Hypoxemia of the lower limbs during robot-assisted radical prostatectomy in Trendelenburg position.

Objectives: The objective of this study is to assess frequency and risk factors for intraoperative hypoxemia of the lower limbs during robot-assisted radical prostatectomy (RARP). Trendelenburg position during RARP may contribute to hypoxemia and compartment syndrome (CS) of the lower limbs as a major but rare complication. Patients and methods: This prospective study included patients undergoing RARP for prostate cancer. Preoperative calculation of the ankle-brachial-index (ABI) was performed. Peripheral oxygen saturation (SpO2) at the toes was routinely measured. Occurrence of SpO2 levels of <90% was defined as hypoxemic events and treated immediately. Blood pressure, intraabdominal pressure, SpO2 of the upper limb and surgery time were monitored in case of hypoxemia. A multivariable logistic regression model was performed with age, BMI, nicotine abuse, MAP, comorbidities as covariates and hypoxemia of the lower limbs as the outcome. Results: A total of 207 patients were included. Among these, 126 patients had ABI measurements with 10.6% having an abnormal ABI value. One, two or at least three events of lower limb hypoxemia occurred intraoperatively in 19.7%, 14.8% and 16.9%, respectively. In 20 events, surgical instruments were affecting vascular perfusion by compression. None of the covariates were statistically significant associated with lower limb hypoxemia. No patient developed a compartment syndrome. Conclusion: Decrease in oxygen saturation of the lower extremities was observed frequently during RARP, without revealing any risk factors for its occurrence. Routine oximetry leads to an early detection of hypoxemia of the lower extremities, giving the anaesthesiologist and surgeon the opportunity to make adequate adjustments (increasing blood pressure and ending iliac vessel compression).

Functional outcome after radical prostatectomy in 1313 patients: A single-center study.

OBJECTIVES: To assess the impact of urinary continence and erectile function on the quality of life in men undergoing radical prostatectomy (RP) for prostate cancer (PC), we analyzed the preoperative and 1-year postoperative outcomes of five functional domains and their influencing factors. PATIENTS AND METHODS: In this prospective study, all patients undergoing open or robot-assisted RP between Febuary 2017 and March 2020 in a single academic center were included. Patient-reported outcomes were assessed pre- and 12 months postoperatively using the Expanded Prostate Index Composite (EPIC-26) survey, evaluating continence, irritative/obstructive micturition, gastrointestinal symptoms, sexuality, and overall vitality. We examined the impact of RP on sexual function and urinary continence using multivariable logistic regression models, accounting for patient and tumor characteristics. RESULTS: Overall, 1313 consecutive patients gave consent for study participation and completed both surveys. The median age was 66 years (IQR: 60-70). The majority of patients (n = 601, 46%) had an intermediate risk PC. Robotic RP was performed in 71.6% and nerve-sparing technique in 81% of the cases. The median pre- versus postoperative scores were the following: urinary continence 100 (IQR: 91.8-100) versus 85.5 (64.8-100), irritative micturition 87.5 (IQR: 75-100) versus 93.8 (IQR: 87.5-100), gastrointestinal symptoms the same with 100 (IQR: 95.8-100), vitality 95 (IQR: 80-100) versus 90 (IQR: 75-100), and erectile function 65.3 (IQR: 38.8-87.5) versus 22.2 (IQR: 12.5-48.7), respectively. Age (p < 0.001), risk classification (p = 0.002), and nerve-sparing surgery (p = 0.016) were associated with good sexual function (EPIC-26 score ≥60), while only age (p = 0.001) was statistically significantly associated with good urinary continence (EPIC-26 score ≥80). CONCLUSION: Non-modifiable factors such as age and PC risk classification impact urinary continence and sexual function after RP. Nevertheless, urologic surgeons should further focus on improving nerve-sparing techniques, the only modifiable variable, to reduce the surgery's negative impact on urinary continence and sexual function.

Avoiding Prostate Biopsies in Patients at Low Risk for Prostate Cancer: A Prospective Evaluation of a PSA-Density-Based Safety Net.

