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Purpose: Accurate prediction of extraprostatic extension (EPE) is pivotal for surgical planning. Herein, we aimed to provide an updated model for predicting EPE among patients diagnosed with MRI-targeted biopsy., Materials and Methods: We analyzed a multi-institutional dataset of men with clinically localized prostate cancer diagnosed by MRI-targeted biopsy and subsequently underwent prostatectomy. To develop a side-specific predictive model, we considered the prostatic lobes separately. A multivariable logistic regression analysis was fitted to predict side-specific EPE. The decision curve analysis was used to evaluate the net clinical benefit. Finally, a regression tree was employed to identify three risk categories to assist urologists in selecting candidates for nerve-sparing, incremental nerve sparing and non-nerve-sparing surgery., Results: Overall, data from 3169 hemi-prostates were considered, after the exclusion of prostatic lobes with no biopsy-documented tumor. EPE was present on final pathology in 1,094 (34%) cases. Among these, MRI was able to predict EPE correctly in 568 (52%) cases. A model including PSA, maximum diameter of the index lesion, presence of EPE on MRI, highest ISUP grade in the ipsilateral hemi-prostate, and percentage of positive cores in the ipsilateral hemi-prostate achieved an AUC of 81% after internal validation. Overall, 566, 577, and 2,026 observations fell in the low-, intermediate- and high-risk groups for EPE, as identified by the regression tree. The EPE rate across the groups was: 5.1%, 14.9%, and 48% for the low-, intermediate- and high-risk group, respectively., Conclusion: In this study we present an update of the first side-specific MRI-based nomogram for the prediction of extraprostatic extension together with updated risk categories to help clinicians in deciding on the best approach to nerve-preservation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objective: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes., Material and Methods: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP., Results: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01)., Conclusion: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA., (© 2023. The Author(s).)

Background: De novo oligometastatic prostate cancer (omPCa) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is a new disease entity and its optimal management remains unknown., Objective: To analyze the outcomes of patients treated with cytoreductive radical prostatectomy (cRP) for omPCa on PSMA-PET., Design, Setting, and Participants: Overall, 116 patients treated with cRP at 13 European centers were identified. Oligometastatic PCa was defined as miM1a and/or miM1b with five or fewer osseous metastases and/or miM1c with three or fewer lung lesions on PSMA-PET., Intervention: Cytoreductive radical prostatectomy., Outcome Measurements and Statistical Analysis: Thirty-day complications according to Clavien-Dindo, continence rates, time to castration-resistant PCa (CRPC), and overall survival (OS) were analyzed., Results and Limitations: Overall, 95 (82%) patients had miM1b, 18 (16%) miM1a, and three (2.6%) miM1c omPCa. The median prebiopsy prostate-specific antigen was 14 ng/ml, and 102 (88%) men had biopsy grade group ≥3 PCa. The median number of metastases on PSMA-PET was 2; 38 (33%), 29 (25%), and 49 (42%) patients had one, two, and three or more distant positive lesions. A total of 70 (60%) men received neoadjuvant systemic therapy, and 37 (32%) underwent metastasis-directed therapy. Any and Clavien-Dindo grade ≥3 complications occurred in 36 (31%) and six (5%) patients, respectively. At a median follow-up of 27 mo, 19 (16%) patients developed CRPC and eight (7%) patients died. The 1-yr urinary continence rate was 82%. The 2-yr CRPC-free survival and OS were 85.8% (95% confidence interval [CI] 78.5-93.7%) and 98.9% (95% CI 96.8-100%), respectively. The limitations include retrospective design and short-term follow-up., Conclusions: Cytoreductive radical prostatectomy is a safe and feasible treatment option in patients with de novo omPCa on PSMA-PET. Despite overall favorable oncologic outcomes, some of these patients have a non-negligible risk of early progression and thus should be considered for multimodal therapy., Patient Summary: We found that patients treated at expert centers with surgery for prostate cancer, with a limited number of metastases detected using novel molecular imaging, have favorable short-term survival, functional results, and acceptable rates of complications., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Salvage radical prostatectomy (sRP) yields poor functional outcomes and relatively high complication rates. Gleason score (GS) 6 prostate cancer (PCa) has genetic and clinical features showing little, if not absent, metastatic potential. However, the behavior of GS 6 PCa recurring after previous PCa treatment including radiotherapy and/or ablation has not been investigated., Objective: To evaluate the oncological outcomes of sRP for radio- and/or ablation-recurrent GS 6 PCa., Design, Setting, and Participants: Retrospective data of sRP for recurrent PCa after local nonsurgical treatment were collected from 14 tertiary referral centers from 2000 to 2021., Intervention: Prostate biopsy before sRP and sRP., Outcome Measurements and Statistical Analysis: A survival analysis was performed for pre-sRP biopsy and sRP-proven GS 6. Concordance between PCa at pre-sRP biopsy and sRP histology was assessed., Results and Limitations: We included GS 6 recurrent PCa at pre-sRP biopsy (n = 142) and at sRP (n = 50), as two cohorts. The majority had primary radiotherapy and/or brachytherapy (83.8% of GS 6 patients at pre-sRP biopsy; 78% of GS 6 patients at sRP) and whole-gland treatments (91% biopsy; 85.1% sRP). Biopsy GS 6 10-yr metastasis, cancer-specific survival (CSS), and overall survival (OS) were 79% (95% confidence interval [CI] 61-89%), 98% (95-99%), and 89% (78-95%), respectively. Upgrading at sRP was 69%, 35.5% had a pT3 stage, and 13.4% had positive nodes. The sRP GS 6 10-yr metastasis-free survival, CSS, and OS were 100%, 100%, and 90% (95% CI 58-98%) respectively; pT3 and pN1 disease were found in 12% and 0%, respectively. Overall complications, high-grade complications, and severe incontinence were experienced by >50%, >10%, and >15% of men, respectively (in both the biopsy and the sRP cohorts). Limitations include the retrospective nature of the study and absence of a centralized pathological review., Conclusions: GS 6 sRP-proven PCa recurring after nonsurgical primary treatment has almost no metastatic potential, while patients experience relevant morbidity of the procedure. However, a significant proportion of GS 6 cases at pre-sRP biopsy are upgraded at sRP. In the idea not to overtreat, efforts should be made to improve the diagnostic accuracy of pre-sRP biopsy., Patient Summary: We investigated the oncological results of salvage radical prostatectomy for recurrent prostate cancer of Gleason score (GS) 6 category. We found a very low malignant potential of GS 6 confirmed at salvage radical prostatectomy despite surgical complications being relatively high. Nonetheless, biopsy GS 6 was frequently upgraded and had less optimal oncological control. Overtreatment for recurrent GS 6 after nonsurgical first-line treatment should be avoided, and efforts should be made to increase the diagnostic accuracy of biopsies for recurrent disease., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objective: It is unknown whether renal transplant receipt (RTR) status can affect perioperative and oncological outcomes of radical prostatectomy (RP). Our aim was to evaluate oncological and functional outcomes of RTR patients treated with RP for cN0M0 prostate cancer (PCa) via comparison with a no-RTR cohort., Methods: RTR patients who had undergone RP at seven European institutions during 2001-2022 were identified. A multi-institutional cohort of no-RTR patients treated with RP during 2004-2022 served as the comparator group. Propensity score matching (PSM) at a ratio of 1:4 was used to match no-RTR patients to the RTR cohort according to age, prostate-specific antigen, and final pathology features. We used Kaplan-Meier plots and multivariable Cox, logistic, and Poisson log-linear regression models to test the outcomes of interest., Key Findings and Limitations: After PSM, we analyzed data for 102 RTR and 408 no-RTR patients. RTR patients experienced higher estimated blood loss (EBL), longer length of hospital stay (LOS) and time to catheter removal, higher postoperative complication rates, and a lower continence recovery rate (all p < 0.001). On multivariable analyses, RTR independently predicted unfavorable operative time (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.18-1.25), LOS (OR 1.57, 95% CI 1.32-1.86), EBL (OR 2.24, 95% CI 2.18-2.30), and time to catheter removal (OR 1.93, 95% CI 1.68-2.21), but not complications or continence recovery. There were no significant differences for any oncological outcomes (biochemical recurrence, local or systemic progression) between the RTR and no-RTR groups. While no PCa deaths were recorded, the overall mortality rate was significantly higher in the RTR group (17% vs 0.5%, p < 0.001)., Conclusions and Clinical Implications: Although RP is feasible for RTR patients, the procedure poses non-negligible surgical challenges, with longer operative time and LOS and higher EBL, but no major differences in terms of complications and continence recovery. The RTR group had similar oncological outcomes to the no-RTR group but significantly higher overall mortality related to causes other than PCa. Therefore, careful selection for RP is required among candidates with previous RTR., Patient Summary: Removal of the prostate for prostate cancer is possible in patients who have had a kidney transplant, and cancer control outcomes are comparable to those for the general population. However, transplant patients have a higher risk of death from causes other than prostate cancer and the prostate surgery is likely to be more challenging., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Current guidelines do not provide strong recommendations on preservation of the neurovascular bundles during radical prostatectomy in case of high-risk (HR) prostate cancer and/or suspicious extraprostatic extension (EPE). We aimed to evaluate when, in case of unilateral HR disease, contralateral nerve sparing (NS) should be considered or not., Materials and Methods: Within a multi-institutional data set we selected patients with unilateral HR prostate cancer, defined as unilateral EPE and/or seminal vesicle invasion (SVI) on multiparametric (mp) magnetic resonance imaging (MRI), or unilateral International Society of Urologic Pathologists (ISUP) 4-5 or prostate specific antigen ≥20 ng/ml. To evaluate when to perform NS based on the risk of contralateral EPE, we relied on chi-square automated interaction detection, a recursive machine-learning partitioning algorithm developed to identify risk groups, which was fit to predict the presence of EPE on final pathology, contralaterally to the prostate lobe with HR disease., Results: A total of 705 patients were identified. Contralateral EPE was documented in 87 patients (12%). Chi-square automated interaction detection identified 3 groups, consisting of 1) absence of SVI on mpMRI and index lesion diameter ≤15 mm, 2) index lesion diameter ≤15 mm and contralateral ISUP 2-3 or index lesion diameter >15 mm and negative contralateral biopsy or ISUP 1, and 3) SVI on mpMRI or index lesion diameter >15 mm and contralateral biopsy ISUP 2-3. We named those groups as low, intermediate and high-risk, respectively, for contralateral EPE. The rate of EPE and positive surgical margins across the groups were 4.8%, 14% and 26%, and 5.6%, 13% and 18%, respectively., Conclusions: Our study challenges current guidelines by proving that wide bilateral excision in men with unilateral HR disease is not justified. Pending external validation, we propose performing NS and incremental NS in case of contralateral low and intermediate EPE risk, respectively.

