Automated Identification of Key Steps in Robotic-Assisted Radical Prostatectomy Using Artificial Intelligence.

PURPOSE: The widespread use of minimally invasive surgery generates vast amounts of potentially useful data in the form of surgical video. However, raw video footage is often unstructured and unlabeled, thereby limiting its use. We developed a novel computer-vision algorithm for automated identification and labeling of surgical steps during robotic-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Surgical videos from RARP were manually annotated by a team of image annotators under the supervision of 2 urologic oncologists. Full-length surgical videos were labeled to identify all steps of surgery. These manually annotated videos were then utilized to train a computer vision algorithm to perform automated video annotation of RARP surgical video. Accuracy of automated video annotation was determined by comparing to manual human annotations as the reference standard. RESULTS: A total of 474 full-length RARP videos (median 149 minutes; IQR 81 minutes) were manually annotated with surgical steps. Of these, 292 cases served as a training dataset for algorithm development, 69 cases were used for internal validation, and 113 were used as a separate testing cohort for evaluating algorithm accuracy. Concordance between artificial intelligence‒enabled automated video analysis and manual human video annotation was 92.8%. Algorithm accuracy was highest for the vesicourethral anastomosis step (97.3%) and lowest for the final inspection and extraction step (76.8%). CONCLUSIONS: We developed a fully automated artificial intelligence tool for annotation of RARP surgical video. Automated surgical video analysis has immediate practical applications in surgeon video review, surgical training and education, quality and safety benchmarking, medical billing and documentation, and operating room logistics.

Vesicourethral Anastomotic Stenosis Following Radical Prostatectomy: Risk Factors, Natural History, and Treatment Outcomes.

PURPOSE: Vesicourethral anastomotic stenosis after radical prostatectomy is a complication with significant adverse quality-of-life implications. Herein, we identify groups at risk for vesicourethral anastomotic stenosis and further characterize the natural history and treatment patterns. MATERIALS AND METHODS: Years 1987-2013 of a prospectively maintained radical prostatectomy registry were queried for patients with the diagnosis of vesicourethral anastomotic stenosis, defined as symptomatic and inability to pass a 17F cystoscope. Patients with follow-up less than 1 year, preoperative anterior urethral stricture, transurethral resection of prostate, prior pelvic radiotherapy, and metastatic disease were excluded. Logistic regression was performed to identify predictors of vesicourethral anastomotic stenosis. Functional outcomes were characterized. RESULTS: Out of 17,904 men, 851 (4.8%) developed vesicourethral anastomotic stenosis at a median of 3.4 months. Multivariable logistic regression identified associations with vesicourethral anastomotic stenosis including adjuvant radiation, BMI, prostate volume, urine leak, blood transfusion, and nonnerve-sparing techniques. Robotic approach (OR 0.39, P < .01) and complete nerve sparing (OR 0.63, P < .01) were associated with reduced vesicourethral anastomotic stenosis formation. Vesicourethral anastomotic stenosis was independently associated with 1 or more incontinence pads/d at 1 year (OR 1.76, P < .001). Of the patients treated for vesicourethral anastomotic stenosis, 82% underwent endoscopic dilation. The 1- and 5-year vesicourethral anastomotic stenosis retreatment rates were 34% and 42%, respectively. CONCLUSIONS: Patient-related factors, surgical technique, and perioperative morbidity influence the risk of vesicourethral anastomotic stenosis after radical prostatectomy. Ultimately, vesicourethral anastomotic stenosis is independently associated with increased risk of urinary incontinence. Endoscopic management is temporizing for most men, with a high rate of retreatment by 5 years.

Intraoperative Blood Transfusion Is Associated With Increased Risk of Venous Thromboembolism After Radical Cystectomy.

