Practical Use of Self-Adjusted Nitrous Oxide During Transrectal Prostate Biopsy: A Double-Blind Randomized Controlled Trial.

PURPOSE: Transrectal prostate biopsy is a common ambulatory procedure that can result in pain and anxiety for some men. Low-dose, adjustable nitrous oxide is increasingly being used to improve experience of care for patients undergoing painful procedures. This study seeks to evaluate the efficacy and safety of low-dose (<45%) nitrous oxide, which has not been previously established for transrectal prostate biopsies. MATERIALS AND METHODS: A single-institution, prospective, double-blind, randomized, controlled trial was conducted on patients undergoing transrectal prostate biopsies. Patients were randomized to receive either self-adjusted nitrous oxide or oxygen, in addition to routine periprostatic bupivacaine block. Nitrous oxide at levels between 20% and 45% were adjusted to patients' desired effect. Patients completed a visual analog scale for anxiety, State Trait Anxiety Inventory, and a visual analog scale for pain immediately before and after biopsy. The blinded operating urologist evaluated ease of procedure. Periprocedural vitals and complications were assessed. Patients were allowed to drive home independently. RESULTS: A total of 133 patients received either nitrous oxide (66) or oxygen (67). There was no statistically significant difference in the primary anxiety end point of State Trait Anxiety Inventory or the visual analog scale for anxiety scores between the nitrous oxide and oxygen groups. However, patients in the nitrous oxide group reported significantly lower visual analog scale for pain scores compared to the oxygen group (P = .026). The operating urologists' rating of tolerance of the procedure was better in the nitrous oxide group (P = .03). There were no differences in biopsy performance time. Complications were similarly low between the 2 groups. CONCLUSIONS: Patient-adjusted nitrous oxide at levels of 20% to 45% is a safe adjunct during transrectal prostate biopsy. Although there was not an observed difference in the primary end point of anxiety, nitrous oxide was associated with lower patient-reported pain scores.

Persistent muscle-invasive bladder cancer after neoadjuvant chemotherapy: an analysis of Surveillance, Epidemiology and End Results-Medicare data.

OBJECTIVES: To evaluate whether patients with persistent muscle-invasive bladder cancer (MIBC) after undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) have worse overall survival (OS) and cancer-specific survival (CSS) than patients with similar pathology who undergo RC alone. MATERIALS AND METHODS: Using the Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified the records of patients with pT2-4N0M0 disease who underwent RC, with and without NAC, for MIBC between 2004 and 2011. To evaluate survival outcomes in those with MIBC after NAC vs patients with MIBC who underwent RC alone, we used Kaplan-Meier time-to-event analysis and Cox proportional hazard regression modelling. Landmark analysis was conducted to mitigate immortal time bias. Propensity scoring was used to decrease the risk of selection bias. RESULTS: Of the 1 886 patients with persistent pT2-4 disease at the time of RC, 1505 underwent RC alone and 381 received NAC + RC. After adjusting for confounders, the propensity-weighted risk of death from bladder cancer after diagnosis did not differ between the groups (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.72-1.08; P = 0.23); however, the risk of death from all causes was worse in the RC-alone group (HR 0.79, 95% CI0.67-0.94; P = 0.006). CONCLUSIONS: Patients who had persistent MIBC after platinum-based NAC + RC vs RC alone derived an OS benefit but not a CSS benefit from NAC. This may represent a selection bias favouring patients who were selected for NAC; however, the OS benefit was not evident in patients with persistent pT3-T4N0M0 disease. This study underscores the importance of future research investigating methods to identify patients who will respond to NAC for bladder cancer. It also highlights the need to consider adjuvant therapy in patients who have persistent MIBC after NAC.

Differences in trends in the use of robot-assisted and open radical cystectomy and changes over time in peri-operative outcomes among selected centres in North America and Europe: an international multicentre collaboration.

