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Background: In a subset of patients with recurrent oligometastatic prostate cancer (PCa) salvage surgery with prostate-specific membrane antigen (PSMA)-targeted radioguidance (PSMA-RGS) might be of value., Objective: To evaluate the oncological outcomes of salvage PSMA-RGS and determine the predictive preoperative factors of improved outcomes., Design, Setting, and Participants: A cohort study of oligorecurrent PCa patients with biochemical recurrence (BCR) after radical prostatectomy and imaging with PSMA positron emission tomography (PET), treated with PSMA-RGS in two tertiary care centers (2014-2020), was conducted., Intervention: PSMA-RGS., Outcome Measurements and Statistical Analysis: Kaplan-Meier and multivariable Cox regression models were used to assess BCR-free (BFS) and therapy-free (TFS) survival. Postoperative complications were classified according to Clavien-Dindo., Results and Limitations: Overall, 364 patients without concomitant treatment were assessed. At PSMA-RGS, metastatic soft-tissue PCa lesions were removed in 343 (94%) patients. At 2-16 wk after PSMA-RGS, 165 patients reached a prostate-specific antigen (PSA) level of <0.2 ng/ml. Within 3 mo, 24 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. At 2 yr, BFS and TFS rates were 32% and 58%, respectively. In multivariable analyses, higher preoperative PSA (hazard ratio [HR]: 1.07, 95% confidence interval [CI]: 1.02-1.12), higher number of PSMA-avid lesions (HR: 1.23, CI: 1.08-1.40), multiple (pelvic plus retroperitoneal) localizations (HR: 1.90, CI: 1.23-2.95), and retroperitoneal localization (HR: 2.04, CI: 1.31-3.18) of lesions in preoperative imaging were independent predictors of BCR after PSMA-RGS. The main limitation is the lack of a control group., Conclusions: As salvage surgery in oligorecurrent PCa currently constitutes an experimental treatment approach, careful patient selection is mandatory based on life expectancy, low PSA values, and low number of PSMA PET-avid lesions located in the pelvis., Patient Summary: We looked at the outcomes from prostate cancer patients with recurrent disease after radical prostatectomy. We found that surgery may be an opportunity to prolong treatment-free survival, but patient selection criteria need to be very narrow., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the prevalence of fluoroquinolone resistant (QR) bacteria, multidrug resistant (MDR) bacteria and Enterococcus faecalis (E. faecalis) in rectal swabs of patients undergoing transrectal prostate biopsy and for evaluating if risk factor assessment is reliable for prediction of QR bacteria, MDR bacteria, or E. faecalis., Patients and Methods: Two hundred consecutive patients received a rectal swab examination prior to transrectal magnetic resonance imaging-guided fusion biopsy, for evaluating the prevalence of QR bacteria, MDR bacteria, and E. faecalis. The results of a standardized risk factor questionnaire, assessing known prognosticators for higher prevalence of resistant bacteria in rectal flora were correlated with the occurrence of QR bacteria, MDR bacteria, and E. faecalis in rectal swabs., Results: QR E. coli was detected in 12 patients (6%). Regarding MDR bacteria, extended spectrum β- lactamase- producing E. coli occurred in 8 patients (4%). E. faecalis was found in 15 patients (7.5%). A total of 193 patients completed the risk factor questionnaire. Of those, 107 (53.2%) patients harbored no risk factors, while 86 (42.8%) had at least 1 risk factor, of which the most common was repeat biopsy. No association was found between any risk factor and occurrence of QR bacteria, MDR bacteria, or E. faecalis (P >.05)., Conclusion: The prevalence of resistant germs in our cohort was lower compared to other series. Moreover, the rate of QR bacteria, MDR bacteria, or E. faecalis in rectal swabs was not reliably associated with risk factor assessment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Nodal metastasis (N1) is a strong prognostic parameter in prostate cancer; however, lymph node evaluation is always incomplete., Objective: To study the prognostic value of lymphatic invasion (L1) and whether it might complement or even replace lymph node analysis in clinical practice., Design, Setting, and Participants: Retrospective analysis of pathological and clinical data from 14 528 consecutive patients., Intervention: Radical prostatectomy., Outcome Measurements and Statistical Analysis: The impact of L1 and N1 on patient prognosis was measured with time to biochemical recurrence as the primary endpoint., Results and Limitations: 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 (p<0.0001 each). N1 was found in 4.3% of 12 501 L0 and in 41% of 2027 L1 carcinomas (p<0.0001). L1 was seen in 11% of 9868 N0 and in 61% of 1360 N1 carcinomas (p<0.0001). Both N1 and L1 were linked to PSA recurrence (p<0.0001 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., Conclusions: 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., Patient Summary: Already minimal amounts of tumor cells inside the lymph nodes or intraprostatic lymphatic vessels have a severe impact on patient prognosis., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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<0.0001) or Gleason grade groups (p<0.0001)., 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., (Copyright © 2017. Published by Elsevier B.V.)

