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This pilot study investigated the effect of sufentanil titration by 3 different analgesia monitoring devices or clinical signs during general anesthesia.Forty-eight patients undergoing radical retropubic prostatectomy with sevoflurane/sufentanil anesthesia were randomly assigned into 4 groups and received sufentanil guided either by 1 of 3 analgesia monitoring devices (Surgical Pleth Index [SPI], Pupillary Pain Index [PPI], Nociception Level [NoL]) or by clinical judgment (control). The primary end point was intraoperative sufentanil consumption. Adrenocorticotropic hormone (ACTH) and cortisol were measured at 4 time points during the day of surgery. Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests and by mixed model and area under the curve (AUC) analyses for group comparisons and time effects of stress hormones.The total amount of sufentanil administration (μg·kg·minute·10) differed between the groups (median [quartiles]: control = 5.6 [4.4-6.4], SPI = 7.2 [4.8-8.4], PPI = 2.0 [1.8-2.9], NoL = 3.8 [3.3-5.1]; PPI versus SPI, -5.1 [-6.6 to -1.3], P.001; NoL versus SPI, -3.0 [-5.2 to 0.2], P = .024; control versus SPI, -1.6 [-3.7 to 1.7], P = .128; NoL versus PPI, 1.7 [0.6-3.4], P.001; control versus PPI, 3.4 [2.0-4.6], P.001; control versus NoL, 1.6 [-0.2 to 3.3], P = .017) (Hodges-Lehmann estimator [99% confidence interval {CI}], P values). The AUC analysis indicated differences among groups in cumulative ACTH levels (ng·liter·minute, natural logarithm (ln)-transformed data) of NoL versus PPI (-1.079 [-1.950 to -0.208], P = .001) and PPI versus SPI (1.192 [0.317-2.068], P= .001), as well as differences in cortisol levels (µg·liter·minute) for PPI versus SPI (46,710 [21,145-72,274], P.001), NoL versus SPI (27,645 [3163-52,126], P = .003), and control versus SPI (31,824 [6974-56,675], P = .001) (differences in means [99% CI], P value). Secondary end points (postoperative recovery, pain level, and analgesia medication) showed no differences.The type of analgesia nociception monitoring affected the total amount of sufentanil administered. Lower sufentanil doses in the PPI group were associated with an increased endocrine stress response. Titration by SPI caused no opioid reduction compared to the control but was associated with a reduced endocrine stress response.

Background Cancer patients often suffer from psychological distress. Psycho‐oncological services (POS) have been established in some health care systems in order to address such issues. This study aims to identify patient and center characteristics that elucidate the use of POS by patients in prostate cancer centers (PCCs). Methods Center‐reported certification and patient survey data from 3094 patients in 44 certified PCCs in Germany were gathered in the observational study (Prostate Cancer Outcomes). A multilevel analysis was conducted. Results Model 1 showed that utilization of POS in PCCs is associated with patients’ age (OR = 0.98; 95%‐CI = 0.96‐0.99; P, The paper identifies patient and center characteristics that account for the use of psycho‐oncological services by prostate cancer patients in certified prostate cancer centers in Germany. Multilevel analysis was conducted. The results indicate that the varying utilization of psycho‐oncological services in certified prostate cancer centers may be better explained by characteristics of the centers and the patients’ clinical characteristics, rather than by the patients’ sociodemographic features.

Purpose The self-reported functional status (sr-FS) of prostate cancer (PCa) patients varies substantially between patients and health-care providers before treatment. Information about this issue is important for evaluating comparisons between health-care providers and to assist in treatment decision-making. There have been few reports on correlates of pretherapeutic sr-FS. The objective of the article, therefore, is to describe clinical and sociodemographic correlates of pretherapeutic sr-FS, based on a subset of the TrueNTH Global Registry, a prospective cohort study. Methods A total of 3094 PCa patients receiving local treatment in 44 PCa centers in Germany were recruited between July 2016 and April 2018. Multilevel regression models were applied to predict five pretherapeutic sr-FS (EPIC-26) scores based on clinical characteristics (standard set suggested by the International Consortium for Health Outcomes Measurement), sociodemographic characteristics, and center characteristics. Results Impaired pretherapeutic sr-FS tended to be associated with lower educational level and poorer disease characteristics—except for “urinary incontinence” which was only associated with age. Notably, age was a risk factor (“urinary incontinence,” “urinary irritative/obstructive,” “sexual”) as well as a protective factor (“hormonal”) for pretherapeutic sr-FS. Pretherapeutic sr-FS varies little across centers. Conclusions Pretherapeutic sr-FS varies by clinical patient characteristics and age as well as by socioeconomic status. The findings point out the benefit of collecting and considering socioeconomic information in addition to clinical and demographic patient characteristics for treatment decision-making and fair comparisons between health-care providers.

To assess the impact of preprostatic lymph node invasion on prostate cancer patients' outcome after radical prostatectomy. It is known that invasion of pelvic lymph nodes is associated with worse oncological outcome, but little is known about invasion of preprostatic lymph nodes. We hypothesized that positive preprostatic lymph nodes may not be as harmful as positive pelvic lymph nodes.A total of 11,107 consecutive patients treated for prostate cancer with radical prostatectomy between 2013 and 2017 were evaluated. 1575 (14.2%) had some type of lymph node invasion, 53 (0.5%) had only one positive preprostatic lymph node and 705 (6.3%) had only one positive pelvic lymph node.Median follow-up was 37.7 months (interquartile range: 24.6-58.7 months). Baseline characteristics of the overall cohort were not statistically significant between the preprostatic vs. pelvic lymph node invasion groups, except for robot-assisted operation (64.2 vs. 32.3%, p 0.001) and count of removed lymph nodes (16 vs. 19, p 0.001). There was no statistically significant difference in 3-years biochemical recurrence rate (56.2 vs. 65.8%, p = 0.5), 3-years metastases free survival rate (87.4 vs. 95.5%, p = 0.5) and overall cancer-specific mortality (1.9 vs 1.0%) between the two groups.Preprostatic lymph node invasion seems to have a similar harmful effect as pelvic lymph node invasion and thus, if detected, may alter treatment and follow-up strategy. Therefore, it is important to perform a histological analysis when removing the preprostatic tissue.

