Hospital volume-outcome relationships for robot-assisted surgeries: a population-based analysis.

BACKGROUND: Associations between procedure volumes and outcomes can inform minimum volume standards and the regionalization of health services. Robot-assisted surgery continues to expand globally; however, data are limited regarding which hospitals should be using the technology. STUDY DESIGN: Using administrative health data for all residents of Ontario, Canada, this retrospective cohort study included adult patients who underwent a robot-assisted radical prostatectomy (RARP), total robotic hysterectomy (TRH), robot-assisted partial nephrectomy (RAPN), or robotic portal lobectomy using 4 arms (RPL-4) between January 2010 and September 2021. Associations between yearly hospital volumes and 90-day major complications were evaluated using multivariable logistic regression models adjusted for patient characteristics and clustering at the level of the hospital. RESULTS: A total of 10,879 patients were included, with 7567, 1776, 724, and 812 undergoing a RARP, TRH, RAPN, and RPL-4, respectively. Yearly hospital volume was not associated with 90-day complications for any procedure. Doubling of yearly volume was associated with a 17-min decrease in operative time for RARP (95% confidence interval [CI] - 23 to - 10), 8-min decrease for RAPN (95% CI - 14 to - 2), 24-min decrease for RPL-4 (95% CI - 29 to - 19), and no significant change for TRH (- 7 min; 95% CI - 17 to 3). CONCLUSION: The risk of 90-day major complications does not appear to be higher in low volume hospitals; however, they may not be as efficient with operating room utilization. Careful case selection may have contributed to the lack of an observed association between volumes and complications.

Hospital learning curves for robot-assisted surgeries: a population-based analysis.

BACKGROUND: Robot-assisted surgery has been rapidly adopted. It is important to define the learning curve to inform credentialling requirements, training programs, identify fast and slow learners, and protect patients. This study aimed to characterize the hospital learning curve for common robot-assisted procedures. STUDY DESIGN: This cohort study, using administrative health data for Ontario, Canada, included adult patients who underwent a robot-assisted radical prostatectomy (RARP), total robotic hysterectomy (TRH), robot-assisted partial nephrectomy (RAPN), or robotic portal lobectomy using four arms (RPL-4) between 2010 and 2021. The association between cumulative hospital volume of a robot-assisted procedure and major complications was evaluated using multivariable logistic models adjusted for patient characteristics and clustering at the hospital level. RESULTS: A total of 6814 patients were included, with 5230, 543, 465, and 576 patients in the RARP, TRH, RAPN, and RPL-4 cohorts, respectively. There was no association between cumulative hospital volume and major complications. Visual inspection of learning curves demonstrated a transient worsening of outcomes followed by subsequent improvements with experience. Operative time decreased for all procedures with increasing volume and reached plateaus after approximately 300 RARPs, 75 TRHs, and 150 RPL-4s. The odds of a prolonged length of stay decreased with increasing volume for patients undergoing a RARP (OR 0.87; 95% CI 0.82-0.92) or RPL-4 (OR 0.77; 95% CI 0.68-0.87). CONCLUSION: Hospitals may adopt robot-assisted surgery without significantly increasing the risk of major complications for patients early in the learning curve and with an expectation of increasing efficiency.

Obesity and Complication Risk From Radical Cystectomy: Identifying a Body Mass Index Threshold.

PURPOSE: There are conflicting reports regarding radical cystectomy complication risk from obesity subcategories, and a BMI threshold below which complication risk is notably reduced is undefined. A BMI threshold may be helpful in prehabilitation to aid patient counseling and inform weight loss strategies to potentially mitigate obesity-associated complication risk. This study aims to identify such a threshold and further investigate the association between BMI subcategories and perioperative complications from radical cystectomy. MATERIALS AND METHODS: Data were extracted from the Canadian Bladder Cancer Information System, a prospective registry across 14 academic centers. Five hundred and eighty-nine patients were analyzed. Perioperative (≤90 days) complications were compared between BMI subcategories. Unconditional multivariable logistic regression and cubic spline analysis were performed to determine the association between BMI and complication risk and identify a BMI threshold. RESULTS: Perioperative complications were reported in 51 (30%), 97 (43%), and 85 (43%) normal, overweight, and obese patients (P = .02). BMI was independently associated with developing any complication (OR 1.04 95% CI 1.01, 1.07). Predicted complication risk began to rise consistently above a BMI threshold of 34 kg/m2. Both overweight (OR 2.00 95% CI 1.26-3.17) and obese (OR 1.98 95% CI 1.24-3.18) patients had increased risk of complications compared to normal BMI patients. CONCLUSIONS: Complication risk from radical cystectomy is independently associated with BMI. Both overweight and obese patients are at increased risk compared to normal BMI patients. A BMI threshold of 34 kg/m2 has been identified, which may inform prehabilitation treatment strategies.