INTRODUCTION AND OBJECTIVES: Decision-making to perform prostate biopsy should include individual risk assessment. Patients classified as low risk by the Rotterdam Prostate Cancer Risk Calculator are advised to forego biopsy (PBx). There is concern about missing clinically significant prostate cancer (csPCa). A clear pathway for follow-up is needed. MATERIAL AND METHODS: Data for 111 consecutive patients were collected. Patients were encouraged to adhere to a PSA-density-based safety net after PBx was omitted. Cut off values indicating a re-evaluation were PSA density >0.15 ng/mL/ccm in PBx-naïve patients and >0.2 ng/mL/ccm in men with past-PBx. Primary endpoint was whether men had their PSA taken regularly. Secondary endpoint was whether a new multiparametric MRI was performed when PSA-density increased. Tertiary endpoint was whether biopsy was performed when risk stratification revealed an increased risk. RESULTS: Median follow-up was 12 months (IQR 9-15 months). The primary endpoint was reached by 97.2% (n = 106). The secondary endpoint was reached by 30% (n = 3). The tertiary endpoint was reached by 50% (n = 2). Histopathologic analyses revealed csPCa in none of these cases. Risk stratification did not change (p = 0.187) with the majority of patients (89.2%, n = 99). CONCLUSION: The concern of missing csPCa when omitting PBx in the risk-stratified pathway may be negated. Changes in risk stratification during follow-up should lead to subsequent PBx. We suggest implementing a safety net based on PSA density and digital rectal examination (DRE).

PROPOSe: A Real-life Prospective Study of Proclarix, a Novel Blood-based Test to Support Challenging Biopsy Decision-making in Prostate Cancer.

BACKGROUND: Prostate-specific antigen (PSA)-based detection of prostate cancer (PCa) often leads to negative biopsy results or detection of clinically insignificant PCa, more frequently in the PSA range of 2-10 ng/ml, in men with increased prostate volume and normal digital rectal examination (DRE). OBJECTIVE: This study evaluated the accuracy of Proclarix, a novel blood-based diagnostic test, to help in biopsy decision-making in this challenging patient population. DESIGN, SETTING, AND PARTICIPANTS: Ten clinical sites prospectively enrolled 457 men presenting for prostate biopsy with PSA between 2 and 10 ng/ml, normal DRE, and prostate volume ≥35 cm3. Transrectal ultrasound-guided and multiparametric magnetic resonance imaging (mpMRI)-guided biopsy techniques were allowed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Serum samples were tested blindly at the end of the study. Diagnostic performance of Proclarix risk score was established in correlation to systematic biopsy outcome and its performance compared with %free PSA (%fPSA) and the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculator (RC) as well as Proclarix density compared with PSA density in men undergoing mpMRI. RESULTS AND LIMITATIONS: The sensitivity of Proclarix risk score for clinically significant PCa (csPCa) defined as grade group (GG) ≥2 was 91% (n = 362), with higher specificity than both %fPSA (22% vs 14%; difference = 8% [95% confidence interval {CI}, 2.6-14%], p = 0.005) and RC (22% vs 15%; difference = 7% [95% CI, 0.7-12%], p = 0.028). In the subset of men undergoing mpMRI-fusion biopsy (n = 121), the specificity of Proclarix risk score was significantly higher than PSA density (26% vs 8%; difference = 18% [95% CI, 7-28%], p < 0.001), and at equal sensitivity of 97%, Proclarix density had an even higher specificity of 33% [95% CI, 23-43%]. CONCLUSIONS: In a routine use setting, Proclarix accurately discriminated csPCa from no or insignificant PCa in the most challenging patients. Proclarix represents a valuable rule-out test in the diagnostic algorithm for PCa, alone or in combination with mpMRI. PATIENT SUMMARY: Proclarix is a novel blood-based test with the potential to accurately rule out clinically significant prostate cancer, and therefore to reduce the number of unneeded biopsies.

Identification of patients at risk for biochemical recurrence after radical prostatectomy with intra-operative frozen section.