The extent of variation in urinary and sexual functional outcomes after radical prostatectomy (RPE) between prostate cancer (PC) operating sites remains unknown. Therefore, this analysis aims to compare casemix-adjusted functional outcomes (EPIC-26 scores incontinence, irritative/obstructive function and sexual function) between operating sites 12 months after RPE.Analysis of a cohort of 7065 men treated with RPE at 88 operating sites (prostate cancer centers, "PCCs") between 2016 and 2019. Patients completed EPIC-26 and sociodemographic information surveys at baseline and 12 months after RPE. Survey data were linked to clinical data. EPIC-26 domain scores at 12 months after RPE were adjusted for relevant confounders (including baseline domain score, clinical and sociodemographic information) using regression analysis. Differences between sites were described using minimal important differences (MIDs) and interquartile ranges (IQR). The effects of casemix adjustment on the score results were described using Cohen's d and MIDs.Adjusted domain scores at 12 months varied between sites, with IQRs of 66-78 (incontinence), 89-92 (irritative/obstructive function), and 20-29 (sexual function). Changes in domain scores after casemix adjustment for sites ≥ 1 MID were noted for the incontinence domain (six sites). Cohen's d ranged between - 0.07 (incontinence) and - 0.2 (sexual function), indicating a small to medium effect of casemix adjustment.Variation between sites was greatest in the incontinence and sexual function domains for RPE patients. Future research will need to identify the factors contributing to this variation.The study is registered at the German Clinical Trial Registry ( https://www.drks.de/drks_web/ ) with the following ID: DRKS00010774.

BACKGROUNDTransrectal ultrasound-guided prostate biopsy (TRUS) is a standard procedure for prostate cancer diagnosis. Because prostate cancer is a multifocal disease in many patients, multiple sampling (n ≥ 10) is required, which may bear the risk of systemic spread of cancer cells.DESIGNUsing the standardized CellSearch® system that allows for the detection of single epithelial cell adhesion molecule-positive circulating tumor cells (CTCs) in blood, we investigated whether prostate biopsy is associated with release of prostatic tumor cells into the circulation. Peripheral blood was obtained before and within 30 min after performing prostate biopsy from 115 men with increased serum prostate-specific antigen.RESULTSThe number of CTCs significantly increased after biopsy in men with histologically confirmed prostate cancer (odds ratio, 7.8; 95% CI, 4.8–12.8), whereas no biopsy-related changes could be detected in men without confirmed prostate cancer. Multivariable analysis showed that biopsy-related increase of CTCs was significantly correlated with a worse progression-free survival (hazard ratio, 12.4; 95% CI, 3.2–48.6) within the median follow-up of 41 months.CONCLUSIONSProstate biopsies may lead to a tumor-associated release of CTCs into the blood circulation. Larger confirmatory trials with longer follow-up periods are required before any change in clinical practice can be recommended.

For patients with prostate cancer, validated and reliable instruments are essential for measuring patient-reported outcomes. The aim of this study was to validate the German version of the widely established Expanded Prostate Cancer Index Composite with 26 items (EPIC-26). A German translation of the original questionnaire was tested in 3094 patients with localized or locally advanced (any T, any N and M0) prostate cancer with treatment intent (including radical prostatectomy, brachytherapy, active surveillance, watchful waiting). They completed the EPIC-26 questionnaire before treatment. A total of 521 of them also completed a questionnaire 12 months afterward. Internal consistency, sensitivity to change, and construct validity were assessed. The internal consistency of all domains was sufficient (Cronbach’s alpha between 0.64 and 0.93). Item-to-scale correlation coefficients showed acceptable associations between items and their domain score (all > 0.30), with the lowest scores for “bloody stools” (r = 0.37) and “breast problems” (r = 0.32). Confirmatory and exploratory factor analysis confirmed the five-dimension structure of the EPIC-26 (comparative fit index 0.95). Psychometric evaluation suggests that the German version of the EPIC-26 is a well-constructed instrument for measuring patient-reported health-related symptoms in patients with prostate cancer.

STAMPEDE arm H demonstrated a survival benefit for newly diagnosed prostate cancer (PCa) patients with low metastatic burden (LMB) who additionally received radiotherapy (RT) to the primary. However, it is unknown if radical prostatectomy (RP) may achieve equivalent results, since existing studies did neither include the same selection criteria nor examine comparable endpoints as STAMPEDE arm H. We retrospectively analysed 78 RP patients (2008–2018) with LMB (

// Till Eichenauer 1, 2, * , Mohammad Hussein 1, * , Claudia Hube-Magg 1 , Martina Kluth 1 , Franziska Buscheck 1 , Doris Hoflmayer 1 , Maria Christina Tsourlakis 1 , Stefan Steurer 1 , Till S. Clauditz 1 , Andreas M. Luebke 1 , Eike Burandt 1 , Waldemar Wilczak 1 , Andrea Hinsch 1 , David Dum 1 , Burkhard Beyer 3 , Thomas Steuber 3 , Hartwig Huland 3 , Markus Graefen 3 , Ronald Simon 1 , Guido Sauter 1 , Nathaniel Melling 4 , Thorsten Schlomm 5 and Sarah Minner 1 1 Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 2 Department of Urology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany 3 Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 4 Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 5 Department of Urology, Charite-Universitatsmedizin Berlin, Berlin, Germany * These authors contributed equally to this work Correspondence to: Ronald Simon, email: R.Simon@uke.de Keywords: GSK3beta; prostate cancer; prognosis; immunohistochemistry Received: January 16, 2019 Accepted: February 15, 2019 Published: March 01, 2019 ABSTRACT Glycogen synthase kinase 3s (GSK3s) regulates many cancer relevant cellular processes and represents a potential therapeutic target. GSK3s overexpression has been linked to adverse tumor features in many cancers, but its role in prostate cancer remains uncertain. We employed immunohistochemical GSK3s expression analysis on a tissue microarray with 12,427 prostate cancers. Cytoplasmic and nuclear GSK3s staining was separately analyzed. GSK3s staining was absent in normal prostate epithelium, whereas 57% of 9,164 interpretable cancers showed detectable GSK3s expression. Cytoplasmic staining was considered weak, moderate, and strong in 36%, 19.5% and 1.5% of tumors and was accompanied by nuclear GSK3s staining in 47% of cases. Cytoplasmic GSK3s staining as well as nuclear GSK3s accumulation was associated with advanced tumor stage, high Gleason grade, presence of lymph node metastasis and early biochemical recurrence ( p < 0.0001 each for cytoplasmic staining and nu-clear accumulation). Prognosis of GSK3s positive cancers became particularly poor if nuclear GSK3s staining was also seen ( p < 0.0001). The prognostic impact of nuclear GSK3s accumu-lation was independent of established preoperative and postoperative parameters in multivari-ate analyses ( p < 0.0001). The significant association of GSK3s expression with deletions of PTEN , 3p13 ( p < 0.0001 each), 5q21 ( p = 0.0014) and 6q15 ( p = 0.0026) suggest a role of GSK3s in the development of genomic instability. In summary, the results of our study identify GSK3s as an independent prognostic marker in prostate cancer.

