Multi-institutional Clinical Tool for Predicting High-risk Lesions on 3Tesla Multiparametric Prostate Magnetic Resonance Imaging.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) for prostate cancer detection without careful patient selection may lead to excessive resource utilization and costs. OBJECTIVE: To develop and validate a clinical tool for predicting the presence of high-risk lesions on mpMRI. DESIGN, SETTING, AND PARTICIPANTS: Four tertiary care centers were included in this retrospective and prospective study (BiRCH Study Collaborative). Statistical models were generated using 1269 biopsy-naive, prior negative biopsy, and active surveillance patients who underwent mpMRI. Using age, prostate-specific antigen, and prostate volume, a support vector machine model was developed for predicting the probability of harboring Prostate Imaging Reporting and Data System 4 or 5 lesions. The accuracy of future predictions was then prospectively assessed in 214 consecutive patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Receiver operating characteristic, calibration, and decision curves were generated to assess model performance. RESULTS AND LIMITATIONS: For biopsy-naïve and prior negative biopsy patients (n=811), the area under the curve (AUC) was 0.730 on internal validation. Excellent calibration and high net clinical benefit were observed. On prospective external validation at two separate institutions (n=88 and n=126), the machine learning model discriminated with AUCs of 0.740 and 0.744, respectively. The final model was developed on the Microsoft Azure Machine Learning platform (birch.azurewebsites.net). This model requires a prostate volume measurement as input. CONCLUSIONS: In patients who are naïve to biopsy or those with a prior negative biopsy, BiRCH models can be used to select patients for mpMRI. PATIENT SUMMARY: In this multicenter study, we developed and prospectively validated a calculator that can be used to predict prostate magnetic resonance imaging (MRI) results using patient age, prostate-specific antigen, and prostate volume as input. This tool can aid health care professionals and patients to make an informed decision regarding whether to get an MRI.

The role of metastatic burden in cytoreductive/consolidative radical cystectomy.

PURPOSE: To describe our institutional experience with cytoreductive/consolidative radical cystectomy (CCRC) for metastatic urothelial carcinoma (UC) and to investigate clinicopathologic features predicting prolonged cancer specific survival (CSS) following CCRC. METHODS: We performed IRB-approved review of our cystectomy database, and identified 43 patients with metastatic UC who underwent CCRC. Baseline demographics, chemotherapy regimen, clinicopathologic features, and perioperative complications were collected. Progression-free survival (PFS) and CSS were estimated from the time of CCRC. Univariate and multivariate Cox regression models were used to identify predictors of improved CSS after CCRC. RESULTS: Of the 43 patients, 32 (74.4%) had clinical evidence of distant metastases, while 11 harbored occult metastases on the surgical specimen. The most common site of metastasis was the retroperitoneal lymph nodes, found in 30 patients. Solitary metastases were found in 22 patients (51.1%). Forty-one (95%) patients received chemotherapy prior to CCRC. Disease progression was detected in 35 patients after CCRC (median PFS 5.9 months), and 34 died of metastatic cancer (median CSS 12.3 months). On multivariate analysis, patients with solitary metastases were found to have improved CSS compared to those with multiple metastases (HR 2.62, 95% CI 1.16-5.90, p = 0.02), with median CSS of 26.0 months vs. 7.9 months (p < 0.001). Median postoperative length of stay was 10 days. Overall, 56% suffered postoperative complications, including one perioperative mortality. CONCLUSIONS: CCRC is feasible in the setting of metastatic UC. Patients with solitary metastasis demonstrated longer CSS than those with multiple metastases, and should be considered candidates for future trials evaluating the role of CCRC for metastatic UC.

Perioperative venous thromboembolism in urologic oncology procedures, risk factors, and prevention.

PURPOSE OF REVIEW: Venous thromboembolism (VTE) is a common complication during the perioperative period for major urologic oncology operations. The present review focuses on the risk factors, the mechanisms of hypercoagulability in this patient population, and the timing and prevention of VTE. RECENT FINDINGS: Although the vast majority of patients undergoing major urologic oncology operations do not develop VTEs, when they do develop they can be fatal. The risk factors for VTEs are important to identify in this patient population. The timing of VTE events are also essential to understanding their prevention. Prevention focused around the perioperative period is the best way to reduce fatal complications secondary to a VTE event. SUMMARY: VTEs are common and can potentially be fatal. Prevention in high-risk patients during the most vulnerable perioperative time period should be the focus of clinical efforts to reduce VTE complications and the associated morbidity and mortality.

Secondary Tumors After Urinary Diversion.

It has been known that urinary diversions juxtaposing the urinary and intestinal tracts lead to increased incidence of secondary malignancies. Although tumorigenesis in ureterosigmoidostomies follows the typical course from adenomas to adenocarcinomas, secondary malignancies arising from isolated intestinal diversions are much more heterogeneous. Research over the last half century has unveiled patterns of incidence and progression, while also uncovering possible mechanisms driving the neoplastic changes. In this review, we summarize the current understanding of these unique tumors, with the hope that the knowledge gained may shed light on the etiologies of other cancers arising from the urinary and intestinal tracts.

