Outcomes of robot-assisted radical prostatectomy in men after trans-urethral resection of the prostate: a matched-pair analysis.

Prior history of transurethral resection of the prostate (TURP) can complicate Robot-assisted radical prostatectomy (RARP). Very few studies analyse the outcomes of RARP in men with a prior history of TURP. We analysed the oncological and functional outcomes of RARP in post-TURP men from our prospectively maintained database. We included the RARP data from January 2016 to January 2022. Thirty men who had RARP with a prior history of TURP were identified (Group 2). They were matched using R software and propensity score matching to 90 men with no previous TURP (Group-1). The groups were matched for age, body mass index (BMI), Gleason score, stage, PSA and D'Amico risk category in a 1:3 ratio. The two-year oncological and functional outcomes were compared. Overall, the study found no significant difference between the groups in the preoperative parameters, such as BMI, age, Gleason grade, clinical stage, PSA, prostate volume, and D'amico risk grouping. There was no difference in the estimated blood loss. The TURP group had a lower chance of having a nerve spare (p = 0.03). The median console time was longer in the TURP group (140 min (120,180) versus 168 (129,190) p = 0.058). The postoperative complications (Clavien-Dindo 3a 2% versus 6.7%) and hospital stay (median of 2 days), positive surgical margins, continence, and biochemical recurrence rates at 3, 12, and 24 months were not statistically different between the groups. In high-volume centres, the oncological and continence outcomes of RARP post-TURP are not inferior to that of men without prior TURP.

Salvage vesiculectomy for local prostate cancer recurrence: surgical technique and early post-operative outcomes.

PURPOSE: Isolated recurrence in remnants of the seminal vesicles (SV) after treatment of primary prostate cancer (PCa) has become a more frequent entity with the widespread use of more sensitive next-generation imaging modalities. Salvage vesiculectomy is hypothesized to be a worthwhile management option in these patients. The primary goal of this study is to describe the surgical technique of this new treatment option. Secondary outcomes are peri- and post-operative complications and early oncological outcomes. METHODS: Retrospective multicenter study, including 108 patients with solitary recurrence in the SV treated between January 2009 and June 2022, was performed. Patients with local recurrences outside the SVs or with metastatic disease were excluded. Both SVs were resected using a robot-assisted or an open approach. In selected cases, a concomitant lymphadenectomy was performed. RESULTS: Overall, 31 patients (29%) reported complications, all but one grade 1 to 3 on the Clavien-Dindo Scale. A median PSA decrease of 2.07 ng/ml (IQR: 0.80-4.33, p < 0.001), translating into a median PSA reduction of 92% (IQR: 59-98%) was observed. At a median follow-up of 14 months, freedom from secondary treatment was 54%. Lymphadenectomy had a significant influence on PSA reduction (p = 0.018). CONCLUSION: Salvage vesiculectomy for PCa recurrence limited to the SV is a safe procedure with excellent PSA response and is a potential curative treatment in a subset of patients. A concomitant lymphadenectomy can best be performed in all patients that did not underwent one at primary treatment.

Self-removal of catheter after robot-assisted radical prostatectomy: a feasibility study.

Self-removal of urinary catheter as an option after robot-assisted radical prostatectomy (RARP) has never been explored in literature. We report the feasibility and outcome of the first study of this novel concept in our hospital. We conducted a prospective audit of self-TWOC (trial without catheter) in men who underwent consecutive RARP in our centre between April 2022 and September 2022. Men who had self-TWOC filled a questionnaire about the outcomes of self-TWOC. Carbon footprint and carbon offset for each hospital TWOC avoided were calculated. Of the 129 who underwent self-TWOC, 112 filled the questionnaire and were hence included in the final analysis. Self-TWOC was successful in all the 112 (100%) men in the study. 99.1% of men were satisfied with self-TWOC at home. We managed to avoid 79.6 ± 36.72 km of travel and 77 min of travel time for every self-TWOC. This also saved 85£/patient on clinic expenses and fuel cost savings of 9.87-15.99£ per patient depending on car engine size/type. The carbon footprint calculated was 20 kg CO2 assuming average engine sized diesel/petrol cars and 10 kg CO2 for an average UK petrol hybrid car. The calculated carbon offset per patient for diesel/petrol cars: 0.32£, petrol hybrid: 0.16£. Self-TWOC for 80-160 patients will save the carbon emissions equivalent to that of a passenger on a London-New York Trans-Atlantic flight. Self-TWOC is safe, affordable and is sustainable to the environment. Widespread acceptance of this practice change will be a small, but steady step towards greener health systems across the world.