Background: Treatment of the primary, termed local therapy (LT), may improve survival in metastatic prostate cancer (mPCa) versus no local therapy (NLT)., Objective: To assess cancer-specific mortality (CSM) after LT versus NLT in mPCa., Design, Setting, and Participants: Within the Surveillance, Epidemiology and End Results database (2004-2013), 13 692 mPCa patients were treated with LT (radical prostatectomy [RP] or radiation therapy [RT]) or NLT., Outcome Measurements and Statistical Analysis: Multivariable competing risk regression analyses (MVA CRR) tested CSM after propensity score matching (PSM) in two analyses, (1) NLT versus LT and (2) RP versus RT, and were complemented with interaction, sensitivity, unmeasured confounder, and landmark analyses., Results and Limitations: Of 13 692 mPCa patients, 474 received LT: 313 underwent RP and 161 RT. In MVA CRR, after PSM, LT (n=474) results in lower CSM (subhazard ratio [SHR] 0.40, 95% confidence interval [CI] 0.32-0.50) versus NLT (n=1896). In MVA CRR after PSM, RP (n=161) results in lower CSM (SHR 0.59, 95% CI 0.35-0.99) versus RT (n=161). Invariably, lowest CSM rates were recorded for Gleason ≤7, ≤cT3, and M1a substage. Interaction and sensitivity analyses confirmed the robustness of results, and landmark analyses rejected the bias favouring LT. A strong unmeasured confounder (HR=5), affecting 30% of NLT patients, could obliterate LT benefit. Data were retrospective., Conclusions: In mPCa, LT results in lower mortality relative to NLT. Within LT, lower mortality is recorded after RP than RT. Patients with most favourable grade, local stage, and metastatic substage derive most benefit from LT. They also derive most benefit from RP, when LT types are compared (RP vs RT). It is important to consider study limitations until ongoing clinical trials confirm the proposed benefits., Patient Summary: Individuals with prostate cancer that spreads outside of the prostate might still benefit from prostate-directed treatments, such as radiation or surgery, in addition to receiving androgen deprivation therapy., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2016 European Association of Urology. All rights reserved.)

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., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The effect of preservation of neurovascular bundles (NVBs) during radical prostatectomy (RP) on continence remains controversial., Objective: To analyze if the differing surgical techniques of nerve-sparing (NS) versus non-nerve-sparing (NNS) RP and not the preservation of the NVB itself may be responsible for differences in continence rates., Design, Setting, and Participants: A total of 18 427 men who underwent RP from 2002 to 2014 in a single high-volume center were analyzed retrospectively. Patients with bilateral NS RP, with primary NNS RP, and with bilateral secondary resection of the NVBs for positive frozen-section results after an initial bilateral nerve sparing (secNNS) RP were studied., Intervention: NS, NNS, or secNNS RP., Outcome Measurements and Statistical Analysis: Multivariable and propensity score matched analyses adjusting for age, prostate volume, and year of surgery were performed to assess differences in continence rates after RP. Continence was defined as the use of no or one safety pad per day., Results and Limitations: Post-RP urinary continence rates at 1 wk, 3 mo, and 12 mo were 59.8%, 76.2%, 85.4% in the NS group, 39.5%, 59.5%, and 87.0% in the secNNS group, and 29.1%, 52.8%, and 70.5% in the NNS group. Continence rates at 12 mo after surgery did not differ significantly between patients who had bilateral NS and patients who had resection of both NVBs after an initial nerve-sparing technique (secNNS). In contrast, when comparing the NNS study groups with initial NNS versus secNNS, the latter group had significantly higher continence rates after 12 mo., Conclusions: Our results indicate that the meticulous apical dissection associated with the NS RP technique rather than the preservation of the NVBs itself may have a positive impact on long-term urinary continence rates., Patient Summary: We looked at continence rates after nerve-sparing (NS) versus non-NS radical prostatectomy (RP). NS surgery technique but not the preservation of the neurovascular bundles led to improved long-term continence rates after RP., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Unlabelled: Prostate-specific membrane antigen (PSMA) overexpression theoretically enables targeting of prostate cancer (PCa) metastases using gallium Ga 68 ((68)Ga)-labeled PSMA ligands for positron emission tomography/computed tomography (PET/CT) imaging. Promising detection rates have been reported when using this approach for functional imaging of recurrent PCa; however, until now, the diagnostic accuracy of (68)Ga-PSMA PET/CT for preoperatively identifying lymph node metastases (LNMs) had not been assessed. We retrospectively compared preoperative (68)Ga-PSMA PET/CT lymph node (LN) findings with histologic work-up after radical prostatectomy (RP). Overall, 608 LNs containing 53 LNMs were detected during RP. LNMs were present in 12 of 30 patients (40%). The (68)Ga-PSMA PET/CT scans identified 4 patients (33.3%) as LN true positive and 8 patients (66.7%) as false negative. Median size of (68)Ga-PSMA-PET/CT-detected versus undetected LNMs was 13.6 versus 4.3 mm (p<0.05). Overall sensitivity, specificity, positive predictive value, and negative predictive value of (68)Ga-PSMA PET/CT for LNM detection were 33.3%, 100%, 100%, and 69.2%, respectively. Per-side analyses revealed corresponding values of 27.3%, 100%, 100%, and 52.9%. Conversely, (68)Ga-PSMA PET/CT enabled tumor visualization in the prostate. In 92.9% of patients, the intraprostatic tumor foci were correctly predicted. Overall, (68)Ga-PSMA PET/CT is a promising tool for functional imaging; however, our initial experience revealed substantial influence of LNM size on the diagnostic accuracy of (68)Ga-PSMA PET/CT., Patient