The evolving use of robotic surgery: a population-based analysis.

INTRODUCTION: Robotic surgery has integrated into the healthcare system despite limited evidence demonstrating its clinical benefit. Our objectives were (i) to describe secular trends and (ii) patient- and system-level determinants of the receipt of robotic as compared to open or laparoscopic surgery. METHODS: This population-based retrospective cohort study included adult patients who, between 2009 and 2018 in Ontario, Canada, underwent one of four commonly performed robotic procedures: radical prostatectomy, total hysterectomy, thoracic lobectomy, partial nephrectomy. Patients were categorized based on the surgical approach as robotic, open, or laparoscopic for each procedure. Multivariable regression models were used to estimate the temporal trend in robotic surgery use and associations of patient and system characteristics with the surgical approach. RESULTS: The cohort included 24,741 radical prostatectomy, 75,473 total hysterectomy, 18,252 thoracic lobectomy, and 4608 partial nephrectomy patients, of which 6.21% were robotic. After adjusting for patient and system characteristics, the rate of robotic surgery increased by 24% annually (RR 1.24, 95%CI 1.13-1.35): 13% (RR 1.13, 95%CI 1.11-1.16) for robotic radical prostatectomy, 9% (RR 1.09, 95%CI 1.05-1.13) for robotic total hysterectomy, 26% (RR 1.26, 95%CI 1.06-1.50) for thoracic lobectomy and 26% (RR 1.26, 95%CI 1.13-1.40) for partial nephrectomy. Lower comorbidity burden, earlier disease stage (among cancer cases), and early career surgeons with high case volume at a teaching hospital were consistently associated with the receipt of robotic surgery. CONCLUSION: The use of robotic surgery has increased. The study of the real-world clinical outcomes and associated costs is needed before further expanding use among additional providers and hospitals.

Low Serum Testosterone in Men with Newly Diagnosed Androgen-Deprivation Therapy-Naïve Prostate Cancer and Its Relationship to Cardiovascular Risk Factors: A RADICAL-PC Substudy.

PURPOSE: Cardiovascular disease is a common cause of death in prostate cancer patients. Low testosterone is associated with increased cardiovascular risk in the general male population. We investigated the relationship between serum testosterone, cardiovascular disease and risk factors in androgen-deprivation therapy-naïve prostate cancer patients. MATERIALS AND METHODS: We performed a cross-sectional analysis of a subgroup of 1,326 androgen-deprivation therapy-naïve men from RADICAL-PC (Role of Androgen-Deprivation Therapy In CArdiovascular Disease-A Longitudinal Prostate Cancer study) in whom serum testosterone was measured at baseline. RADICAL-PC is a prospective multicenter cohort study of men (2,565) enrolled within 1 year of prostate cancer diagnosis, or within 6 months of commencing androgen-deprivation therapy for the first time. Cardiovascular risk factors, cancer characteristics and total serum testosterone were collected at baseline. Low testosterone was defined as total serum testosterone <11 nmol/L (<320 ng/dL). A Framingham cardiovascular risk score ≥15 was considered high risk for future cardiovascular events. We performed logistic regression to calculate odds ratios for the association between testosterone and cardiovascular risk. RESULTS: Among 1,326 participants (median age 67 years, range 45-93), 553 (42%) had low testosterone. Low testosterone was associated with existing cardiovascular disease, diabetes, elevated hemoglobin A1c, obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension and Framingham score >15. Among patients with low testosterone, the odds ratio for high cardiovascular risk was 1.33 (1.02-1.73) after adjusting for ethnicity, education, alcohol use, cancer characteristics, physical activity and body mass index. CONCLUSIONS: Among androgen-deprivation therapy-naïve prostate cancer patients, low testosterone is common and associated with increased cardiovascular risk factors.