OBJECTIVE: To identify patients at risk for biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) with intra-operative whole-mount frozen section (FS) of the prostate. MATERIAL AND METHODS: We examined differences in BCR between patients with initial negative surgical margins at FS, patients with final negative surgical margins with initial positive margins at FS without residual PCa after secondary tumour resection, and patients with final negative surgical margins with initially positive margins at FS with residual PCa in the secondary tumour resection specimen. Institutional data of 883 consecutive patients undergoing RP were collected. Intra-operative whole-mount FS was routinely used to check for margin status and, if necessary, to resect more periprostatic tissue in order to achieve negative margins. Patients with lymph node-positive disease or final positive surgical margins were excluded from the analysis. Kaplan-Meier curves and multivariable Cox proportional hazards regression analyses adjusting for clinical covariates were employed to examine differences in biochemical recurrence-free survival (BRFS) according to the resection status mentioned above. RESULTS: The median follow-up was 22.4 months. The 1- and 2-year BRFS rates in patients with (81.0% and 72.9%, respectively; P = 0.001) and without residual PCa (90.3% and 82.3%, respectively; P = 0.033) after secondary tumour resection were significantly lower compared to patients with initial R0 status (93.4% and 90.9%, respectively). On multivariable Cox regression only residual PCa in the secondary tumour resection was associated with a higher risk of BCR compared to initial R0 status (hazard ratio 1.99, 95% confidence interval 1.01-3.92; P = 0.046). CONCLUSION: Despite being classified as having a negative surgical margin, patients with residual PCa in the secondary tumour resection specimen face a high risk of BCR. These findings warrant closer post-RP surveillance of this particular subgroup. Further research of this high-risk subset of patients should focus on examining whether these patients benefit from early salvage therapy and how resection status impacts oncological outcomes in the changing landscape of PCa treatment.

Determinants of self-reported functional status (EPIC-26) in prostate cancer patients prior to treatment.

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.

Changing the Prostate Cancer Detection Paradigm: Clinical Application of European Association of Urology Guideline-recommended Magnetic Resonance Imaging-based Risk Stratification in Men with Suspected Prostate Cancer.

BACKGROUND: Multiparametric magnetic resonance imaging using the Prostate Imaging Reporting and Data System version 2.1 allows for a personalized, risk-stratified approach to indicating prostate biopsies (PBx) in order to reduce PBx and concomitant complications in men with suspected prostate cancer (PCa). One way to achieve this goal is to implement the risk-stratified pathway (RSP) using the Rotterdam Prostate Cancer Risk Calculator. OBJECTIVE: To describe the clinical implementation of the RSP and to examine its impact on the number of PBx and the resulting changes in the PCa detection pattern compared with men undergoing PBx in a detection-focused pathway (DFP) without prior risk assessment. DESIGN, SETTING, AND PARTICIPANTS: An institutional dataset of 505 consecutive patients with suspected PCa between July 2019 and February 2020 was used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Chi-square test and Mann-Whitney U test were employed to examine differences in the number of PBx and the PCa detection pattern between the DFP (n = 195, 38.6%) and the RSP (n = 310, 61.4%). To minimize differences in risk stratification, inverse probability of treatment weighting was used. RESULTS AND LIMITATIONS: After implementing the RSP, the overall biopsy rate could be reduced by 11.2% (100% vs 88.8%, p < 0.001. Additionally, compared with the DFP, the number of biopsy cores per patient was reduced in the RSP (14 [interquartile range {IQR} 14-15] vs 14 [IQR 6-14], p < 0.001) and the detection of clinically significant PCa was increased (44.3% vs 57.7%, p = 0.038). Overdiagnosis of clinically insignificant disease was decreased in the RSP (22.8% vs 12.6%, p = 0.039). CONCLUSIONS: Implementation of the RSP in clinical practice reduced the number of PBx and brought forth a shift in the PCa detection pattern toward clinically significant disease, while reducing overdiagnosis of clinically insignificant disease. PATIENT SUMMARY: In this study, we examined the impact of risk stratification on the number of prostate biopsies (PBx) and the consecutive detection pattern in men with suspected prostate cancer (PCa). We found that the risk-stratified pathway reduced the number of PBx while simultaneously shifting the PCa detection pattern toward clinically significant PCa.

Salvage lymph node dissection in hormone-naïve men: How effective is surgery?