Summary: We assessed the diagnostic accuracy of (68)Ga-PSMA PET/CT in high-risk prostate cancer patients prior to radical prostatectomy. We found that lymph node metastasis detection rates were substantially influenced by lymph node metastasis size., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To determine the rates of lymph nodes and lymph node metastases in periprostatic fat pads yielded during exposure of the anterior surface of the dorsal vein complex, puboprostatic ligaments, and endopelvic fascia during radical prostatectomy., Methods: Histopathologic examination was performed in 356 patients who underwent radical prostatectomy between July 2010 and September 2010 at a single institution. Separate histologic work-up of the periprostatic fat pads addressed the presence of lymph nodes and possible metastatic invasion of lymph nodes within this area. Descriptive analyses and multivariable analyses to predict the presence of lymph node metastases within these fat pads were performed., Results: Lymph nodes within periprostatic fat pads were detected in 19 (5.5%) patients. Among these patients, tumor infiltration was found in 4 (1.2%). Three of these 4 patients harbored lymph node metastases without any other lymph node metastasis during standard lymphadenectomy. No relationship was detected between the total number of lymph nodes removed and the detection of lymph nodes within periprostatic fat pads (P = .6)., Conclusion: Our analysis demonstrates that periprostatic fat pads harbor lymph nodes. No relationship between the presence of lymph node metastases in periprostatic fat pads and the presence of lymph node metastases in other areas was found. Similarly, no relationship exists between the presence of lymph nodes in this area and the total number of lymph nodes yielded in other lymphatic fields. Therefore, for guaranteeing precise lymph node staging, implementing routinely pathologic work-up of periprostatic fat pads yielded during radical prostatectomy should be considered., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Statistical prediction tools are increasingly common, but there is considerable disagreement about how they should be evaluated. Three tools--Partin tables, the European Society for Urological Oncology (ESUO) criteria, and the Gallina nomogram--have been proposed for the prediction of seminal vesicle invasion (SVI) in patients with clinically localized prostate cancer who are candidates for a radical prostatectomy., Objectives: Using different statistical methods, we aimed to determine which of these tools should be used to predict SVI., Design, Settings, and Participants: The independent validation cohort consisted of 2584 patients treated surgically for clinically localized prostate cancer at four North American tertiary care centers between 2002 and 2007., Interventions: Robot-assisted laparoscopic radical prostatectomy., Outcome Measurements and Statistical Analysis: Primary outcome was the presence of SVI. Traditional (area under the receiver operating characteristic [ROC] curve, calibration plots, the Brier score, sensitivity and specificity, positive and negative predictive value) and novel (decision curve analysis and predictiveness curves) statistical methods quantified the predictive abilities of the three models., Results and Limitations: Traditional statistical methods (ie, ROC plots and Brier scores) could not clearly determine which one of the three SVI prediction tools should be preferred. For example, ROC plots and Brier scores seemed biased against the binary decision tool (ESUO criteria) and gave discordant results for the continuous predictions of the Partin tables and the Gallina nomogram. The results of the calibration plots were discordant with those of the ROC plots. Conversely, the decision curve indicated that the Partin tables represent the best strategy for stratifying the risk of SVI, resulting in the highest net benefit within the whole range of threshold probabilities., Conclusions: When predicting SVI, surgeons should prefer the Partin tables over the ESUO criteria and the Gallina nomogram because this tool provided the highest net benefit. In contrast to traditional statistical methods, decision curve analysis gave an unambiguous result applicable to both continuous and binary models, providing an insight into clinical utility., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Intraoperative frozen-section analysis allows real-time histologic assessment of surgical margins (SMs) and identification of candidates for nerve-sparing (NS) procedures., Objective: To examine the efficacy and oncologic safety of a systematic neurovascular structure-adjacent frozen-section examination (NeuroSAFE) during NS radical prostatectomy (RP)., Design, Setting, and Participants: From January 2002 to June 2011, 11 069 consecutive RPs were performed at the University Medical Center Hamburg-Eppendorf. Of these, 5392 (49%) were conducted with NeuroSAFE., Surgical Procedure: Our NeuroSAFE approach included the whole laterorectal circumference of the prostate to determine the SM status of the complete neurovascular tissue-corresponding prostatic surface., Outcome Measurements and Statistical Analysis: The impact of NeuroSAFE on NS frequency, SM status, and biochemical recurrence (BCR) was analyzed by chi-square test, and by Kaplan-Meier analyses in propensity score-based matched cohorts., Results and Limitations: Positive SMs (PSMs) were detected in 1368 (25%) NeuroSAFE RPs, leading to a secondary resection of the ipsilateral neurovascular tissue. Secondary wide resection resulted in conversion to a definitive negative SM (NSM) status in 1180 (86%) patients. In NeuroSAFE RPs, frequency of NS was significantly higher (all stages: 97% vs 81%; pT2: 99% vs 92%; pT3a: 94% vs 72%; pT3b: 88% vs 40%; p<0.0001) and PSM rates were significantly lower (all stages: 15% vs 22%; pT2: 7% vs 12%; pT3a: 21% vs 32%; p<0.0001) than in the matched non-NeuroSAFE RPs. In propensity score-based comparisons, NeuroSAFE