PURPOSE: Our objective was to examine whether perioperative blood transfusion is associated with venous thromboembolism following radical cystectomy adjusting for both patient- and disease-related factors. MATERIALS AND METHODS: Patients who underwent radical cystectomy for bladder cancer from 1980-2020 were identified in the Mayo Clinic cystectomy registry. Blood transfusion during the initial postoperative hospitalization was analyzed as a 3-tiered variable: no transfusion, postoperative transfusion alone, or intraoperative with or without postoperative transfusion. The primary outcome was venous thromboembolism within 90 days of radical cystectomy. Associations between clinicopathological variables and 90-day venous thromboembolism were assessed using multivariable logistic regression, with transfusion analyzed as both a categorical and a continuous variable. RESULTS: A total of 3,755 radical cystectomy patients were identified, of whom 162 (4.3%) experienced a venous thromboembolism within 90 days of radical cystectomy. Overall, 2,112 patients (56%) received a median of 1 (IQR: 0-3) unit of blood transfusion, including 811 (38%) with intraoperative transfusion only, 572 (27%) with postoperative transfusion only, and 729 (35%) with intraoperative and postoperative transfusion. On multivariable analysis, intraoperative with or without postoperative blood transfusion was associated with a significantly increased risk of venous thromboembolism (adjusted OR 1.73, 95% CI 1.17-2.56, P = .002). Moreover, when analyzed as a continuous variable, each unit of blood transfused intraoperatively was associated with 7% higher odds of venous thromboembolism (adjusted OR 1.07, 95% CI 1.01-1.13, P = .03). CONCLUSIONS: Intraoperative blood transfusion was significantly associated with venous thromboembolism within 90 days of radical cystectomy. To ensure optimal perioperative outcomes, continued effort to limit blood transfusion in radical cystectomy patients is warranted.

Efficacy of RestoreX after prostatectomy: open-label phase of a randomized controlled trial.

OBJECTIVE: To report open-label phase data from a recent randomized controlled trial (RCT), after previous data from that study showed improved penile length and erectile function among post-prostatectomy men treated with Restorex penile traction therapy (RxPTT). MATERIALS AND METHODS: An RCT (NCT05244486) was performed to evaluate RxPTT vs no treatment (Tx) for 5 months, which was followed by a 3-month open-label phase. Men were stratified based on as-treated data: Group 1 = No Tx; Group 2 = No Tx → Tx; Group 3 = Tx → No Tx; Group 4 = Tx. Assessments included stretched penile length and standardized (International Index of Erectile Function [IIEF]) and non-standardized questionnaires. RESULTS: A total of 82 men were enrolled (mean age 58.6 years) with 9-month data available in 45 of the men. Baseline characteristics were similar among the cohorts. Comparing Group 1 and Group 4 (respectively), notable differences included: IIEF Erectile Function domain (IIEF-EF) score (-8 vs -0.5; P = 0.16), penile length (-0.1 vs +1.7 cm; P < 0.01), intracavernosal injection use (86% vs 14%; P < 0.01), Sexual Encounter Profile (SEP) Question 2 (50% vs 100%; P < 0.01), SEP Question 3 (33% vs 100%; P < 0.01). Men who crossed over to Tx (Group 2) failed to achieve equivalent improvements in length (+0.5 cm) or sexual function (IIEF-EF score -6) compared to men treated early (Groups 3 and 4). Those who crossed over to no treatment after initial treatment (Group 3) experienced preserved length (+1.8 cm), and erectile function (IIEF-EF score +0) despite therapy discontinuation. CONCLUSIONS: Use of RxPTT beginning 1 month post-prostatectomy results in improved penile length and erectile function, with benefits maintained after discontinuing therapy. If confirmed, these results represent the first postoperative therapy shown in a RCT to improve erectile function post-prostatectomy. External validation is warranted.

Role of Lymphadenectomy during Radical Cystectomy for Nonmuscle-Invasive Bladder Cancer: Results from a Multi-Institutional Experience.

PURPOSE: While lymph node dissection (LND) at radical cystectomy (RC) for muscle-invasive bladder cancer has been studied extensively, the role of LND for nonmuscle-invasive bladder cancer (NMIBC) remains incompletely defined. Herein, we aim to assess the association between extent of LND during RC for NMIBC and local pelvic recurrence-free survival (LPRS), cancer-specific survival (CSS) and overall survival (OS). MATERIALS AND METHODS: A multi-institutional retrospective review was performed of patients with NMIBC undergoing RC at 3 large tertiary referral centers. To identify a threshold for lymph node yield (LNY) to optimize LPRS, CSS and OS, separate Cox regression models were developed for each possible LNY threshold. Model performance including Q-statistics and hazard ratios (HRs) were used to identify optimal LNY thresholds. RESULTS: A total of 1,647 patients underwent RC for NMIBC, with a median LNY of 15 (quartiles 9,23). Model performance curves suggested LNY of 10 and 20 to optimize LPRS and CSS/OS, respectively. On multivariable regression, LNY >10 was associated with lower risk of LPR compared to LNY ≤10 (HR 0.63, 95% CI 0.42-0.93, p=0.02). Similarly, LNY >20 was associated with improved CSS (HR 0.67, 95% CI 0.52-0.87, p=0.002) and OS (HR 0.75, 95% CI 0.64-0.88, p <0.001) compared to LNY ≤20. Similar results were observed in the cT1 and cTis subgroups. CONCLUSIONS: Greater extent of LND during RC for NMIBC is associated with improved LPRS, CSS and OS, supporting the inclusion of LND during RC for NMIBC, particularly among patients with cTis or cT1 disease. Future prospective studies are warranted to assess the ideal anatomical template of LND in NMIBC.

Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer.

INTRODUCTION AND OBJECTIVES: PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. This study aims to investigate the association of PD-L1 and B7-H3 tumor expression with oncological outcomes in patients who underwent radical cystectomy (RC) and received subsequent adjuvant chemotherapy. MATERIALS AND METHODS: Immunohistochemistry was performed on paraffin-embedded sections from bladder and lymph node specimens of 81 patients who had RC for bladder cancer. PD-L1 and B7-H3 expression on tumor cells was assessed by immunohistochemistry in both primary tumors and lymph node specimens. Association with clinicopathologic outcomes was determined using Fisher's exact test and postoperative survival using Kaplan-Meier survival curves and Cox regression model. RESULTS: B7-H3 expression in cystectomy specimens was more common than PD-L1 expression (72.8% vs. 35.8%). For both markers, no association was found with pathologic tumor stage, lymph node (LN) status, and histological subtype. Similar findings were observed for double-positive tumors (PD-L1+B7-H3+). Concordance between the primary tumor and patient-matched lymph nodes was found in 76.2% and 54.1% of patients for PD-L1 and B7-H3, respectively. PD-L1 tumor expression was not associated with oncologic outcomes. However, B7-H3 expression was associated with recurrence-free survival (HR: 2.38, 95% CI 1.06-5.31, p = 0.035) and cancer-specific survival (HR: 2.67, 95% CI 1.18-6.04, p = 0.019). CONCLUSIONS: In our single institutional study, B7-H3 is highly expressed in patients with UC treated with adjuvant chemotherapy and it was associated with decreased recurrence-free survival and cancer-specific survival. Pending further validation in larger cohorts, B7-H3 expression may function as a predictor of response to adjuvant chemotherapy and thus be useful in patient and regimen selection.

Efficacy of a Novel Penile Traction Device in Improving Penile Length and Erectile Function Post Prostatectomy: Results from a Single-Center Randomized, Controlled Trial.

PURPOSE: RestoreX is a novel penile traction therapy device, with randomized, controlled data demonstrating improvements in penile length and erectile function after 30 to 90 minutes of daily use in men with Peyronie's disease. We sought to determine if similar improvements could be achieved post prostatectomy. MATERIALS AND METHODS: Men post prostatectomy were randomly assigned to control or one of 2 penile traction therapy protocols for 6 months, followed by a 3-month open-label phase. The current study presents data from the randomized phase. The primary outcome was changes in stretched penile length; secondary outcomes were changes in International Index of Erectile Function (IIEF) scores, adverse events, satisfaction and subjective measures. RESULTS: In all, 82 men (mean age 58.6 years) were randomized, with 6-month data available in 25 controls and 30 penile traction therapy cases. At 6 months, penile traction therapy achieved greater improvements/preservation of penile length (+1.6 vs +0.3 cm, p <0.01), erectile function (IIEF-Erectile Function +0 vs -6.5, p=0.03), intercourse satisfaction (IIEF-Intercourse Satisfaction +1 vs -3.5, p <0.01) and overall sexual satisfaction (IIEF-Overall Sexual Satisfaction 0 vs -3, p <0.01). Erectogenic therapy use was lower in penile traction therapy men (phosphodiesterase-5 inhibitors 86% vs 94%, p=0.44; intracavernosal injections 19% vs 50%, p <0.05). More penile traction therapy men reported satisfaction or improvement in penile length than controls. Adverse events were transient and mild; 87% would choose to repeat therapy, and 93% would recommend it to others. CONCLUSIONS: The use of a novel penile traction therapy device results in significant improvements in objective and subjective penile length post prostatectomy and measures of erectile function, intercourse satisfaction and overall sexual satisfaction. External validation is warranted.

The Impact of Upper Tract Urothelial Carcinoma Diagnostic Modality on Intravesical Recurrence after Radical Nephroureterectomy: A Single Institution Series and Updated Meta-Analysis.

