Vitamin D Metabolites in Nonmetastatic High-Risk Prostate Cancer Patients with and without Zoledronic Acid Treatment after Prostatectomy.

There are limited and discrepant data on prostate cancer (PCa) and vitamin D. We investigated changes in three vitamin D3 metabolites in PCa patients after prostatectomy with zoledronic acid (ZA) treatment regarding their metastasis statuses over four years. In 32 patients from the ZEUS trial, 25(OH)D3, 24,25(OH)2D3, and 1,25(OH)2D3 were measured with liquid chromatography coupled with tandem mass spectrometry at four time points. All the patients received daily calcium and vitamin D3. Bone metastases were detected in 7 of the 17 ZA-treated patients and in 5 of the 15 controls (without ZA), without differences between the groups (p = 0.725). While 25(OH)D3 and 24,25(OH)2D3 increased significantly after the study's start, with following constant values, the 1,25(OH)2D3 concentrations remained unchanged. ZA treatment did not change the levels of the three metabolites. 25(OH)D3 and 24,25(OH)2D3 were not associated with the development of bone metastases. In contrast, 1,25(OH)2D3 was also higher in patients with bone metastasis before the study's start. Thus, in high-risk PCa patients after prostatectomy, 25(OH)D3, 24,25(OH)2D3, and 1,25(OH)2D3 were not affected by supportive ZA treatment or by the development of metastasis over four years, with the exception of 1,25(OH)2D3, which was constantly higher in metastatic patients. There might be potential prognostic value if the results can be confirmed.

Comparison of PHI and PHI Density for Prostate Cancer Detection in a Large Retrospective Caucasian Cohort.

BACKGROUND: Beyond prostate-specific antigen (PSA), other biomarkers for prostate cancer (PCa) detection are available and need to be evaluated for clinical routine. OBJECTIVE: The aim of the study was to evaluate the Prostate Health Index (PHI) density (PHID) in comparison with PHI in a large Caucasian group >1,000 men. METHODS: PHID values were used from available patient data with PSA, free PSA, and [-2]pro-PSA and prostate volume from 3 former surveys from 2002 to 2014. Those 1,446 patients from a single-center cohort included 701 men with PCa and 745 with no PCa. All patients received initial or repeat biopsies. The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curves comparing area under the ROC curves (AUCs), precision-recall approach, and decision curve analysis (DCA). RESULTS: PHID medians differed almost 2-fold between PCa (1.12) and no PCa (0.62) in comparison to PHI (48.6 vs. 33; p always <0.0001). However, PHID and PHI were equal regarding the AUC (0.737 vs. 0.749; p = 0.226), and the curves of the precision-recall analysis also overlapped in the sensitivity range between 70 and 100%. DCA had a maximum net benefit of only ∼5% for PHID versus PHI between 45 and 55% threshold probability. Contrary, in the 689 men with a prostate volume ≤40 cm3, PHI (AUC 0.732) showed a significant larger AUC than PHID (AUC 0.69, p = 0.014). CONCLUSIONS: Based on DCA, PHID had only a small advantage in comparison with PHI alone, while ROC analysis and precision-recall analysis showed similar results. In smaller prostates, PHI even outperformed PHID. The increment for PHID in this large Caucasian cohort is too small to justify a routine clinical use.

PHI density prospectively improves prostate cancer detection.