had no negative impact on BCR (pT2, p=0.06; pT3a, p=0.17, pT3b, p=0.99), and BCR-free survival of patients with conversion to NSM did not differ significantly from patients with primarily NSM (pT2, p=0.16; pT3, p=0.26). The accuracy of our NeuroSAFE approach was 97% with a false-negative rate of 2.5%. The major limitations of this study are its retrospective nature and relatively short follow-up., Conclusions: NeuroSAFE enables real-time histologic monitoring of the oncologic safety of a NS procedure. Systematic NeuroSAFE significantly increases NS frequencies and reduces PSMs. Patients with a NeuroSAFE-detected PSM could be converted to a prognostically more favorable NSM status by secondary wide resection., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To examine the effect of annual prostatectomy volume (APV) on contemporary intraoperative rectal laceration (RL) rates after radical prostatectomy., Methods: From 1999 to 2008, 36 699 radical prostatectomy procedures were performed in Florida. First, logistic regression models predicting the RL rate were fitted. Second, other logistic regression models were used to examine the association between RL and 2 other secondary outcomes: prolonged length of stay (>3 days) and increased hospital charges (>$37 621). The covariates included APV quintiles, surgical approach (minimally invasive vs open radical prostatectomy), lymph node dissection status, age, year of surgery, race, and baseline Charlson comorbidity index., Results: The overall RL rate was 0.7%. The RL rate was 0.3%, 0.6%, 0.7%, 0.9%, and 1.0% for the very high, high, intermediate, low, and very low APV quintiles, respectively (P < .001). In multivariate analyses predicting RL, patients treated by intermediate (odds ratio 2.39, P = .003), low (odds ratio 2.95, P < .001), and very low (odds ratio 3.26, P < .001) APV surgeons had a greater likelihood of experiencing an RL relative to patients treated by very high APV surgeons. Second, in the multivariate analyses, patients with a RL were 9.1-fold more likely to have a prolonged length of stay (P < .001) and were 3.4-fold more likely to have increased total hospital charges (P < .001)., Conclusion: A greater APV exerts a protective effect on RL rates. Additionally, RL increases the length of stay and hospital charges., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To examine the homologous blood transfusion (HBT), autologous blood transfusion (ABT) and intraoperative blood conservation technique (IOBCT) rates and trends at open (ORP) and minimally invasive radical prostatectomy (MIRP)., Methods: The Nationwide Inpatient Sample was queried. Multivariable logistic regression models focused on all three transfusion types. Covariables consisted of procedure specific annual hospital caseload (AHC), year of surgery, age, Charlson Comorbidity Index, and region., Results: Overall, 119,966 patients underwent radical prostatectomy between 1998 and 2007. The HBT, ABT, and IOBCT rates were 6.2%, 6.0%, and 1.2%, respectively. HBT rates ranged from 5.1-5.1% between 1998 and 2007 (P=.49) vs 9.4-2.7% (P<.001) for ABT vs 1.9-0.9% (P=.003) for IOBCT in the same time period, respectively. In multivariable analyses, ORP patients treated at intermediate (odds ratio [OR] 1.48, P=.003) and low (OR 2.73, P<.001) AHC institutions were more likely to receive an HBT than ORP patients treated at high AHC institutions. Conversely, MIRP patients treated at high (OR 0.46, P=.040), intermediate (OR 0.27, P=.001), and low (OR 0.59, P=.015) AHC institutions were less likely to receive an HBT than ORP patients treated at high AHC institutions., Conclusion: Our results indicate that the overall transfusion rate at radical prostatectomy decreased within the last decade because of a substantial decline in ABT use. Moreover, MIRP protects from HBT, even when performed at low AHC Centers., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Context: Prostate cancer (PCa) patients have many options within the realms of surgery or radiation therapy (RT). Technical advancements in RT planning and delivery have yielded different approaches, such as external beam, brachytherapy, and newer approaches such as image-guided tomotherapy or volumetric-modulated arc therapy. The selection of the optimal RT treatment for the individual is still a point of discussion, and the debate centres on two important outcomes-namely, cancer control and reduction of side-effects., Objective: To critically review and summarise the available literature on functional outcomes and rectal sequelae following RT for PCa treatment., Evidence Acquisition: A review of the literature published between 1999 and 2010 was performed using Medline and Scopus search. Relevant reports were identified using the terms prostate cancer, radiotherapy, functional outcomes, external beam radiation, brachytherapy, IMRT, quality of life, and tomotherapy and were critically reviewed and summarised., Evidence Synthesis: Related to nonuniform definition of their assessed functional end points and uneven standards of reporting, only a minority of series retrieved could be selected for analyses. Moreover, patterns of patient selection for different types of RT, inherent differences in the RT modalities, and the presence or absence of hormonal treatment also limit the ability to synthesise results from different publications or perform meta-analyses across the different treatment types. Nonetheless, several studies agree that recent technical improvements in the field of RT planning and delivery enable the administration of higher doses with equal or less toxicity. Regardless of the type of RT, the most frequently considered functional end points in the published analyses are gastrointestinal (GI) complications and rectal bleeding. Established risk factors for acute or late toxicities after RT include advanced age, larger rectal volume, a history of prior abdominal surgery, the concomitant use of androgen deprivation, preexisting diabetes mellitus, haemorrhoids, and