Purpose Social service counseling (SSC) is an important instrument to support cancer patients, for example, regarding legal support, or rehabilitation. Several countries have established on-site SSC in routine care. Previous analyses have shown that SSC utilization varies across cancer centers. This analysis investigates patient and center-level predictors that explain variations in SSC utilization between centers. Methods Logistic multilevel analysis was performed with data from 19,865 prostate cancer patients from 102 prostate cancer centers in Germany and Switzerland. Data was collected within an observational study between July 2016 and June 2020 using survey (online and paper) and tumor documentation. Results The intraclass correlation coefficient for the null model implies that 51% of variance in SSC utilization is attributable to the center a patient is treated in. Patients aged 80 years and older, with higher education, private insurance, without comorbidities, localized intermediate risk, and undergoing androgen deprivation therapy before study inclusion were less likely to utilize SSC. Undergoing primary radiotherapy, active surveillance, or watchful waiting as compared to prostatectomy was associated with a lower likelihood of SSC utilization. Significant negative predictors at the center level were university hospital, center’s location in Switzerland, and a short period of certification. Conclusion The results show that patient and center characteristics contribute to explaining the variance in SSC utilization in prostate cancer centers to a large extent. The findings may indicate different organizational processes in the countries included and barriers in the sectoral structure of the healthcare system. In-depth analyses of processes within cancer centers may provide further insights into the reasons for variance in SSC utilization.

Burkhard Beyer, Praktische Tipps für die Edition landesgeschichtlicher Quellen (Materialien der Historischen Kommission für Westfalen, Bd. 15), Historische Kommission für Westfalen, Landschaftsverband Westfalen-Lippe 2018. 80 S.; https://www.lwl.org/hiko-download/HiKo-Materialien_015_(2018 – 03).pdf (letzter Abruf: 04.12.2018)

Several benefits have been reported after applying the principles of enhanced recovery after surgery (ERAS) into the perioperative care of patients undergoing robot-assisted radical prostatectomy (RARP). Nevertheless, there are still barriers. We aimed to identify the key areas by systematically surveying urology departments in Germany and Austria. A 27-question survey on the adoption of ERAS principles for the perioperative care of RARP patients was designed, in compliance with the guidelines on good practice in conducting and reporting of survey research. After positive testing for face and content validity, the survey was distributed via postal mail to 82 departments performing RARP. In total, 39 departments responded to our survey (response rate 48%). The ERAS adoption rates ranged from 21 to 97%, with nine ERAS principles being widely adopted (72–92% of the departments). The lowest adoption rates and, subsequently, the largest potential for optimization were detected for the preoperative nutrition counselling (21%), preoperative pelvic floor physiotherapy (54%), postoperative early initiation of nutrition (44%) and postoperative patient audit for further quality improvement (36%). High-volume centers performed more frequently a perioperative nutrition counselling (8/27; 30%) than low-volume centers (0/12; 0%; p = 0.036). The implementation of the ERAS principles into the perioperative care algorithm were medium-to-high, yet not optimal. Our real-world data assessment revealed four key areas showing low adoption rates (nutrition counselling, preoperative pelvic floor physiotherapy, early initiation of nutrition and patient audit), implying a great potential for further optimization.

Purpose To give an overview of the multicenter Prostate Cancer Outcomes (PCO) study, involving paper-based and web-based collection of patient-reported outcome measures (PROM) in patients undergoing local treatment for prostate cancer in certified centers in Germany. The PCO study is part of the larger Movember-funded TrueNTH Global Registry. The article reports on the study’s design and provides a brief progress report after the first 2 years of data collection. Methods Prostate cancer centers (PCCs) certified according to German Cancer Society requirements were invited to participate in collecting patient-reported information on symptoms and function before and at least once (at 12 months) after treatment. The data were matched with disease and treatment information. This report describes progress in patient inclusion, response rate, and variations between centers relative to online/paper use, and also data quality, including recruitment variations relative to treatment in the first participating PCCs. Results PCC participation increased over time; 44 centers had transferred data for 3094 patients at the time of this report. Patient recruitment varied widely across centers. Recruitment was highest among patients undergoing radical prostatectomy. The completeness of the data was good, except for comorbidity information. Conclusions The PCO study benefits from a quality improvement system first established over 10 years ago, requiring collection and harmonization of a predefined clinical dataset across centers. Nevertheless, establishing a PROM routine requires substantial effort on the part of providers and constant monitoring in order to achieve high-quality data. The findings reported here may be useful for guiding implementation in similar initiatives.

Background This RCT investigated the effect of opioid titration by three different nociception monitoring devices or clinical signs during general anaesthesia. Methods Ninety-six patients undergoing radical retropubic prostatectomy with propofol/remifentanil anaesthesia were randomised into one of four groups to receive remifentanil guided by one of three nociception monitoring devices (surgical pleth index [SPI], pupillary pain index [PPI], or nociception level [NOL]) or by clinical judgement (control). Intraoperative remifentanil requirement was the primary endpoint, whereas recovery parameters and stress hormone levels were secondary endpoints. Results The mean [95% confidence interval {CI}] remifentanil administration rate differed between the groups: control 0.34 (0.32–0.37), SPI 0.46 (0.38–0.55), PPI 0.07 (0.06–0.08), and NOL 0.16 (0.12–0.21) μg kg−1 min−1(P Conclusions The nociception monitoring devices and clinical signs reflect the extent of nociception differently, leading to dissimilar doses of remifentanil. Very low remifentanil doses were associated with an increase and higher remifentanil doses were accompanied by a decrease in serum cortisol concentrations. Use of nociception monitoring devices for guiding intra-operative opioid dosing needs further validation. Clinical trial registration NCT03380949.