Adverse events following robotic surgery: population-based analysis.

BACKGROUND: Robotic surgery was integrated into some healthcare systems despite there being few well designed, real-world studies on safety or benefit. This study compared the safety of robotic with laparoscopic, thoracoscopic, and open approaches in common robotic procedures. METHODS: This was a population-based, retrospective study of all adults who underwent prostatectomy, hysterectomy, pulmonary lobectomy, or partial nephrectomy in Ontario, Canada, between 2008 and 2018. The primary outcome was 90-day total adverse events using propensity score overlap weights, and secondary outcomes were minor or major morbidity/adverse events. RESULTS: Data on 24 741 prostatectomy, 75 473 hysterectomy, 18 252 pulmonary lobectomy, and 6608 partial nephrectomy operations were included. Relative risks for total adverse events in robotic compared with open surgery were 0.80 (95 per cent c.i. 0.74 to 0.87) for radical prostatectomy, 0.44 (0.37 to 0.52) for hysterectomy, 0.53 (0.44 to 0.65) for pulmonary lobectomy, and 0.72 (0.54 to 0.97) for partial nephrectomy. Relative risks for total adverse events in robotic surgery compared with a laparoscopic/thoracoscopic approach were 0.94 (0.77 to 1.15), 1.00 (0.82 to 1.23), 1.01 (0.84 to 1.21), and 1.23 (0.82 to 1.84) respectively. CONCLUSION: The robotic approach is associated with fewer adverse events than an open approach but similar to a laparoscopic/thoracoscopic approach. The benefit of the robotic approach is related to the minimally-invasive approach rather than the platform itself.

Visceral adipose tissue loss and 24-hour urinary profile changes post-bariatric surgery.

INTRODUCTION: The relationship between obesity and nephrolithiasis is a well-documented phenomenon. Visceral adipose tissue (VAT) has been proposed to be an accurate indicator of metabolic derangement. We present a study that investigates the relationship between computed tomography (CT) delineated VAT measurements and 24-hour urine (24 HU) profiles in the context of profound weight loss. MATERIALS AND METHODS: A total of 86 patients with a history of nephrolithiasis who underwent bariatric surgery were reviewed. All patients had pre and postoperative 24 HU analysis and CT kidney and urinary bladder performed. CT-based fat delineation program, AnalyzePro, was used to measure VAT at levels L4-L5 (VAT 1) and L1-L2 (VAT2). Univariate and multivariate analysis was utilized to examine associations between VAT measurements and comorbidities, 24 HU values, and postoperative urinary changes. RESULTS: Preoperative VAT2 was correlated with preoperative serum creatinine and all 24 HU (R2: 0.23-0.43, p = < 0.001-0.030). Only VAT1 and VAT2 had relationships with hypertension, dyslipidemia, and metabolic syndrome (R2: 0.25-0.30, p = 0.004-0.015). The percent change in VAT1 and VAT2 was a significant predictor of change in 24 HU uric acid (respectively, R2: 0.14, beta: -0.03, p = 0.002 and R2: 0.13, beta: -0.03, p = 0.003). CONCLUSIONS: This study found VAT to have strong correlations with urinary outcomes in obese patients, especially in the excretion of uric acid. These findings support a potential use of CT delineated measurements of fat as a surrogate measure for urinary metabolites, and may be used as a marker for patient counseling in stone prevention.

Robotic thoracic surgery in Canada: Are patients willing to pay out of pocket?

Robotic-assisted thoracoscopic surgery (RTS) is safe and effective, but is associated with high capital and operating costs that are not reimbursed by the Canadian government. Currently, patients have access to RTS only when it is supported by research or philanthropic funds. In a recent study, we assessed the extent of patient-reported satisfaction with RTS, whether patients would have been willing to pay out of pocket for it, and what factors were associated with patients' willingness to pay. Many patients (290 of 411 [70.56%]) stated that they would have paid the additional $2000 to supplement the government health care coverage to have access to RTS. Factors found to be significantly associated with participants' willingness to pay were an annual income of $60 000 or more (p = 0.034), private insurance coverage (p = 0.007), overall experience with RTS rated as 8 or higher out of 10 (p < 0.001), and overall postoperative postdischarge experience rated as satisfying or very satisfying (p = 0.004).