inflammatory bowel disease (IBD). Similarly, mild acute irritative urinary symptoms are reported in several studies, whereas total urinary incontinence and other severe urinary symptoms are rare. Pretreatment genitourinary complaints, prior transurethral resection of the prostate (TURP), and the presence of acute genitourinary toxicity are suggested as contributing to long-term urinary morbidity. Erectile dysfunction (ED) is not an immediate side-effect of RT, and the occurrence of spontaneous erections before treatment is the best predictor for preserving erections sufficient for intercourse. In addition, the use of magnetic resonance imaging (MRI) permits a reduction in the dose delivered to vascular structures critical for erectile function., Conclusions: In the future, further improvement in RT planning and delivery will decrease side-effects and permit administration of higher doses. Related to the anatomy of the prostate, these higher doses may favour rectal sparing while not readily sparing the urethra and bladder neck. As a consequence, there may be a future shift from dose-limiting long-term rectal morbidity towards long-term urinary morbidity. In the absence of prospective randomised trials comparing different types of surgical and RT-based treatments in PCa, the introduction of validated tools for reporting functional and clinical outcomes is crucial for evaluating and identifying each individual's best treatment choice., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Existing population-based reports on complication rates after minimally invasive radical prostatectomy (MIRP) did not address temporal trends., Objective: To examine contemporary temporal trends in perioperative MIRP outcomes., Design, Setting, and Participants: Between 2001 and 2007, 4387 patients undergoing MIRP were identified using the Nationwide Inpatient Sample., Measurements: To examine the rates and trends of intraoperative and postoperative complications, transfusion rates, length of stay in excess of the median, and in-hospital mortality. We tested the effect of the late (2006-2007) versus the early (2001-2005) study period on all outcomes using multivariable logistic regression models controlled for clustering among hospitals., Results and Limitations: Intraoperative and postoperative complications decreased from 7.0% to 0.8% (p < 0.001) and from 28.5% to 8.7% (p < 0.001), respectively. Transfusion rates decreased from 3.5% to 2.1% (p = 0.3). Hospital length of stay >2 d decreased from 56% to 15% (p < 0.001). In multivariable analyses, intraoperative (odds ratio [OR]: 0.41; p = 0.002) and postoperative (OR: 0.65; p = 0.007) complications were less frequent in the late versus the early study period. Late study period patients were less likely to stay >2 d than early study period patients (OR: 0.34; p > 0.001). Limitations of these findings include the lack of adjustment for several patient variables including disease characteristics, surgeon variables including surgeon caseload, and the restriction to in-hospital events., Conclusions: Our analyses demonstrate that in-hospital complication rates and length of stay after MIRP decreased over time. This implies that temporal differences specific to complication rates after MIRP must be considered when comparisons are made with other radical prostatectomy techniques., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Knowledge about the staging significance of the prostate cancer antigen 3 (PCA3) score to better identify pathologic features after radical prostatectomy (RP) is limited and controversial., Objective: Our aim was to study the clinical staging significance of PCA3 to identify pathologic favorable and/or unfavorable features in the RP specimen., Design, Setting, and Participants: Complete retrospective clinical and pathologic data of consecutive men who had undergone RP from three tertiary referral centers including preoperative PCA3 scores (n=305) and computer-assisted planimetrically measured tumor volume data (n=160) were available., Intervention: All patients were treated with RP., Measurements: PCA3 scores were assessed using the PROGENSA assay (Gen-Probe, San Diego, CA, USA). Beyond standard risk factors (age, digital rectal examination, prostate-specific antigen, prostate volume, biopsy Gleason score, percentage of positive cores), five different PCA3 codings were used in logistic regression models to identify five distinct pathologic end points: (1) low-volume disease (<0.5 ml), (2) insignificant prostate cancer (PCa) according to the Epstein criteria, (3) extracapsular extension (ECE), (4) seminal vesicle invasion (SVI), and (5) aggressive disease defined as Gleason sum ≥7. Accuracy estimates of each end point were quantified using the area under the curve (AUC) of the receiver operator characteristic analysis in models with and without PCA3., Results and Limitations: PCA3 scores were significantly lower in low-volume disease and insignificant PCa (p ≤ 0.001). AUC of multivariable low-volume disease (+2.4 to +5.5%) and insignificant PCa models (+3 to +3.9%) increased when PCA3 was added to standard clinical risk factors. In contradistinction, regardless of its coding, PCA3 scores were not significantly elevated in pathologically confirmed ECE (p=0.4) or SVI (p=0.5), respectively. Higher PCA3 scores were associated with aggressive disease (p<0.001). Importantly, the addition of PCA3 to multivariable intermediate- and high-grade models did not improve prediction. Despite reporting the largest pathologic PCA3 study, the main limitation resides in its small sample size., Conclusions: PCA3 was confirmed as a valuable predictor of pathologically confirmed low-volume disease and insignificant PCa. Further exploration of its role as an additional marker to select patients for active surveillance may be warranted. In contradistinction, assessment of pathologically advanced or aggressive PCa is not improved using PCA3., (Copyright © 2010 European Association of Urology. All rights reserved.)