OBJECTIVES: To compare trends in the use of robot-assisted radical cystectomy (RARC) and changes over time in peri-operative outcomes in selected North American and European centres. MATERIALS AND METHODS: We conducted a retrospective evaluation of 2401 patients treated with open radical cystectomy (ORC) or RARC for bladder cancer at 12 centres in North America and Europe between 2006 and 2018. We used the Kruskal-Wallis and chi-squared test to evaluate differences between continuous and categorical variables. RESULTS: Overall, 49.5% of patients underwent RARC and 51.5% ORC. RARC became the most commonly performed procedure in contemporary patients, with an increase from 29% in 2006-2008 to 54% in 2015-2018 (P < 0.001). In the North American centres the use of RARC was higher than that of ORC from 2006, and remained stable over time, whereas in the European centres its use increased exponentially from 2% to 50%. In both groups patients who underwent RARC had less advanced T stages (P < 0.001), lower American Society of Anesthesiologists scores (P < 0.05), lower blood loss (P = 0.001) and shorter length of hospital stay (P < 0.05). No differences were found in early complications. Early readmission and re-operation rates were worse for patients treated with RARC in the European centres; however, when contemporary patients only were considered, the statistical significance was lost. CONCLUSION: The present study shows that the use of RARC has constantly increased since its introduction, overtaking ORC in the most contemporary series. While RARC was more frequently performed than ORC since its introduction in the North American centres and its use remained substantially stable over time, its use increased exponentially in the European centres. The different trends in use of RARC/ORC and changes over time in peri-operative outcomes between the North American and European centres can be attributed to the earlier introduction and spread of RARC in the former compared with the latter.

Racial Disparities in Active Surveillance for Prostate Cancer.

PURPOSE: Active surveillance protocols track low risk prostate cancer progression over time. However, given the lack of uniform criteria for managing low risk prostate cancer, men who qualify for active surveillance might have less intensive surveillance and, thus, experience poorer outcomes. In this study we examined racial disparities in the frequency and intensity of active surveillance between African-American and Caucasian men. MATERIALS AND METHODS: Using the linked SEER-Medicare data set we identified 13,374 men with low risk prostate cancer (defined by the D'Amico criteria) diagnosed from 2004 to 2009 and then followed through 2011. A total of 2,916 men did not receive any treatment (radiation, hormonal therapy or surgery) within 1 year after diagnosis. Men were considered to be on active surveillance if they had at least 1 of the following 3 surveillance strategies within 2 years after diagnosis, namely 1 or more prostate biopsies, 4 or more prostate specific antigen tests, and/or 4 or more visits to the doctor with prostate cancer listed as the diagnosis. To compare the frequency of active surveillance between the groups (African-American vs Caucasian) we used the chi-square test. To estimate the odds ratio of active surveillance we used multivariable logistic regression after adjusting for possible confounders such as year of diagnosis, age at diagnosis, socioeconomic status and Charlson score. RESULTS: Of the 2,916 untreated men 1,141 (39%), including 963 (37%) Caucasian men and 178 (58%) African-American men (p <0.0001), did not undergo any of the 3 surveillance strategies but instead were essentially on watchful waiting. Caucasian men (vs African-American) were more likely to be on active surveillance, with 1,646 (63.1%) vs 129 (42.0%) opting for 1 surveillance strategy (p <0.0001), 783 (30.0%) vs 50 (16.3%) opting for any 2 strategies (p <0.0001) and 193 (7.4%) vs 11 (3.6%) going through all 3 (p=0.01). On multivariable analysis African-American men had significantly lower odds of being on active surveillance than Caucasian men (OR 0.52, 95% CI 0.40-0.67). Men with more comorbidities (Charlson score 1 or greater) had significantly higher odds of being placed on active surveillance than watchful waiting (OR 1.7, 95% CI 1.46-2.12). CONCLUSIONS: Among those not treated for low risk prostate cancer, Caucasian men were placed on active surveillance more frequently than African-American men, who often defaulted to de facto watchful waiting after an initial period of active surveillance. This discrepancy raises questions about the factors favoring watchful waiting over active surveillance. Moreover, given the lack of consensus regarding the most efficient active surveillance strategy, we anticipate that racial disparities in the use of active surveillance will persist, especially in African-American patients.

Radiation-induced complex anterior urinary fistulation for prostate cancer: a retrospective multicenter study from the Trauma and Urologic Reconstruction Network of Surgeons (TURNS).