Objectives: To build a machine learning (ML) model to detect extraprostatic extension (EPE) of prostate cancer (PCa), based on radiomics features extracted from prostate MRI index lesions., Methods: Consecutive MRI exams of patients undergoing radical prostatectomy for PCa were retrospectively collected from three institutions. Axial T2-weighted and apparent diffusion coefficient map images were annotated to obtain index lesion volumes of interest for radiomics feature extraction. Data from one institution was used for training, feature selection (using reproducibility, variance and pairwise correlation analyses, and a correlation-based subset evaluator), and tuning of a support vector machine (SVM) algorithm, with stratified 10-fold cross-validation. The model was tested on the two remaining institutions' data and compared with a baseline reference and expert radiologist assessment of EPE., Results: In total, 193 patients were included. From an initial dataset of 2436 features, 2287 were excluded due to either poor stability, low variance, or high collinearity. Among the remaining, 14 features were used to train the ML model, which reached an overall accuracy of 83% in the training set. In the two external test sets, the SVM achieved an accuracy of 79% and 74% respectively, not statistically different from that of the radiologist (81-83%, p = 0.39-1) and outperforming the baseline reference (p = 0.001-0.02)., Conclusions: A ML model solely based on radiomics features demonstrated high accuracy for EPE detection and good generalizability in a multicenter setting. Paired to qualitative EPE assessment, this approach could aid radiologists in this challenging task., Key Points: • Predicting the presence of EPE in prostate cancer patients is a challenging task for radiologists. • A support vector machine algorithm achieved high diagnostic accuracy for EPE detection, with good generalizability when tested on multiple external datasets. • The performance of the algorithm was not significantly different from that of an experienced radiologist., (© 2021. The Author(s).)

Purpose: To examine the predictive and prognostic value of preoperative Systemic Immune-inflammation Index (SII) in patients with radio-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP)., Materials and Methods: This multicenter retrospective study included 214 patients with radio-recurrent PCa, treated with SRP between 2007 and 2015. SII was measured preoperatively (neutrophils × platelets/lymphocytes) and the cohort was stratified using optimal cut-off. Uni- and multivariable logistic and Cox regression analyses were performed to evaluate the predictive and prognostic value of SII as a preoperative biomarker., Results: A total of 81 patients had high preoperative SII (≥ 730). On multivariable logistic regression modeling, high SII was predictive for lymph node metastases (OR 3.32, 95% CI 1.45-7.90, p = 0.005), and non-organ confined disease (OR 2.55, 95% CI 1.33-4.97, p = 0.005). In preoperative regression analysis, high preoperative SII was an independent prognostic factor for cancer-specific survival (CSS; HR 10.7, 95% CI 1.12-103, p = 0.039) and overall survival (OS; HR 8.57, 95% CI 2.70-27.2, p < 0.001). Similarly, in postoperative multivariable models, SII was associated with worse CSS (HR 22.11, 95% CI 1.23-398.12, p = 0.036) and OS (HR 5.98, 95% CI 1.67-21.44, p = 0.006). Notably, the addition of SII to preoperative reference models improved the C-index for the prognosis of CSS (89.5 vs. 80.5) and OS (85.1 vs 77.1)., Conclusions: In radio-recurrent PCa patients, high SII was associated with adverse pathological features at SRP and survival after SRP. Preoperative SII could help identify patients who might benefit from novel imaging modalities, multimodal therapy or a closer posttreatment surveillance., (© 2021. The Author(s).)

Purpose: To present the step-by-step description of an ejaculation-sparing anatomic photo-selective vaporization of the prostate (PVP) technique. To report the results of a series of ejaculation-sparing versus non-ejaculation-sparing anatomic PVPs., Methods: Sexually active, benign prostatic hyperplasia (BPH) patients undergoing an anatomic PVP between 11/2018 and 2/2020 were included. Patients were divided into group A (ejaculation-sparing surgery) and group B (control group). Baseline, peri-operative and 6-months follow-up data were evaluated. Lower urinary tract symptoms (LUTS) and sexual function were assessed through internationally validated questionnaires. Groups were matched by an inverse probability of treatment weighting (IPTW) analysis. Logistic univariable regression analysis was performed to detect predictors of antegrade ejaculation preservation., Results: Overall, 76 patients were included, among which 15 in group A and 61 in group B. Median (inter-quartile range, IQR) age was 72 (66.5-77) years, median (IQR) prostate volume 63.5 (54.5-98.5) cc. No differences about peri-operative outcomes were detected, included high-grade complications. At 6-months follow-up, no differences in urinary or erectile function were detected between groups, while ejaculation-sparing patients showed better Male Sexual Health Questionnaire (MSHQ) scores [7 (1-13) vs. 1 (1-1), p < 0.001] and higher rates of antegrade ejaculation (60% vs. 13.1%, p < 0.001). The ejaculation-sparing technique was identified as a predictor of post-operative antegrade ejaculation (OR 19.3, CI 95% 7.2-51.2, p < 0.001)., Conclusion: The ejaculation-sparing anatomic PVP showed superiority over the control group in post-operative ejaculatory function scores and antegrade ejaculation rates. Besides, preliminary results suggested similar effectiveness in LUTS relief at a short-term follow-up., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP show improved results. Our objectives were to evaluate sRP oncological outcomes and predictors of positive margins and biochemical recurrence (BCR)., Methods: We retrospectively collected data of sRP for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers in United States, Australia and Europe, from 2000 to 2016. SM and BCR were evaluated in a univariate and multivariable analysis. Overall and cancer-specific survival were also assessed., Results: We included 414 cases, 63.5% of them performed after radiotherapy. Before sRP the majority of patients had biopsy Gleason score (GS) ≤7 (55.5%) and imaging negative or with prostatic bed involvement only (93.3%). Final pathology showed aggressive histology in 39.7% (GS ≥9 27.6%), with 52.9% having ≥pT3 disease and 16% pN+. SM was positive in 29.7%. Five years BCR-Free, cancer-specific survival and OS were 56.7%, 97.7% and 92.1%, respectively. On multivariable analysis pathological T (pT3a odds ratio [OR] 2.939, 95% confidence interval [CI] 1.469-5.879; ≥pT3b OR 2.428-95% CI 1.333-4.423) and N stage (pN1 OR 2.871, 95% CI 1.503-5.897) were independent predictors of positive margins. Pathological T stage ≥T3b (OR 2.348 95% CI 1.338-4.117) and GS (up to OR 7.183, 95% CI 1.906-27.068 for GS >8) were independent predictors for BCR. Limitations include the retrospective nature of the study and limited follow-up., Conclusions: In a contemporary series, sRP showed promising oncological control in the medium term despite aggressive pathological features. BCR risk increased in case of locally advanced disease and higher GS. Future studies are needed to confirm our findings., (Copyright © 2020. Published by Elsevier Inc.)

Aims: The objective of the study was to analyze short-term outcomes and safety profile of the newly designed artificial urinary sphincters (AUSs) VICTO® and VICTOplus®., Methods: Data from the implant of VICTO® or VICTOplus® AUSs on a series of consecutive male patients with stress urinary incontinence (SUI) following radical prostatectomy (RP) were retrospectively collected in 3 tertiary referral centers between May 2017 and December 2019. Patients were affected by moderate-severe genuine SUI (200-400 or >400 g urine leakage in 24-h pad test) refractory to conservative treatment. Outcomes were evaluated through the 24-h pad test and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF). Follow-up was scheduled after 3, 6, and 12 months and then when clinically needed. Nonparametric tests were applied in subgroup analyses., Results: Seventeen patients were enrolled: 8 were implanted with the VICTO® device and 9 with VICTOplus®. The median age at surgery was 69 (interquartile range (IQR) 60-75) years. The median follow-up was 15 (IQR 12-18) months. At 12 months, the dry rate was 76.4% and the social continence rate was 94%. The postoperative complication rate was 17.6%. All complications were classified as Clavien-Dindo I. No difference in terms of outcomes was observed between the VICTO® and the VICTOplus® subgroups., Conclusions: Preliminary outcomes of the VICTO® and VICTOplus® implantation are satisfactory. These devices may represent a safe and realistic solution for patients with moderate-severe SUI following RP., (© 2021 S. Karger AG, Basel.)