Background: At radical prostatectomy (RP), pelvic lymph node dissection (PLND) represents the most accurate staging procedure for the presence of lymph node (LN) metastases., Objective: We evaluated the rate of PLND use and its lymph node count (LNC) over the last two decades. We also tested the relationship between LNC and the rate of pN1 stage., Design, Setting, and Participants: Between 1988 and 2006, 130,080 RPs were recorded in 17 Surveillance Epidemiology and End Results registries., Measurements: The statistical significance of temporal trends was evaluated with the chi-square trend test. Separate univariable and multivariable regression analyses tested the relationship between predictors and two end points: (1) lack of LN staging (pNx) and (2) presence of LN metastases (pN1)., Results and Limitations: Stage pNx was recorded in 25.9% of patients, and pNx rate was higher in more contemporary years (30.1% in 2000-2006 vs 20.8% in 1988-1993; multivariable p < 0.001). When PLND was performed, an average of 7.4 LNs (median: 6) were removed. The average LNC decreased from 12.0 nodes (median: 12) in 1988 to 6.0 nodes (median: 4) in 2006. Overall pN1 rate was 3.4% and decreased from 10.7% to 3.1% between 1988 and 2006 (p < 0.001). LNC was an independent predictor of pN1 stage (multivariable p < 0.001)., Conclusions: An increasingly larger proportion of prostate cancer patients remain without LN staging at RP. Fewer LNs were removed at PLND over time, resulting in fewer patients diagnosed with pN1 stage at RP. The impact of this phenomenon on cancer control outcomes is still to be verified., (Copyright © 2010 European Association of Urology. All rights reserved.)

Background: Several models can predict the rate of biochemical recurrence (BCR) after radical prostatectomy (RP)., Objective: We tested the three most commonly used models-the D'Amico risk stratification scheme, the Cancer of the Prostate Risk Assessment (CAPRA) score, and the Stephenson nomogram-in a European cohort of RP patients., Design, Setting, and Participants: We relied on preoperative characteristics and prostate-specific antigen follow-up data of 1976 patients, as required by the three tested models. All patients were treated with an open RP between 1992 and 2006., Measurements: Analyses included tests of accuracy (Harrell's concordance index) and calibration between predicted and observed BCR rates at 3 yr and 5 yr after RP. Additionally, we relied on decision curve analyses to compare the three models directly in a head-to-head fashion., Results and Limitations: The median follow-up of censored patients was 32 mo. BCR-free rates at 3 yr and 5 yr after RP were 80.2% and 72.6%, respectively. The concordance index for 3-yr BCR predictions was 70.4%, 74.3%, and 75.2% for the D'Amico, CAPRA, and Stephenson models, respectively, versus 67.4%, 72.9%, and 73.5% for 5-yr BCR predictions. Calibration results supported the use of either the CAPRA or Stephenson models. Decision curve analyses indicated a small benefit for the CAPRA score relative to the Stephenson nomogram. Our findings apply to German patients treated with RP at a high-volume tertiary care centre. Consequently, the rank order reported in this paper may not be the same in North American or other European cohorts., Conclusions: Different methods yield different results, and it may be difficult to reconcile concordance index, calibration, and decision curve analysis findings. Our data suggest that the CAPRA score outperforms the other models when decision curve analysis and calibration were used as benchmarks. Conversely, the Stephenson nomogram outperformed the other models when concordance index was used as a metric., (Crown Copyright © 2009. Published by Elsevier B.V. All rights reserved.)

Objectives: To compare stage at radical cystectomy (RC) and cancer-specific mortality (CSM) after RC between non-urachal adenocarcinoma (ADK) and urothelial carcinoma (UC) of the urinary bladder., Methods: Within 17 Surveillance, Epidemiology and End Results registries, we identified ADK and UC patients who underwent a RC between 1988 and 2006. We examined differences in stage and grade at RC between ADK and UC patients. Kaplan-Meier plots depicted CSM after RC. Cox regression analyses examined CSM rates, adjusted for T and N stages, tumor grade, age, gender, race, and year of surgery. Thereafter, we relied on statistically significant variables from the multivariate Cox regression model to match ADK and UC patients. Finally, we plotted Kaplan-Meier survival curves of the matched ADK and UC patients., Results: Of 306 ADK and 11 697 UC patients, 188 (61.4%) and 5538 (47.3%), respectively, showed extravesical disease (pT(3-4); P <.001) and 26.5% vs 21.7% had lymph node metastases at RC (P = .04), respectively. After adjustment for all covariates, including stage and grade, ADK was not associated with worse prognosis than UC (hazard ratio, 1.05; P = .6). Similarly, after matching, no difference in CSM was recorded between the 2 histologic subtypes (hazard ratio, 1.07; P = .5)., Conclusions: ADK patients undergo RC at more advanced disease stages. However, stage- and grade-adjusted CSM is the same between ADK and UC patients. Efforts should be aimed at providing definitive treatment at earlier stages, especially in patients with ADK histologic subtype., (2010. Published by Elsevier Inc.)