PURPOSE: Diagnostic ureteroscopic biopsy for upper tract urothelial carcinoma (UTUC) has been hypothesized to increase intravesical recurrence of urothelial carcinoma after radical nephroureterectomy (RNU). Moreover, the impact of ureteroscopy without biopsy or percutaneous biopsy on intravesical recurrence remains unknown. Herein, we compared post-RNU intravesical recurrences across UTUC diagnostic modalities. MATERIALS AND METHODS: Patients undergoing RNU at our institution between 1995 and 2019 were categorized by UTUC diagnostic modality: 1) no ureteroscopy or percutaneous biopsy; 2) percutaneous biopsy; 3) ureteroscopy without biopsy; 4) ureteroscopic biopsy. Intravesical recurrences were compared using Kaplan-Meier analyses and Cox-proportional hazard models. Results of group 4 vs 1 were pooled with the literature using a fixed effects meta-analysis. RESULTS: In a cohort of 834 RNU patients, 210 (25.2%) had undergone no ureteroscopy, 57 (6.6%) percutaneous biopsy, 125 (15.0%) ureteroscopy without biopsy, and 442 (53.0%) ureteroscopic biopsy. Two-year intravesical recurrence rates were 15.0%, 12.7%, 18.4%, and 21.9% for groups 1 through 4, respectively (p=0.09). Multivariable analysis found that group 4 had increased intravesical recurrences (HR 1.40, p=0.04) relative to group 1 while group 2 (HR 1.07, p=0.87) and group 3 (HR 1.15, p=0.54) did not. Group 4 remained associated with intravesical recurrence on subset analyses accounting for post-RNU surveillance cystoscopy frequency. On meta-analysis including 11 other series, ureteroscopic biopsy was associated with intravesical recurrence (HR 1.47, p <0.01). CONCLUSIONS: Ureteroscopic biopsy before RNU, but not percutaneous biopsy or ureteroscopy without biopsy, was associated with increased intravesical recurrence. Clinical trials of intravesical chemotherapy after ureteroscopic biopsy are warranted to reduce intravesical recurrences.

A Contemporary Analysis of Urethral Recurrence following Radical Cystectomy.

PURPOSE: Oncologic outcomes following urethral recurrence (UR) remain incompletely described, with reports limited by small cohort sizes. We evaluated risk factors for UR as well as cancer-specific survival (CSS) and overall survival (OS) among patients with UR. MATERIALS AND METHODS: We reviewed our institutional radical cystectomy (RC) registry to identify patients with UR. Cox proportional hazards regression was used to assess risk factors for UR. Kaplan-Meier and Cox models were used to assess the relationship between UR and CSS/OS as well as to compare outcomes following symptomatic vs asymptomatic presentation of UR. RESULTS: Overall, 2,930 patients underwent RC from 1980 to 2018, with a median postoperative followup of 7.1 years (IQR 2.8-13.1), of whom 144 (4.9%) were subsequently diagnosed with UR. Carcinoma in situ (HR 1.98, 95% CI 1.30-3.04), multifocal disease (HR 1.59, 95% CI 1.07-2.36) and prostatic urethral involvement at RC (HR 3.01, 95% CI 1.98-4.57) were associated with increased risk of UR. UR was associated with decreased CSS (HR 7.30, 95% CI 5.46-9.76) and OS (HR 1.86, 95% CI 1.54-2.24). A total of 63/144 patients were diagnosed with UR based on symptoms, while 104/144 patients with UR underwent urethrectomy. Patients with symptomatic UR had higher tumor stage at urethrectomy (≥pT2 in 13.1% vs 3.1%, p=0.007), while patients with asymptomatic UR experienced longer median CSS (12.1 vs 6.1 years) and OS (8.30 vs 4.82 years; p=0.05 for both). CONCLUSIONS: We identified pathological risk factors for UR after RC and report adverse subsequent survival outcomes for these patients. Presentation with symptomatic UR was associated with higher tumor stage and poorer prognosis, supporting a value to continued urethral surveillance after RC.

Cigarette smoking is associated with adverse pathological response and increased disease recurrence amongst patients with muscle-invasive bladder cancer treated with cisplatin-based neoadjuvant chemotherapy and radical cystectomy: a single-centre experience.