Here, we present a functional assay to detect the repair switch to the alternative PARP1-dependent end joining (PARP1-EJ) pathway and the associated susceptibility to PARPi-mediated radiosensitization in freshly collected tumor samples from prostate cancer (PCa) patients, thereby facilitating the selection of patients who should benefit from combined PARPi plus radiotherapy (RT) treatment. Our optimized ex-vivo approach sustains tumor slices for up to 15 days under culture conditions that maintain proliferation and oxygenation rates, as measured by EdU incorporation and pimonidazole staining, respectively. We present a robust system to analyze DSB repair using, for the first time in an ex vivo tumor slice setting, two DSB-markers simultaneously i.e. γH2AX and 53BP1. A computer-based processing method (i) controls variations in DNA content and slicing on the number of repair foci and (ii) measures the PARPi-mediated enhancement ratio on DSB foci numbers to ensure inter-patient-comparability. We validated this approach using a PC3 xenograft model with its previously described repair switch to PARP1-EJ. More importantly, we show that approximately 30% of the analyzed tumor tissue samples collected from PCa patients display a switch to PARP1-EJ, as indicated by the enhanced number of residual γH2AX/53BP1 foci exclusively after PARPi+RT. Furthermore, normal prostatic tissues show no repair switch to PARP1-EJ, indicating that this repair switch and its associated radiosensitizing effect is tumor-specific. Collectively, we present here a predictive assay for the switch to PARP1-EJ that enables individualization of anti-cancer treatment using a combination of RT and radiosensitizing anticancer agents such as PARPi in PCa.

Objective Androgen deprivation therapy (ADT) enhances survival of advanced prostate cancer patients and is therefore used as a concomitant therapy. However, ADT has been reported to cause negative side effects on cognition and emotional processing. So far, research referred to the effects of short-term treatment. Since the brain may adapt to androgen deprivation, we were especially interested in the long-term effects of ADT on cognitive and socioeconomic decision making. Methods Participants underwent a battery of tests that have been associated with testosterone. We compared the results of three matched test groups: (1) prostate cancer patients with ADT up to 20 years, (2) prostate cancer controls without treatment and (3) healthy controls. We further measured the morning testosterone content in participants' saliva. Results Testosterone concentration was positively associated with visuospatial performance across and within the test groups. Patients with long-term ADT showed an overall decline in cognitive performance. Compared with untreated patients, ADT was also associated with a reduced intergroup bias during socioeconomic decision making, which was in line with previous observations in young men suggesting that testosterone may promote ingroup favoritism. Finally, depression scores were increased in ADT, while quality of life was negatively associated with the treatment. Conclusion These findings conform to results made after short-term treatment. ADT promotes negative side effects on cognitive function. We also show for the first time that testosterone deprivation may affect socioeconomic decision making. Nevertheless, it should be emphasized that these effects cannot outweigh the previously described advantages of ADT in the treatment of prostate cancer.

Combined high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) is a favorable treatment option in non-metastatic prostate cancer. However, reports on toxicity and outcome have mainly focused on younger patients. We aimed to determine toxicity and biochemical control rates after combined HDR-BT and EBRT in men ≥75 years. From 1999 to 2015, 134 patients aged ≥75 years (median 76 years; 75–82 years) were identified. Patients received 18 Gy of HDR-BT (9 Gy/fraction on days 1 and 8) with an iridium-192 source. After 1 week, supplemental EBRT with a target dose of 50.4 Gy was started (delivered in 1.8 Gy fractions). Median follow-up time was 25 months (0–127 months). No severe (grade 4) gastrointestinal (GIT) or genitourinary (GUT) toxicities were observed. In 76 patients (56.7%), 3D conformal radiation therapy (CRT) and in 34.3% intensity-modulated radiotherapy (IMRT) was applied. CRT-treated patients were at a 2.17-times higher risk (hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.31–3.57, p = 0.002) of experiencing GUT. GIT risks could be reduced by 78% using IMRT (HR: 0.22, 95% CI: 0.07–0.75, p = 0.015). Patients with a higher T stage (T2c–3a/b) were less likely to experience GIT or GUT (HR: 0.49, 95% CI: 0.29–0.85, p = 0.011 and HR: 0.5, 95% CI: 0.3–0.81, p = 0.005, respectively). HDR-BT/EBRT is a well-tolerated treatment option for elderly men ≥75 years with a limited number of comorbidities and localized intermediate- or high-risk prostate cancer. IMRT should be favored since side effects were significantly reduced in IMRT-treated patients.

Background Presence of small (tertiary) Gleason 5 pattern is linked to a higher risk of biochemical recurrence in prostate cancer. It is unclear, however, how to integrate small Gleason 5 elements into clinically relevant Gleason grade groups. Objective To analyze the prognostic impact of Gleason 5 patterns in prostate cancer and to develop a method for integrating tertiary Gleason 5 patterns into a quantitative Gleason grading system. Design, setting, and participants Prostatectomy specimens from 13 261 consecutive patients and of 3295 matched preoperative biopsies were available. Percentages of Gleason 3, 4, and 5 had been recorded for each cancer. Outcome measurements and statistical analysis: Results and limitations Our data demonstrate that minimal Gleason 5 areas have strong prognostic impact in Gleason 7 carcinomas, while further expansion of the Gleason 5 pattern population has less impact. We thus defined an integrated quantitative Gleason score (IQ-Gleason) by adding a lump score of 10 to the percentage of unfavorable Gleason pattern (Gleason 4/5) if any Gleason 5 was present and by adding another 7.5 points in case of a Gleason 5 fraction >20%. There was a continuous increase of the risk of prostate-specific antigen recurrence with increasing IQ-Gleason. This was also true for subgroups with identical Cancer of the Prostate Risk Assessment Postsurgical scores ( p p Conclusions The IQ-Gleason represents a simple and efficient approach for combining both quantitative Gleason grading and tertiary Gleason grades in one highly prognostic numerical variable. Patient summary Prostatectomy specimens (13 261) were analyzed to estimate the relevance of small Gleason 5 elements in prostate cancers. Even the smallest Gleason 5 areas markedly increased the risk of prostate-specific antigen recurrence after surgery. Larger fractions of Gleason 5 patterns had less further impact on prognosis. Based on this, a numerical Gleason score (integrated quantitative Gleason score) was defined by the percentages of Gleason 4 and 5 patterns, enabling a refined estimate of patient prognosis.