OBJECTIVE: Salvage lymph node dissection (SLND) is still a questionable treatment approach for patients with nodal recurrence of prostate cancer after radical prostatectomy. We assessed the oncological benefit after SLND in hormone-naïve patients as well as the diagnostic accuracy of preoperative prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) scanning. MATERIAL AND METHODS: The study relied on retrospective collected data of 43 hormone-naïve men who received transperitoneal SLND between February 2011 and March 2017 at our institution. The oncological outcome for each patient was observed by serum prostate-specific antigen testing. Postoperative complications within 30 and 90 days were assessed according to the Clavien-Dindo classification. The accuracy of PSMA PET/CT was characterized by calculated sensitivity, specificity, positive, and negative predictive values. RESULTS: Overall 8 patients (18.6%) had a complete biochemical response 40 days after SLND. The median time from SLND to biochemical recurrence was 2 months. Adjuvant treatment encompassing radiotherapy, androgen deprivation therapy, or a combination of both, was administrated in 62.8%. According to the Clavien-Dindo classification, no high-grade complications were observed. Sensitivity and specificity for PSMA PET/CT were respectively 32% (95% confidence interval [CI]: 17.21-51.59) and 91.74% (95% CI: 85.45-95.45). Calculated positive predictive values (PPV) and negative predictive values (NPV) of PSMA PET/CT were 44.44% (95% CI: 25.98-64.58) and 86.72% (95% CI: 83.23-89.57). CONCLUSIONS: For most hormone-naïve men with a nodal recurrence of prostate cancer transperitoneal SLND is neither an appropriate treatment to cure nor an option to delay the need for salvage hormone manipulation. PSMA PET/CT scans in hormone-naïve patients are currently too imprecise to diagnose metastatic sites.

Transurethral resection of bladder tumours: established and new methods of tumour visualisation.

Transurethral resection (TUR) of bladder tumours does not only serve diagnostic purposes by securing histological proof of the disease but might also resemble the final therapy. During recent years, technical innovations improved the intraoperative detection and visibility of tumourous lesions during TUR. The most important techniques, which have individually found their way into international guidelines, are photodynamic imaging (PDI) and narrowband imaging (NBI). Furthermore, there are more or less experimental approaches such as optical coherence tomography (OCT), confocal laser endomicroscopy (CLE), red/green/blue analysis (RGB) of WLC. Moreover, the combination of two or more techniques in a multiparametric setting is another development in improving intraoperative imaging. The aim of this review is to describe today's knowledge of the more established methods and to depict the most recent developments in intraoperative imaging.

De novo neurogenic bladder dysfunction after salvage lymph node dissection in patients with nodal recurrence of prostate cancer.

AIMS: To examine the impact of Salvage lymph node dissection (SLND) on bladder function and oncological outcome in hormone naïve patients with nodal recurrence of prostate cancer (PCa) after radical prostatectomy (RP). METHODS: In a prospective study between October 2015 and November 2016, 20 patients underwent transperitoneal SLND for nodal recurrence of PCa after RP at our institution. Standardized urodynamics were performed pre- and postoperatively after 6 weeks, 3, and 6 to 12 months. Prostate-specific antigen (PSA) levels were used to monitor the oncological outcome. Perioperative outcomes encompassed, among others, type of complications after surgery classified to Clavien-Dindo. RESULTS: The proportion of patients with neurogenic bladder dysfunction was postoperative at 6 weeks, 3, and 6 to 12 months 78.5%, 70%, and 45.5%, respectively. Compared to preoperative urodynamics, follow-ups revealed a statistical significant cleavage of bladder wall compliance until six to twelve months after SLND (34.5 vs 22 mL/cmH2 O, P = 0.044). Referring to the oncological outcome all patients experienced a PSA progression, 10 patients (50%) within 11 weeks after surgery. Overall, four patients (20%) suffered from a postoperative complication after SLND, which comprises Clavien grade I-IIIa. CONCLUSIONS: Transperitoneal SLND, as a treatment option for patients with nodal recurrence of PCa after RP reveals additional potential pitfalls than previously reported. Urodynamics reveal a significant impact of SLND on postoperative functional bladder dysfunctions. Therefore, informed consent prior to SLND should include the risk of persistent low compliance bladder.

Effectiveness of Adjuvant Chemotherapy After Radical Cystectomy for Locally Advanced and/or Pelvic Lymph Node-Positive Muscle-invasive Urothelial Carcinoma of the Bladder: A Propensity Score-Weighted Competing Risks Analysis.