Cardiovascular Risk in Men with Prostate Cancer: Insights from the RADICAL PC Study.

PURPOSE: We describe the cardiovascular risk profile in a representative cohort of patients with prostate cancer treated with or without androgen deprivation therapy. MATERIALS AND METHODS: We prospectively characterized in detail 2,492 consecutive men (mean age 68 years) with prostate cancer (newly diagnosed or with a plan to prescribe androgen deprivation therapy for the first time) from 16 Canadian sites. Cardiovascular risk was estimated by calculating Framingham risk scores. RESULTS: Most men (92%) had new prostate cancer (intermediate risk 41%, high risk 50%). The highest level of education achieved was primary school in 12%. Most (58%) were current or former smokers, 22% had known cardiovascular disease, 16% diabetes, 45% hypertension, 31% body mass index 30 kg/m2 or greater, 24% low levels of physical activity, mean handgrip strength was 37.3 kg and 69% had a Framingham risk score consistent with high cardiovascular risk. Participants in whom androgen deprivation therapy was planned had higher Framingham risk scores than those not intending to receive androgen deprivation therapy, and this risk was abolished after adjustment for confounders. CONCLUSIONS: Two-thirds of men with prostate cancer are at high cardiovascular risk. There is a positive association between a plan to use androgen deprivation therapy and baseline cardiovascular risk factors. However, this association is explained by confounding factors.

Development and Acceptability Testing of a Patient Decision Aid for Urinary Diversion with Radical Cystectomy.

PURPOSE: The choice of urinary diversion at cystectomy is a life altering decision. Patient decision aids are clinical tools that promote shared decision making by providing information about management options and helping patients communicate their values. We sought to develop and evaluate a patient decision aid for individuals undergoing cystectomy with urinary diversion. MATERIALS AND METHODS: We used the IPDAS (International Patient Decision Aids Standards) to guide a systematic development process. A literature review was performed to determine urinary diversion options and the incidence of outcomes. We created a prototype using the Ottawa Decision Support Framework. A 10-question survey was used to assess patient decision aid acceptability among patients, allied health professionals and urologists. The primary outcome was acceptability of the patient decision aid. RESULTS: Ileal conduit and orthotopic neobladder were included as primary urinary diversion options because they had the most evidence and are most commonly performed. Continent cutaneous diversion was identified as an alternative option. Outcomes specific to ileal conduit were stomal stenosis and parastomal hernia. Outcomes specific to neobladder were daytime and nighttime urinary incontinence and urinary retention. Acceptability testing was completed by 8 urologists, 9 patients and 1 advanced practice nurse. Of the respondents 94% reported that the language was appropriate, 94% reported that the length was adequate and 83% reported that option presentation was balanced. The patient decision aid met all 6 IPDAS defining criteria, all 6 certification criteria and 21 of 23 quality criteria. CONCLUSIONS: We created a novel patient decision aid to improve the quality of decisions made by patients when deciding among urinary diversion options. Effectiveness testing will be performed prospectively.

Use of machine learning to predict early biochemical recurrence after robot-assisted prostatectomy.

OBJECTIVES: To train and compare machine-learning algorithms with traditional regression analysis for the prediction of early biochemical recurrence after robot-assisted prostatectomy. PATIENTS AND METHODS: A prospectively collected dataset of 338 patients who underwent robot-assisted prostatectomy for localized prostate cancer was examined. We used three supervised machine-learning algorithms and 19 different training variables (demographic, clinical, imaging and operative data) in a hypothesis-free manner to build models that could predict patients with biochemical recurrence at 1 year. We also performed traditional Cox regression analysis for comparison. RESULTS: K-nearest neighbour, logistic regression and random forest classifier were used as machine-learning models. Classic Cox regression analysis had an area under the curve (AUC) of 0.865 for the prediction of biochemical recurrence. All three of our machine-learning models (K-nearest neighbour (AUC 0.903), random forest tree (AUC 0.924) and logistic regression (AUC 0.940) outperformed the conventional statistical regression model. Accuracy prediction scores for K-nearest neighbour, random forest tree and logistic regression were 0.976, 0.953 and 0.976, respectively. CONCLUSIONS: Machine-learning techniques can produce accurate disease predictability better that traditional statistical regression. These tools may prove clinically useful for the automated prediction of patients who develop early biochemical recurrence after robot-assisted prostatectomy. For these patients, appropriate individualized treatment options can improve outcomes and quality of life.