Pelvic lymph node dissection (PLND) is recommended for patients with prostate cancer (PCa) and significant risk for nodal metastases. This study aimed to assess guideline adherence regarding PLND according to the German S3 guideline as example for a national but highly used guideline on prostate cancer and to compare the rate of complications different approaches for radical prostatectomy (RP). Patients undergoing open (RRP), laparoscopic (LARP) or robot-assisted (RARP) RP in six centers in Germany and Austria were included. The primary endpoint was the total number of removed lymph nodes (LN) between the different surgical approaches according to recent guideline recommendations. Secondary endpoints were the number of patients undergoing a sufficient PLND, defined as a removal of at least 10 LN and associated complication rates. 2634 patients undergoing RP were included (RRP: 66%, RARP/LARP: 34%). PLND was performed in 88% (RRP: 88.5%, RARP/LARP: 86.8%, p = 0.208). In intermediateor high risk PCa, PLND was performed in 97.2% (RRP: 97.7%, RARP/LARP: 96.2, p = 0.048). Of those, the mean number of LN was 19 (RRP: 19 vs. RARP/LARP: 17, p

Polymorphisms of the base excision repair gene APE1 may be associated with an increased risk for developing prostate cancer. In other cancer types, altered APE1 protein expression is a candidate prognostic marker. Using immunohistochemistry, we thus analyzed APE1 expression in 9763 prostate cancers in a tissue microarray (TMA) with attached clinical and molecular data. The comparison with normal prostate tissue revealed an upregulation of APE1 in cancer samples. APE1 immunostaining was considered weak in 20.2%, moderate in 36.7%, and strong in 33.4% of cancers. Strong APE1 expression was markedly more frequent in prostate cancers harboring the TMPRSS2:ERG fusion (52.9%) than in ERG-negative cancers (19.1%, P

The A Disintegrin and Metalloproteinase (ADAM) family of endopeptidases plays a role in many solid cancers and includes promising targets for anticancer therapies. Deregulation of ADAM15 has been linked to tumor aggressiveness and cell line studies suggest that ADAM15 overexpression may also be implicated in prostate cancer. To evaluate the impact of ADAM15 expression and its relationship with key genomic alterations, a tissue microarray containing 12,427 prostate cancers was analyzed by immunohistochemistry. ADAM15 expression was compared to phenotype, prognosis and molecular features including TMPRSS2:ERG fusion and frequent deletions involving PTEN, 3p, 5q and 6q. Normal prostate epithelium did not show ADAM15 staining. In prostate cancers, negative, weak, moderate, and strong ADAM15 staining was found in 87.7%, 3.7%, 5.6%, and 3.0% of 9826 interpretable tumors. Strong ADAM15 staining was linked to high Gleason grade, advanced pathological tumor stage, positive nodal stage and resection margin. ADAM15 overexpression was also associated with TMPRSS2:ERG fusions and PTEN deletions (P

Background While the optimal use and timing of secondary therapy after radical prostatectomy (RP) remain controversial, there are limited data on patient-reported outcomes following multimodal therapy. Objective To assess the impact of additional radiation therapy (RT) and/or androgen deprivation therapy (ADT) on urinary continence, potency, and quality of life (QoL) after RP. Design, setting, and participants Among 13150 men who underwent RP from 1992 to 2013, 905 received RP + RT, 407 RP + ADT and 688 RP + RT + ADT. Outcome measurements and statistical analyses Urinary function, sexual function, and overall QoL were evaluated annually using self-administered validated questionnaires. Propensity score–matched and bootstrap analyses were performed, and the distributions for all functional outcomes were analyzed as a function of time after RP. Results and limitations Patients who received RP + RT had a 4% higher overall incontinence rate 3 yr after surgery, and 1% higher rate for severe incontinence (>3 pads/24h) compared to matched RP-only patients. ADT further increased the overall and severe incontinence rates by 4% and 3%, respectively, compared to matched RP + RT patients. RP + RT was associated with an 18% lower rate of potency compared to RP alone, while RP + RT + ADT was associated with a further 17% reduction compared to RP + RT. Additional RT reduced QoL by 10% and additional ADT by a further 12% compared to RP only and RP + RT, respectively. The timing of RT after RP had no influence on continence, but adjuvant compared to salvage RT was associated with significantly lower potency (37% vs 45%), but higher QoL (60% vs 56%). Limitations of our study include the observational study design and potential for selection bias in the treatments received. Conclusions Secondary RT and ADT after RP have an additive negative influence on urinary function, potency, and QoL. Patients with high-risk disease should be counseled before RP on the potential net impairment of functional outcomes due to multimodal treatment. Patient summary Men with high-risk disease choosing surgery upfront should be counseled on the potential need for additional radiation and or androgen deprivation, and the potential net impairment of functional outcomes arising from multimodal treatment.

Background Prostate cancer (PCa) is among the most commonly diagnosed malignancies in men. Although 5-year survival in patients with localised disease reaches nearly 100%, metastatic disease still remains incurable. Therefore, there is a need for markers indicating metastatic dissemination. Methods EGFR overexpression (EGFRover) was tracked in 1039 primary tumours, circulating tumour cells from 39 d’Amico high-risk patients and metastatic samples from 21 castration-resistant PCa cases. EGFR status was compared to clinical parameters and multiple molecular factors were assessed using immunohistochemistry and gene ontology analysis. The functional aspect of EGFR was evaluated by plating PC-3 cells on soft and rigid matrices. Results EGFRover was found in 14% of primary tumours, where it was associated with shorter metastasis-free survival and was an independent indicator of worse overall survival. EGFRover correlated with a pro-migratory and pro-metastatic phenotype of tumour cells as well as rich collagen fibre content. All circulating tumour cells (detected in 13% of cases) were positive for EGFR, independent of their EMT-related phenotype. EGFRover was more prevalent in castration-resistant bone metastases (29% of patients) and supported growth of human PCa cells on rigid matrices mimicking bone stiffness. Conclusions EGFRover is a stable, EMT-independent marker of PCa disseminating to rigid organs, preferentially bones.

Claudin-1 is a membrane-tight junction protein and important for the sealing of the paracellular cleft in epithelial and endothelial cells. Differential expression of Claudin-1 is linked to disease outcome in various cancers. To evaluate the potential relevance of Claudin-1 expression in prostate cancer, a tissue microarray containing samples of 17,747 tumors with annotated clinico-pathological and molecular data was immunohistochemically analyzed for Claudin-1 expression. In normal prostate, glandular cells were always Claudin-1-negative while there was a strong staining of gland-surrounding basal cells. In contrast to normal prostatic glands, a positive Claudin-1 immunostaining, was found, however, in 38.7% of 12,441 interpretable cancers and was considered weak in 12.7%, moderate in 13.2%, and strong in 12.8% of cases. Positive Claudin-1 immunostaining was associated with favorable tumor features like low pT (p = 0.0032), low Gleason grade (p