BACKGROUND: The benefit of adjuvant chemotherapy (AC) for muscle-invasive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) is controversial. OBJECTIVE: To assess the effectiveness of AC after RC for muscle-invasive UCB in contemporary European routine practice. DESIGN, SETTING, AND PARTICIPANTS: By using a prospectively collected European multicenter database, we compared survival outcomes between patients who received AC versus observation after RC for locally advanced (pT3/T4) and/or pelvic lymph node-positive (pN+) muscle-invasive UCB in 2011. INTERVENTION: AC versus observation after RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Inverse probability of treatment weighting (IPTW)-adjusted Cox regression and competing risks analyses were performed to compare overall survival (OS) as well as cancer-specific and other-cause mortality between patients who received AC versus observation. RESULTS AND LIMITATIONS: Overall, 224 patients who received AC (n = 84) versus observation (n = 140) were included. The rate of 3-yr OS in patients who received AC versus observation was 62.1% versus 40.9%, respectively (p = 0.014). In IPTW-adjusted Cox regression analysis, AC versus observation was associated with an OS benefit (hazard ratio: 0.47; 95% confidence interval [CI]: 0.25-0.86; p = 0.014). In IPTW-adjusted competing risks analysis, AC versus observation was associated with a decreased risk of cancer-specific mortality (subhazard ratio: 0.51; 95% CI: 0.26-0.98; p = 0.044) without any increased risk of other-cause mortality (subhazard ratio: 0.48; 95% CI: 0.14-1.60; p = 0.233). Limitations include the relatively small sample size as well as the potential presence of unmeasured confounders related to the observational study design. CONCLUSIONS: We found that AC versus observation was associated with a survival benefit after RC in patients with pT3/T4 and/or pN+ UCB. These results should encourage physicians to deliver AC and researchers to pursue prospective or large observational investigations. PATIENT SUMMARY: Overall survival and cancer-specific survival benefit was found in patients who received adjuvant chemotherapy relative to observation after radical cystectomy for locally advanced and/or pelvic lymph node-positive bladder cancer.

Optimizing outcome reporting after radical cystectomy for organ-confined urothelial carcinoma of the bladder using oncological trifecta and pentafecta.

UNLABELLED: Radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) is associated with heterogeneous functional and oncological outcomes. The aim of this study was to generate trifecta and pentafecta criteria to optimize outcome reporting after RC. METHODS: We interviewed 50 experts to consider a virtual group of patients (age ≤ 75 years, ASA score ≤ 3) undergoing RC for a cT2 UCB and a final histology of ≤pT3pN0M0. A ranking was generated for the three and five criteria with the highest sum score. The criteria were applied to the Prospective Multicenter Radical Cystectomy Series 2011. Multivariable binary logistic regression analyses were used to evaluate the impact of clinical and histopathological parameters on meeting the top selected criteria. RESULTS: The criteria with the highest sum score were negative soft tissue surgical margin, lymph node (LN) dissection of at least 16 LNs, no complications according to Clavien-Dindo grade 3-5 within 90 days after RC, treatment-free time between TUR-BT with detection of muscle-invasive UCB and RC <3 months and the absence of local UCB-recurrence in the pelvis ≤12 months. The first three criteria formed trifecta, and all five criteria pentafecta. A total of 334 patients qualified for final analysis, whereas 35.3 and 29 % met trifecta and pentafecta criteria, respectively. Multivariable analyses showed that the relative probability of meeting trifecta and pentafecta decreases with higher age (3.2 %, p = 0.043 and 3.3 %, p = 0.042) per year, respectively. CONCLUSIONS: Trifecta and pentafecta incorporate essential criteria in terms of outcome reporting and might be considered for the improvement of standardized quality assessment after RC for UCB.