Quality Improvement in Cystectomy Care with Enhanced Recovery (QUICCER) study.

OBJECTIVES: To determine if patients managed with a cystectomy enhanced recovery pathway (CERP) have improved quality of care after radical cystectomy (RC), as defined by a decrease in length of hospital stay (LOS) without an increase in complications or readmissions compared with those not managed with CERP. SUBJECTS AND METHODS: The Quality Improvement in Cystectomy Care with Enhanced Recovery (QUICCER) study was a non-randomized quasi-experimental study. Data were collected between June 2011 and April 2015. The CERP was implemented in July 2013. The primary endpoint was LOS. Secondary endpoints were quality scores, complications and readmissions. Multivariable regression was performed. Propensity score matching was carried out to further simulate randomized clinical trial conditions. A CERP quality composite score was created and evaluated with regard to adherence to CERP elements. RESULTS: The study included 79 patients managed with CERP and 121 who were not managed with CERP. After matching, there were 75 patients in the non-CERP group. The LOS was significantly different between the groups: the median LOS was 5 and 8 days for the CERP and non-CERP group, respectively (P < 0.001). Multivariable linear regression showed that any complication was the most significant predictor of total LOS at 90 days after RC. The higher the quality composite score the shorter the LOS (P < 0.001). There was no association between CERP and a greater number of complications or readmissions. CONCLUSIONS: Audited quality measures in the CERP are associated with a reduction in LOS with no increase in readmissions or complications. The CERP is important for the future improvement of peri-operative care for RC and provides an opportunity to improve the quality of care provided.

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.

The Future of Enhanced Recovery for Radical Cystectomy: Current Evidence, Barriers to Adoption, and the Next Steps.

Radical cystectomy (RC) is a complex procedure that can involve long postoperative hospital stays and complicated, burdensome recoveries. Enhanced recovery after surgery is a broad term encompassing an overall approach to perioperative management of postsurgical patients and is becoming more widely accepted for cystectomy patients. This review examines the current evidence for using enhanced recovery protocols for RC as well as current rates of adoption of enhanced recovery among urologists performing RC. We also discuss the next steps for overcoming barriers to the widespread implementation of enhanced recovery for RC.

Are we doing "better"? The discrepancy between perception and practice of enhanced recovery after cystectomy principles among urologic oncologists.

PURPOSE: The concept of enhanced recovery after surgery has been around since the 1990s when it was first introduced as a means to improve postoperative recovery of general surgical patients. In the field of urology, the uptake of enhanced recovery pathways has been slow for unclear reasons. Recently, interest in enhanced recovery after cystectomy (ERAC) has been increasing, but the current urologic oncology practice patterns remain unclear. In this study, we investigate modern perioperative patterns of care and rates of application of ERAC principles by cystectomy surgeons. MATERIALS AND METHODS: ERAC principles were identified by reviewing urology and general surgery literature. An adapted version of The Royal College of Surgeons of England fast-track surgical principles survey was used. Preoperative education, bowel preparation avoidance, nasogastric tubes avoidance, normothermia, opioid avoidance, early ambulation, and early feeding were all practices queried with the survey. Surveys were distributed electronically to faculty of Society of Urologic Oncology fellowships with bladder cancer as a special area of interest. Additional participants were identified by recent publications on cystectomies for bladder cancer. In total, 128 surveys were e-mailed to the previously identified experts. Of these, 61 (48%) completed the survey. Responses were classified as congruent with commonly accepted ERAC principles (ERAC group) or noncongruent (non-ERAC group). Chi-square test was used for categorical variables and Wilcoxon-Mann-Whitney for ordinal variables. RESULTS: Of the urologists who classified themselves in the ERAC group (64%), the average length of stay was reported to be 6.1 days and 7.2 days in the non-ERAC group (P = 0.02). Only 20% were practicing all interventions. Among the ERAC surgeons 1, 2 or 3 of the interventions were omitted by 13%, 25%, and 23% of the respondents, respectively. Significant differences were found between the self-reported ERAC adopters and nonadopters in the use of bowel preparation (P = 0.01), nasogastric tubes (P = 0.007), alvimopan (P<0.001), and the average day of advancement to clear liquids (P<0.001). There were no differences in postoperative ambulation and opiate or nonsteroidal anti-inflammatory drug use. Lack of convincing evidence was cited as the main reason for the non-ERAC group not yet implementing an ERAC pathway followed by lack of resource availability. CONCLUSION: Urologists who consider themselves as practicing ERAC do not universally practice all of the pathway tenets. A significant gap exists between self-perception and practice of enhanced recovery. ERAC implementation is challenging but represents a significant opportunity to improve the quality of care for cystectomy patients.

Cost-Effectiveness of Extended Duration Venous Thromboembolism Prophylaxis in High Risk Urological Oncology Surgical Patients.