OBJECTIVE: To investigate the association between smoking status and pathological response to cisplatin-based neoadjuvant chemotherapy (NAC) and survival outcomes in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy (RC). PATIENTS AND METHODS: We reviewed 201 patients treated with NAC and RC for cT2-cT4N0M0 BC between 01/1999 and 01/2015. Smoking status was categorised as: 'never', 'former', and 'current' smoker. Pathological response to NAC was defined as: complete (ypT0N0), partial (ypTis/Ta/T1, N0), and no response (ypT2-4 or ypN+). Clinicopathological characteristics were analysed according to smoking status. Logistic regression analyses tested the association between smoking status and pathological response to NAC. Cox regression analyses tested risk factors associated with recurrence, overall (OM) and cancer-specific mortality (CSM). RESULTS: Overall, there were 58 (28.9%) never smokers, 87 (43.3%) former smokers, and 56 (27.9%) current smokers. No response to NAC was more frequently noted in current smokers (73.2%; P = 0.007). Former smoker (odds ratio [OR] 2.28; P = 0.024) and current smoker statuses (OR 4.52; P < 0.001) were significantly associated with no response to NAC, after adjusting for age, gender, Charlson Comorbidity Index, and clinical stage. Similarly, current smoking status (hazard ratio [HR] 2.14; P = 0.03) and extravesical pathological tumour stage (HR 3.31; P < 0.001) were independently associated with an increased risk of recurrence after RC. CONCLUSION: Cigarette smoking was significantly associated with adverse pathological response to cisplatin-based NAC in patients with MIBC treated with RC. Current smokers were at significantly higher risk of disease recurrence as compared to former and never smokers.

A risk-stratified approach to neoadjuvant chemotherapy in muscle-invasive bladder cancer: implications for patients classified with low-risk disease.

PURPOSE: To validate published risk criteria for informing use of neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC), and to examine outcomes of low-risk (LR) patients treated with immediate radical cystectomy (RC). METHODS: We identified 1931 patients who underwent RC for MIBC from 1980 to 2016. Patients were considered high risk (HR) with hydronephrosis, lymphovascular invasion, variant histology and/or cT3/4 disease. Kaplan-Meier survival estimates were compared to patients classified as LR, and logistic regression was used to examine factors associated with pathologic downstaging. RESULTS: A total of 1025 LR and 906 HR patients were identified. Median follow-up was 6.3 years (IQR 2.6-12), during which time 1321 (68%) patients died, 753 (39%) from bladder cancer. HR patients had significantly lower 5-year CSS than LR patients (50% vs. 68%, p = 0.001). Of 561 cisplatin-eligible LR patients treated with RC without NAC, 293 (52%) had pathologic non-organ confined disease; of these, 81 (14%) received adjuvant chemotherapy; 78 (14%) did not due to a perioperative event, while 134 (24%) did not due to patient/provider choice. NAC in LR patients was associated with greater odds of pT0 (OR 3.05; p < 0.001) and < pT2 (OR 2.53; p < 0.001) disease, but was not significantly associated with CSS (p = 0.31). CONCLUSIONS: Our results validate the proposed risk groups. Among LR patients treated without NAC, 52% experienced pathologic upstaging, and 14% were unable to receive adjuvant chemotherapy due to a perioperative event. These data support offering NAC to both HR and LR MIBC patients, and may be useful for patient counseling.

Clinical predictors and survival outcome of patients receiving suboptimal neoadjuvant chemotherapy and radical cystectomy for muscle-invasive bladder cancer: a single-center experience.

PURPOSE: To investigate the prevalence of and factors' association with receiving suboptimal neoadjuvant chemotherapy (NAC) and its impact on survival outcomes in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy (RC). METHODS: We reviewed 1119 patients treated with NAC and/or RC for cT2-cT4N0M0 BC. Patients were segregated into three groups: (i) suboptimal NAC (received < 3 cycles of cisplatin-based NAC or non-cisplatin-based regimen), (ii) optimal NAC and (iii) no NAC. Clinical characteristics were compared among groups. Logistic regression analyses tested the association between clinical variables and the odds of receiving suboptimal NAC. To adjust for potential baseline confounders, propensity score matching was performed. Pathologic outcomes were compared between groups and Cox regression analyses tested the risk factors associated with recurrence, overall (OM) and cancer-specific mortality (CSM). RESULTS: Before matching, 84/315 (26.6%) patients received a suboptimal NAC regimen. Lower general health status and impaired renal functions were the most significant factors associated with the administration of a suboptimal NAC. After matching, the optimal NAC group achieved higher rates of complete pathological response as compared to the suboptimal group (p = 0.03). Suboptimal NAC (HR 1.77; p = 0.015) and no NAC (HR 1.52; p = 0.03) were both associated with higher risk of recurrence and OM (HR 1.71; p = 0.02 and HR 1.61; p = 0.02) as compared to optimal NAC. CONCLUSION: One out of four MIBC patients received a suboptimal NAC regimen before RC. Receiving a suboptimal NAC regimen was associated with worse disease recurrence and survival outcomes following surgery, as compared to an optimal NAC regimen.