Context: Optimal management of prostate cancer (PCa) patients with lymph node invasion at radical prostatectomy and pelvic lymph node dissection still remains unclear., Objective: To assess the effectiveness of postoperative treatment strategies for pathologically node-positive PCa patients. The secondary aim was to identify the most relevant prognostic factors to guide the management of pN1 patients., Evidence Acquisition: A systematic review was performed in January 2020 using Medline, Embase, and other databases. A total of 5063 articles were screened, and 26 studies including 12 537 men were selected for data synthesis and included in the current review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations., Evidence Synthesis: Ten-year biochemical recurrence (BCR)-free, clinical recurrence-free, cancer-specific (CSS), and overall (OS) survival rates ranged from 28% to 56%, 70% to 92%, 72% to 98%, and 60% to 87.6%, respectively. A total of seven, five, and six studies assessed the oncological outcomes of observation, adjuvant radiotherapy (aRT), or adjuvant androgen deprivation therapy (ADT), respectively. Initial observation followed by salvage therapies at the time of recurrence represents a safe option in selected patients with a low disease burden. The use of aRT with or without ADT might improve survival in men with locally advanced disease and a higher number of positive nodes. Risk stratification according to pathological Gleason score, number of positive nodes, pathological stage, and surgical margins status is the key to risk stratification and selection of the optimal postoperative therapy. Limitations of this systematic review are the retrospective design of the studies included and the lack of data on adverse events., Conclusions: While the majority of men with pN1 disease would experience BCR after surgery, long-term disease-free survival has been reported in selected patients. Management options to improve oncological outcomes include observation versus adjuvant therapies such as aRT and/or ADT. Disease characteristics should be used to select the optimal postoperative management for pN1 PCa patients., Patient Summary: Finding node-positive prostate cancer after a radical prostatectomy often leads to high postoperative prostate-specific antigen levels and is overall a poor prognostic factor. However, this does not necessarily translate into poor survival for all men. Management can be tailored to the severity of disease and options include observation, androgen deprivation therapy, and/or radiotherapy., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

There is limited scientific literature regarding the management outcomes for end-stage erectile dysfunction (ED) following radical cystoprostatectomy (RCP). This study aims to evaluate the surgical outcomes of penile prosthesis (PP) implantation. A retrospective analysis over 17 years (2004-2017) was performed from the clinical records of patients in four tertiary referral centres, whom previously had undergone RCP, followed by PP implantation for end-stage ED. Outcome measures include both intra and postoperative complications, operative duration, a 5-point Likert hematoma scale as well as length of hospital stay. Additionally, a matched-pair cohort analysis was performed, dividing patients in 2 groups according to the type of urinary diversion (neobladder versus ileal conduit/cutaneous ureterostomy). The median time elapsed between RCP and PP implantation was 38 months (IQR 20-56). The median follow-up was 18 months (IQR 12-156). A 3-piece inflatable PP was implanted in 43 patients (91.5%) whereas a semirigid device was implanted in the remainder. Reservoir position was extra-peritoneal (utilising a separate abdominal incision) in 24 patients (54.8%), while an ectopic high-submuscular placement was preferred in the remainder. PP infection and mechanical failure occurred in 1 (2.1%) and 3 cases (6.3%) respectively. The comparative analysis of surgical outcomes did not show any statistically significant difference between the two groups. Our evidence suggests that PP implantation in patients with refractory ED following RCP may represent a safe and effective procedure associated with a low incidence of complications. The main limitation of this study is represented by the non-randomised, retrospective nature as well as the lack of patients' functional outcomes and the limited follow-up.

Objective: To evaluate the accuracy in histologic grading of MRI/US image fusion biopsy by comparing histopathology between systematic biopsies (SB), targeted biopsies (TB) and the combination of both (SB + TB) with the final histopathologic outcomes of radical prostatectomy specimens., Materials and Methods: Retrospective, multicentric study of 443 patients who underwent SB and TB using MRI/US fusion technique (Urostation ® and Trinity ® ) prior to radical prostatectomy between 2010 and 2017. Cochran's Q test and McNemar test were conducted as a post hoc test. Uni-multivariable analyses were performed on several clinic-pathological variables to analyze factors predicting histopathological concordance for targeted biopsies., Results: Concordance in ISUP (International Society of Urological Pathology) grade between SB, TB and SB + TB with final histopathology was 49.4%, 51.2%, and 63.2% for overall prostate cancer and 41.2%, 48.3%, and 56.7% for significant prostate cancer (ISUP grade ≥ 2), respectively. Significant difference in terms of concordance, downgrading and upgrading was found between SB and TB (ISUP grade ≥ 2 only), SB and SB + TB, TB and SB + TB (overall ISUP grade and ISUP grade ≥ 2) (p < 0.001). Total number of cores and previous biopsies were significant independent predictive factors for concordance with TB technique., Conclusion: In this retrospective study, combination of SB and TB significantly increased concordance with final histopathology despite a limited additional number of cores needed.

Purpose: Salvage radical prostatectomy has historically yielded a poor functional outcome and a high complication rate. However, recent reports of robotic salvage radical prostatectomy have demonstrated improved results. In this study we assessed salvage radical prostatectomy functional outcomes and complications when comparing robotic and open approaches., Materials and Methods: We retrospectively collected data on salvage radical prostatectomy for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers from 2000 to 2016. The Clavien-Dindo classification was applied to classify complications. Complications and functional outcomes were evaluated by univariable and multivariable analysis., Results: We included 395 salvage radical prostatectomies, of which 186 were open and 209 were robotic. Robotic salvage radical prostatectomy yielded lower blood loss and a shorter hospital stay (each p <0.0001). No significant difference emerged in the incidence of major and overall complications (10.1%, p=0.16, and 34.9%, p=0.67), including an overall low risk of rectal injury and fistula (1.58% and 2.02%, respectively). However, anastomotic stricture was more frequent for open salvage radical prostatectomy (16.57% vs 7.66%, p <0.01). Overall 24.6% of patients had had severe incontinence, defined as 3 or more pads per day, for 12 or 6 months. On multivariable analysis robotic salvage radical prostatectomy was an independent predictor of continence preservation (OR 0.411, 95% CI 0.232-0.727, p=0.022). Limitations include the retrospective nature of the study and the absence of a standardized surgical technique., Conclusions: In this contemporary series to our knowledge salvage radical prostatectomy showed a low risk of major complications and better functional outcomes than previously reported. Robotic salvage radical prostatectomy may reduce anastomotic stricture, blood loss and hospital stay, and improve continence outcomes.

Background: Cool and dry gas insufflation during laparoscopy induces hypothermia and cytokine increase, with significant perioperative morbidity. Our aim was to assess if warmed and humidified CO 2 insufflation with HumiGard™ device can achieve significant benefits over standard insufflation in terms of risk of hypothermia, cytokine response, blood gases, and intra- and postoperative parameters, in the setting of robot-assisted radical prostatectomy (RARP)., Methods: This was a prospective, randomized controlled clinical trial. Sixty-four patients with prostate cancer undergoing RARP were randomized to receive warmed and humidified CO 2 insufflation with HumiGard device, plus hot air warming blanket (treatment group, H + WB), or standard CO 2 insufflation, plus hot air warming blanket (control group, WB). Body core temperature (BCT), plasma levels of IL-6 and TNF-α, pain scores, and intraoperative parameters were recorded. The data were analyzed according to the Bayesian paradigm., Results: Intraoperative BCT increased in both groups during surgery, with a statistically significant difference favoring group H + WB, ending at 0.2°C higher on average than group WB. No difference across groups was shown for cytokine levels. Blood gas parameters were not affected by warmed CO 2 insufflation. No statistical differences were noted for pain scores and the other intra- and postoperative parameters., Conclusions: During RARP, warm and humidified CO 2 insufflation with the HumiGard device was more effective than the standard CO 2 insufflation in maintaining the patient's heat homeostasis, even if the difference was minimal. No imbalances were detected on blood gas analyses. No benefit could be shown in terms of cytokine levels and pain scores.

