.5 % of patients never requiring a pad postoperatively. Predictive parameters for immediate continence were erectile function, ECOG, bilateral nerve-sparing, less blood transfusion and Gleason score. Furthermore, the surgeon's experience but not his operative technique had a significant impact on immediate postoperative continence.

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.

[Intratumoral heterogeneity in renal cell carcinoma. Molecular basis and translational implications]. / Intratumorale Heterogenität des Nierenzellkarzinoms. Molekulare Grundlagen und translationale Implikationen.

Advanced clear cell renal cell carcinoma is characterized by extensive intratumoral genomic heterogeneity and branched as well as convergent evolutionary traits with genomically different subclones evolving in parallel in the same tumor. Distinct driver mutations can be found in spatially separated subclones, which may hinder the development of novel targeted therapies. However, truncal mutations of the VHL tumor suppressor gene and chromosome 3p loss were ubiquitously detected and will hence continue to be a focus of future drug development. Nevertheless, genomic instability, enhanced tumor genome plasticity and intratumoral heterogeneity are likely to represent major challenges towards biomarker development and personalized patient care.