Impact of time from biopsy to surgery on complications, functional and oncologic outcomes following radical prostatectomy.

INTRODUCTION: To determine the impact of time from biopsy to surgery on outcomes following radical prostatectomy (RP) as the optimal interval between prostate biopsy and RP is unknown. MATERIAL AND METHODS: We identified 7, 350 men who underwent RP at our institution between 1994 and 2012 and had a prostate biopsy within one year of surgery. Patients were grouped into five time intervals for analysis: ≤ 3 weeks, 4-6 weeks, 7-12 weeks, 12-26 weeks, and > 26 weeks. Oncologic outcomes were stratified by NCCN disease risk for comparison. The associations of time interval with clinicopathologic features and survival were evaluated using multivariate logistic and Cox regression analyses. RESULTS: Median time from biopsy to surgery was 61 days (IQR 37, 84). Median followup after RP was 7.1 years (IQR 4.2, 11.7) while the overall perioperative complication rate was 19.7% (1,448/7,350). Adjusting for pre-operative variables, men waiting 12-26 weeks until RP had the highest likelihood of nerve sparing (OR: 1.45, p = 0.02) while those in the 4-6 week group had higher overall complications (OR: 1.33, p = 0.01). High risk men waiting more than 6 months had higher rates of biochemical recurrence (HR: 3.38, p = 0.05). Limitations include the retrospective design. CONCLUSIONS: Surgery in the 4-6 week time period after biopsy is associated with higher complications. There appears to be increased biochemical recurrence rates in delaying RP after biopsy, for men with both low and high risk disease.

The Association of Aspirin Use with Survival Following Radical Cystectomy.

PURPOSE: Aspirin may have antineoplastic properties through the inhibition of inflammatory cytokines that regulate cell proliferation, angiogenesis and apoptosis. In patients with nonmuscle invasive bladder cancer aspirin use has been linked to a reduced risk of recurrence. We evaluated the association of aspirin with survival following radical cystectomy. MATERIALS AND METHODS: A total of 1,061 patients underwent radical cystectomy at our institution between 2007 and 2016, of whom 461 (43%) were aspirin users at the time of surgery. Survival estimates were assessed by the Kaplan-Meier method. The Cox proportional hazards model was applied to evaluate associations between patient features and survival. RESULTS: Median followup after radical cystectomy among survivors was 4.2 years (IQR 2-6.2). During this time 442 patients died, including 331 of bladder cancer. Aspirin users were significantly older, more likely to have a history of cardiovascular disease and diabetes, and more likely to use metformin or statin (each p <0.05). Nevertheless, we found that patients who ingested a daily aspirin had significantly higher 5-year cancer specific survival (68% vs 60%, p = 0.02) and overall survival (59% vs 52%, p = 0.03) compared to nonusers. Moreover, after multivariable adjustment aspirin use remained independently associated with lower cancer specific mortality (HR 0.64, 95% CI 0.45-0.89, p = 0.01) as well as all cause mortality (HR 0.70, 95% CI 0.53-0.93, p = 0.02) but not with distant metastasis (p >0.05). CONCLUSIONS: Daily aspirin use was associated with significantly improved survival outcomes following radical cystectomy. Further research is warranted to evaluate the potential underlying biological mechanisms and investigate causality.

Extravesical robotic ureteral reimplantation for ureterovaginal fistula.

INTRODUCTION: We present a video describing the technical considerations for performing an extravesical robotic ureteral reimplantation. METHODS: A 55-year old woman presented with urinary incontinence secondary to a ureterovaginal fistula after robotic-assisted hysterectomy. After failure of more conservative measures, she proceeded to a robotic ureteral reimplantation. Following port placement, the ureter is identified at the level of the iliac vessels and dissected circumferentially. The ureter is dissected free to the level of the ureterovaginal fistula, transected, and the distal remnant ligated. The ureter is spatulated, a cystotomy created, and a running anastomosis with mucosa-to-mucosa apposition performed over a stent. Care is taken to ensure it is tension free. The integrity of the anastomosis is tested with retrograde filling of the bladder. Postoperatively, a drainage catheter is left to allow for adequate healing. Follow-up imaging is performed to ensure a patent anastomosis. RESULTS: The patient had an uncomplicated postoperative course. A cystogram showed adequate healing at 10 days, and the stent was removed at 6 weeks. A follow-up renal ultrasound 6 weeks later showed no hydronephrosis. CONCLUSIONS: Extravesical robotic ureteral reimplantation is a useful technique for managing ureterovaginal fistula; here we highlight pertinent technical considerations.