Etrolizumab as induction and maintenance therapy in patients with moderately to severely active Crohn's disease (BERGAMOT): a randomised, placebo-controlled, double-blind, phase 3 trial.

BACKGROUND: Etrolizumab is a gut-targeted anti-ß7 monoclonal antibody targeting α4ß7 and αEß7 integrins. We aimed to compare the safety and efficacy of two doses of etrolizumab with placebo in patients with Crohn's disease. METHODS: BERGAMOT was a randomised, placebo-controlled, double-blind, phase 3 study done at 326 treatment centres worldwide. We included patients aged 18-80 years with moderately to severely active Crohn's disease (Crohn's Disease Activity Index [CDAI] score of 220-480, and a mean daily stool frequency score of ≥6 or a mean daily stool frequency score of >3, and a mean daily abdominal pain score of >1, as well as the presence of active inflammation on screening ileocolonoscopy) who had intolerance, inadequate response, or no response to one or more of corticosteroids, immunosuppressants, or anti-TNF therapy within the past 5 years. BERGAMOT consisted of three induction cohorts (a placebo-controlled, double-blind exploratory cohort [cohort 1]; an active treatment cohort not containing a placebo control [cohort 2]; and a placebo-controlled, double-blind pivotal cohort [cohort 3]) and one maintenance cohort. In induction cohort 3, during the 14-week induction, patients were randomly assigned (2:3:3) to receive matched placebo, 105 mg etrolizumab subcutaneously every 4 weeks (at weeks 0, 4, 8, and 12) or 210 mg etrolizumab subcutaneously (at weeks 0, 2, 4, 8, and 12), stratified by concomitant treatment with oral corticosteroids, concomitant treatment with immunosuppressants, baseline disease activity, and previous exposure to anti-TNF therapy. To preserve masking, all patients received two injections at weeks 0, 4, 8, and 12 and one injection at week 2. Week 14 etrolizumab responders from all cohorts were re-randomly assigned (1:1) to receive 105 mg etrolizumab (etrolizumab maintenance group) or placebo (placebo maintenance group) every 4 weeks for 52 weeks; patients in the induction placebo group underwent a sham re-randomisation to preserve masking. During maintenance, randomisation was stratified by CDAI remission status, concomitant treatment with oral corticosteroids, induction dose regimen, and previous exposure to anti-TNF therapy. All participants and study site personnel were masked to treatment assignment for both induction and maintenance. Co-primary induction endpoints at week 14 (placebo vs 210 mg etrolizumab) were clinical remission (mean stool frequency ≤3 and mean abdominal pain ≤1, with no worsening) and endoscopic improvement (≥50% reduction in Simple Endoscopic Score for Crohn's Disease [SES-CD]). Co-primary maintenance endpoints at week 66 (placebo vs etrolizumab) were clinical remission and endoscopic improvement. Efficacy was analysed using a modified intention-to-treat (mITT) population, defined as all randomised patients who received at least one dose of study drug (induction) and as all patients re-randomised into maintenance who received at least one dose of study drug in the maintenance phase (maintenance). Safety analyses included all patients who received at least one dose of study drug. Maintenance safety analyses include all adverse events occurring in both induction and maintenance. This trial is registered with ClinicalTrials.gov, NCT02394028, and is closed to recruitment. FINDINGS: Between March 20, 2015, and Sept 7, 2021, 385 patients (209 [54%] male and 326 [85%] white) were randomly assigned in induction cohort 3 to receive placebo (n=97), 105 mg etrolizumab (n=143), or 210 mg etrolizumab (n=145). 487 patients had a CDAI-70 response in any of the induction cohorts and were enrolled into the maintenance cohort, of whom 434 had a response to etrolizumab and were randomly assigned to placebo (n=217) or 105 mg etrolizumab (n=217). At week 14, 48 (33%) of 145 patients in the 210 mg induction etrolizumab group versus 28 (29%) of 96 patients in the placebo induction group were in clinical remission (adjusted treatment difference 3·8% [95% CI -8·3 to 15·3]; p=0·52), and 40 (27%) versus 21 (22%) showed endoscopic improvement (5·8% [-5·4 to 17·1]; p=0·32). At week 66, a significantly higher proportion of patients receiving etrolizumab than those receiving placebo had clinical remission (76 [35%] of 217 vs 52 [24%] of 217; adjusted treatment difference 11·3% [95% CI 2·7-19·7]; p=0·0088) and endoscopic improvement (51 [24%] vs 26 [12%]; 11·5% [4·1-18·8]; p=0·0026). Similar proportions of patients reported one or more adverse events during induction (95 [66%] of 143 in the 105 mg etrolizumab group, 85 [59%] of 145 in the 210 mg etrolizumab group, and 51 [53%] of 96 in the placebo group) and maintenance (189 [87%] of 217 in the etrolizumab group and 190 [88%] of 217 in the placebo group). During induction, the most common treatment-related adverse events were injection site erythema (six [4%] of 143 in the 105 mg etrolizumab group, four [3%] of 145 in the 210 mg etrolizumab group, and none of 96 in the placebo group), and arthralgia (two [1%], one [1%], and four [4%]). In the maintenance cohort, the most common treatment-related adverse events were injection site erythema (six [3%] of 217 in the etrolizumab group vs 14 [6%] of 217 in the placebo: group), arthralgia (five [2%] vs eight [4%]), and headache (five [2%] vs seven [3%]). The most common serious adverse event was exacerbation of Crohn's disease (14 [6%] of 217 patients taking placebo and four [2%] of 217 patients taking 105 mg etrolizumab in the maintenance cohort). INTERPRETATION: A significantly higher proportion of patients with moderately to severely active Crohn's disease achieved clinical remission and endoscopic improvement with etrolizumab than placebo during maintenance, but not during induction. FUNDING: F Hoffmann-La Roche.