PURPOSE: To evaluate the Prostate Health Index (PHI) density (PHID) in direct comparison with PHI in a prospective large cohort. METHODS: PHID values were calculated from prostate-specific antigen (PSA), free PSA and [- 2]proPSA and prostate volume. The 1057 patients included 552 men with prostate cancer (PCa) and 505 with no evidence of malignancy (NEM). In detail, 562 patients were biopsied at the Charité Hospital Berlin and 495 patients at the Sana Hospital Offenbach. All patients received systematic or magnetic resonance imaging (MRI)/ultrasound fusion-guided biopsies. The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curves comparing areas under the ROC-curves (AUC). The decision curve analysis (DCA) was performed with the MATLAB Neural Network Toolbox. RESULTS: PHID provided a significant larger AUC than PHI (0.835 vs. 0.801; p = 0.0013) in our prospective cohort of 1057 men from 2 centers. The DCA had a maximum net benefit of ~ 5% for PHID vs. PHI between 35 and 65% threshold probability. In those 698 men within the WHO-calibrated PSA grey-zone up to 8 ng/ml, PHID was also significantly better than PHI (AUC 0.819 vs. 0.789; p = 0.0219). But PHID was not different from PHI in the detection of significant PCa. CONCLUSIONS: Based on ROC analysis and DCA, PHID had an advantage in comparison with PHI alone to detect any PCa but PHI and PHID performed equal in detecting significant PCa.

The discriminative ability of Prostate Health Index to detect prostate cancer is enhanced in combination with miR-222-3p.

BACKGROUND: There is an urgent need for better prostate cancer (PCa) biomarkers due to the low specificity of prostate specific antigen (PSA). OBJECTIVE: Prostate Health Index (PHI) is an advanced PSA-based test for early detection of PCa. The present study aim was to investigate the potential improvement of diagnostic accuracy of PHI by its combination with suitable discriminative microRNAs (miRNAs). METHODS: A two-phase study was performed. In a discovery phase, a panel of 177 miRNAs was measured in ten men with biopsy proven PCa and ten men with histologically no evidence of malignancy (NEM). These results were validated in a second phase including 25 patients in each group. The patients of all groups were matched regarding their PSA values and PHI were measured. RESULTS: Based on data in the discovery phase, four elevated miRNAs were selected as potential miRNA candidates for further validation. A combination of miR-222-3p as the best discriminative miRNA with PHI extended the diagnostic accuracy of PHI from an AUC value of 0.690 to 0.787 and resulted in a sensitivity of 72.0% and a specificity of 84.0%. CONCLUSION: Circulating microRNAs show useful diagnostic potential in combination with common used biomarkers to enhance their diagnostic power.

A Novel Predictor Tool of Biochemical Recurrence after Radical Prostatectomy Based on a Five-MicroRNA Tissue Signature.

Within five to ten years after radical prostatectomy (RP), approximately 15-34% of prostate cancer (PCa) patients experience biochemical recurrence (BCR), which is defined as recurrence of serum levels of prostate-specific antigen >0.2 µg/L, indicating probable cancer recurrence. Models using clinicopathological variables for predicting this risk for patients lack accuracy. There is hope that new molecular biomarkers, like microRNAs (miRNAs), could be potential candidates to improve risk prediction. Therefore, we evaluated the BCR prognostic capability of 20 miRNAs, which were selected by a systematic literature review. MiRNA expressions were measured in formalin-fixed, paraffin-embedded (FFPE) tissue RP samples of 206 PCa patients by RT-qPCR. Univariate and multivariate Cox regression analyses were performed, to assess the independent prognostic potential of miRNAs. Internal validation was performed, using bootstrapping and the split-sample method. Five miRNAs (miR-30c-5p/31-5p/141-3p/148a-3p/miR-221-3p) were finally validated as independent prognostic biomarkers. Their prognostic ability and accuracy were evaluated using C-statistics of the obtained prognostic indices in the Cox regression, time-dependent receiver-operating characteristics, and decision curve analyses. Models of miRNAs, combined with relevant clinicopathological factors, were built. The five-miRNA-panel outperformed clinically established BCR scoring systems, while their combination significantly improved predictive power, based on clinicopathological factors alone. We conclude that this miRNA-based-predictor panel will be worth to be including in future studies.

Serum Vitamin D is Not Helpful for Predicting Prostate Cancer Aggressiveness Compared with the Prostate Health Index.

