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Background Nodal metastasis is the strongest risk factor of disease recurrence in patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP). Objective To develop a model that allows quantification of the likelihood that a pathologically node-negative patient is indeed free of nodal metastasis. Design, setting, and participants Data from patients treated with RP and pelvic lymph node dissection (PLND; n = 7135) for PCa between 2000 and 2011 were analyzed. For external validation, we used data from patients (n = 4209) who underwent an anatomically defined extended PLND. Intervention RP and PLND. Outcome measurements and statistical analysis We developed a novel pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative based on the number of examined nodes and the patient's characteristics. Results and limitations In the development and validation cohorts, the probability of missing a positive node decreases with an increasing number of nodes examined. Whereas in pT2 patients, a 90% pNSS was achieved with one single examined node in both the development and validation cohort, a similar level of nodal staging accuracy was achieved in pT3a patients by examining five and nine nodes, respectively. The pT3b/T4 patients achieved a pNSS of 80% and 70% when 17 and 20 nodes in the development and validation cohort were examined, respectively. This study is limited by its retrospective design and multicenter nature. The number of nodes removed was not directly correlated with the extent/template of PLND. Conclusions Every patient needs PLND for accurate nodal staging. However, a one-size-fits-all approach is too inaccurate. We developed a tool that indicates a node-negative patient is indeed free of lymph node metastasis by evaluating the number of examined nodes, pT stage, RP Gleason score, surgical margins, and prostate-specific antigen. This tool may help in postoperative decision making. © 2013 European Association of Urology.

Background: Positive surgical margins (PSMs) are a known risk factor for biochemical recurrence in patients with prostate cancer (PCa) and are potentially affected by surgical technique and volume. Objective: To investigate whether radical prostatectomy (RP) modality and volume affect PSM rates. Design, setting, and participants: Fourteen institutions in Europe, the United States, and Australia were invited to participate in this study, all of which retrospectively provided margins data on 9778 open RP, 4918 laparoscopic RP, and 7697 robotic RP patients operated on between January 2000 and October 2011. Outcome measurements and statistical analyses: The outcome measure was PSM rate. Multivariable logistic regression analyses and propensity score methods identified odds ratios for risk of a PSM for one modality compared with another, after adjustment for age, preoperative prostate-specific antigen, postoperative Gleason score, pathologic stage, and year of surgery. Classic adjustment using standard covariates was also implemented to compare PSM rates based on center volume for each minimally invasive surgical cohort. Results and limitations: Open RP patients had higher-risk PCa at time of surgery on average and were operated on earlier in the study time period on average, compared with minimally invasive cohorts. Crude margin rates were lowest for robotic RP (13.8%), intermediate for laparoscopic RP (16.3%), and highest for open RP (22.8%); significant differences persisted, although were ameliorated, after statistical adjustments. Lower-volume centers had increased risks of PSM compared with the highest-volume center for both laparoscopic RP and robotic RP. The study is limited by its nonrandomized nature; missing data across covariates, especially year of surgery in many of the open cohort cases; lack of standardized histologic processing and central pathology review; and lack of information regarding potential confounders such as patient comorbidity, nerve-sparing status, lymph node status, tumor volume, and individual surgeon caseload. Conclusions: This multinational, multi-institutional study of 22 393 patients after RP suggests that PSM rates might be lower after minimally invasive techniques than after open RP and that PSM rates are affected by center volume in laparoscopic and robotic cases. Patient summary: In this study, we compared the effectiveness of different types of surgery for prostate cancer by looking at the rates of cancer cells left at the margins of what was removed in the operations. We compared open, keyhole, and robotic surgery from many centers across the globe and found that robotic and keyhole operations appeared to have lower margin rates than open surgeries. How many cases a center and surgeon do seems to affect this rate for both robotic and keyhole procedures. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Background:Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status.Methods:We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes.Results:In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1-6 nodes in cT1 and 6-8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively.Conclusions:Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis. © 2014 Cancer Research UK.