Multicentric experience in Retzius-sparing robot-assisted radical prostatectomy performed by expert surgeons for high-risk prostate cancer.

BACKGROUND: The study aim was to report the results of Retzius-Sparing robot-assisted radical Prostatectomy (RSP) in high-risk prostate cancer (HR-PCa) patients in a multicentric setting of expert surgeons and to analyze predictors of positive surgical margins (PSMs) and urinary continence recovery. METHODS: We retrospectively evaluated all consecutive HR-PCa patients who underwent RSP by expert surgeons in 7 centers. Pre-, peri- and postoperative features were collected. Minimum surgical experience required was 100 RSP cases. The oncological outcomes evaluated were PSMs and biochemical relapse (BCR). Urinary continence was defined as no pad or safety pad. Erectile function was defined as erections sufficient for intercourse. RESULTS: We collected 579 patients operated by 9 surgeons. Median age was 66, median PSA was 9,6 ng/mL. ISUP biopsy was 1 in 3.8%, 2 in 23%, 3 in 32,6%, 4 in 19,9%, 5 in 20,7; median surgical time was 195 minutes. Pathological stage was pT2 in 40,1%, pT3a in 35,9%, pT3b in 23,1%, and pT4 in 0,9% of cases. PSMs were present in 31,3% of cases. Urinary continence was achieved in 66,8% of cases one week after catheter removal. At 22 months (median follow-up), 89,1% patients were continent, BCR occurred in 27,5% patients. In multivariate analysis, PSA, prostate volume, surgical time were independent predictors of PSMs; ASA score and PSMs predicted urinary continence. CONCLUSIONS: We report the first multicentric experience of RSP for HR-PCa. Considering HR cases as those with the worst functional results, 89% of continent patients confirms that RSP helps achieve good functional results.