Purpose: Salvage radical prostatectomy (sRP) represents a curative option for prostate cancer (PCa) biochemical recurrence (BCR) after radiation therapy (RT). In this review, we aimed to outline the contemporary results and use of sRP., Methods: A web search was performed on the Ovid platform using Embase and Medline databases from January 2010 using pre-defined search terms. Web search was implemented by manual search. Oncological and functional outcomes and complications were summarized using standard classification systems, when feasible., Results: sRP is currently underused, being chosen for radio-recurrent PCa treatment in around 1% of the cases. Surgery is complex due to radiation-induced tissue changes making posterior planes and apex dissection particularly challenging. Patient selection is paramount to maximize the oncological benefit. Most series report a BCR-free survival > 60%, mainly at the end of a short- to intermediate-term follow-up. Five-year progression-free survival is nearly 50% and 5-year cancer-specific survival rates are around 90%. Major peri-operative complications, anastomotic leaks and strictures, still more frequent than in a primary RP setting, have been steering towards more acceptable rates in recent years, when compared to historical series. Continence rates are widely variable, often in between 39 and 60%. Potency remains difficult to recover., Conclusions: sRP represents a curative option with promising short- to medium-term oncological results and acceptable side effects, in high-volume institutions. In appropriately selected patients, the procedure should not be underused due to the fear of poor functional outcomes and/or complications. Prospective studies are needed to assess the long-term outcomes and to further refine patient selection criteria.

Background: Given the prolonged natural history of clinically localized, high-risk prostate cancer, there is a need for the identification of intermediate clinical endpoints (ICEs) to predict long-term overall survival (OS)., Objective: To explore the role of novel potential ICEs based on clinical follow-up to predict long-term survival in patients with high-risk prostate cancer., Design, Setting, and Participants: Overall, 3507 patients treated at 12 tertiary referral centers between 1988 and 2016 were evaluated., Intervention: Radical prostatectomy (RP) with extended pelvic lymph node dissection., Outcome Measurements and Statistical Analysis: The impact of biochemical recurrence (BCR) and clinical recurrence (CR) within 1, 3, 5, and 7yr after surgery on the risk of OS was evaluated in multivariable Cox regression analyses. In patients with BCR, the impact of progression to CR within 6mo and 1, 3, and 5yr on long-term OS was investigated. Discrimination was assessed using Harrell's c index., Results and Limitations: Median follow-up for survivors was 76mo. The 5- and 10-yr OS and cancer-specific survival rates were 94% and 81% versus 98% and 95%, respectively. On a time-varying multivariable analysis, BCR (hazard ratio [HR]: 1.02; 95% confidence interval [CI]: 1.00, 1.04) and CR (HR: 1.05; 95% CI: 1.03-1.07) emerged as predictors of OS (p<0.001). The development of CR within 5yr after surgery was the most informative ICE for predicting OS (c index: 0.74). In patients with BCR, progression to CR within 12mo represented the most informative predictor for the subsequent risk of dying from all causes. Patients who developed BCR within 5yr after RP and progressed to CR within 12mo had a 10-yr OS rate of 47%. These results require prospective validation., Conclusions: When predicting long-term survival in surgically treated high-risk patients, progression to CR within 5yr of RP confers the highest discrimination with respect to other landmark points. In men experiencing BCR, progression to CR within the subsequent 12mo achieved the highest discrimination. Further studies are needed to validate our findings., Patient Summary: We investigated the most informative intermediate clinical endpoints for predicting overall survival (OS). Occurrence of clinical recurrence within 5yr after radical prostatectomy confers the highest discrimination to a model predicting OS., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: To assess the predictive accuracy and the clinical value of a recent nomogram predicting cancer-specific mortality-free survival after surgery in pN1 prostate cancer patients through an external validation., Methods: We evaluated 518 prostate cancer patients treated with radical prostatectomy and pelvic lymph node dissection with evidence of nodal metastases at final pathology, at 10 tertiary centers. External validation was carried out using regression coefficients of the previously published nomogram. The performance characteristics of the model were assessed by quantifying predictive accuracy, according to the area under the curve in the receiver operating characteristic curve and model calibration. Furthermore, we systematically analyzed the specificity, sensitivity, positive predictive value and negative predictive value for each nomogram-derived probability cut-off. Finally, we implemented decision curve analysis, in order to quantify the nomogram's clinical value in routine practice., Results: External validation showed inferior predictive accuracy as referred to in the internal validation (65.8% vs 83.3%, respectively). The discrimination (area under the curve) of the multivariable model was 66.7% (95% CI 60.1-73.0%) by testing with receiver operating characteristic curve analysis. The calibration plot showed an overestimation throughout the range of predicted cancer-specific mortality-free survival rates probabilities. However, in decision curve analysis, the nomogram's use showed a net benefit when compared with the scenarios of treating all patients or none., Conclusions: In an external setting, the nomogram showed inferior predictive accuracy and suboptimal calibration characteristics as compared to that reported in the original population. However, decision curve analysis showed a clinical net benefit, suggesting a clinical implication to correctly manage pN1 prostate cancer patients after surgery., (© 2018 The Japanese Urological Association.)

Background: Accurate prediction of survival after radical prostatectomy (RP) is important for making decisions regarding multimodal therapies. There is a lack of tools to predict prostate cancer-related death (PCRD) in patients with high-risk features., Objective: To develop and validate a prognostic model that predicts PCRD combining pathologic features and using competing-risks analysis., Design, Setting, and Participants: This was a retrospective multi-institutional observational cohort study of 5876 patients affected by high-risk prostate cancer. Patients were treated using RP and pelvic lymph node dissection (PLND) in a multimodal setting, with median follow-up of 49 mo., Outcome Measurements and Statistical Analysis: For PCRD prediction, a multivariate model with correction for competing risks was constructed to evaluate pathologic high-risk features (pT3b-4, Gleason score ≥8, and pN1) as predictors of mortality. All possible associations of the predictors were combined, and then subgroups with similar risk of PCRD were collapsed to obtain a simplified model encoding subgroups with significantly differing risk. Eightfold cross-validation of the model was performed., Results and Limitations: After applying exclusion criteria, 2823 subjects were identified. pT3b-4, Gleason score ≥8, and pN1 were all independent predictors of PCRD. The simplified model included the following prognostic groups: good prognosis, pN0 with 0-1 additional predictors; intermediate prognosis, pN1 with 0-1 additional predictors; poor prognosis, any pN with two additional predictors. The cross-validation yielded excellent median model accuracy of 88%. The retrospective design and the short follow-up could limit our findings., Conclusions: We developed and validated a novel and easy-to-use prognostic instrument to predict PCRD after RP+PLND. This model may allow clinicians to correctly counsel patients regarding the intensity of follow-up and to tailor adjuvant treatments., Patient Summary: Prediction of mortality after primary surgery for prostate cancer is important for subsequent treatment plans. We present an accurate postoperative model to predict cancer mortality after radical prostatectomy for high-risk prostate cancer., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The aim of this review was to summarize the current evidence and to highlight the main issues future research needs to address regarding prostate cancer (PCa) treatment in renal transpant recipients (RTRs). We conducted a search of AMED, Medline and Embase up to 17 November 2016 to investigate oncological and functional outcomes of PCa treatment in RTR. Type and use/protocols of immunosuppression and peri-operative antibiotic drugs were also assessed. The search was implemented manually. Exclusion criteria were absence of full text or absence of information that allowed us to differentiate oncological and/or functional outcomes of each therapeutic approach used. We included 241 patients from 27 retrospective studies published between 1991 and 2016; seven of the studies were case-control and 20 were case series. We also considered nine case reports published between 1999 and 2016. Follow-up ranged from 1 to 120 months. PCa was organ-confined, with Gleason score ≤6 in 75.2% and 60.4% of patients. Surgery was the most frequent treatment used (n = 186), for which cancer-specific (CSS) and overall survival (OS) rates were both 96.8%. Functional outcomes, including continence and erectile function, and complications were less frequently reported and were generally similar to those reported for radical prostatectomy (RP) in non-RTRs. Other treatment methods in the patients included in the review were radiotherapy (RT) ± androgen deprivation therapy (ADT; n = 34; OS 88.2%; CSS 88.2%), ADT alone (n = 14; OS 42.9%; CSS 64.3%), brachytherapy (BT; n = 11; OS and CSS 100%), watchful waiting (n = 4) and active surveillance (n = 1). Overall no treatment-related graft loss occurred. Immunosuppression and antibiotic schemes were poorly reported and inconsistent. Outcomes of PCa treatment in RTRs are encouraging and do not appear to be inferior to those of non-RTR. RP was the most commonly assessed approach, whilst RT, BT and ADT were less frequent. Immunosuppression and antibiotic use were poorly reported and highly variable. High-quality studies are needed because the current level of evidence is low, and our results should therefore be interpreted with caution., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Background/Aims/Objectives: Our aim was to evaluate the accuracy of systematic transperineal sector mapping biopsy (TPSMB) in predicting Gleason score (GS) at radical prostatectomy (RP), to compare its accuracy with standard transrectal ultrasound-guided biopsies (TRUS) and to establish the clinical impact of discordance between biopsies and RP on subsequent surgical management., Methods: Two hundred fifty-five patients from 2008 to 2013 who underwent RP following TPSMB (n = 204) or TRUS (n = 51), were included in this retrospective multi-institutional study. Concordance between biopsies and RPs GS was assessed both as percentages and with Cohen's Kappa coefficient. All mismatches between biopsies and RP were assessed for significance by 3 urologists using the Delphi method., Results: No differences were present among the groups. Concordance between biopsy and RP GS was 75.49% for TPSMB and 64.70% for TRUS. Kappa coefficient was 0.42 and 0.39 respectively. The Delphi method showed lower clinical impact of GS discordances for TPSMB with 7.8% of patients having significant change, thus being potentially more suitable for other treatment modalities, compared to TRUS (13.7%)., Conclusions: TPSMB had a higher accuracy for predicting the GS grade at RP showing superior GS concordance compared with standard TRUS. TPSMB provides an effective technique for systematic prostate biopsy to evaluate overall prostate cancer GS., (© 2017 S. Karger AG, Basel.)