Risk stratification for locoregional recurrence after radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: To externally validate the Christodouleas risk model incorporating pathological tumor stage, lymph node (LN) count and soft tissue surgical margin (STSM) and stratifying patients who develop locoregional recurrence (LR) after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). In addition, we aimed to generate a new model including established clinicopathological features that were absent in the Christodouleas risk model. METHODS: Prospectively assessed multicenter data from 565 patients undergoing RC for UCB in 2011 qualified for final analysis. For the purpose of external validation, risk group stratification according to Christodouleas was performed. Competing-risk models were calculated to compare the cumulative incidences of LR after RC. RESULTS: After a median follow-up of 25 months (interquartile range 19-29), the LR-rate was 11.5 %. The Christodouleas model showed a predictive accuracy of 83.2 % in our cohort. In multivariable competing-risk analysis, tumor stage ≥pT3 (HR 4.32, p < 0.001), positive STSM (HR 2.93, p = 0.005), lymphovascular invasion (HR 3.41, p < 0.001), the number of removed LNs <10 (HR 2.62, p < 0.001) and the administration of adjuvant chemotherapy (HR 0.40, p = 0.008) independently predicted the LR-rate. The resulting risk groups revealed significant differences in LR-rates after 24 months with 4.8 % for low-risk patients, 14.7 % for intermediate-risk patients and 38.9 % for high-risk patients (p < 0.001 for all), with a predictive accuracy of 85.6 %, respectively. CONCLUSIONS: The Christodouleas risk model has been successfully externally validated in the present prospective series. However, this analysis finds that overall model performance may be improved by incorporating lymphovascular invasion. After external validation of the newly proposed risk model, it may be used to identify patients who benefit from an adjuvant therapy and suit for inclusion in clinical trials.

Impact of real-time elastography on magnetic resonance imaging/ultrasound fusion guided biopsy in patients with prior negative prostate biopsies.

PURPOSE: The fusion of multiparametric resonance imaging and ultrasound has been proven capable of detecting prostate cancer in different biopsy settings. The addition of real-time elastography promises to increase the precision of the outcome of targeted biopsies. We investigated whether real-time elastography improves magnetic resonance imaging/transrectal ultrasound fusion targeted biopsy in patients after previous negative biopsies. MATERIALS AND METHODS: Prospectively 121 men underwent 3T magnetic resonance imaging. Using magnetic resonance imaging/real-time elastography fusion every suspicious lesion was characterized according to its tissue density and sampled by 2 fusion guided targeted biopsies. Additionally, all patients underwent 12-core systematic biopsy. The detection rate of clinically significant and insignificant cancers was compared between targeted und systematic biopsies. The accuracy to predict high grade prostate cancer was evaluated for with the PI-RADS scoring system and compared to the magnetic resonance imaging/real-time elastography fusion score. RESULTS: Overall prostate cancer was detected in 52 patients (43%). Targeted fusion guided biopsy revealed prostate cancer in 32 men (26.4%) and systematic biopsy in 46 (38%). The proportion of clinically significant cancers was higher for targeted biopsy (90.6%) compared to systematic biopsy (73.9%). The detection rate per core was higher for targeted biopsies (14.7%) compared to systematic biopsies (6.5%, p <0.001). The prediction of biopsy result according to magnetic resonance imaging/real-time elastography fusion was better (AUC 0.86) than magnetic resonance imaging alone (AUC 0.79). Sensitivity and specificity for magnetic resonance imaging/real-time elastography fusion was 77.8% and 77.3% vs 74.1% and 62.9% for magnetic resonance imaging. CONCLUSIONS: Magnetic resonance imaging/transrectal ultrasound fusion enhances the likelihood of detecting clinically significant cancers in a repeat biopsy setting. Adding real-time elastography to magnetic resonance imaging supports the characterization of cancer suspicious lesions.

Effect of perioperative complications and functional outcomes on health-related quality of life after radical prostatectomy.

PURPOSE: Radical prostatectomy is a commonly performed procedure with perioperative complication rates of 30 % using standardized reporting methodology. We aim to determine whether perioperative complications and functional outcomes impact quality of life 1 year after surgical treatment. PATIENTS AND METHODS: Quality of life, functional and oncological outcomes were assessed in patients who underwent open retropubic radical prostatectomy at a single academic institution between 2003 and 2009, preoperatively and 1 year after surgery using the EORTC QLQ-C30, the IIEF-5 and an institutional questionnaire. Perioperative complications were recorded using the Clavien-Dindo classification. Patients without complications were compared to patients with any, low- or high-grade complications. The global health score domain of the EORTC QLQ-C30 is reported for various oncological and functional outcomes and contrasted to stratified categories of complications and functional outcomes. RESULTS: A full dataset was available for 29.5 % (n = 856) of all patients. The overall complication rate was 27.5 % (235/856). A total of 307 complications were recorded of whom 88.9 % (273/307) were low grade. In this study, population global health perception did not decline after surgery (70.5 ± 21.2 vs. 74.4 ± 19.7; p < 0.0001). Complications showed only statistical but no clinical meaningful influence on global health perception as well as on functional and symptom scales. Patients who met combined outcome criteria experienced the best postoperative global health score (86.0 ± 13.1 and 86.0 ± 14.2). CONCLUSIONS: Perioperative complications and functional outcomes have a measurable impact on quality of life 1 year following surgery. While perioperative complications have a statistical effect, functional outcomes showed a clinically more profound effect on postoperative global health perception.