Robot-assisted salvage seminal vesicle excision for isolated recurrence after low-dose-rate prostate brachytherapy.

OBJECTIVES: To report clinical and functional outcomes for patients who have undergone salvage robot-assisted seminal vesicle excision (RA-SVE) for the focal treatment of isolated seminal vesical (SV) recurrence after treatment for prostate cancer by low-dose-rate brachytherapy. PATIENTS AND METHODS: Patients with rising prostate-specific antigen (PSA) after low-dose-rate prostate brachytherapy (LDR-PB) underwent multi-parametric magnetic resonance imaging (mp-MRI) of the prostate and 11 C-Choline or 68 Ga-prostate-specific membrane antigen (68 Ga-PSMA) positron emission tomography/computed tomography (PET/CT) scan, followed by targeted transperineal biopsy of the prostate and SVs. Isolated SV recurrence were identified in 17 (0.38%) LDR-PB patients. These 17 patients were offered RA-SVE. RESULTS: The median total operative time was 90 min and blood loss 50 mL with no postoperative transfusions required. The median hospital stay was 1 day. No intra- or postoperative complications were documented. Continence status was unaffected, no patient required urinary pads. Postoperative pathology confirmed SV invasion in all specimens. Surgical margins were positive in seven (41%) patients. All patients had at least one positive imaging study, although three (18%) mp-MRI and five (29%) PET/CT assessments were negative. One (6%) pre-SVE biopsy was also negative but with positive imaging. Salvage SVE failure, defined as three consecutive PSA rises or the need for further treatment, occurred in six patients of whom three had a positive margin. Overall failure-free survival rates were 86%, 67%, and 53% at 1, 2, and 3 years after SVE, respectively. CONCLUSIONS: Salvage RA-SVE appears to be a safe focal treatment, with very low morbidity, for patients with localised SV recurrence after LDR-PB. It permits deferral of androgen deprivation therapy in selected patients. Bilateral SVE is mandatory. This surgical option should be considered in patients with isolated prostate cancer recurrence to the SV.

Feasibility and safety of radical prostatectomy for oligo-metastatic prostate cancer: the Testing Radical prostatectomy in men with prostate cancer and oligo-Metastases to the bone (TRoMbone) trial.

OBJECTIVES: To test the feasibility of randomisation to radical prostatectomy (RP) plus pelvic lymphadenectomy in addition to standard-of-care (SOC) systemic therapy in men with newly diagnosed oligo-metastatic prostate cancer. PATIENTS AND METHODS: A prospective, randomised, non-blinded, feasibility clinical trial with an embedded QuinteT Recruitment Intervention (QRI) to optimise recruitment was conducted in nine nationwide tertiary care centres undertaking high-volume robotic surgery. We aimed to randomise 50 men with synchronous oligo-metastatic prostate cancer within an 18-month recruitment period to SOC systemic therapy vs SOC plus RP (intervention arm). The main outcome measures were: ability to randomise patients, optimised by a QRI; EuroQoL five Dimensions five Levels (EQ-5D-5L) questionnaires to capture quality-of-life (QoL) data at baseline and 3 months post-randomisation; routine clinicopathological assessment to capture adverse events and prostate-specific antigen in both arms, plus standard perioperative parameters in the surgical arm. RESULTS: A total of 51 men were randomised within 14 months (one was subsequently deemed ineligible), with 60-83% accrual rate in centres that recruited at least two patients. All patients completed the trial follow-up; one patient in the intervention arm subsequently did not undergo the surgical intervention and one in the SOC arm refused all therapies. The QRI positively impacted recruitment. QoL data showed similarly high functioning in both study arms. Surgery for men with oligo-metastatic prostate cancer was found to be safe and had similar impact on early functional outcomes as surgery for standard indication. CONCLUSION: It is feasible to randomise men with synchronous oligo-metastatic prostate cancer to a surgical intervention in addition to standard systemic therapies. While surgery appeared safe with no substantial impact on QoL in this feasibility study, a large randomised controlled trial is now warranted to examine treatment effectiveness of this additional component in the multimodality management of oligo-metastatic prostate cancer.