Objectives: To investigate cancer-specific mortality and other-cause mortality in prostate cancer patients with nodal metastases., Methods: The study included 411 patients treated with radical prostatectomy and pelvic lymph node dissection for prostate cancer with lymph node metastases at 10 tertiary care centers between 1995 and 2014. Kaplan-Meier analyses were used to assess cancer-specific mortality-free survival rates at 8 years' follow up in the overall population, and after stratifying patients according to clinical and pathological parameters. Uni- and multivariable competing risk Cox regression analyses were used to assess cancer-specific mortality and other-cause mortality. Finally, cumulative-incidence plots were generated for cancer-specific mortality and other-cause mortality after stratifying patients according to the number of positive lymph nodes and the median age at surgery, according to the competing risks method., Results: Men with prostate-specific antigen ≤40 ng/mL and those with one to three positive lymph nodes showed higher cancer-specific mortality-free survival estimates as compared with their counterparts with prostate-specific antigen >40 ng/mL and >3 metastatic lymph nodes, respectively (all P < 0.001). At multivariable Cox regression analyses, preoperative prostate-specific antigen >40 ng/mL, >3 lymph node metastases and pathological Gleason score 8-10 were all independent predictors of cancer-specific mortality (all P-values ≤0.001). On competing risk analysis, when patients were stratified according to the number of positive lymph nodes (namely, ≤3 vs >3), the 8-year cancer-specific mortality rates were 27.4% versus 44.8% for patients aged <65 years, and 15.2% versus 52.6% for patients aged ≥65 years, respectively., Conclusions: Three positive lymph nodes represent the best prognostic cut-off in node-positive prostate cancer patients. In those individuals with >3 positive lymph nodes, the overall mortality rate is completely related to prostate cancer in young patients., (© 2016 The Japanese Urological Association.)

Introduction: The aim of the study was to identify the appropriate level of Charlson comorbidity index (CCI) in older patients (>70 years) with high-risk prostate cancer (PCa) to achieve survival benefit following radical prostatectomy (RP)., Methods: We retrospectively analyzed 1008 older patients (>70 years) who underwent RP with pelvic lymph node dissection for high-risk prostate cancer (preoperative prostate-specific antigen >20 ng/mL or clinical stage ≥T2c or Gleason ≥8) from 14 tertiary institutions between 1988 and 2014. The study population was further grouped into CCI < 2 and ≥2 for analysis. Survival rate for each group was estimated with Kaplan-Meier method and competitive risk Fine-Gray regression to estimate the best explanatory multivariable model. Area under the curve (AUC) and Akaike information criterion were used to identify ideal 'Cut off' for CCI., Results: The clinical and cancer characteristics were similar between the two groups. Comparison of the survival analysis using the Kaplan-Meier curve between two groups for non-cancer death and survival estimations for 5 and 10 years shows significant worst outcomes for patients with CCI ≥ 2. In multivariate model to decide the appropriate CCI cut-off point, we found CCI 2 has better AUC and p value in log rank test., Conclusion: Older patients with fewer comorbidities harboring high-risk PCa appears to benefit from RP. Sicker patients are more likely to die due to non-prostate cancer-related causes and are less likely to benefit from RP.

Purpose: A sentinel lymph node (SNL) is the primary landing zone of cancer cells that spreads through the lymphatic vessels. The rational of the detection of sentinel node (SLN) during radical prostatectomy (RP) for prostate cancer (PCa) is the removal of the first nodal stations to provide a restriction of the template of node dissection. A review of the outcomes of SNL detection during RP for PCa was performed., Materials and Methods: A systematic review of the literature was conducted, searching on PubMed and Web of Science, using the following keywords: lymph node dissection, prostatic neoplasm, sentinel node., Results: Twenty articles were selected and analyzed including over 2000 PCa patients. Although promising and technically feasible, many points remain to be clarified before clinical application can be recommended., Conclusions: The technique of SNL detection is feasible and provides a higher sensitivity and detection rate than standard lymphadenectomy, especially for organ-confined tumors. Larger series and long-term follow-up data are mandatory to assess the oncologic effectiveness of the detection of SNL for PCa.

Objective: In patients with a long life expectancy with high-risk (HR) prostate cancer (PCa), the chance to die from PCa is not negligible and may change significantly according to the time elapsed from surgery. The aim of this study was to evaluate long-term survival patterns in young patients treated with radical prostatectomy (RP) for HRPCa., Materials and Methods: Within a multiinstitutional cohort, 600 young patients (≤59 years) treated with RP between 1987 and 2012 for HRPCa (defined as at least one of the following adverse characteristics: prostate specific antigen>20, cT3 or higher, biopsy Gleason sum 8-10) were identified. Smoothed cumulative incidence plot was performed to assess cancer-specific mortality (CSM) and other cause mortality (OCM) rates at 10, 15, and 20 years after RP. The same analyses were performed to assess the 5-year probability of CSM and OCM in patients who survived 5, 10, and 15 years after RP. A multivariable competing risk regression model was fitted to identify predictors of CSM and OCM., Results: The 10-, 15- and 20-year CSM and OCM rates were 11.6% and 5.5% vs. 15.5% and 13.5% vs. 18.4% and 19.3%, respectively. The 5-year probability of CSM and OCM rates among patients who survived at 5, 10, and 15 years after RP, were 6.4% and 2.7% vs. 4.6% and 9.6% vs. 4.2% and 8.2%, respectively. Year of surgery, pathological stage and Gleason score, surgical margin status and lymph node invasion were the major determinants of CSM (all P≤0.03). Conversely, none of the covariates was significantly associated with OCM (all P≥ 0.09)., Conclusions: Very long-term cancer control in young high-risk patients after RP is highly satisfactory. The probability of dying from PCa in young patients is the leading cause of death during the first 10 years of survivorship after RP. Thereafter, mortality not related to PCa became the main cause of death. Consequently, surgery should be consider among young patients with high-risk disease and strict PCa follow-up should enforce during the first 10 years of survivorship after RP., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: No data exist on the patterns of biochemical recurrence (BCR) and their effect on survival in patients with high-risk prostate cancer (PCa) treated with surgery. The aim of our investigation was to evaluate the natural history of PCa in patients treated with radical prostatectomy (RP) alone., Materials and Methods: Overall, 2,065 patients with high-risk PCa treated with RP at 7 tertiary referral centers between 1991 and 2011 were identified. First, we calculated the probability of experiencing BCR after surgery. Particularly, we relied on conditional survival estimates for BCR after RP. Competing-risks regression analyses were then used to evaluate the effect of time to BCR on the risk of cancer-specific mortality (CSM)., Results: Median follow-up was 70 months. Overall, the 5-year BCR-free survival rate was 55.2%. Given the BCR-free survivorship at 1, 2, 3, 4, and 5 years, the BCR-free survival rates improved by+7.6%,+4.1%,+4.8%,+3.2%, and+3.7%, respectively. Overall, the 10-year CSM rate was 14.8%. When patients were stratified according to time to BCR, patients experiencing BCR within 36 months from surgery had higher 10-year CSM rates compared with those experiencing late BCR (19.1% vs. 4.4%; P<0.001). At multivariate analyses, time to BCR represented an independent predictor of CSM (P<0.001)., Conclusions: Increasing time from surgery is associated with a reduction of the risk of subsequent BCR. Additionally, time to BCR represents a predictor of CSM in these patients. These results might help provide clinicians with better follow-up strategies and more aggressive treatments for early BCR., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The value of radical prostatectomy (RP) as an approach for very high-risk prostate cancer (PCa) patients is controversial. To examine the risk of 10-year cancer-specific mortality (CSM) and other-cause mortality (OCM) according to clinical and pathological characteristics of very high-risk cT3b/4 PCa patients treated with RP as the primary treatment option., Methods: In a multi-institutional cohort, 266 patients with very high-risk cT3b/4 PCa treated with RP were identified. All patients underwent RP and pelvic lymph-node dissection. Competing-risk analyses assessed 10-year CSM and OCM before and after stratification for age and Charlson comorbidity index (CCI)., Results: Overall, 34 (13%) patients died from PCa and 73 (28%) from OCM. Ten-year CSM and OCM rates ranged from 5.6% to 12.9% and from 10% to 38%, respectively. OCM was the leading cause of death in all subgroups. Age and comorbidities were the main determinants of OCM. In healthy men, CSM rate did not differ among age groups (10-year CSM rate for ⩽64, 65-69 and ⩾70 years: 16.2%, 11.5% and 17.1%, respectively). Men with a CCI ⩾1 showed a very low risk of CSM irrespective of age (10-year CSM: 5.6-6.1%), whereas the 10-year OCM rates increased with age up to 38% in men ⩾70 years., Conclusion: Very high-risk cT3b/4 PCa represents a heterogeneous group. We revealed overall low CSM rates despite the highly unfavorable clinical disease. For healthy men, CSM was independent of age, supporting RP even for older men. Conversely, less healthy patients had the highest risk of dying from OCM while sharing very low risk of CSM, indicating that this group might not benefit from an aggressive surgical treatment. Outcome after RP as the primary treatment option in cT3b/4 PCa patients is related to age and comorbidity status.