PURPOSE: We evaluated the usefulness of serum 25-hydroxyvitamin D as a marker of aggressive prostate cancer and for active surveillance compared to PHI (Prostate Health Index). MATERIALS AND METHODS: Of 480 prospectively biopsied men 222 had prostate cancer and 258 had no evidence of malignancy. In all men prostate specific antigen was less than 20 ng/ml. We measured 25-hydroxyvitamin D, prostate specific antigen, free prostate specific antigen and -2proPSA using a commercially available immunoassay system. PHI was calculated according to the equation, -2proPSA/free prostate specific antigen × âˆšPSA. We determined 25-hydroxyvitamin D using a 2-step competitive binding immunoenzymatic vitamin D assay. RESULTS: The 25-hydroxyvitamin D concentrations were not associated with Gleason grade according to the 2014 ISUP (International Society of Urological Pathology) consensus conference Gleason grading system. PHI values were higher with increasing Gleason grade. Median 25-hydroxyvitamin D did not differ between men with prostate cancer vs no evidence of malignancy (50.6 vs 48.2 nmol/l, p = 0.192) or in ISUP Gleason subgroups despite seasonal variations of 25-hydroxyvitamin D. However, PHI values significantly differed between the subgroup with no evidence of malignancy and all Gleason subgroups (p <0.0001). The ROCs of all men revealed an advantage of PHI over 25-hydroxyvitamin D (AUC 0.78 vs 0.535, p <0.0001). PHI could also significantly better separate patients with no evidence of malignancy from those with nonaggressive disease (ISUP Gleason grade 1) from those with aggressive prostate cancer (ISUP Gleason grades 2-5). CONCLUSIONS: It remains highly improbable that 25-hydroxyvitamin D could be used as decision or selection marker for aggressive prostate cancer or for active surveillance compared to accepted markers, as recently suggested.

Integration of tissue metabolomics, transcriptomics and immunohistochemistry reveals ERG- and gleason score-specific metabolomic alterations in prostate cancer.

Integrated analysis of metabolomics, transcriptomics and immunohistochemistry can contribute to a deeper understanding of biological processes altered in cancer and possibly enable improved diagnostic or prognostic tests. In this study, a set of 254 metabolites was determined by gas-chromatography/liquid chromatography-mass spectrometry in matched malignant and non-malignant prostatectomy samples of 106 prostate cancer (PCa) patients. Transcription analysis of matched samples was performed on a set of 15 PCa patients using Affymetrix U133 Plus 2.0 arrays. Expression of several proteins was immunohistochemically determined in 41 matched patient samples and the association with clinico-pathological parameters was analyzed by an integrated data analysis. These results further outline the highly deregulated metabolism of fatty acids, sphingolipids and polyamines in PCa. For the first time, the impact of the ERG translocation on the metabolome was demonstrated, highlighting an altered fatty acid oxidation in TMPRSS2-ERG translocation positive PCa specimens. Furthermore, alterations in cholesterol metabolism were found preferentially in high grade tumors, enabling the cells to create energy storage. With this integrated analysis we could not only confirm several findings from previous metabolomic studies, but also contradict others and finally expand our concepts of deregulated biological pathways in PCa.

Synthesis, crystal structure and effect of indeno[1,2-b]indole derivatives on prostate cancer in vitro. Potential effect against MMP-9.

A highly regiospecific synthesis of a series of indenoindoles is reported, together with X-ray studies and their activity against human prostate cancer cells PC-3 and LNCaP in vitro. The most effective compound 7,7-dimethyl-5-[(3,4-dichlorophenyl)]-(4bRS,9bRS)-dihydroxy-4b,5,6,7,8,9bhexahydro-indeno[1,2-b]indole-9,10-dione 7q reduced the viability in both cell lines in a time and dose-dependent manner. Inhibitory effects were also observed on the adhesion, migration, and invasion of the prostate cancer cells as well as on clonogenic possibly by inhibition of MMP-9 activity. Molecular docking of 7q and 6k into MMP-9 human active site was also performed to determine the probable binding mode.

Urinary thiosulfate as failed prostate cancer biomarker - an exemplary multicenter re-evaluation study.