INTRODUCTION: Major urological oncology surgery carries a significant risk of postoperative venous thromboembolism events, resulting in major morbidity, possible mortality and substantial costs. We determined the incremental cost-effectiveness for in-hospital and low molecular weight heparin extended duration prophylaxis for venous thromboembolism prevention in patients at high risk following major urological oncology surgery. METHODS: A decision analytical model was developed to compare inpatient hospital costs, venous thromboembolism incidence within 365 days and outcomes associated with extended duration prophylaxis for 4 prophylaxis strategies. The 4 strategies grouped by protocol adherence were 1) per protocol in-hospital prophylaxis with extended duration prophylaxis in 88 cases, 2) per protocol in-hospital prophylaxis without extended duration prophylaxis in 42, 3) not per protocol in-hospital prophylaxis with extended duration prophylaxis in 80 and 4) not per protocol in-hospital prophylaxis without extended duration prophylaxis in 99. Between June 2011 and March 2014, 707 patients underwent major urological oncology surgery. Using the Caprini risk score 309 patients were at high risk. RESULTS: The group 1 strategy was the dominant (most effective) strategy when the probability of preventing venous thromboembolism with extended duration prophylaxis was greater than 80%. Effectiveness for preventing venous thromboembolism was most influenced by the group 2 venous thromboembolism incidence rate. Costs in group 1 vs group 2 were calculated at $1,531 vs $1,563. Using the incremental cost-effectiveness ratio to compare groups 1 and 2, which were the 2 groups with the closest costs and effectiveness, an overall cost savings of $1,390 per patient was seen. CONCLUSIONS: Compared with competing strategies in-hospital and extended duration prophylaxis for venous thromboembolism prevention in patients at high risk undergoing major urological oncology surgery is effective to prevent venous thromboembolism and it is cost saving.

Effectiveness and safety of extended-duration prophylaxis for venous thromboembolism in major urologic oncology surgery.

PURPOSE: To examine the association between extended-duration prophylaxis (EDP), low-molecular-weight heparin prophylaxis for 28 days after surgery for urologic cancer in patients at high risk of developing a venous thromboembolism (VTE), the risk of VTE, and the complications resulting from VTE prophylaxis. MATERIALS AND METHODS: The cohort included 332 patients at high risk for VTE who were surgically treated for urologic cancer from June 2011 to June 2014. Adherence to VTE prophylaxis protocol, VTEs, and complications within 365 days from surgery were tracked. Patients were grouped as follows: (1) per protocol in-hospital prophylaxis with EDP (n = 107), (2) per protocol in-hospital prophylaxis without EDP (n = 42), (3) not per protocol in-hospital prophylaxis with EDP (n = 83), and (4) not per protocol in-hospital prophylaxis without EDP (n = 100). The risk of VTE was compared between the 4 groups using the Cox model, with adjustment for baseline risk factors. RESULTS: The rates of VTEs and median times to VTE were 7% and 58 days in group 1, 17% and 44 days in group 2, 17% and 46 days in group 3, and 21% and 15 days in group 4, respectively. Adjusted hazard ratios (HR) for VTE were HR = 0.27 (95% CI: 0.11-0.70) for groups 1 vs. 4; HR = 0.66 (95% CI: 0.25-1.60) for groups 2 vs. 4; and HR = 0.66 (95% CI: 0.29-1.26) for groups 3 vs. 4 with a trend of P = 0.002. The incidence of complications from VTE prophylaxis was not significantly different between the groups, with a rate of 8% in group 1, 17% in group 2, 6% in group 3, and 12% in group 4 (P = 0.33). CONCLUSIONS: In high-risk urologic cancer surgery patients, a clinical protocol, with perioperative and EDP, is safe and effective in reducing VTE events.

Bladder cancer incidence and mortality in patients treated with radiation for uterine cancer.

OBJECTIVE: To estimate the effect of radiation therapy (RT) administered for uterine cancer (UtC) on bladder cancer (BC) incidence, tumour characteristics at presentation, and mortality. PATIENTS AND METHODS: In this retrospective cohort study, records of 56 681 patients diagnosed with UtC as their first primary malignancy during 1980-2005 were obtained from the Surveillance, Epidemiology and End-Results (SEER) database. Follow-up for incident BC ended on 31 December 2008. Occurrences of BC diagnoses and BC deaths in patients with UtC managed with or without RT were summarised with counts and person-time incidence rates (counts divided by person-years of observation). Age adjustment of rates was performed by direct standardisation. Incident BC cases were described in terms of histological types, grades and stages. RESULTS: With a mean follow-up of 15 years, BC was diagnosed in 146 (0.93%) of 15 726 patients with UtC managed with RT, and in 197 (0.48%) of 40 955 patients with UtC managed without RT, with an age-adjusted rate ratio of 2.0 (95% confidence interval [CI] 1.6-2.5). Fatal BC occurred in 39 (0.25%) and 36 (0.09%) of patients with UtC managed with vs without RT, respectively, with an age-adjusted rate ratio of 2.9 (95% CI 1.8-4.6). Incident BC cases diagnosed in patients with UtC managed with vs without RT had similar distributions of histological types, grades, and stages. CONCLUSIONS: Use of RT for UtC is associated with increased BC incidence and mortality later in life. Heightened awareness should help identify women with new voiding symptoms or haematuria, all of which should be fully evaluated.