Autoantibodies against the cell surface-associated chaperone GRP78 stimulate tumor growth via tissue factor.

Tumor cells display on their surface several molecular chaperones that normally reside in the endoplasmic reticulum. Because this display is unique to cancer cells, these chaperones are attractive targets for drug development. Previous epitope-mapping of autoantibodies (AutoAbs) from prostate cancer patients identified the 78-kDa glucose-regulated protein (GRP78) as one such target. Although we previously showed that anti-GRP78 AutoAbs increase tissue factor (TF) procoagulant activity on the surface of tumor cells, the direct effect of TF activation on tumor growth was not examined. In this study, we explore the interplay between the AutoAbs against cell surface-associated GRP78, TF expression/activity, and prostate cancer progression. First, we show that tumor GRP78 expression correlates with disease stage and that anti-GRP78 AutoAb levels parallel prostate-specific antigen concentrations in patient-derived serum samples. Second, we demonstrate that these anti-GRP78 AutoAbs target cell-surface GRP78, activating the unfolded protein response and inducing tumor cell proliferation through a TF-dependent mechanism, a specific effect reversed by neutralization or immunodepletion of the AutoAb pool. Finally, these AutoAbs enhance tumor growth in mice bearing human prostate cancer xenografts, and heparin derivatives specifically abrogate this effect by blocking AutoAb binding to cell-surface GRP78 and decreasing TF expression/activity. Together, these results establish a molecular mechanism in which AutoAbs against cell-surface GRP78 drive TF-mediated tumor progression in an experimental model of prostate cancer. Heparin derivatives counteract this mechanism and, as such, represent potentially appealing compounds to be evaluated in well-designed translational clinical trials.

Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells.

BACKGROUND: Prostate cancer (PC) patients in advanced stages of the disease have high risk of blood coagulation complications. The procoagulant molecule Tissue factor (TF), and the fibrinolysis inhibitor plasminogen activator inhibitor-1 PAI-1 play important role in this complication. Extracellular vesicles (EV) shed from cancer cells may contribute to the regulation of TF and PAI-1. The procoagulant activity of EV can be associated with the oncogenic and metastatic characteristics of their cells. METHODS: We have expressed EGFRvIII in DU145 cells to assess the role of this oncogene in the procoagulant activity of EV. The intercellular exchange of TF via EV was assessed by downregulating its expression in DU145 cells using shRNA vector, and determining the transfer of TF via EV enriched with the protein. Two PC cell lines with different metastatic potential were used to assess the correlation between the procoagulant activity of EV and the metastatic potential of PC cells. Photometric assays were used to determine FXa-activity and thrombin generation as indicators for the procoagulant activity of EV. Double-tagged proteinase-activated receptor 1(PAR-1) expressed in CHO cells to assess its activation by EV. RESULTS: The expression of EGFRvIII in DU145 cells led to increased mRNA levels for TF and PAI-1, but the increase in these proteins expression was detected mostly in the EV. EV with enhanced levels of TF protein conferred higher TF procoagulant activity on the acceptor cells by intercellular exchange of this protein. Procoagulant activity of EV, assessed by FXa activity, and thrombin generation, was correlated with the oncogenic and metastatic potential of PC cells. The ability of EV to generate thrombin led to the activation of PAR-1, which was evident by the truncation of tagged-PAR-1. CONCLUSION: The active oncogene EGFRvIII increases the concentration of TF and PAI-1 in EV. The procoagulant activity of EV is associated with the oncogenic and metastatic characteristics of their PC cells. Also, EV may contribute to the high procoagulant activity in the tumour microenvironment by the intercellular exchange of TF. Finally, through the generation of thrombin, EV can activate PAR-1, which evidently contributes to cancer progression, linking the coagulation system to tumor progression.