Vaginal cuff recurrence after radical cystectomy: an under - studied site of bladder cancer relapse.

INTRODUCTION: Vaginal cuff recurrence of tumor following radical cystectomy is a rare site of disease recurrence, however it has never been specifically studied. The aim of the study is to evaluate incidence, risk factors, and long-term oncologic outcomes of vaginal cuff recurrence in a cohort of female patients treated with radical cystectomy for invasive urothelial carcinoma of the bladder. MATERIALS AND METHODS: From 1985 to 2012, a prospectively maintained institutional bladder cancer registry was queried for vaginal cuff recurrence post radical cystectomy. Overall mortality and cancer-specific mortality were reported using the Kaplan-Meier method for patients with vaginal cuff recurrence, recurrence at another local or distant site, and those without evidence of recurrence. Comparisons were performed using the log-rank test. Cox proportional hazards regression model was performed to assess predictors of vaginal cuff recurrence. RESULTS: From 469 women treated with radical cystectomy for bladder cancer, 34 patients (7.3%) developed vaginal cuff recurrence, 130 patients (27.7%) had recurrence involving either a local or distant site, and 305 patients (65%) had no evidence of recurrence. The 5-year overall mortality-free survival rate was 32.4% for vaginal cuff recurrence, but 25.0% for other sites of recurrence. Cancer-specific mortality-free survival rate was 32.4% for vaginal cuff recurrence, and 30.3% for the other sites of recurrence. Multivariate Cox proportional hazards regression analysis demonstrated that the presence of tumor in posterior location at radical cystectomy (Hazard Ratio [HR], 0.353 [95% CI, 0.159-0.783]) and anterior vaginectomy, compared to no vaginectomy (HR, 2.595 [95% CI, 1.077-6.249]) were independently associated with vaginal cuff recurrence. CONCLUSION: Anterior vaginectomy, despite our best attempts, is perhaps not sufficient to prevent vaginal cuff recurrence. Therefore, follow-up evaluation is essential, and further studies are necessary to address the optimal approach for initial management. Patient Summary: Although vaginal cuff recurrence is an unusual site of recurrence, careful evaluation is needed before cystectomy and during follow-up to identify patients at risk.

Independent Validation of the American Joint Committee on Cancer 8th Edition Prostate Cancer Staging Classification.

PURPOSE: We sought to independently validate the AJCC (American Joint Committee on Cancer) 8th edition prostate cancer staging classification, which includes the elimination of pT2 subcategories and the reclassification of patients with prostate specific antigen 20 ng/ml or greater and Gleason Grade Group 5 as stage groups III-A and III-C, respectively. MATERIALS AND METHODS: We identified 13,839 men who underwent radical prostatectomy at Mayo Clinic between 1987 and 2011 from our institutional registry. Outcomes included biochemical recurrence-free, metastasis-free and cancer specific survival. Kaplan-Meier analyses and Cox regression models with the c-index were used. RESULTS: Median followup was 10.5 years (IQR 7.1-15.3). Among patients with pT2 prostate cancer the subclassification demonstrated limited discrimination for biochemical recurrence-free, metastasis-free and cancer specific survival (c-index 0.531, 0.545 and 0.525, respectively). At the same time patients with 7th edition stage group II prostate cancer and prostate specific antigen 20 ng/ml or greater had significantly worse 15-year biochemical recurrence-free survival (42.2% vs 58.8%), metastasis-free survival (78.2% vs 88.8%) and cancer specific survival (88.0% vs 94.4%, all p <0.001) than patients with 7th edition stage group II prostate cancer and prostate specific antigen less than 20 ng/ml. However, patients with 7th edition stage group II prostate cancer and prostate specific antigen 20 ng/ml or greater had significantly better 15-year biochemical recurrence-free survival (42.2% vs 31.3%, p = 0.007), metastasis-free survival (78.2% vs 68.0%, p <0.001) and cancer specific survival (88.0% vs 83.4%, p = 0.01) than patients with 7th edition stage group III. Also, patients with 7th edition stage group II prostate cancer and Gleason Grade Group 5 had significantly worse 15-year biochemical recurrence-free survival (37.1% vs 57.9%, p <0.001), metastasis-free survival (63.8% vs 88.5%, p <0.001) and cancer specific survival (73.0% vs 94.3%, p <0.001) than patients with 7th edition stage group II prostate cancer and Gleason Grade Group 1-4 as well as worse 15-year cancer specific survival (73.0% vs 83.4%, p = 0.005) than patients with 7th edition stage group III prostate cancer. CONCLUSIONS: Our data support the changes in the new AJCC classification.