BACKGROUND: In 2013, thiosulfate in urine has been proposed as promising prostate cancer (PCa) biomarker. However, a missing comparison with other proven PCa markers suggested a re-evaluation study. Therefore, together with the authors from the initial study, the diagnostic accuracy of thiosulfate was compared with that of urinary prostate cancer associated 3 (PCA3), serum prostate health index (Phi), and percent free prostate-specific antigen (%fPSA). Thiosulfate was further measured in a multicenter approach to exclude center-related biases. METHODS: Thiosulfate, calculated as ratio of thiosulfate to urinary creatinine (TS/Crea ratio), was measured in two cohorts in a total of 269 patients. In the retrospective study (n=160) PCA3, Phi, PSA, and %fPSA were compared with the TS/Crea ratio between patients with and without PCa according to the prostate needle biopsy results. The second prospective cohort included 109 patients from four centers. RESULTS: The median TS/Crea ratio was not statistically different between the patients with and without PCa. The receiver-operating characteristics showed that the TS/Crea ratio was unable to discriminate between patients with and without PCa in contrast to %fPSA, Phi, and PCA3. In all four centers, the low median TS/Crea ratios (<1 mmol/mol) in both patient cohorts were confirmed and thiosulfate was again not able to distinguish between them (p-values, 0.13-0.90). CONCLUSIONS: This study could not confirm the previously observed high median TS/Crea ratio in PCa patients in comparison to non-PCa patients. Thiosulfate subsequently failed as PCa biomarker while PCA3 and Phi showed the expected diagnostic improvement.

Bone turnover markers in serum and urine as diagnostic, prognostic and monitoring biomarkers of bone metastasis.

Bone metastases are characterized by increased osteoblastic and/or osteolytic processes depending on the tumor type. The altogether destructive effect of metastasis formation promoted by increased metabolic activity raises the release of components from the osseous metabolism into the blood stream. These components are either enzymes directly involved in the alteration processes, metabolites/proteins that develop during this or bone matrix proteins released during this. These biomarkers are categorized in relation to their involvement in the bone formation or resorption as bone formation and resorption markers. Based on a PubMed literature search, a critical appraisal of the various biomarkers for diagnostic, prognostic, and monitoring purposes is given for patients with skeletal metastases caused by breast, prostate, lung, or renal cell carcinomas.

Serum testosterone improves the accuracy of Prostate Health Index for the detection of prostate cancer.

OBJECTIVE: Prostate cancer (PCa) detection suffers from low specificity when using the prostate-specific antigen (PSA) alone. The aim of this study was to investigate the applicability of total testosterone (tT), free testosterone (fT), the fraction (%) of fT to tT (%fT), and bioavailable testosterone (bioT) in serum to improve the diagnostic validity of the serum (-2)pro-PSA-based Prostate Health Index (PHI). DESIGN AND METHODS: Total and free PSA (tPSA, fPSA), (-2)pro-PSA, testosterone, and sex-hormone-binding globulin were measured by automated immunoassays from serum of 193 men scheduled for prostate biopsy (99 PCa, 94 without PCa). fT and bioT were calculated using an online calculator. Statistical analyses were performed by non-parametric tests (Wilcoxon signed rank, Mann-Whitney, Kruskal-Wallis), binary logistic regression, and receiver operating characteristic (ROC) analyses. RESULTS: Compared with the non-malignant controls, PCa patients had significantly higher tPSA concentrations and PHI values, but lower %fPSA values and lower concentrations of tT, fT, and bioT. PCa could be differentiated from controls by PHI, tT, fT, bioT, and %fPSA. PHI showed the largest area under the ROC curve (AUC=0.73) that was increased further by the inclusion of bioT or tT in a binary logistic regression model. The AUC of PHI in patients with tT concentrations of <8nmol/L (indicating biochemical hypogonadism) was significantly larger than that in patients with higher tT values (0.86 vs. 0.70; P=0.024). CONCLUSIONS: The PHI-based discrimination between PCa patients and non-malignant controls could be improved by the simultaneous determination of testosterone. Patients with testosterone concentrations of <8nmol/L have the greatest benefit.