Background The D'Amico risk stratification, Cancer of the Prostate Risk Assessment (CAPRA) score, and Stephenson nomogram are widely used prediction tools for biochemical recurrence and survival after radical prostatectomy (RP). These models have not been compared with respect to cancer-specific mortality (CSM) prediction. Objective To validate and compare the prediction tools for 10-yr CSM. Design, setting, and participants Overall, 2485 prostate cancer patients underwent RP in a European tertiary care center. Outcome measurements and statistical analysis Three preoperative models (D'Amico, CAPRA, and Stephenson) were compared in terms of their ability to predict 10-yr CSM; therefore, accuracy tests (area under the receiver operating characteristic curve [AUC]), calibration plots, and decision curve analysis (DCA) were assessed for each model. Results and limitations CSM at 10 yr was 3.6%. The AUC was 0.76, 0.77, and 0.80 for the D'Amico, CAPRA, and Stephenson models, respectively. In calibration plots, predicted probabilities were close to the observed probabilities for the D'Amico model but showed underestimation of CSM for the Stephenson nomogram and overestimation of CSM for the CAPRA score. DCA identified a benefit for the CAPRA score. These results apply to patients treated at a European tertiary care center. Conclusions Despite good discriminatory power, all tested models had some shortcomings in terms of prediction of 10-yr CSM. All three models showed good performance in North American cohorts, but our results suggested a lack of generalizability to European patients. To overcome this issue, local recalibration of the variable weights could be performed. Another possibility is the development of more universal markers that are independent of regional practice differences or, alternatively, the development of better tools to quantify clinical practice differences. Patient summary Prediction tools can predict cancer survival prior surgery, relying on points for age, prostate-specific antigen levels, aggressiveness, and percentage of cancer at biopsy. These tools are reliable in North American patients but have shortcomings for identifying patients at high risk of prostate cancer death in Europe.

Background Gleason grading is the strongest prognostic parameter in prostate cancer. Gleason grading is categorized as Gleason ≤6, 3+4, 4+3, 8, and 9–10, but there is variability within these subgroups. For example, Gleason 4 components may range from 5–45% in a Gleason 3+4=7 cancer. Objective To assess the clinical relevance of the fractions of Gleason patterns. Design, setting, and participants Prostatectomy specimens from 12823 consecutive patients and of 2971 matched preoperative biopsies for which clinical data with an annual follow-up between 2005 and 2014 were available from the Martini-Klinik database. Outcome measurements and statistical analysis To evaluate the utility of quantitative grading, the fraction of Gleason 3, 4, and 5 patterns seen in biopsies and prostatectomies were recorded. Gleason grade fractions were compared with prostatectomy findings and prostate-specific antigen recurrence. Results and limitations Our data suggest a striking utility of quantitative Gleason grading. In prostatectomy specimens, there was a continuous increase of the risk of prostate-specific antigen recurrence with increasing percentage of Gleason 4 fractions with remarkably small differences in outcome at clinically important thresholds (0% vs 5%; 40% vs 60% Gleason 4), distinguishing traditionally established prognostic groups. Also, in biopsies, the quantitative Gleason scoring identified various intermediate risk groups with respect to Gleason findings in corresponding prostatectomies. Quantitative grading may also reduce the clinical impact of interobserver variability because borderline findings such as tumors with 5%, 40%, or 60% Gleason 4 fractions and very small Gleason 5 fractions (with pivotal impact on the Gleason score) are disclaimed. Conclusions Quantitative Gleason pattern data should routinely be provided in addition to Gleason score categories, both in biopsies and in prostatectomy specimens. Patient summary Gleason score is the most important prognostic parameter in prostate cancer, but prone to interobserver variation. The results of our study show that morphological aspects that define the Gleason grade in prostate cancer represent a continuum. Quantitation of Gleason patterns provides clinically relevant information beyond the traditional Gleason grading categories ≤3+3, 3+4, 4+3, 8, 9–10. Quantitative Gleason scoring can help to minimize variations between different pathologists and substantially aid in optimized therapy decision-making.

Objective: The impact of positive surgical margin (SM) on cancer control outcomes in prostate cancer patients is a subject of continuous debate. We test the hypothesis that the impact of SM on clinical recurrence (CR) rate may vary based on the other clinical/pathologic characteristics of the tumor. Materials and Methods: We focused on 5290 patients treated with robot-assisted radical prostatectomy and pelvic node dissection, between 2002 and 2013, at three tertiary care centers. Regression tree analysis stratified patients into risk groups based on their tumor characteristics and the corresponding CR rate. Kaplan-Meier log-rank and multivariable Cox regression models tested the relationship between SM status and CR rate in each tree-generated risk group. Results: Mean (median) follow-up time was 47.7 (39.0) months. Regression tree analysis that considered all available covariates, except SM status, divided patients based on their CR risk into the following risk groups: (1) high risk (any pT3b/pT4 disease); (2) intermediate risk (≤pT3a disease and pGS 8-10); (3) low risk (≤pT3a, pGS ≤7, and prostate-specific antigen [PSA] >9 ng/mL); and (4) very low risk (≤pT3a, pGS ≤7, and PSA ≤9 ng/mL). Positive SM had a significant detrimental impact on CR risk only in two groups: intermediate risk (p < 0.001) and high risk (p = 0.01). These observations were confirmed by multivariable analyses. Conclusions: Our findings show that positive SM had a detrimental impact on CR only in a minority of patients (15%), specifically in those with advanced pathologic stage and/or pathologically poorly differentiated tumor. For all the remaining patients (85%), positive SM by itself did not increase the risk of CR.

Prostate cancers harboring DNA repair gene alterations are particularly sensitive to PARP inhibitor treatment. We report a case of an advanced prostate cancer patient profiled within the NCT-MASTER (Molecularly Aided Stratification for Tumor Eradication Research) precision oncology program using next-generation sequencing. Comprehensive genomic and transcriptomic analysis identified a pathogenic germline PALB2 variant as well as a mutational signature associated with disturbed homologous recombination together with structural genomic rearrangements. A molecular tumor board identified a potential benefit of targeted therapy and recommended PARP inhibition and platinum-based chemotherapy. Single-agent treatment with the PARP inhibitor olaparib as well as subsequent combination with platinum-based chemotherapy resulted in disease stabilization and substantial improvement of clinical symptoms. Upon progression, we performed whole-exome and RNA sequencing of a liver metastasis, which demonstrated up-regulation of several genes characteristic for the neuroendocrine prostate cancer phenotype as well as a novel translocation resulting in an in-frame, loss-of-function fusion of RB1. We suggest that multidimensional genomic characterization of prostate cancer patients undergoing PARP inhibitor therapy will be necessary to capture and understand predictive biomarkers of PARP inhibitor sensitivity and resistance.