The effect of selection and referral biases for the treatment of localised prostate cancer with surgery or radiation.

BACKGROUND: Consultation with radiation oncologists, in addition to urologists, is advocated for patients diagnosed with prostate cancer. Treatment patterns for patients receiving consultation from radiation oncologists in addition to urologists have not previously been described. METHODS: We conducted a matched cohort study of men with newly diagnosed non-metastatic prostate cancer in Ontario, Canada. Patients who underwent consultation with a radiation oncologist prior to treatment were matched 1:1 with patients managed by a urologist alone based on tumour and patient characteristics. We examined rates of active treatment (surgery or radiotherapy) within one year following diagnosis. RESULTS: Among 5708 matched pairs (11,416 patients), those who received radiation oncology consultation were more likely to undergo active treatments whether they had intermediate or high-risk disease (88.6% vs. 65.9%, p < 0.0001; adjusted odds ratio 4.0, 95% CI: 3.6-4.4) or low-risk disease (56.1% vs. 13.3%, p < 0.0001; adjusted odds ratio 8.4, 95% CI: 6.7-10.6). This effect persisted after considering age, comorbidity, tumour volume and year of diagnosis. CONCLUSIONS: Patients newly diagnosed with prostate cancer who receive radiation oncology consultation are associated with a higher rate of active treatment, compared to patients managed by urologists only. Selection and referral biases, and unmeasured confounding such as patient preference must be considered as important factors attributing this association.

High-intensity Focused Ultrasound (HIFU) as salvage therapy for radio-recurrent prostate cancer: predictors of disease response.

BACKGROUND: Some men with localized radio-recurrent prostate cancer may benefit from salvage high-intensity focused ultrasound (HIFU). Herein, we describe oncologic outcomes and predictors of disease response after salvage whole gland HIFU from our prospective cohort. MATERIALS AND METHODS: Patients with localized radio-recurrent prostate cancer were prospectively enrolled from January 2005 to December 2014. Participants had to meet both biochemical and histological definitions of recurrence. Exclusion criteria included the receipt of prior salvage therapy, presence of metastatic disease, and administration of ADT in the 6-months prior to enrollment. Participants were treated with a single session of whole-gland HIFU ablation with the AblathermTM device (EDAP, France). The primary endpoint was recurrence-free survival (RFS), defined as a composite endpoint of PSA progression (Phoenix criteria), receipt of any further salvage therapy, receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis was used to determine the primary end-point and stratifications were used to determine the significance of 6 pre-specified predictors of improved RFS (TRUS biopsy grade, number of study entry TRUS biopsy cores positive, palpable disease at study enrollment, pre-HIFU PSA, an undetectable post-HIFU PSA nadir, and receipt of prior hormone therapy). Survival analysis was performed on participants with a minimum of 1-year follow-up. RESULTS: Twenty-four participants were eligible for study inclusion with a median follow-up of 31.0 months. Median PSA at study entry was 4.02ng/ml. Median time to PSA nadir was 3 months after treatment and median post-HIFU PSA nadir was 0.04ng/ ml. Median 2-year and 5-year RFS was 66.3% and 51.6% respectively. Of our 6 pre-specified predictors, an undetectable PSA nadir was the only significant predictor of improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P<0.001). One participant underwent an intervention for a urethral stricture. No participants developed osteitis pubis or rectourethral fistulae. CONCLUSIONS: Salvage HIFU allows for disease control in selected patients with localized radio-recurrent prostate cancer. An undetectable PSA nadir serves as an early predictor of disease response.

Adjuvant radiation therapy, androgen deprivation, and docetaxel for high-risk prostate cancer postprostatectomy: Results of NRG Oncology/RTOG study 0621.