Impact of Radical Prostatectomy on Long-Term Oncologic Outcomes in a Matched Cohort of Men with Pathological Node Positive Prostate Cancer Managed by Castration.

PURPOSE: Long-term data supporting the role of primary tumor resection in node positive prostate cancer are lacking. We evaluated the impact of adding radical retropubic prostatectomy to surgical castration on long-term oncologic outcomes in pathological node positive prostate cancer. MATERIALS AND METHODS: We identified men who underwent pelvic lymphadenectomy and orchiectomy within 90 days for pathological node positive prostate cancer from 1966 to 1995. Men treated with radical retropubic prostatectomy in addition to orchiectomy were matched 1:1 to men who underwent orchiectomy alone based on age, year of surgery, clinical grade, clinical T stage, number of positive nodes and preoperative serum prostate specific antigen, the latter from 1987 and thereafter. Kaplan-Meier and Cox regression analyses were done to compare cancer specific and overall survival. RESULTS: The matched cohort included 158 men with 79 in each group. Of men who underwent orchiectomy alone 76 died, including 60 of prostate cancer. Of patients treated with radical retropubic prostatectomy plus orchiectomy 70 died, including 28 of prostate cancer. On Kaplan-Meier analyses prostatectomy plus orchiectomy vs orchiectomy alone was associated with prolonged cancer specific survival (at 20 years 59% vs 18%, log rank p <0.001) and overall survival (at 20 years 22% vs 9%, log rank p <0.001). In Cox models prostatectomy plus orchiectomy vs orchiectomy alone was associated with improved cancer specific survival (HR 0.28, 95% CI 0.17-0.46, p <0.001) and overall survival (HR 0.48, 95% CI 0.34-0.66, p <0.001). Findings were similar in the subset with available preoperative prostate specific antigen values. CONCLUSIONS: With lifelong followup in nearly the entire cohort, this study demonstrates that adding radical retropubic prostatectomy to surgical castration for pathological node positive prostate cancer is associated with improved cancer specific and overall survival. When technically feasible in well selected patients, aggressive locoregional resection should be considered for node positive prostate cancer as part of a multimodal approach.

Radical cystectomy for recurrent urothelial carcinoma after prior partial cystectomy: perioperative and oncologic outcomes.

PURPOSE: To evaluate perioperative and oncologic outcomes of patients undergoing radical cystectomy (RC) for recurrence of urothelial carcinoma (UC) after prior partial cystectomy (PC), and to compare these outcomes to patients undergoing primary RC. METHODS: Patients who underwent RC for recurrence of UC after prior PC were matched 1:3 to patients undergoing primary RC based on age, pathologic stage, and decade of surgery. Perioperative and oncologic outcomes were compared using Wilcoxon sign-rank test, McNemars test, the Kaplan-Meier method, and Cox proportional hazards regression analyses. RESULTS: Overall, the cohorts were well matched on clinical and pathological characteristics. No difference was noted in operative time (median 322 versus 303 min; p = 0.41), estimated blood loss (median 800 versus 700 cc, p = 0.10) or length of stay (median 9 versus 10 days; p = 0.09). Similarly, there were no differences in minor (51.7 versus 44.3%; p = 0.32) or major (10.3 versus 12.6%; p = 0.66) perioperative complications. Median follow-up after RC was 5.0 years (IQR 1.5, 13.1 years). Notably, CSS was significantly worse for patients who underwent RC after PC (10 year-46.8 versus 65.9%; p = 0.03). On multivariable analysis, prior PC remained independently associated with an increased risk of bladder cancer death (HR 2.28; 95% CI 1.17, 4.42). CONCLUSIONS: RC after PC is feasible, without significantly adverse perioperative outcomes compared to patients undergoing primary RC. However, the risk of death from bladder cancer may be higher, suggesting the need for careful patient counseling prior to PC and the consideration of such patients for adjuvant therapy after RC.