Etrolizumab for maintenance therapy in patients with moderately to severely active ulcerative colitis (LAUREL): a randomised, placebo-controlled, double-blind, phase 3 study.

BACKGROUND: Etrolizumab is a gut-targeted anti-ß7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab for maintenance of remission in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, placebo-controlled, double-blind, phase 3 study (LAUREL) across 111 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. During open-label induction, participants received subcutaneous etrolizumab 105 mg once every 4 weeks. Participants who had clinical response at week 10 (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) proceeded into the double-blind maintenance phase and were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or matched placebo until week 62. Randomisation was stratified by baseline concomitant treatment with corticosteroids, treatment with immunosuppressants, baseline disease activity, and week 10 remission status. All participants and study site personnel were masked to treatment assignment. The primary endpoint was remission at week 62 (MCS ≤2, with individual subscores ≤1, and rectal bleeding subscore of 0) among patients with a clinical response at week 10, measured in the modified intention-to-treat population (all randomised patients who received at least one dose of study drug). This trial is registered with ClinicalTrials.gov, NCT02165215, and is now closed to recruitment. FINDINGS: Between Aug 12, 2014, and June 4, 2020, 658 patients were screened for eligibility and 359 were enrolled into the induction phase. 214 (60%) patients had a clinical response at week 10 and were randomly assigned to receive etrolizumab (n=108) or placebo (n=106) in the maintenance phase. 80 (74%) patients in the etrolizumab group and 42 (40%) in the placebo group completed the study through week 62. Four patients in the placebo group did not receive study treatment and were excluded from the analyses. At week 62, 32 (29·6%) of 108 patients in the etrolizumab group and 21 (20·6%) of 102 in the placebo group were in remission (adjusted treatment difference 7·7% [95% CI -4·2 to 19·2]; p=0·19). A greater proportion of patients reported one or more adverse events in the placebo group (82 [80%] of 102) than in the etrolizumab group (70 [65%] of 108); the most common adverse event in both groups was ulcerative colitis (16 [15%] patients in the etrolizumab group and 37 [36%] in the placebo group). Ten (9%) patients in the etrolizumab group and eight (8%) in the placebo group reported one or more serious adverse events. No deaths were reported in either treatment group. INTERPRETATION: No significant differences were observed between maintenance etrolizumab and placebo in the primary endpoint of remission at week 62 among patients who had a clinical response at week 10. Etrolizumab was well tolerated in this population and no new safety signals were identified. FUNDING: F Hoffmann-La Roche.

Can Tumour Volume Percentage in Radical Prostatectomy Predict Cancer Biochemical Recurrence? Determining a Cut-off Point and Composite Risk Factors Approach.