BACKGROUND: Phase 3 trials have demonstrated a benefit from adjuvant radiation therapy (ART) for men who have adverse factors at radical prostatectomy (RP). However, some patients have a high risk of progression despite ART. The role of systemic therapy with ART in this high-risk group remains to be defined. METHODS: Patients who had either a post-RP prostate-specific antigen (PSA) nadir > 0.2 ng/mL and a Gleason score ≥7 or a PSA nadir ≤0.2 ng/mL, a Gleason score ≥8, and a pathologic tumor (pT) classification ≥ pT3 received 6 months of androgen-deprivation therapy (ADT) plus radiotherapy and 6 cycles of docetaxel. The primary objective was to assess whether the addition of ADT and docetaxel to ART resulted in a freedom from progression (FFP) rate ≥ 70% compared with an expected rate of 50%. Multivariate logistic and Cox regression analyses were used to model associations between factors and outcomes. RESULTS: In total, 74 patients were enrolled. The median follow-up was 4.4 years. The pathologic tumor classification was pT2 in 4% of patients, pT3 in 95%, and pT4 in 1%. The Gleason score was 7 in 18% of patients and ≥8 in 82%. Post-RP PSA levels were ≤0.2 ng/mL in 53% of patients and >0.2 ng/mL in 47%. The 3-year FFP rate was 73% (95% confidence interval, 61%-83%), and the 3-year cumulative incidence of biochemical, distant, and local failure was 26%, 7%, and 0%, respectively. In multivariate models, postprostatectomy PSA nadir was associated with 3-year FFP, Gleason score, and PSA with biochemical failure. Grade 3 and 4 neutropenia was common; however, only 3 episodes of febrile neutropenia occurred. Late toxicities were not impacted by the addition of systemic therapy. CONCLUSIONS: Combined ADT, docetaxel, and ART for men with high-risk prostate cancer after prostatectomy exceeded the prespecified study endpoint of 70% 3-year FFP. Phase 3 trials assessing combined local and systemic therapies for these high-risk patients are warranted. Cancer 2017;123:2489-96. © 2017 American Cancer Society.

Towards development and validation of an intraoperative assessment tool for robot-assisted radical prostatectomy training: results of a Delphi study.

INTRODUCTION: As urology training shifts toward competency-based frameworks, the need for tools for high stakes assessment of trainees is crucial. Validated assessment metrics are lacking for many robot-assisted radical prostatectomy (RARP). As it is quickly becoming the gold standard for treatment of localized prostate cancer, the development and validation of a RARP assessment tool for training is timely. MATERIALS AND METHODS: We recruited 13 expert RARP surgeons from the United States and Canada to serve as our Delphi panel. Using an initial inventory developed via a modified Delphi process with urology residents, fellows, and staff at our institution, panelists iteratively rated each step and sub-step on a 5-point Likert scale of agreement for inclusion in the final assessment tool. Qualitative feedback was elicited for each item to determine proper step placement, wording, and suggestions. RESULTS: Panelist's responses were compiled and the inventory was edited through three iterations, after which 100% consensus was achieved. The initial inventory steps were decreased by 13% and a skip pattern was incorporated. The final RARP stepwise inventory was comprised of 13 critical steps with 52 sub-steps. There was no attrition throughout the Delphi process. CONCLUSIONS: Our Delphi study resulted in a comprehensive inventory of intraoperative RARP steps with excellent consensus. This final inventory will be used to develop a valid and psychometrically sound intraoperative assessment tool for use during RARP training and evaluation, with the aim of increasing competency of all trainees.

Incidence, Characteristics and Implications of Thromboembolic Events in Patients with Muscle Invasive Urothelial Carcinoma of the Bladder Undergoing Neoadjuvant Chemotherapy.