Objectives: To examine the perioperative mortality rates at 90 days (90 dM) after nephroureterectomy (NU) and to devise a model capable of identifying individuals at an elevated 90 dM risk. NU represents the surgical standard of care for patients with invasive, nonmetastatic upper-tract urothelial carcinoma. However, this major abdominal surgery may be associated with a nonnegligible rate of perioperative mortality., Methods: We identified 6078 upper-tract urothelial carcinoma patients treated with NU from 17 registries of the Surveillance, Epidemiology, and End Results database, between 1988 and 2006. Stratified analyses quantified 90 dM rates according to age, gender, race, year of diagnosis, tumor location, surgery type, T stage, tumor grade, and lymph node status. Subsequently, multivariable logistic regression models identified predictors of 90 dM within the development cohort (n = 3039). The accuracy and calibration of the model were tested in an independent validation cohort (n = 3039)., Results: The overall 90 dM rate was 4.4%. Continuously coded age and T and N stages achieved an independent predictor status in multivariable logistic regression models and represented key variables for prediction of individual 90 dM risk after NU, with 73.4% accuracy. Excellent correlation between predicted and observed 90 dM rates after NU was recorded., Conclusions: In this large-scale population-based analysis of perioperative mortality after NU, age and T and N stages emerged as the most informative predictor of 90 dM. We recommend the use of this tool in individual decision-making and in informed consent considerations., (2010. Published by Elsevier Inc.)

Objectives: To examine the effect of gender in upper tract urothelial carcinoma (UTUC) stage at nephroureterectomy (NU), as well as on cancer-specific mortality (CSM) after NU in patients with American Joint Committee on Cancer stages I-III UTUC., Methods: Our analyses relied on 2903 (59.9%) males and 1947 (40.1%) females who underwent an NU for pT(1-3)N(0/x)M(0) UTUC between 1988 and 2006, within 17 Surveillance, Epidemiology, and End Results registries. Univariable and multivariable logistic regression models examined the effect of gender on stage and grade distribution at NU. Subsequently, cumulative incidence plots explored the impact of gender on CSM rates, after accounting for other-cause mortality (OCM). Finally, competing-risks regression models tested the independent predictor status of gender in CSM analyses. Covariates consisted of pT stage, pN stage, tumor grade, primary tumor location, type and year of surgery, age, and race., Results: Relative to males, females had a higher proportion of pT(3) UTUC (43.1% vs 39%; P = .02) and a higher proportion of grade III/IV UTUC (63.8% vs 59.8%; P = .04) at NU. The female gender represented an independent predictor of pT(3) UTUC at NU (hazard ratio [HR]: 1.15; P = .03). After accounting for OCM, CSM rates in females were higher than those in males (HR: 1.18; P = .03). However, in multivariable competing-risks regression models, no statistically significant differences in survival were recorded between males and females (HR: 1.07; P = .4)., Conclusions: Females are more likely to have more advanced pathologic T stage and higher tumor grade at NU than males. After accounting for OCM, stage, grade, and noncancer characteristics, gender no longer affects CSM., (Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.)

Background: Open nerve-sparing retropubic prostatectomy (nsRP) is still the most common surgical approach for the treatment of localised prostate cancer. Even though the principles of the technique and its oncological efficacy have often been published, ongoing refinements allow further improvements in functional outcome and morbidity., Objective: To describe our current technique of open nsRP with data addressing urinary continence, potency, cancer control rates, and perioperative morbidity., Design, Setting, and Participants: Our analyses relied on 1150 patients who were treated with nsRP in the Martini-Clinic by two high-volume surgeons from April 2005 to December 2007., Surgical Procedure: Key elements are a selective ligation of the dorsal vein complex and early release of the neurovascular bundles using a high anterior tension- and energy-free intrafascial technique. During dissection of the urethra, its posterior insertion at Denonvilliers' fascia (DF) is preserved. DF is left in situ, and it is selectively opened above the seminal vesicles (SV). The SV are completely removed inside DF, and five muscle-sparing interrupted sutures are used for anastomosis., Measurements: Functional and oncological outcome data were prospectively assessed using validated questionnaires. Moreover, intra- and perioperative morbidity were evaluated., Results and Limitations: Age and extent of nerve-sparing approach influenced urinary continence and potency. Complete urinary continence 1 yr after nsRP was found in 97.4% (men <60 yr) to 84.1% (men >70 yr) of patients. In preoperative potent men, erections sufficient for intercourse were reported between 84-92% and 58.3-70% of patients following bilateral and unilateral nerve sparing, respectively. Median blood loss was 580 ml (range: 130-1800 ml), and the transfusion rate was 4.3%. Median operative time was 165 min (range: 85-210 min). In organ-confined cancers, recurrence-free survival and cancer-specific-survival 10 yr after retropubic prostatectomy were 87% and 98.3%, respectively., Conclusions: Open intrafascial nsRP combines excellent long-term cancer control rates with superior functional outcome and a low morbidity.

Background: Insufficient sensitivity and specificity of prostate biopsies for cancer detection., Objectives: Based on evidence from our microarray analyses, we hypothesized that considerable molecular changes precede morphologically detectable malignant transformation of prostate epithelial tissues. The identification of such changes could lead to novel strategies in the clinical management of prostate cancer., Design, Setting, and Participants: Histologically normal, fresh prostate tissue from prostate cancer patients, healthy donors, and cancer suspect patients with continuous negative biopsies were analyzed., Measurements: To identify molecular changes between 29 tumor-free prostate tissues from healthy donors and 27 patients with proven prostate cancer, we performed a global microarray screening. Based on this screening as well as literature data, we selected a subset of 29 genes for validation by arrayed real-time reverse transcription-polymerase chain reaction (RT-PCR) using histologically tumor-free biopsy samples from 114 patients representing three prostate cancer risk groups., Results and Limitations: We identified five genes (FOS, EGR1, MYC, TFRC, and FOLH1), which displayed significant differential expression between morphologically normal prostate tissues from men of each of the three risk groups. These results were independent from age, prostate-specific antigen (PSA), frequency and timing of previous prostate biopsies, tissue composition, tumor stage, and tumor grade. In univariate logistic regression analyses, the transcript levels of these genes were found to be highly indicative for the presence or absence of cancer in the entire prostate. The study was designed as a proof of principle. The clinical relevance of our results has to be evaluated in a larger clinical setting., Conclusions: Our results suggest a measurable molecular cancer phenotype in histologically normal prostate tissue indicating the presence of prostate cancer elsewhere in the organ.