Comparison of surgical technique (open vs. laparoscopic) on pathological and long term functional outcomes following radical prostatectomy.

BACKGROUND: Few studies to date have directly compared outcomes of retropubic (RRP) and laparoscopic (LRP) radical prostatectomy. We investigated a single institution experience with RRP and LRP with respect to functional and pathological outcomes. METHODS: 168 patients who underwent RRP were compared to 171 patients who underwent LRP at our institution. Pathological and functional outcomes including postoperative urinary incontinence and erectile dysfunction (ED) of the two cohorts were examined. RESULTS: Patients had bilateral, unilateral and no nerve sparing technique performed in 83.3%, 1.8% and 14.9% of cases for RRP and 23.4%, 22.8% and 53.8% of cases for LRP, respectively (p < 0.001). Overall positive surgical margin rates were 22.2% among patients who underwent RRP compared to 26.5% of patients who underwent LRP (p = 0.435). Based upon pads/day, urinary continence postoperatively was achieved in 83.2% and 82.8% for RRP and LRP, respectively (p = 0.872). Analysis on postoperative ED was limited due to lack of information on the preoperative erectile status. However, postoperatively there were no differences with respect to ED between the two cohorts (p = 0.151). Based on ICIQ-scores, surgeons with more experience had lower rates of postoperative incontinence irrespective of surgical technique (p = 0.001 and p < 0.001 for continuous and stratified data, respectively). CONCLUSIONS: RRP and LRP represent effective surgical approaches for the treatment of clinically localized prostate cancer. Pathological outcomes are excellent for both surgical techniques. Functional outcomes including postoperative urinary incontinence and ED are comparable between the cohorts. Surgeon experience is more relevant than surgical technique applied.

Tissue metabolite profiling identifies differentiating and prognostic biomarkers for prostate carcinoma.

Metabolomic research offers a deeper insight into biochemical changes in cancer metabolism and is a promising tool for identifying novel biomarkers. We aimed to evaluate the diagnostic and prognostic potential of metabolites in prostate cancer (PCa) tissue after radical prostatectomy. In matched malignant and nonmalignant prostatectomy samples from 95 PCa patients, aminoadipic acid, cerebronic acid, gluconic acid, glycerophosphoethanolamine, 2-hydroxybehenic acid, isopentenyl pyrophosphate, maltotriose, 7-methylguanine and tricosanoic acid were determined within a global metabolite profiling study using gas chromatography/liquid chromatography-mass spectrometry. The data were related to clinicopathological variables like prostate volume, tumor stage, Gleason score, preoperative prostate-specific antigen and disease recurrence in the follow-up. All nine metabolites showed higher concentrations in malignant than in nonmalignant samples except for gluconic acid and maltotriose, which had lower levels in tumors. Receiver -operating characteristics analysis demonstrated a significant discrimination for all metabolites between malignant and nonmalignant tissue with a maximal area under the curve of 0.86 for tricosanoic acid, whereas no correlation was observed between the metabolite levels and the Gleason score or tumor stage except for gluconic acid. Univariate Cox regression and Kaplan-Meier analyses showed that levels of aminoadipic acid, gluconic acid and maltotriose were associated with the biochemical tumor recurrence (prostate-specific antigen > 0.2 ng/mL). In multivariate Cox regression analyses, aminoadipic acid together with tumor stage and Gleason score remained in a model as independent marker for prediction of biochemical recurrence. This study proved that metabolites in PCa tissue can be used, in combination with traditional clinicopathological factors, as promising diagnostic and prognostic tools.

N'-Formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide as a potential anti-tumour agent for prostate cancer in experimental studies.