BACKGROUND: Incidence of biochemical recurrence (BCR) after radical prostatectomy is relatively high and overall survival can be poor. Debate exists whether tumour volume predicts BCR and when treatments should be administered. In this study, we aimed to i) assess the impact of tumour volume percentage (TVP) as a predictor for BCR, ii) determine TVP cut-off point for BCR and iii) evaluate single and composite predictors of BCR. METHODS: From March 2000 to December 2013, 1777 patients underwent laparoscopic radical prostatectomy for localized prostate cancer. None received neoadjuvant or adjuvant therapy. One hundred and forty-six patients experienced BCR (range 3 months-10 years). Using D'Amico classification, 146 matched controls without BCR were compared. Liu cut-point analysis was used to identify TVP with optimal sensitivity and specificity. Single and composite BCR risk predictors were analyzed using Cox hazards regression in cases and controls. RESULTS: Median TVP was 10% (range 1-90%). Most of BCR peaked after 3 years of follow-up. TVP ≥8% was an independent predictor of BCR with HR 1.6 (p= 0.001, 95% CI= 1.11-2.48). TVP of 8% was associated with the highest accuracy: sensitivity 74% and specificity 53% (ROC curve= 0.7). At TVP ≥8%, pathological stage pT3 was associated with 1.7-fold higher risk of BCR compared to T2. Lymph node invasion was associated with 1.4-fold higher risk of BCR compared to no invasion. Combining TVP ≥8%, pT3 and lymph node invasion, HR jumped to 3.73 (p< 0.001, 95% CI= 2.27-6.14), whereas combining TVP ≥8%, positive surgical margin and lymph node invasion, HR was 2.68 (p= 001, 95% CI= 1.50-4.77). CONCLUSION: TVP can be used as an independent predictor of BCR after radical prostatectomy for prostate cancer. TVP cut-point of ≥8% allows the best discrimination. TVP should be considered in combination with other clinico-pathological factors to improve prediction of long-term oncological outcomes and to stratify BCR risk.

Comparative Outcomes of Salvage Retzius-Sparing versus Standard Robotic Prostatectomy: An International, Multi-Surgeon Series.

PURPOSE: Salvage radical prostatectomy is rare due to the risk of postoperative complications. We compare salvage Retzius-sparing robotic assisted radical prostatectomy (SRS-RARP) with salvage standard robotic assisted radical prostatectomy (SS-RARP). MATERIALS AND METHODS: A total of 72 patients across 9 centers were identified (40 SRS-RARP vs 32 SS-RARP). Demographics, perioperative data, and pathological and functional outcomes were compared using Student's t-test and ANOVA. Cox proportional hazard models and Kaplan-Meier curves were constructed to assess risk of incontinence and time to continence. Linear regression models were constructed to investigate postoperative pad use and console time. RESULTS: Median followup was 23 vs 36 months for SRS-RARP vs SS-RARP. Console time and estimated blood loss favored SRS-RARP. There were no differences in complication rates or oncologic outcomes. SRS-RARP had improved continence (78.4% vs 43.8%, p <0.001 for 0-1 pad, 54.1% vs 6.3%, p <0.001 for 0 pad), lower pads per day (0.57 vs 2.03, p <0.001), and earlier return to continence (median 47 vs 180 days, p=0.008). SRS-RARP was associated with decreased incontinence defined as >0-1 pad (HR 0.28, 95% CI 0.10-0.79, p=0.016), although not when defined as >0 pad (HR 0.56, 95% CI 0.31-1.01, p=0.053). On adjusted analysis SRS-RARP was associated with decreased pads per day. Lymph node dissection and primary treatment with stereotactic body radiation therapy were associated with longer console time. CONCLUSIONS: SRS-RARP is a feasible salvage option with significantly improved urinary function outcomes. This may warrant increased utilization of SRS-RARP to manage men who fail nonsurgical primary treatment for prostate cancer.

Retzius-Sparing versus Standard Robot-Assisted Radical Prostatectomy: A Comparative Prospective Study of Nearly 500 Patients.