Objectives: To determine whether an increased body mass index (BMI) is a predictor of advanced pathologic findings in European men undergoing radical prostatectomy (RP). The relationship between obesity and prostate cancer is controversial. Studies, predominantly derived from the United States, have suggested that an increased BMI is a significant predictor of adverse pathologic findings in patients treated with open RP., Methods: From April 2005 to June 2008, 1538 consecutive patients were treated with open RP at a single tertiary referral center. We tested the effect of BMI on the rate of extracapsular extension, seminal vesicle invasion, lymph node invasion, and positive surgical margins in univariate and multivariate logistic regression models. The covariates consisted of clinical stage, prostate-specific antigen, biopsy Gleason score, age, prostate volume, and rate of nerve-sparing surgery., Results: On multivariate analysis, both continuously coded and categorically coded BMI was unrelated to the rate of extracapsular extension (odds ratio [OR] 1.02, P = .5), seminal vesicle invasion (OR 1.03, P = .3), lymph node invasion (OR 0.98, P = .7), or positive surgical margins (OR 1.03, P = .3)., Conclusions: Obese patients who are candidates for open RP should not expect to have worse pathologic findings after surgery than their nonobese counterparts. Differences in patients' weight and height between North America and Europe might explain the lack of adverse effects of an elevated BMI in this European cohort.

Background: The presence of a tertiary Gleason grade (TGG) pattern in radical prostatectomy (RP) specimens has been described as associated with adverse pathology and a higher biochemical recurrence (BCR) rate after RP., Objective: To assess the prevalence of a TGG in a contemporary, consecutive, single-centre RP series and its association with adverse pathology., Design, Setting, and Participants: From January to August 2007, 800 eligible patients (no prior neoadjuvant hormonal therapy) underwent RP for clinically localised prostate cancer (pCA) in our institution. The presence of the third most prevalent Gleason pattern was documented, regardless of whether it was better or worse than the two predominant Gleason grades., Measurements: The overall prevalence of a TGG was described. Uni- and multivariate logistic regression analyses tested the association between the presence of a TGG <5% versus >or=5% of the whole tumour volume and extracapsular extension (ECE), seminal vesicle invasion (SVI), positive surgical margins (PSM), and lymph node invasion (LNI). Subanalyses were performed to assess the impact of different TGGs at various Gleason scores., Results and Limitations: A TGG was reported in 180 RP specimens (22.5%). In univariate analysis, the presence of a TGG >/=5% was significantly associated with ECE, SVI, PSM, and LNI (p<0.001). In multivariate analysis, a TGG >or=5% showed an independent association with ECE and PSM (p<0.05). Accordingly, in subanalyses, a significant association with adverse pathology was only documented if the amount of a TGG was at least 5% of the tumour volume. Our study is limited by the relatively low overall frequency of a TGG, thereby reducing the statistical expressiveness, especially for subanalyses., Conclusions: Our findings confirm the association of the presence of a TGG with adverse pathologic features. Further follow-up is needed to assess the prognostic impact of a TGG on the risk of BCR and overall survival following RP.

Background: Conventional gray scale ultrasound has a low sensitivity and specificity for prostate cancer detection. Better imaging modalities are needed., Objective: To determine sensitivity and specificity for prostate cancer detection with ultrasound-based real-time elastography (elastography) in patients scheduled for radical prostatectomy (RP)., Design, Setting, and Participants: Between July and October 2007, 109 patients with biopsy-proven localized prostate cancer (PCa) underwent elastography before RP. The investigator was blinded to clinical data., Measurements: A EUB-6500HV ultrasound system with a V53W 7.5MHz end-fire transrectal probe was used preoperatively. Areas found to be suspicious for PCa were recorded for left and right side of the apex, mid-gland, and base. These findings were correlated with the obtained whole-mount sections after RP., Results and Limitations: Sensitivity and specificity for detecting PCa were 75.4% and 76.6%, respectively. A total of 439 suspicious areas in elastography were recorded, and 451 cancerous areas were found in the RP specimens. Positive predictive value, negative predictive value, and accuracy for elastography were 87.8%, 59%, and 76%, respectively. Nevertheless, there are limitations to our studies because we investigated specific patients scheduled for RP with apparent PCa. Whether elastography is practical as a diagnostic tool or can be used to target a biopsy and be at least as sensitive in tumor detection as extended biopsy schemes has yet to be determined., Conclusion: Elastography can detect prostate cancer foci within the prostate with good accuracy and has potential to increase ultrasound-based PCa detection. Further studies need to be done to approve these data and to evaluate whether tumor detection can be increased by elastography-guided biopsies.