OBJECTIVES: Benzothiazoles (BZTs) represent organic compounds with different biological actions. In this study we aimed to investigate ten newly synthesized BZT derivatives as potential anti-tumour agents against prostate cancer in vitro and in vivo. METHODS: The cytotoxic effect of these compounds was screened on the human prostate cancer cell lines PC-3 and LNCaP. The most effective compound, N'-formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide, was further characterized regarding its dose- and time-dependent effects on cell viability and proliferation (XTT test) as well as on adhesion and spreading (real-time cell analyzer xCelligence), migration (scratch-wound repair assay) and invasion (Boyden chamber) of the cells. This BZT derivative was also tested as an inhibitor of angiogenesis (chicken chorioallantoic membrane assay), clonogenic activity (soft agar) and matrix metalloproteinase 9 (gelatin zymography). KEY FINDINGS: N'-Formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide significantly inhibited all tested properties of the prostate cancer cell lines and showed low toxic in vitro and in vivo effects. The in vitro anti-tumour activity of this compound was confirmed by the in vivo effects on PC-3 xenografts in nude mice. Tumour growth was decreased in treated compared with untreated mice. CONCLUSIONS: These results suggest the potential capacity of BZTs and in particular N'-formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide as anti-tumour agents for the treatment of prostate cancer.

Impact of positive surgical margins on oncological outcome following laparoscopic radical prostatectomy (LRP): long-term results.

PURPOSE: The impact of positive surgical margins (PSM) on biochemical recurrence (BCR) has been heavily debated in laparoscopic radical prostatectomy (LRP). The aim of this study was to investigate the impact of PSM on BCR following LRP in patients with extended follow-up. METHODS: Retrospective chart review of 1,845 patients who underwent LRP from 1999 to 2007. Predictors of PSM and BCR were identified utilizing univariate and multivariable logistic and Cox regression analyses, respectively. RESULTS: Five hundred and thirty-seven patients (29.1%) had a PSM. Median postoperative follow-up was 56 months. 10-year BCR-free survival was 59.2 and 82.9% for patients with and without PSM, respectively (p < 0.0001). Clinical stage T2 (OR 1.66; CI 1.23-2.25; p = 0.001), a biopsy Gleason sum > 7 (OR 1.84; CI 1.06-3.18; p = 0.031) and preoperative prostate-specific antigen (PSA) levels of 10-20 ng/mL (OR 1.58; CI 1.12-2.23; p = 0.010) and >20 ng/mL (OR 6.82; CI 3.51-13.27; p < 0.0001) were independent predictors of PSM. Prostate size was inversely associated with PSM (OR 0.99; CI 0.98-1.00; p = 0.002). On multivariable analysis, LRP Gleason score of 7 (HR 2.45; CI 1.67-3.40; p < 0.0001) and >7 (HR 4.76; CI 3.15-7.19; p < 0.0001), PSM (HR 1.49; CI 1.14-2.00; p = 0.003), advanced pathological stages (p < 0.001), and PSA 10-20 ng/mL (HR 1.46; CI 1.13-1.89; p = 0.004) were independent predictors of BCR. CONCLUSIONS: We demonstrated the independent predictive value of PSM for BCR in our LRP cohort with extended follow-up. Our results could potentially be transferred to robotic RP, in which long-term follow-up is lacking.

Value of prostate specific antigen density and percent free prostate specific antigen for prostate cancer prognosis.