Background: Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa., Objective: To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice., Design, Setting, and Participants: This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010., Intervention: Retropubic RP and pelvic lymphadenectomy., Outcome Measurements and Statistical Analysis: Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression., Results and Limitations: In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period., Conclusions: These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa., Patient Summary: Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To compare the concordance of prostate cancer (PCa) laterality between the extended transperineal (TP) or transrectal (TR) prostate biopsy (BP) and radical prostatectomy (RP) specimens. To identify predictors of laterality agreement between BP and RP., Materials and Methods: Data from 533 consecutive patients with PCa (278 TP and 255 TR-diagnosed) treated with RP were analyzed. A 12-core technique was used for both TP and TR biopsies. Additional cores were obtained when necessary., Results: Overall, the percentage of agreement of PCa laterality between BP and RP was 60% (K = 0.27, p < 0.001). However, the RP confirmation of unilaterality at BP was obtained in just 33% of the cases. Considering the concordance on bilaterality as the ″target″ of our analysis, the sensitivity and specificity were 54.3% and 98.2% , respectively, with TP and 47.5% and 92.5%, respectively with TR. Focusing on patients with unilaterality at biopsy, none of the evaluated preoperative variables (biopsy technique, age, total positive biopsy cores, PSA, prostate volume, Gleason score on biopsy) were able to predict RP bilaterality in the multivariate analyses., Conclusions: Most of the patients with unilateral involvement at BP harbored bilateral PCa after RP. TR and TP biopsy showed no difference in their capacity to predict the concordance of tumor laterality at RP. None of the preoperative evaluated variables can predict the tumor laterality at RP. Using BP unilaterality to include patients in focal therapy (FT) protocols may hinder the oncologic efficacy of FT.

Objectives: A dendritic cell-based cancer vaccine has recently received Food and Drug Administration approval in the USA based on its ability to prolong the survival of prostate cancer patients with advanced disease. However, tumor-mediated immunosuppressive mechanisms might represent an obstacle to optimal performance of this therapy. We have recently shown that monocytes from the blood of prostate cancer patients can fully mature to dendritic cells only after the tumor is removed. Here, we have tested the hypothesis that these tumor-driven monocytes correspond to the recently described subset of CD14(+) HLA-DR(low) immunosuppressor cells., Methods: Prostate cancer patients were studied before and 1 month after prostatectomy. Pre- and postsurgical patients with colorectal cancer were also included for comparison. Flow cytometric analysis was applied to define CD14(-) HLA-DR(low) CD33(+) CD11b(+) (myeloid) and CD14(+) HLA-DR(low) (monocytic) suppressor cells. Interferon-γ release was used to assess the immunocompetence of lymphocytes., Results: In both prostate cancer and colorectal cancer patients, the percentage of CD14(+) HLA-DR(low) cells was several-fold higher compared with normal subjects. This was not the case for CD14(-) HLA-DR(low) CD33(+) CD11b(+) cells. Furthermore, postsurgical normalization of CD14(+) HLA-DR(low) cells only occurred in prostate cancer patients. In all patients, the interferon-γ response of T lymphocytes to phorbolmyristate acetate-ionomycin was higher compared with normal donors, but it was further increased after tumor ablation only in prostate cancer patients., Conclusions: The direct link between CD14(+) HLA-DR(low) increase and presence of primary tumor suggests a distinguishing immunosuppressive profile of prostate cancer. This observation supports the principle that the appropriate setting for prostate cancer vaccine therapy is a minimal disease status., (© 2013 The Japanese Urological Association.)

Purpose of Review: Surgery for high-risk prostate cancer (PCa) is applied frequently nowadays. Nevertheless, this approach is still surrounded by many controversies. The present review discusses the most recent literature regarding surgery for high-risk PCa., Recent Findings: As there is no standard definition of high-risk PCa, outcome comparison between series and treatment approaches is hampered. Nevertheless, recent radical prostatectomy series have shown excellent cancer-specific survival in patients with high-risk PCa. Even for very-high-risk PCa (cT3b-T4 or any cT, N1), surgery may be applied to highly selected patients as a first step of a multimodality approach. Recent experience with robot-assisted surgery opens new possibilities for a minimally invasive approach in this field.Patient selection for surgery was also addressed in recent studies. Excellent cancer-specific survival is seen when specimen-confined PCa is found at final histopathology; a recently published nomogram enables the prediction of specimen-confined disease. Another issue in high-risk PCa is the impact of age and comorbidities on cancer-specific and overall mortality. In a recent study, it was shown that patients with low comorbidity scores, even when at least 70 years old, had a significant risk of dying from their cancer and may benefit most from a surgical approach. A modified extended pelvic lymphadenectomy template was presented, providing optimal removal of positive lymph nodes., Summary: Radical prostatectomy with extended pelvic lymphadenectomy delivers very good cancer-related outcomes in high-risk and very-high-risk PCa, often within a multimodal approach. Minimally invasive surgery and improved patient selection will be key to further improve oncological and functional outcomes.

Background: Survival after surgical treatment using competing-risk analysis has been previously examined in patients with prostate cancer (PCa). However, the combined effect of age and comorbidities has not been assessed in patients with high-risk PCa who might have heterogeneous rates of competing mortality despite the presence of aggressive disease., Objective: To examine the risk of 10-yr cancer-specific mortality (CSM) and other-cause mortality (OCM) according to clinical and pathologic characteristics of patients treated with radical prostatectomy (RP) for high-risk PCa., Design, Setting, and Participants: Within a multi-institutional cohort, 3828 men treated with RP for high-risk PCa (defined as the presence of at least one of these risk factors: prostate-specific antigen >20 ng/ml, biopsy Gleason score 8-10, clinical stage ≥ T3) were identified., Intervention: All patients underwent RP and pelvic lymph node dissection., Outcome Measurements and Statistical Analysis: Competing-risk Poisson regression analyses were performed to simultaneously assess the 10-yr CSM and OCM rates after RP. The same analyses were also conducted after stratification of patients according to age at surgery, comorbidity status assessed by the Charlson Comorbidity Index (CCI), and number of risk factors (one vs two or more)., Results and Limitations: Overall, 229 patients (5.9%) died from PCa; 549 (14.3%) died from other causes. The 10-yr CSM and OCM rates ranged from 5.1% to 12.8% and from 4.3% to 37.4%, respectively. Age and CCI were the major determinants of OCM; their impact on CSM was minimal. OCM was the leading cause of death in all patient groups except in young men (≤ 59 yr) with no comorbidities, regardless of the number of risk factors (10-yr CSM and OCM 6.9-12.8% and 5.5-6.3%, respectively). The main limitation was the lack of patients managed conservatively., Conclusions: Even in the context of high-risk PCa, long-term CSM after RP is modest and represents the leading cause of death only in young, healthy patients. Conversely, older and sicker patients with multiple risk factors are at the highest risk of dying from OCM while sharing very low CSM rates., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To analyze positive surgical margins (PSM) after radical prostatectomy (RP) in the overall population and in patients previously treated with transurethral resection of the prostate (TURP)., Materials and Methods: 2,408 patients treated with RP for clinically localized prostate cancer (PCa) were consecutively enrolled in 135 departments. We correlated PSM rates and all preoperative, surgical and pathological features. We stratified the site of PSM as unique or multifocal. Moreover, we analyzed differences between 75 patients who had undergone previous TURP and the remaining 2,333 patients., Results: In the entire study population, we identified 702 patients with PSM (29%). Using univariate analysis, we reported a significant correlation between overall PSM and prostate-specific antigen (PSA), stage cT, biopsy Gleason score, number of biopsy cores, number of positive cores, percentage of positive cores and nerve-sparing approach. PSM proved to be strongly dependent on pT in particular in patients with pT2 PCa. When we compared the data from 75 patients previously treated with TURP and those from 2,333 without previous prostatic surgery, a statistically significant difference in margin localization was found. Moreover, we analyzed the 75 patients mentioned above, stratified in incidental PCa diagnosed at TURP or PCa detected with prostate biopsy for PSA rising during the post-TURP follow-up: no statistical differences were found between the 2 groups regarding margin status, even if PSM were more frequent in incidental PCa with no significance deriving from the stratification for PSM location at the apex or base., Conclusion: Men treated with TURP before RP presented an overall incidence of PSM similar to those without previous TURP, but with a higher risk of PSM at the bladder neck and a lower risk of PSM at the prostatic apex., (Copyright © 2013 S. Karger AG, Basel.)