PURPOSE: We compared standard robot-assisted radical prostatectomy and Retzius-sparing robot-assisted radical prostatectomy in a multicenter study using prospective patient reported outcome measures of functional recovery and quality of life plus standard pentafecta outcomes. MATERIALS AND METHODS: Patient and physician reported data on 483 patients who underwent robot-assisted radical prostatectomy and Retzius-sparing robot-assisted radical prostatectomy from August 2017 to April 2020 by 3 experienced surgeons had been prospectively collected. Perioperative and pentafecta outcomes were analyzed using SPSS software. Patient reported outcome measures for urinary function, erectile function and quality of life were reported at baseline and at 7 days and 1, 3, 6, 9 and 12 months postoperatively. RESULTS: A total of 201 patients underwent robot-assisted radical prostatectomy and 282 had Retzius-sparing robot-assisted radical prostatectomy. Patient and tumor characteristics were similar except for fewer low risk and more intermediate risk disease in robot-assisted radical prostatectomy vs Retzius-sparing robot-assisted radical prostatectomy (p <0.001). High risk disease was similar between groups (p=0.071). Immediate urinary continence was higher in Retzius-sparing robot-assisted radical prostatectomy group (70.4% vs 58.1%, p=0.02), with less nocturnal enuresis prevalence (p=0.011) and bother (p=0.009) with no significant differences afterwards. A better quality of life (p=0.004) was reported 1 week after surgery. No other differences in functional or quality of life outcomes, perioperative parameters, complications or margin rates were found. CONCLUSIONS: Retzius-sparing robot-assisted radical prostatectomy is associated with better immediate continence than anterior robot-assisted radical prostatectomy with no differences in longer-term functional recovery, quality of life or other important outcomes. The overall similarity in outcomes between groups lends support to the view that the surgical technique matters less than the surgeon performing it.

Retzius-sparing robot-assisted radical prostatectomy: early learning curve experience in three continents.

OBJECTIVE: To assess the effect of surgical experience on peri-operative, functional and oncological outcomes during the first 50 Retzius-sparing robot-assisted radical prostatectomy (RsRARP) cases performed by surgeons naïve to this novel approach. MATERIALS AND METHODS: We retrospectively evaluated the initial cases operated by 14 surgeons in 12 different international centres. Pre-, peri- and postoperative features of the first 50 patients operated by each surgeon in all the participating centres were collected. The effect of surgical experience on peri-operative, functional and oncological outcomes was firstly evaluated after stratification by level of surgical experience (initial [≤25 cases] and expert [>25 cases]) and after using locally weighted scatterplot smoothing to graphically explore the relationship between surgical experience and the outcomes of interest. RESULTS: We evaluated 626 patients. The median follow-up was 13 months in the initial group and 9 months in the expert group (P = 0.002). Preoperative features overlapped between the two groups. Shorter console time (140 vs 120 min; P = 0.001) and a trend towards lower complications rates (13 vs 5.5%; P = 0.038) were observed in the expert group. The relationship between surgical experience and console time, immediate urinary continence recovery and Clavien-Dindo grade ≥2 complications was linear, without reaching a plateau, after 50 cases. Conversely, a non-linear relationship was observed between surgical experience and positive surgical margins (PSMs). CONCLUSIONS: In this first report of a multicentre experience of RsRARP during the learning curve, we found that console time, immediate urinary continence recovery and postoperative complications are optimal from the beginning and further quickly improve during the learning process, while PSM rates did not clearly improve over the first 50 cases.

Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology.

BACKGROUND: Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. OBJECTIVE: To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. RESULTS AND LIMITATIONS: A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation. CONCLUSIONS: The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential. PATIENT SUMMARY: The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population.

Current Status of Hemostatic Agents and Sealants in Urologic Surgical Practice.

There has been a recent and near exponential increase in the use of hemostatic agents and sealants to supplement the rapidly evolving methods in the surgical management of urologic patients. This article reviews the use of hemostatic agents and sealants in current urologic practice.

An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes.

Cancers are characterized by non-random chromosome copy number alterations that presumably contain oncogenes and tumor-suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here we report a cross-species in vivo screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models, we validate eight new ependymoma oncogenes and ten new ependymoma TSGs that converge on a small number of cell functions, including vesicle trafficking, DNA modification and cholesterol biosynthesis, identifying these as potential new therapeutic targets.

Oncogenic KRAS promotes malignant brain tumors in zebrafish.