Prediction of 90-day mortality after radical cystectomy for bladder cancer in a prospective European multicenter cohort.

BACKGROUND: Despite recent improvements, radical cystectomy (RC) is still associated with adverse rates for 90-d mortality. OBJECTIVE: To validate the performance of the Isbarn nomogram incorporating age and postoperative tumor characteristics for predicting 90-d RC mortality in a multicenter series and to generate a new nomogram based strictly on preoperative parameters. DESIGN, SETTING, AND PARTICIPANTS: Data of 679 bladder cancer (BCa) patients treated with RC at 18 institutions in 2011 were prospectively collected, from which 597 patients were eligible for final analysis. INTERVENTION: RC for BCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: An established prediction tool, the Isbarn nomogram, was applied to our cohort. For the purpose of external validation, model discrimination was measured using the receiver operating characteristics-derived area under the curve. Calibration plots examined the relationship between predicted and observed probabilities. Univariable and multivariable logistic regression models were fitted to assess the impact of preoperative characteristics on 90-d mortality. RESULTS AND LIMITATIONS: The 30-, 60-, and 90-d mortality rates in the development cohort (n=597) were 2.7%, 6.7%, and 9.0%, respectively. The Isbarn nomogram predicted individual 90-d mortality with an accuracy of 68.6%. Our preoperative multivariable model identified age (odds ratio [OR]:1.052), American Society of Anesthesiologists score (OR: 2.274), hospital volume (OR: 0.982), clinically lymphatic metastases (OR: 4.111), and clinically distant metastases (OR: 7.788) (all p<0.05) as independent predictors of 90-d mortality (predictive accuracy: 78.8%). Our conclusions are limited by the lack of an external validation of the preoperative model. CONCLUSIONS: The Isbarn nomogram was validated with moderate discrimination. Our newly developed model consisting of preoperative characteristics might outperform existing models. Our model might be particularly suitable for preoperative patient counseling. PATIENT SUMMARY: The current report validated an established nomogram predicting 90-d mortality in patients with bladder cancer after radical cystectomy (RC). We developed a new prediction tool consisting of strictly preoperative parameters, thus allowing clinicians an optimal consultation for RC candidates.

MicroRNA-205, a novel regulator of the anti-apoptotic protein Bcl2, is downregulated in prostate cancer.

Decreased expression of the microRNA miR-205 has been observed in multiple tumour types due to its role in the epithelial to mesenchymal transition, which promotes metastasis. We determined the expression of miR-205 in 111 archival samples of prostate carcinoma and found it to be strongly reduced in most samples, with a median expression level of 16% in comparison to benign tissue from the same patient. Lower miR-205 expression correlated significantly with tumour size and miR-205 levels decreased with increasing Gleason score from 7a=3+4 to 8=4+4. In addition, we describe the anti-apoptotic protein BCL2 as a target of miR-205, relevant for prostate cancer due to its role in prognosis of primary tumours and in the appearance of androgen independence. The repression of BCL2 by miR-205 was confirmed using reporter assays and western blotting. BCL2 mRNA expression in the same collective of prostate cancer tissue samples was associated with higher Gleason score and extracapsular extension of the tumour (pT3). Consistent with its anti-apoptotic target BCL2, miR-205 promoted apoptosis in prostate cancer cells in response to DNA damage by cisplatin and doxorubicin in the prostate cancer cell lines PC3 and LnCap. MiR-205 also inhibited proliferation in these cell lines.

Intraoperative frozen section of the prostate decreases positive margin rate while ensuring nerve sparing procedure during radical prostatectomy.