PURPOSE: Limited data exist on the relationship of percent free prostate specific antigen and prostate specific antigen density with prostate cancer prognosis. Therefore, we compared percent free prostate specific antigen and prostate specific antigen density with prostate specific antigen, Gleason sum and stage to predict prostate cancer prognosis in a large cohort using a single prostate specific antigen and free prostate specific antigen assay. MATERIALS AND METHODS: Between 1999 and 2007 a total of 1,656 patients with prostate cancer underwent laparoscopic radical prostatectomy at the Charité Berlin. There were 322 patients excluded from analysis for a variety of reasons. The final 1,334 patients had prostate specific antigen, free prostate specific antigen, prostate volume and complete pathological analysis available. RESULTS: Median followup was 60.3 months (range 0.2 to 135). Median age (63 years, range 43 to 75) did not differ between the 1,092 patients without and the 242 with biochemical recurrence (p = 0.956), but prostate volume, prostate specific antigen and percent free prostate specific antigen differed significantly (p <0.0001). While prostate specific antigen and prostate specific antigen density increased significantly in patients with Gleason less than 7, 7 and greater than 7 tumors, percent free prostate specific antigen decreased significantly (p <0.0001). Prostate specific antigen, percent free prostate specific antigen and prostate specific antigen density differed significantly between pT2 and pT3 tumors, and between patients with vs without positive surgical margins. On univariate analysis Gleason sum, pathological stage, positive surgical margin, total prostate specific antigen, percent free prostate specific antigen and prostate specific antigen density were predictors of biochemical recurrence-free survival. Multivariate Cox regression analysis identified Gleason sum, pathological stage, positive surgical margin and prostate specific antigen density as independent predictors of biochemical recurrence-free survival, while percent free prostate specific antigen and total prostate specific antigen failed to be significant. CONCLUSIONS: Few models for prostate cancer prognosis include prostate specific antigen density. There is substantial value in prostate specific antigen density but not in percent free prostate specific antigen for improving prostate cancer prognosis and biochemical recurrence prediction.

Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Over the past decade, minimally invasive laparoscopic radical prostatectomy and more recently robot-assisted laparoscopic prostatectomy have been introduced and have proven equally effective compared with open surgery in terms of mid-term cancer control and complication rates. Because long-term data is lacking, open prostatectomy is still considered the 'gold standard' by some authors, who argue that minimally invasive approaches have to measure up to the excellent long-term results of open surgery. This study represents one of the largest series (1845 patients) of minimally invasive radical prostatectomy with extended follow-up (11.3 years) and detailed data on oncological outcome and postoperative incontinence. It therefore supplies previously lacking information on these details for minimally invasive prostate surgery and provides important information for patient counselling. OBJECTIVE: • To investigate biochemical recurrence (BCR) rates and data on postoperative incontinence in a large laparoscopic radical prostatectomy (LRP) cohort with extended follow-up. MATERIALS AND METHODS: • BCR and independent predictors of BCR were identified using Kaplan-Meier and Cox regression analysis of 1845 patients who underwent LRP from 1999 to 2007. • Urinary incontinence was evaluated by pads per day and stratified as follows: 0-1 pad: no incontinence; 2-3 pads: mild incontinence; and ≥ 3 pads: severe incontinence. RESULTS: • Organ-confined disease, extraprostatic extension, seminal vesicle invasion and lymph node metastasis were present in 71.3%, 20.5%, 6.7% and 3.2% of patients, respectively. The positive surgical margin rate was 29.2%. • Postoperatively, 74.9% of the patients were continent, while 9.2% had mild and 15.9% severe incontinence. • The mean follow-up was 5 years with a maximum follow-up of 11.3 years. • There were 51 overall deaths and six deaths from prostate cancer. The 5-year, 8-year and 10-year BCR-free survival rates were 83.9%, 78.6% and 75.6%, respectively. • On univariate analyses preoperative D'Amico risk classification, pathological tumour stage, postoperative Gleason sum and surgical margin status were predictors of BCR (P < 0.001). • On multivariable analysis, D'Amico classification, Gleason sum (P < 0.001), postoperative tumour stage (P < 0.001), nodal status (P < 0.001) and surgical margin status (P = 0.002) were independent predictors of BCR. CONCLUSIONS: • LRP offers excellent long-term functional and oncological results with a low incidence of BCR for patients with localized disease. • These results could be used for patient counselling before robot-assisted laparascopic prostatectomy (RALP) until long-term follow-up data for RALP is available.

Outcome prediction for prostate cancer detection rate with artificial neural network (ANN) in daily routine.