BACKGROUND: Zebrafish have been used as a vertebrate model to study human cancers such as melanoma, rhabdomyosarcoma, liver cancer, and leukemia as well as for high-throughput screening of small molecules of therapeutic value. However, they are just emerging as a model for human brain tumors, which are among the most devastating and difficult to treat. In this study, we evaluated zebrafish as a brain tumor model by overexpressing a human version of oncogenic KRAS (KRAS(G12V)). METHODS: Using zebrafish cytokeratin 5 (krt5) and glial fibrillary acidic protein (gfap) gene promoters, we activated Ras signaling in the zebrafish central nervous system (CNS) through transient and stable transgenic overexpression. Immunohistochemical analyses were performed to identify activated pathways in the resulting brain tumors. The effects of the MEK inhibitor U0126 on oncogenic KRAS were evaluated. RESULTS: We demonstrated that transient transgenic expression of KRAS(G12V) in putative neural stem and/or progenitor cells induced brain tumorigenesis. When expressed under the control of the krt5 gene promoter, KRAS(G12V) induced brain tumors in ventricular zones (VZ) at low frequency. The majority of other tumors were composed mostly of spindle and epithelioid cells, reminiscent of malignant peripheral nerve sheath tumors (MPNSTs). In contrast, when expressed under the control of the gfap gene promoter, KRAS(G12V) induced brain tumors in both VZs and brain parenchyma at higher frequency. Immunohistochemical analyses indicated prominent activation of the canonical RAS-RAF-ERK pathway, variable activation of the mTOR pathway, but no activation of the PI3K-AKT pathway. In a krt5-derived stable and inducible transgenic line, expression of oncogenic KRAS resulted in skin hyperplasia, and the MEK inhibitor U0126 effectively suppressed this pro-proliferative effects. In a gfap-derived stable and inducible line, expression of oncogenic KRAS led to significantly increased mitotic index in the spinal cord. CONCLUSIONS: Our studies demonstrate that zebrafish could be explored to study cellular origins and molecular mechanisms of brain tumorigenesis and could also be used as a platform for studying human oncogene function and for discovering oncogenic RAS inhibitors.

Minimum 5-year follow-up of 1138 consecutive laparoscopic radical prostatectomies.

OBJECTIVES: To investigate the long-term outcomes of laparoscopic radical prostatectomy (LRP). PATIENTS AND METHODS: In all, 1138 patients underwent LRP during a 163-month period from 2000 to 2008, of which 51.5%, 30.3% and 18.2% were categorised into D'Amico risk groups of low-, intermediate- and high-risk, respectively. All intermediate- and high-risk patients were staged by preoperative magnetic resonance imaging or computed tomography and isotope bone scanning, and had a pelvic lymph node dissection (PLND), which was extended after April 2008. The median (range) patient age was 62 (40-78) years; body mass index was 26 (19-44) kg/m(2) ; prostate-specific antigen level was 7.0 (1-50) ng/mL and Gleason score was 6 (6-10). Neurovascular bundle was preservation carried out in 55.3% (bilateral 45.5%; unilateral 9.8%) of patients. RESULTS: The median (range) gland weight was 52 (14-214) g. The median (range) operating time was 177 (78-600) min and PLND was performed in 299 patients (26.3%), of which 54 (18.0%) were extended. The median (range) blood loss was 200 (10-1300) mL, postoperative hospital stay was 3 (2-14) nights and catheterisation time was 14 (1-35) days. The complication rate was 5.2%. The median (range) LN count was 12 (4-26), LN positivity was 0.8% and the median (range) LN involvement was 2 (1-2). There was margin positivity in 13.9% of patients and up-grading in 29.3% and down-grading in 5.3%. While 11.4% of patients had up-staging from T1/2 to T3 and 37.1% had down-staging from T3 to T2. One case (0.09%) was converted to open surgery and six patients were transfused (0.5%). At a mean (range) follow-up of 88.6 (60-120) months, 85.4% of patients were free of biochemical recurrence, 93.8% were continent and 76.6% of previously potent non-diabetic men aged <70 years were potent after bilateral nerve preservation. CONCLUSIONS: The long-term results obtainable from LRP match or exceed those previously published in large contemporary open and robot-assisted surgical series.