PURPOSE: Neoadjuvant chemotherapy and pelvic surgery are significant risk factors for thromboembolic events. Our study objectives were to investigate the timing, incidence and characteristics of thromboembolic events during and after neoadjuvant chemotherapy and subsequent radical cystectomy in patients with muscle invasive bladder cancer. MATERIALS AND METHODS: We performed a multi-institutional retrospective analysis of 761 patients who underwent neoadjuvant chemotherapy and radical cystectomy for muscle invasive bladder cancer from 2002 to 2014. Median followup from diagnosis was 21.4 months (range 3 to 272). Patient characteristics included the Khorana score, and the incidence and timing of thromboembolic events (before vs after radical cystectomy). Survival was calculated using the Kaplan-Meier method. The log rank test and multivariable Cox proportional hazards regression were used to compare survival between patients with vs without thromboembolic events. RESULTS: The Khorana score indicated an intermediate thromboembolic event risk in 88% of patients. The overall incidence of thromboembolic events in patients undergoing neoadjuvant chemotherapy was 14% with a wide variation of 5% to 32% among institutions. Patients with thromboembolic events were older (67.6 vs 64.6 years, p = 0.02) and received a longer neoadjuvant chemotherapy course (10.9 vs 9.7 weeks, p = 0.01) compared to patients without a thromboembolic event. Of the thromboembolic events 58% developed preoperatively and 72% were symptomatic. On multivariable regression analysis the development of a thromboembolic event was not significantly associated with decreased overall survival. However, pathological stage and a high Khorana score were adverse risk factors for overall survival. CONCLUSIONS: Thromboembolic events are common in patients with muscle invasive bladder cancer who undergo neoadjuvant chemotherapy before and after radical cystectomy. Our results suggest that a prospective trial of thromboembolic event prophylaxis during neoadjuvant chemotherapy is warranted.

How I do it: Prescribing abiraterone acetate for metastatic castration resistant prostate cancer.

Abiraterone acetate (AA) is a selective irreversible inhibitor of CYP 17, a key enzyme in androgen biosynthesis. The efficacy and safety of AA in improving survival and quality of life in metastatic castration resistant prostate cancer (mCRPC) has been demonstrated in two landmark clinical trials (COU-AA-301 and COU-AA-302). This article will review the rationale, pharmacology, clinical indications and contraindications, administration, and adverse effects of AA administration in mCRPC.

Is there a role for anterior zone sampling as part of saturation trans-rectal ultrasound guided prostate biopsy?

BACKGROUND: The prostatic anterior zone (AZ) is not targeted routinely by TRUS guided prostate biopsy (TRUS-Pbx). MRI is an accurate diagnostic tool for AZ tumors, but is often unavailable due to cost or system restrictions. We examined the diagnostic yield of office based AZ TRUS-Pbx. METHODS: 127 men at risk for AZ tumors were studied: Patients with elevated PSA and previous extended negative TRUS-Pbx (group 1, n = 78) and actively surveyed low risk prostate cancer patients (group 2, n = 49). None of the participants had a previous AZ biopsy. Biopsy template included suspicious ultrasonic areas, 16 peripheral zone (PZ), 4 transitional zone (TZ) and 6 AZ cores. All biopsies were performed by a single urologist under local peri-prostatic anaesthetic, using the B-K Medical US System, an end-firing probe 4-12 MHZ and 18 ga/25 cm needle. All samples were reviewed by a single specialized uro-pathologist. Multivariate analysis was used to detect predictors for AZ tumors accounting for age, PSA, PSA density, prostate volume, BMI, and number of previous biopsies. RESULTS: Median PSA was 10.4 (group 1) and 7.3 (group 2). Age (63.9, 64.5), number of previous biopsies (1.5) and cores (17.8, 21.3) and prostate volume (56.4 cc, 51 cc) were similar for both groups. The overall diagnostic yield was 34.6% (group 1) and 85.7% (group 2). AZ cancers were detected in 21.8% (group 1) and 34.7% (group 2) but were rarely the only zone involved (1.3% and 4.1% respectively). Gleason ≥ 7 AZ cancers were often accompanied by equal grade PZ tumors. In multivariate analysis only prostate volume predicted for AZ tumors. Patients detected with AZ tumors had significantly smaller prostates (36.9 cc vs. 61.1 cc p < 0.001). Suspicious AZ ultrasonic findings were uncommon (6.3%). CONCLUSIONS: TRUS-Pbx AZ sampling rarely improves the diagnostic yield of extended PZ sampling in patients with elevated PSA and previous negative biopsies. In low risk prostate cancer patients who are followed by active surveillance, AZ sampling changes risk stratification in 6% but larger studies are needed to define the role of AZ sampling in this population and its correlation with prostatectomy final pathological specimens.