Unlabelled: What's known on the subject? and What does the study add? Nowadays radical prostatectomy (RP) is considered an effective treatment in high-risk prostate cancer (PCa) and the indications for a surgical approach are expanding, even in cases of very high PSA or node-positive disease. We explored the outcomes of debulking surgery in the setting of these very high-risk PCa patients, in order to assess its feasibility. This review confirms the important role achieved by surgery in the complex setting of patients with very high-risk PCA. Excellent survival rates have been reported, even when PSA exceeds 100 ng/mL. The completion of RP with lymphadenectomy might give a survival benefit in patients who were found intraoperatively to be node-positive. Furthermore, salvage RP confirmed to be the most effective treatment option after RT failure. On the contrary, up-to-date surgery of isolated nodal recurrences has shown only little benefit. Finally, there is no evidence supporting the efficacy of debulking surgery in metastatic or in hormone-refractory tumours. An accurate selection of the patient is essential., Objective: To conduct a critical analysis of the available literature on the feasibility of debulking surgery in the setting of very high-risk prostate cancer (PCa) scenarios., Patients and Methods: We performed a systematic literature search of PubMed and Embase using combinations of the following keywords: radical prostatectomy, surgery, high-risk, high PSA (prostate-specific antigen), radiorecurrent, hormone-refractory, metastatic prostate cancer, salvage. With the term 'very high-risk PCa' we indicated a clinical disease beyond the common definition of high-risk PCa, i.e. any clinical stage > T3, N0 or N+, any PSA level > 50 ng/mL and any recurrent disease after primary treatment., Results: Radical prostatectomy (RP) achieved excellent survival rates in high-risk PCa, even in patients with very high PSA level. The completion of RP with lymphadenectomy might give a survival benefit in patients who were found intraoperatively to be node-positive. Salvage RP was confirmed to be the most effective treatment option after radiotherapy failure, with increased functional outcomes and decreased side-effects in the most recent series. Surgery of isolated nodal recurrences after previous radical therapy has shown little benefit according to the few available series. There is no evidence supporting the efficacy of debulking surgery in metastatic or hormone-refractory PCa., Conclusion: Debulking surgery achieved an important role in several aggressive PCa scenarios. An accurate selection of the patient is essential., (© 2012 BJU INTERNATIONAL.)

Purpose: Patients with high risk prostate cancer with pT3 tumor and positive surgical margins have a high risk of biochemical failure after radical prostatectomy and adjuvant androgen deprivation therapy. Predictors of cancer related death in this patient group are necessary., Materials and Methods: We performed subset analysis of a prospective trial including 550 consecutive patients with preoperative high risk prostate cancer (prostate specific antigen greater than 20 ng/ml ± cT3/4 ± biopsy Gleason 8-10). Men who underwent radical prostatectomy and received continuous adjuvant androgen deprivation therapy for pT3a/b N0-1 positive surgical margin disease were included in the analysis, and none of the patients received neoadjuvant androgen deprivation therapy or adjuvant radiation therapy., Results: Overall 173 of 550 patients (31.5%) with a median followup of 67 months met the study inclusion criteria. For these men the estimated 8-year prostate cancer specific and overall survival rates were 86.3% and 77.0%, respectively. Tumor stage and positive surgical margin at the bladder neck were independent predictors of prostate cancer specific survival and overall survival, and were used to substratify cases. Those with pT3b disease with positive surgical margins at the bladder neck had the highest risk of death (5-year cancer specific survival 60.0% and overall survival 52.3%), while pT3a disease (regardless of positive surgical margin location and lymph node invasion) and pT3b tumors with negative bladder neck margins had 8-year prostate cancer specific survival and overall survival rates of 92.0% and 84.9%, respectively., Conclusions: The results of this trial demonstrated the heterogeneity of high risk prostate cancer cases with T3 tumors and positive surgical margins. The presented substratification by tumor stage and positive surgical margin location identifies men at high risk for prostate cancer related death and might help in the design of adjuvant therapy trials., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to present the long-term outcomes and determine outcome predictors in very high-risk (cT3b-T4) prostate cancer (PCa) after radical prostatectomy (RP)., Material and Methods: Between January 1989 and December 2004, 51 patients with cT3b-T4 PCa underwent RP. Kaplan-Meier survival analysis was used to calculate the biochemical progression-free survival (BPFS), clinical progression-free survival (CPFS), cancer-specific survival (CSS) and overall survival (OS) rate. Multivariate Cox proportional hazard models were used to determine the predictive power of clinical and pathological variables in BPFS and CPFS., Results: Median follow-up was 108 months [interquartile range (IQR) 73.5-144.5]. The median serum prostate-specific antigen (PSA) was 16.9 ng/ml (IQR 7-37.2). Median biopsy and pathological Gleason (pGS) score were both scored as 7 (range 4-10 and 5-9, respectively). Overstaging was frequent (37.2%); four patients (7.8%) had organ-confined stage pT2, while 15 (29.4%) had extracapsular extension only (pT3a). Another 23 (45.1%) were confirmed with seminal vesicle invasion (pT3b) and nine (17.7%) had adjacent structure invasion (pT4). Eleven patients (21.6%) had lymph-node involvement. Thirty-two patients (62.7%) had positive surgical margins. The BPFS, CPFS, CSS and OS at 5 and 10 years were 52.7%, 45.8%;78.0%, 72.5%; 91.9%, 91.9% and 88.0%, 70.7%. In the multivariate Cox proportional hazard models, pathological stage was an independent predictor of BPFS while preoperative PSA and pGS was an independent predictor of CPFS., Conclusions: The management of cT3b-T4 PCa typically consists of a multimodality treatment in which RP is a valuable first step. Overstaging was frequent (37.2%), and almost one-quarter of the patients remained free of additional treatments. Long-term cancer-related outcomes were very satisfactory.

Purposes: The aim was to analyze the prognostic role of preoperative chromogranin A CgA) as a marker of poor prognosis and recurrence after radical prostatectomy (RP) and to find a correlation with the other well known prognostic variables., Materials and Methods: This study comprises 306 patients with prostate cancer prospectively recruited who underwent RP from between 2000 and 2005. A blood sample for the determination of serum preoperative CgA value was obtained in all cases. Spearman correlation test was used to compare CgA to other variables, Kruskal-Wallis test to analyze CgA differences among > or = 3 groups (PSA, GS, Stage), Mann-Whitney test for 2 grouping variables. Survival analysis was estimated by Kaplan-Meier method, log-rank test to estimate differences among the analyzed variables., Results: Median CgA level was 68 ng/ml. Correlation between age and CgA levels was positive and statistically significant (p < 0.001). Patient were divided in 2 groups based on median age.The difference was statistically significant (p = 0.002). Comparison of CgA among patients grouped according to other variables and patient stratified on normal (123 ng/ml) and cut-off value (68 ng/ml) of CgA did not achieve significant risk stratification., Conclusion: Studies on a possible prognostic role of CgA have provided conflicting results. In our series we found a significant positive correlation between CgA and age, but no significant statistical correlation with other available variables analyzed.

Background: The current role of radical prostatectomy (RP) in patients with high-risk disease remains controversial., Objective: To identify which high-risk prostate cancer (PCa) patients might have favorable pathologic outcomes when surgically treated., Design, Setting, and Participants: We evaluated 1366 patients with high-risk PCa (ie, at least one of the following risk factors: prostate-specific antigen [PSA]>20 ng/ml, cT3, biopsy Gleason 8-10) treated with RP and pelvic lymph node dissection (PLND) at eight European centers between 1987 and 2009. A favorable pathologic outcome was defined as specimen-confined (SC) disease-namely, pT2-pT3a, node negative PCa with negative surgical margins., Intervention: All patients underwent radical retropubic prostatectomy and PLND., Measurements: Univariable and multivariable logistic regression models tested the association between predictors and SC disease. A logistic regression coefficient-based nomogram was developed and internally validated using 200 bootstrap resamples. The Kaplan-Meier method was used to depict biochemical recurrence (BCR) and cancer-specific survival (CSS) rates., Results and Limitations: Overall, 505 of 1366 patients (37%) had SC disease at RP. All preoperative variables (ie, age and PSA at surgery, clinical stage, and biopsy Gleason sum) were independent predictors of SC PCa at RP (all p≤0.04). Patients with SC disease had significantly higher 10-yr BCR-free survival and CSS rates than patients without SC disease at RP (66% vs 47% and 98 vs 88%, respectively; all p<0.001). A nomogram including PSA, age, clinical stage, and biopsy Gleason sum demonstrated 72% accuracy in predicting SC PCa. This study is limited by its retrospective design and by the lack of an external validation of the nomogram., Conclusions: Roughly 40% of patients with high-risk PCa have SC disease at final pathology. These patients showed excellent long-term outcomes when surgically treated, thus representing the ideal candidates for RP as the primary treatment for PCa. Prediction of such patients is possible using a nomogram based on routinely available clinical parameters., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: We carried out a mini-review of the literature in order to obtain a snapshot of the present state of the art of surgical techniques costs available for radical prostatectomy., Materials and Methods: We developed a MEDLINE search strategy and one economist assessed the included studies using the NHS EED guidelines for reviewers., Results: When observing costs by the author, it is possible to trace up a trend line of increasing costs which starts off with RPP, passes through RRP and LRP and ends up with robot-assisted radical prostatectomy. Two studies do not agree with this. One author claims that LRP is less costly than radical retropubic prostatectomy whereas another one agrees on radical perineal prostatectomy and radical retropubic prostatectomy but does not on RAP, which he claims to be less costly., Conclusions: The data shown in our study outline a situation by which the observed studies highlight: different costs of the techniques and incapability to achieve a conclusion about the technique with less average costs. These results can be considered in an explorative way and cannot be generalized. They maintain a strictly approximate value in local realities having only an informative purpose., (Copyright © 2010 S. Karger AG, Basel.)