Objectives: To determine if the number of lymph nodes (LNs) removed is an independent predictor of biochemical recurrence (BCR) in patients without LN metastases undergoing radical prostatectomy (RP). Material and methods: Retrospective analysis of 7,310 patients treated at 7 centers with RP and pelvic LN dissection for clinically localized prostate cancer between 2000 and 2011. Patients with LN metastases (n = 398) and other reasons (stated later in the article) (n = 372) were excluded, which left 6,540 patients for the final analyses. Results: Overall, median biopsy and RP Gleason score were both 7; median prostate specific antigen level was 6. ng/ml (interquartile range [IQR]: 5); and median number of LNs removed was 6 (IQR: 8). A total of 3,698 (57%), 2,064 (32%), and 508 (8%) patients had ≥6, ≥10, and ≥20 LNs removed, respectively. Patients with more LNs removed were older, had a higher prostate specific antigen level, had higher clinical and pathologic T stage, and had higher RP Gleason score (all P

To evaluate the reliability of sentinel lymphadenectomy compared to extended lymphadenectomy in men undergoing radical prostatectomy (RP).A consecutive cohort of men with intermediate- to high-risk prostate cancer underwent RP with sentinel LA with intraoperative frozen section. In addition, extended LA was carried out in all cases. The endpoint was lymph node-positivity.In total, 54 men with a mean age of 65.3 (50.9-75.6) years were analyzed. The mean preoperative prostate-specific antigen was 10.6 (2.8-66.5) ng/ml, mean number of disease-positive cores was 5.8 (1-13), digital rectal examination was positive in 29 men (53.7%). In 12 men (22.2%), a positive lymph node was found (pN1). sLA was positive in 11 cases. One patient had a positive lymph node in eLA not found with sLA. The positive predictive value of frozen section was 50%; the respective figure for sLA compared to eLA was 91.6%.In this cohort, revealing a high prevalence of disease-positive lymph nodes, sLA was a reliable technique with a low rate of false negativity.

Prostate-specific antigen (PSA) doubling-time (PSA-DT) is an important indicator of progression and survival in men with prostate cancer. Three major limitations regarding PSA-DT determination may lead to inconsistent results: the variety of mathematical methods currently applied, the non-standardized handling of input variables and the potential lack of accuracy due to PSA variability. The aim of this project was to develop a reproducible PSA-DT determination tool which simultaneously provides a PSA-DT error estimation.An internet-based PSA-DT calculation tool via nonlinear optimization implementing the least squares error method using the most recent three PSA values was developed. PSA-DT calculation error is estimated via randomly disturbed measurement data streams (n=65) based on a variable (5-25%) PSA variability.According to a simulation in five men, PSA-DT was calculated to be between 1.7 and 15 month (mean: 6.3 month) and determined with another standard tool between 1.3 and 14.5 month (mean: 4.2 month).We present a defined, open and reproducible PSA-DT calculation and PSA-DT error estimation tool based on a standardized PSA data input. This tool is not better compared to other methods but is scientifically standardized and freely accessible via the following internet address: http://adam.drahtwarenhandlung.at/webapp/mg2008/chapter_prostata4/example_psa.

In vitro generation of dysmorphic erythrocytes. In hematuria, dysmorphic red blood cells found in the urine sediment are known to indicate glomerular origin of bleeding. To better understand the mechanisms which might cause the typical membrane changes in dysmorphic erythrocytes in vivo, we have exposed normal human erythrocytes in vitro to an osmotic and enzymatic environment similar to that of the nephron. In addition, treated or untreated erythrocytes were exposed to a hemolytic environment. The morphology of the cells was evaluated by light and electron microscopy in comparison of that of dysmorphic erythrocytes obtained in vivo. Neither the passage of erythrocytes in sequence through various solutions each simulating the tubule fluid in a different part of the nephron, nor exposure to urinary or renal enzymes or to serum per se causes the typical membrane alterations. Upon exposure of passaged erythrocytes to a hemolytic environment, however, 50 to 90% of the cells become dysmorphic in a time and dose dependent fashion. By light and electron microscopy these dysmorphic erythrocytes obtained in vitro are indistinguishable from those obtained in vivo. In contrast, non-passaged red blood cells are not affected by the same hemolytic environment. We conclude that osmotically challenged erythrocytes exposed to a hemolytic environment develop dysmorphic membrane alterations.