OBJECTIVES To analyse time trends and contemporary rates of postoperative complications after radical prostatectomy (RP) and to compare the complication profile of open RP (ORP) and robot-assisted laparoscopic RP (RALP) using standardised reporting systems. PATIENTS AND METHODS Retrospective analysis of 13 924 RP patients in a single institution (2005-2015). Complications were collected during hospital stay and via standardised questionnaire 3 months after, and grouped into eight schemes. Since 2013, the revised Clavien-Dindo classification was used (n = 4 379). Annual incidence rates of different complications were graphically displayed. Multivariable logistic regression analyses compared complications between ORP and RALP after inverse probability of treatment weighting (IPTW). RESULTS After the introduction of standardised classification systems, complication rates have increased with a contemporary rate of 20.6% (2013-2015). While minor Clavien-Dindo grades represented the majority (I: 10.6%; II: 7.9%), severe complications (Grades IV-V) were rare (

HSD3B2 plays a crucial role in steroid hormone biosynthesis and is thus of particular interest in hormone dependent tumors such as prostate cancer. To clarify the clinical relevance of HSD3B2 expression in prostate cancer, we analyzed HSD3B2 protein expression by immunohistochemistry on our preexisting tissue microarray with 12.247 annotated cancers. Compared with normal tissue cytoplasmic HSD3B2 staining was stronger in prostate cancers. In 9371 interpretable cancers, HSD3B2 expression was found in 95.5% of cancers and was considered weak in 29.9%, moderate in 40.7% and strong in 24.9%. HSD3B2 up regulation was linked to advanced pathological tumor stage (pT), high Gleason grade, elevated preoperative PSA levels (p 0.0001 each), lymph node metastasis (p = 0.0019), accelerated cell proliferation (p 0.0001), androgen receptor (AR) expression (p 0.0001), and early biochemical recurrence (p 0.0001). HSD3B2 up regulation was only marginally more frequent in ERG positive (98%) than in ERG negative cancers (94%; p 0.0001) and was strongly linked to deletions of 5q and 6q (p 0.0001 each). Multivariate analyses showed that the prognostic impact of HSD3B2 expression was independent of established preoperative, but not of postoperative prognostic parameters. In summary, the results of our study demonstrate that HSD3B2 is strongly up regulated in a fraction of prostate cancers that are characterized by increased AR signaling, adverse tumor phenotype and early biochemical recurrence.

Objectives To examine the impact of marital status on prostate cancer characteristics at radical prostatectomy and oncological outcome after surgery at a high-volume center. Methods We relied on the Martini-Clinic Prostate Cancer database and investigated 8088 prostate cancer patients treated with radical prostatectomy between January 2000 and March 2011. We analyzed differences in clinical and pathological characteristics according to marital status (married and partnership vs single). Additionally, we relied on multivariable Cox regression analyses to predict biochemical recurrence, metastases and death after radical prostatectomy. Finally, Kaplan–Meier analyses were used in a propensity score-matched cohort, adjusted for clinical and pathological characteristics, to examine differences in biochemical recurrence-free, metastases-free and overall survival according to marital status. Results According to marital status, no significant differences were recorded within clinical and pathological characteristics (all P > 0.05). The impact of marital status on biochemical recurrence (hazard ratio 1.0, 95% confidence interval 0.9–1.3, P = 0.7), metastases (hazard ratio 1.3, 95% confidence interval 0.8–2.1, P = 0.3) and death (hazard ratio 0.8, 95% confidence interval 0.4–1.6, P = 0.6) after radical prostatectomy was not significant (median follow up 48 months). Kaplan–Meier analyses recorded no significant differences for biochemical recurrence-free, metastases-free and overall survival (all log–rank P > 0.05) according to marital status. Conclusions Marital status does not affect the clinical and pathological characteristics of radical prostatectomy patients treated at a high-volume center. Furthermore, marital status does not affect biochemical recurrence-free and metastases-free survival after radical prostatectomy.

Experimental evidence suggests that phosphodiesterase type 5 inhibitors may suppress tumor growth, postpone metastasis and prolong survival, but clinical data are lacking. We studied the effect of phosphodiesterase type 5 inhibitors on biochemical recurrence after radical prostatectomy for prostate cancer.The study was comprised of 4,752 consecutive patients with localized prostate cancer treated with bilateral nerve sparing radical prostatectomy between January 2000 and December 2010. Of these patients 1,110 (23.4%) received phosphodiesterase type 5 inhibitors postoperatively while 3,642 (76.6%) did not. The risk of biochemical recurrence was compared between the phosphodiesterase type 5 inhibitor group and the nonphosphodiesterase type 5 inhibitor group. Cox multivariate proportional hazard models and confidence intervals were used to estimate the hazard ratio of biochemical recurrence associated with phosphodiesterase type 5 inhibitor use. Propensity score matched analysis was performed.Median followup was 60.3 months (IQR 36.7-84.5). Five-year biochemical recurrence-free survival estimates in the phosphodiesterase type 5 inhibitor vs nonphosphodiesterase type 5 inhibitor groups were 84.7% (95% CI 82.1-87.0) and 89.2% (95% CI 88.1-90.3), respectively (p=0.0006). Multivariate regression analysis showed that phosphodiesterase type 5 inhibitor use was an independent risk factor for biochemical recurrence (HR 1.38, 95% CI 1.11-1.70, p=0.0035) and this was also true after propensity score matching.Contrary to experimental data, the use of phosphodiesterase type 5 inhibitors after radical prostatectomy may adversely impact biochemical recurrence. Further studies are needed to validate our results.

Nodal metastasis (N1) is a strong prognostic parameter in prostate cancer; however, lymph node evaluation is always incomplete.To study the prognostic value of lymphatic invasion (L1) and whether it might complement or even replace lymph node analysis in clinical practice.Retrospective analysis of pathological and clinical data from 14 528 consecutive patients.Radical prostatectomy.The impact of L1 and N1 on patient prognosis was measured with time to biochemical recurrence as the primary endpoint.Nodal metastases were found in 1602 (12%) of 13 070 patients with lymph node dissection. L1 was seen in 2027 of 14 528 patients (14%) for whom lymphatic vessels had been visualized by immunohistochemistry. N1 and L1 continuously increased with unfavorable Gleason grade, advanced pT stage, and preoperative prostate-specific antigen (PSA) values (p0.0001 each). N1 was found in 4.3% of 12 501 L0 and in 41% of 2027 L1 carcinomas (p0.0001). L1 was seen in 11% of 9868 N0 and in 61% of 1360 N1 carcinomas (p0.0001). Both N1 and L1 were linked to PSA recurrence (p0.0001 each). This was also true for 17 patients with isolated tumor cells (ie,200 unequivocal cancer cells without invasive growth) and 193 metastases ≤1mm. Combined analysis of N and L status showed that L1 had no prognostic effect in N1 patients but L1 was strikingly linked to PSA recurrence in N0 patients. N0L1 patients showed a similar outcome as N1 patients.Analysis of lymphatic invasion provides comparable prognostic information than lymph node analysis. Even minimal involvement of the lymphatic system has pivotal prognostic impact in prostate cancer. Thus, a thorough search for lymphatic involvement helps to identify more patients with an increased risk for disease recurrence.Already minimal amounts of tumor cells inside the lymph nodes or intraprostatic lymphatic vessels have a severe impact on patient prognosis.