Objectives: To assess the factors associated with continence recovery 1 month after radical prostatectomy (RP) and to identify the correlation between these factors., Methods: In total, 2408 men treated with RP for prostate cancer (PCa) were enrolled in the present multicenter prospective study. Clinical (age, body mass index) and urological (catheterization or transurethral resection of the prostate) records, quality of life (QOL) scores determined using various instruments (including the International Index of Erectile Function [IIEF] and University of California Los Angeles, Prostate Cancer Index [UCLA-PCI]), PCa characteristics (clinical stage [cT], prostate-specific antigen, biopsy Gleason score), surgical features (surgical approach, nerve and bladder neck sparing, catheterization), and pathologic outcomes (pT, pN+, Gleason score, positive surgical margins) were recorded. Continence status prior to surgery and at 1 month after RP was assessed and classified as followed: (i) full continence; (ii) 0-1 pads/day; or (iii) >1 pad/day. Only patients determined to have full continence prior to surgery were included in the analysis. Data were evaluated using Spearman's correlation analysis and multivariate logistic regression., Results: Data from 1972 patients with full continence preoperatively and complete postoperative data were analyzed. At 1 month after RP, 644 patients (32.7%) were fully continent, 810 (41.1%) were using 0-1 pads/day, and 518 (26.3%) were using >1 pad/day. Univariate analysis indicated that clinical and urological data, QOL, PCa characteristics, surgical features, and pathologic outcomes were determinants for continence recovery. Multivariate analysis indicated that preoperative sexual activity (UCLA-PCI Sexual Function P = 0.005; IIEF P = 0.040), bladder neck sparing (P = 0.003), catheterization time (P = 0.007), and catheter diameter (P = 0.046) were associated with 1 month continence recovery., Conclusions: Age and nerve sparing are not significant predictors of continence recovery 1 month after RP. Preoperative erectile function can predict post-prostatectomy incontinence. Bladder neck preservation has a significant effect on early continence recovery after RP., (© 2011 The Japanese Urological Association.)

Objective: • To assess the feasibility of radical prostatectomy (RP) in a series of patients with prostate cancer with very high prostate-specific antigen (PSA) levels by comparing the clinical outcomes of different PSA thresholds (20.1-50 ng/mL, 50.1-100 ng/mL and >100 ng/mL, respectively)., Patients and Methods: • Within a multicentre European retrospective database of 712 RP in patients with a baseline PSA level >20 ng/mL, we identified 48 patients with prostate cancer with a preoperative PSA level >100 ng/mL, 137 with a PSA level between 50.1 and 100 ng/mL and 527 with PSA values between 20.1 and 50 ng/mL. • Comparisons between groups were performed using chi-square test, analysis of variance and Kaplan-Meier analysis with log-rank test., Results: • Ten-year projected cancer-specific survival (79.8% in the PSA >100 ng/mL group vs 85.4% in the PSA 50.1-99 ng/mL group vs 90.9% in the PSA 20.1-50 ng/mL interval; P = 0.037) but not overall survival (59.6% in the PSA >100 ng/mL group vs 71.8% in the PSA 50.1-99 ng/mL group vs 75.3% in the PSA 20.1-50 ng/mL interval; P = 0.087) appeared significantly affected by the different PSA thresholds. • At a median follow-up of 78.7 months, 25.8%, 6.6% and 8.3% of patients in the PSA level groups for 20.1-50 ng/mL, 50.1-100 ng/mL and >100 ng/mL respectively, were cured by surgery alone., Conclusions: • Ten-year cancer-specific survival, while showing significant reduction with increasing PSA values intervals, remain relatively high even for PSA levels >100 ng/mL. • As part of a multimodal treatment strategy, RP may therefore be an option, even in selected patients with prostate cancer whose PSA level is >100 ng/mL., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Introduction: Preservation of sexual function after surgery represents a major issue for patients undergoing radical prostatectomy (RP)., Aim: To investigate determinants of patients' desire to preserve sexual activity before RP and surgeons' final decision to perform a nerve-sparing RP (NSRP)., Methods:   Overall, 2,408 prostate cancer patients, candidates to RP, from 136 urologic departments across the Italian territory were evaluated in a multicenter prospective observational study. All patients underwent RP, according to single-center indications and procedures., Main Outcome Measures: Age, body mass index, previous benign prostatic hyperplasia history, preoperative tumor characteristics, quality of life through the Short Form Health Survey (SF-12), and the University of California Los Angeles Prostate Cancer Index (UCLA-PCI), erectile function through the International Index of Erectile Function (IIEF-5), desire to preserve sexual activity, NS operative outcomes, and surgical margins status were recorded., Results: Overall, 1,667 were interested to preserve sexual activity. Age, physical component summary of SF12 (PCS-12), sexual function score of UCLA-PCI, and IIEF-5 score were the main determinants of such interest. Only 1,246 patients were suitable for a NSRP according to guidelines. Surgeons performed a non-NSRP (NNSRP) in 1,234 patients, a unilateral NSRP in 318 and a bilateral NSRP in 856. Age, bioptical Gleason score, percentage of positive cores, PCS-12, and patient's desire to preserve sexual activity were the main determinants of final decision for a NSRP. Surgeons performed a NSRP in 424 not suitable and in 121 not interested patients. Positive surgical margins in not suitable patients submitted to NSRP were not higher if compared to that obtained after NNSRP in the same subgroup. Limits include lack of oncological and functional follow-up., Conclusions: Most patients are interested to preserve sexual activity. Discrepancies exist among patients' preferences, guidelines' indications, and surgeon's final decision., (© 2011 International Society for Sexual Medicine.)

Objective: To verify the presence of deviated dendritic cell (DC) precursors and of suppressor lymphocytes (Treg) in tumor bearing prostate cancer (PCa) patients and to monitor the corrective effect of tumor ablation., Methods: Monocytes isolated from the blood of patients before and 1 month after prostatectomy were allowed to reach complete maturation (mDC) ex vivo in a clinical grade two-step process. T-regulatory cells were identified in the lymphocyte cell fraction by the CD4(+)CD25(high)FoxP3(+)/CD4(+)CD25(high)CD127(low/-) phenotype., Results: Despite loss of the monocytes marker CD14, cytokine-matured DCs of tumor bearing patients expressed lower levels of the costimulatory molecule CD80 and of the maturation markers CD83 and CCR7 compared to mDC of normal subjects (NS, P = 0.001, 0.001, and 0.008, respectively). Prostatectomy restored CD80, CD83, and CCR7 expression to values not different from those of NS (P = 0.15, 0.60, and 0.71) and significantly higher than those of the pre-surgery state (CD83, P = 0.0003 and CCR7, P = 0.002). The frequency of Tregs, identified as either CD4 + CD25(high)FoxP3(+) or CD4(+)CD25(high)CD127(low/-), was significantly higher in pre-surgery patients than in NS (P = 0.0001 and 0.0003) and significant recovery of the CD4(+)CD25(high)CD127(low/-) (P = 0.0005) was observed after surgery., Conclusions: The presence of defective DC precursors and suppressor lymphocytes in the tumor-bearing, but not tumor-free stage, positions the latter as the ideal setting for clinical success of PCa vaccine therapy., (Copyright © 2010 Wiley-Liss, Inc.)

Background: Prostate cancer (PCa) patients with pretreatment prostate-specific antigen (PSA) >20 ng/ml have a high risk of biochemical and clinical failure and even cancer-related death after local therapy. Pretreatment predictors of outcome after radical prostatectomy (RP) in this patient group are necessary., Objective: Our aim was to assess how the use of additional high-risk factors (biopsy Gleason score [bGS] > or = 8 or clinical stage 3-4) can improve prediction of treatment failure and cancer-related death after RP in patients with PSA >20., Design, Setting, and Participants: In a retrospective multicentre cohort study from six European centres between 1987 and 2005, 712 patients with PSA >20 ng/ml underwent RP and bilateral pelvic lymphadenectomy., Measurements: Subgroups were analysed to determine the relationship between the number of high-risk factors and histopathology, biochemical progression-free survival, clinical evidence of progressive disease, prostate cancer-specific mortality (PCSM), and overall mortality. Kaplan-Meier analysis with log-rank test and Cox multivariable analysis were applied., Results and Limitations: Median follow-up was 77 mo. The number of high-risk factors was significantly associated with unfavourable histopathology. Among patients with only PSA >20 ng/ml, 33% had pT2 PCa, 57.9% had bGS <7, 54% had negative surgical margins, and 85% were lymph node negative (pN0), whereas among patients with all three high-risk factors, 4.5% had pT2 PCa, 2.3% had bGS <7, 20.5% had negative margins, and 49% were pN0 (p<0.001). The strongest predictor of progression and mortality was bGS. PSA >20 ng/ml associated with bGS < or =7 resulted in 10-yr PCSM of 5%; when associated with bGS > or =8, PCSM was 35%. The main limitations of the study were retrospective design and varying treatment modalities., Conclusions: PCa patients with PSA >20 ng/ml have varying risk levels of disease progression and PCSM. Considering additional risk factors further stratifies this group into four subgroups that can guide the clinician in preoperative patient counselling., (Copyright 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)