BACKGROUND: We evaluated the use of the artificial neural network (ANN) program "ProstataClass" of the Department of Urology and the Institute of Medical Informatics at the Charité-Universitätsmedizin Berlin in daily routine to increase prostate cancer (CaP) detection rate and to reduce unnecessary biopsies. MATERIALS AND METHODS: From May 2005 to April 2007, a total of 204 patients were included in the study. The Beckman Access PSA assay was used, and pretreatment prostate specific antigen (PSA) was measured prior to digital rectal examination (DRE) and 12 core systematic transrectal ultrasound (TRUS) guided biopsies. The individual ANN predictions were generated with the use of the ANN application for the Beckman Access PSA and free PSA assays, which relies on age, PSA, percent free prostate specific antigen (%fPSA), prostate volume, and DRE. Diagnostic validity of total prostate specific antigen (tPSA), %fPSA, and the ANN was evaluated by ROC curve analysis. RESULTS: PSA and %fPSA ranged from 4.01 to 9.91 ng/ml (median: 6.65) and 5% to 48% (median: 15%), respectively. Of all men, 46 (22.5%) demonstrated suspicious DRE findings. Total prostate volume ranged from 7.1 to 119.2 cc (median: 35). Overall, 71 (34.8%) CaP were detected. Of men with suspicious DRE, 28 (60.9%) had CaP on initial biopsy. The ANN was 78% accurate in the original report. The AUC of ROC curve analysis was 0.51 for PSA, 0.66 for %PSA, and 0.72 for the ANN-Output, respectively. CONCLUSIONS: Our results in this independent cohort show that ANN is a very helpful parameter in daily routine to increase the CaP detection rate and reduce unnecessary biopsies.

Effect of quinolinyl acrylate derivatives on prostate cancer in vitro and in vivo.

Quinolines and acrylates are chemical compounds which were previously described as potential antitumor agents. In this study, a series of seven new quinolinyl acrylate derivatives were synthesized and evaluated against human prostate cancer cells PC-3 and LNCaP in vitro and in vivo. The most effective compound (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4 hydroxyphenyl) acrylate reduced the viability in both cell lines in a time- and dose-dependent manner. Inhibitory effects were also observed on the adhesion, migration, and invasion of the prostate cancer cells as well as on the neoangiogenesis, clonogenic and MMP-9 activity. The effect in vivo was studied in PC-3 xenografts in nude mice. The results were concordant with the in vitro effects and showed decreased tumor growth in treated animals compared to controls. The study suggests the multi-target efficacy of the quinolinyl derivate against human prostate cancer cells and supports its potential therapeutic usefulness.

Impact of fast-track postoperative care on intestinal function, pain, and length of hospital stay after laparoscopic radical prostatectomy.

BACKGROUND AND PURPOSE: Postoperative recovery of intestinal function, ability to ambulate, and effective pain management are main features to establish an effective fast-track surgery model. We investigated pain scores, ambulation rate, and recovery of intestinal function in a cohort of patients who were undergoing laparoscopic radical prostatectomy (LRP). PATIENTS AND METHODS: Fifty patients who underwent LRP in our institution were randomized to receive either conventional or fast-track postoperative care. Postoperative intestinal function was quantified by clinical signs of intestinal motility. Ambulation data were collected by means of step-count devices. Pain scores were measured by a visual analog scale. Overall satisfaction and additional measures to describe patient satisfaction with the clinical course were used as quality-of-life variables. RESULTS: Fast-track patients had significantly earlier propulsive intestinal motility without increased intestinal complications. Enforced mobilization led to a significantly shorter period to first deflation/defecation. Despite significantly increased ambulation rates in the fast-track group, these patients reported significantly less pain sentience during a significantly shorter hospital stay. Overall satisfaction was significantly higher in the fast-track cohort during the hospital stay. CONCLUSION: With the implementation of fast-track concepts for LRP, patients can be discharged to home earlier with fewer complications, lower pain scores, and an overall higher satisfaction with life.