To compare the duration of sick leave in patients with localized prostate cancer after robot-assisted radical prostatectomy (RARP) and open retropubic RP (ORP) at a German high-volume prostate cancer center.The data of 1,415 patients treated with RP at Martini Klinik, Prostate Cancer Center between 2012 and 2016 were, retrospectively, analyzed. Information on employment status, monthly revenues and days of work missed due to sickness were assessed via online questionnaire. Additional data were retrieved from our institutional database. Medians and interquartile ranges (IQR) were reported for continuous data. Cox proportional hazard analysis was performed to compare both surgical techniques for return to work time after RP.Median time elapsed between surgery and return to work comprised 42 days in patients undergoing RARP (IQR: 21-70) and ORP (IQR: 28-84, P = 0.05). In Cox regression analysis, surgical approach showed no impact on return to work time (RARP vs. ORP hazard ratio = 1, 95% CI: 0.91-1.16, P = 0.69). Return to work time was significantly associated with employment status, physical workload and monthly income (all P0.001). Limitation of this study is the nonrandomized design in a single-center.As the surgical approach did not show any influence on the number of days missed from work in patients undergoing RP, no superiority of either RARP or ORP could be identified for return to work time in a German cohort. Both surgical approaches are safe options usually allowing the patients to resume normal activities including work after an appropriate convalescence period.

Background Results from population-based studies and the Prostate Testing for Cancer and Treatment trial reported worse urinary continence (UC) and erectile function (EF) for radical prostatectomy (RP) patients compared with their radiation or active surveillance counterparts. Objective To investigate functional outcomes for patients undergoing RP in a high-volume center. Data, setting, and participants A total of 8573 consecutive RP patients (2008–2012) were analyzed. Intervention RP. Outcome measurements and statistical analysis Standardized questionnaires assessing EF, UC, and quality of life (QoL), were completed at baseline and annually thereafter. UC was defined as use of 0 or 1 safety pad/d, whereas the regular use of 1 pad/d was considered incontinent. EF was defined as ≥3 points in the International Index of Erectile Function question two. QoL was assessed using the EORTC-QLQ-C30 Global Health/QoL item. Statistics relied on comparison of means and proportions. Results and limitations EF and UC rates significantly decreased after RP. Overall, 12-mo, 24-mo, and 36-mo EF rates were 45%, 51%, and 53%, but reached up to 65.7% in preoperatively potent patients with bilateral nerve sparing. At 36 mo, 13% reported problems in their partnership. However, at the same time point, 77% were satisfied with their sexual intercourse. UC rates were 89.1%, 91.3%, and 89.0% at 12-mo, 24-mo, and 36-mo postoperatively. Mean EORTC-QLQ-C30 scores ranged from 74 to 79 and remained constant compared to baseline. Conclusions Although varying definitions hinder direct comparisons to other studies, functional outcomes seemed favorable for patients undergoing RP in a high-volume center and most patients reported excellent QoL. Patient summary Results of functional outcomes (urinary continence and potency) after radical prostatectomy are better in a high-volume center compared with those obtained from population-based data, and most patients report excellent quality of life after radical prostatectomy.

Objective To examine the accuracy of HistoScanning (HS) in detecting seminal vesicle (SV) invasion (SVI) within prostate cancer (PCa) patients. Methods We relied on our prospective institutional database. Patients who received HS before radical prostatectomy were included in the study cohort. An experienced HS examiner retrospectively reanalyzed the HS data blinded to patient characteristics and pathologic results. The HS results for every single SV were compared with the corresponding findings from the final pathologic report after radical prostatectomy. An area under the receiver operating characteristic curve for the prediction of SVI by HS was calculated. Depending on HS signal volume cut-offs (>0, >0.2, and >0.5 mL), the sensitivity, specificity, positive predictive value, and negative predictive value for the prediction of SVI were assessed. Results Overall, 131 patients and 262 SVs were assessable. Of those, 23 (17.5%) men had SVI, and 39 (14.9%) single SVs were infiltrated by tumor overall. The area under the receiver operating characteristic curve for predicting SVI by HS was 0.54. Depending on the HS signal volume cut-offs (>0, >0.2, and >0.5 mL), the sensitivity, specificity, positive predictive value, and negative predictive value for predicting SVI were 76.9%, 10.8%, 13.1%, and 72.7%; 61.5%, 24.2%, 12.4%, and 78.3%; and 46.2%, 50.2%, 14.0%, and 84.2%, respectively. Conclusion HS results did not allow a reliable prediction of SVI within PCa patients. Despite, the application of HS signal volume cut-offs (>0.2 and >0.5 mL), the prediction of SVI within PCa patients remained insufficient.

Das Prostatakarzinom ist der haufigste bosartige Tumor des Mannes. Die Neuerkrankungsrate allein in Deutschland lag im Jahre 2012 bei ca. 63.700 Mannern. Neben der hohen Inzidenz ist, u.a. dank der Einfuhrung des PSA-Tests, die Sterblichkeit zuruckgegangen. Es werden immer mehr kleine Karzinome diagnostiziert, die sich in einem organbegrenzten Stadium befinden und eine kurative Behandlung des Patienten erlauben. Hier muss unterschieden werden zwischen einem klinisch manifesten, signifikanten Karzinom, das einer aktiven Therapie bedarf und einem unbedeutenden, nichtsignifikanten Karzinom, bei dem ein aktives Uberwachen als Behandlungsstrategie eine Option darstellt. Eine verlassliche Identifizierung dieser nichtsignifikanten Karzinome ist notig, um Patienten vor einer belastenden „Ubertherapie“ zu schutzen. Zu den allgemein geltenden Kriterien des nichtsignifikanten Prostatakarzinoms (iPCa) zahlen ein Tumorvolumen von ≤ 5ml, ein Gleason-Score von (≤3+3) und ein organbegrenzter Tumor. Das ursprunglich von Stamey et al. determinierte Tumorvolumen von ≤ 5ml wurde von Wolters et al. in ihrer 2011 erschienenen Publikation in Frage gestellt und eine Anhebung der Tumorvolumengrenze auf