PURPOSE: We evaluated whether intraoperative frozen section analysis of the prostate surface might provide significant information to ensure nerve sparing and minimize the positive margin rate. MATERIALS AND METHODS: In 236 patients treated with radical prostatectomy between June 2011 and September 2012 whole surface frozen section analysis of the removed prostate was done intraoperatively. The apex and base were circumferentially dissected as well as the whole posterolateral tissue corresponding to the neurovascular bundles. Multiple perpendicular sections were cut systematically for frozen section analysis. Pathology results were reported to navigate the procedure. RESULTS: Frozen section analysis identified positive surgical margins in 22% of cases, including the neurovascular bundles in 56.9%, apex in 34.5% and base in 8.6%. Of positive frozen section cases 92.3% could be converted to negative status, while 7.7% remained positive. The final positive margin rate in the total cohort was 3%, including a false-negative frozen section rate of 1.6%. In 14.8% of cases the initial nerve sparing plan was changed intraoperatively due to the positive frozen section and the secondary resected specimen detected cancer in 25%. Final pathology results showed Gleason upgrading or up-staging in 40.7% of cases compared to preoperative variables. When comparing patients with positive vs negative frozen sections, preoperative variables did not significantly differ, while postoperatively pathological stage, tumor volume, operative time and final margin status differed significantly. Of patients with exclusively unilateral positive biopsies 13% had a positive surgical margin intraoperatively on the opposite, biopsy negative side. CONCLUSIONS: The surface frozen section technique is associated with a low false-negative surgical margin rate. It might allow for safer preservation of functional anatomical structures in misclassified patients or even patients at higher preoperative risk.

Multiparametric ultrasound of the prostate: adding contrast enhanced ultrasound to real-time elastography to detect histopathologically confirmed cancer.

PURPOSE: We prospectively assessed whether a combined approach of real-time elastography and contrast enhanced ultrasound would improve prostate cancer visualization. MATERIAL AND METHODS: Between June 2011 and January 2012, 100 patients with biopsy proven prostate cancer underwent preoperative transrectal multiparametric ultrasound combining real-time elastography and contrast enhanced ultrasound. After initial elastographic screening for suspicious lesions, defined as blue areas with decreased tissue strain, each lesion was allocated to the corresponding prostate sector. The target lesion was defined as the largest cancer suspicious area. Perfusion was monitored after intravenous injection of contrast agent. Target lesions were examined for hypoperfusion, normoperfusion or hyperperfusion. Imaging results were correlated with final pathological evaluation on whole mount slides after radical prostatectomy. RESULTS: Of 100 patients 86 were eligible for final analysis. Real-time elastography detected prostate cancer with 49% sensitivity and 73.6% specificity. Histopathology confirmed malignancy in 56 of the 86 target lesions (65.1%). Of these 56 lesions 52 (92.9%) showed suspicious perfusion, including hypoperfusion in 48.2% and hyperperfusion in 48.2%, while only 4 (7.1%) showed normal perfusion patterns (p = 0.001). The multiparametric approach decreased the false-positive value of real-time elastography alone from 34.9% to 10.3% and improved the positive predictive value of cancer detection from 65.1% to 89.7%. CONCLUSIONS: Perfusion patterns of prostate cancer suspicious elastographic lesions are heterogeneous. However, the combined approach of real-time elastography and contrast enhanced ultrasound in this pilot study significantly decreased false-positive results and improved the positive predictive value of correctly identifying histopathological cancer.

Type 10 soluble adenylyl cyclase is overexpressed in prostate carcinoma and controls proliferation of prostate cancer cells.

cAMP signaling plays an essential role in modulating the proliferation of different cell types, including cancer cells. Until now, the regulation of this pathway was restricted to the transmembrane class of adenylyl cyclases. In this study, significant overexpression of soluble adenylyl cyclase (sAC), an alternative source of cAMP, was found in human prostate carcinoma, and therefore, the contribution of this cyclase was investigated in the prostate carcinoma cell lines LNCaP and PC3. Suppression of sAC activity by treatment with the sAC-specific inhibitor KH7 or by sAC-specific knockdown mediated by siRNA or shRNA transfection prevented the proliferation of prostate carcinoma cells, led to lactate dehydrogenase release, and induced apoptosis. Cell cycle analysis revealed a significant rise in the G(2) phase population 12 h after sAC inhibition, which was accompanied by the down-regulation of cyclin B(1) and CDK1. sAC-dependent regulation of proliferation involves the EPAC/Rap1/B-Raf signaling pathway. In contrast, protein kinase A does not play a role. In conclusion, this study suggests a novel sAC-dependent signaling pathway that controls the proliferation of prostate carcinoma cells.