PURPOSE: To characterize anterior urinary fistulae following radiotherapy for prostate cancer. METHODS: Over 10 years, 31 men were identified to have an anterior urinary fistula. A retrospective database was created to evaluate patient demographics, presentation, diagnostic procedures, operative interventions, outcomes, and complications. Comparisons between men who underwent cystectomy versus bladder-sparing surgeries were performed. RESULTS: At a median age of 73 (interquartile range (IQR) 68.5, 79) years, presenting symptoms included as follows: pubic pain (19/31, 61%), urine drainage via fistula (10/31, 32%), or a superficial wound infection (6/31, 19%). Recent instrumentation prior to diagnosis of anterior urinary fistula was reported by 18/31 (58%) at a median of 14.9 months (IQR 7.9, 103.8) after manipulation. Anterior fistula formation was either isolated to the pubic symphysis (19/31, 61%) or the thigh (12/31, 38%). Nineteen men underwent a cystectomy, whereas 12 men underwent a fistula repair. Excluding grades 1 and 2, 30- and 90-day postoperative complications were limited to four and two men, respectively, all of whom had a grade 3 complication. At 6-month follow-up, 26/31 (84%) men reported their pain had resolved. There was one fistula recurrence managed with subsequent cystectomy. CONCLUSIONS: Complex anterior urinary fistulae to the pubic symphysis and thigh are devastating yet treatable conditions. Universally, these men have a history of radiotherapy and repeated endoscopic interventions. Surgical intervention with either cystectomy or primary repair was highly successful.

Biomonitoring DNA Adducts of Cooked Meat Carcinogens in Human Prostate by Nano Liquid Chromatography-High Resolution Tandem Mass Spectrometry: Identification of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine DNA Adduct.

Epidemiologic studies have reported an association between frequent consumption of well-done cooked meats and prostate cancer risk. However, unambiguous physiochemical markers of DNA damage from carcinogens derived from cooked meats, such as DNA adducts, have not been identified in human samples to support this paradigm. We have developed a highly sensitive nano-LC-Orbitrap MS n method to measure DNA adducts of several carcinogens originating from well-done cooked meats, tobacco smoke, and environmental pollution, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-9H-pyrido[2,3-b]indole (AαC), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), benzo[a]pyrene (B[a]P), and 4-aminobiphenyl (4-ABP). The limit of quantification (LOQ) of the major deoxyguanosine (dG) adducts of these carcinogens ranged between 1.3 and 2.2 adducts per 10 9 nucleotides per 2.5 µg of DNA assayed. The DNA adduct of PhIP, N-(deoxyguanosin-8-yl)-PhIP (dG-C8-PhIP) was identified in 11 out of 35 patients, at levels ranging from 2 to 120 adducts per 10 9 nucleotides. The dG-C8 adducts of AαC and MeIQx, and the B[a]P adduct, 10-(deoxyguanosin-N 2 -yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (dG-N 2 -B[a]PDE) were not detected in any specimen, whereas N-(deoxyguanosin-8-yl)-4-ABP (dG-C8-4-ABP) was identified in one subject (30 adducts per 10 9 nucleotides). PhIP-DNA adducts also were recovered quantitatively from formalin fixed paraffin embedded (FFPE) tissues, signifying FFPE tissues can serve as biospecimens for carcinogen DNA adduct biomarker research. Our biomarker data provide support to the epidemiological observations implicating PhIP, one of the most mass-abundant heterocyclic aromatic amines formed in well-done cooked meats, as a DNA-damaging agent that may contribute to the etiology of prostate cancer.

Forget Forgotten Stents: Review of Ureteral Stent Tracking Systems.

INTRODUCTION: Our objective was to assess existing systems for tracking ureteral stents after urological surgery and determine if these systems impact the rate of retained and forgotten stents. METHODS: We performed a scoping review using the search terms ("ureteral stents" "ureteral catheters" "nephroureteral stents" "nephroureteral catheters" or "double J stents") and ("tracking" or "lost stents" or "forgotten stents"). Two of the authors individually selected relevant articles based on title and abstract and performed full review of manuscripts and references. RESULTS: Nine different studies focusing on forgotten ureteral stents were identified. Tracking mechanisms included electronic medical records algorithms, cellphone, chat or computer-based applications. Rates of lost or delayed removal of stents in hospitals prior to using a tracking system were 0%-13%. With a tracking mechanism, the rate of lost or delayed removal was reduced to 1% or less in the studies we identified. CONCLUSIONS: Stent tracking systems successfully reduced delayed removal of ureteral stents and reduced the rates of retained stents; however, these systems are institution specific, and no universal solution is readily available. Such a solution would be beneficial for the urological community to investigate further and for industry partners to invest in.

Comparative Effectiveness in Perioperative Outcomes of Robotic versus Open Radical Cystectomy: Results from a Multicenter Contemporary Retrospective Cohort Study.

BACKGROUND: The comparative effectiveness of robotic-assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) in terms of perioperative outcomes is still a matter of debate affecting payors, physicians, and patients. OBJECTIVE: To evaluate comparative perioperative and longer-term morbidity of RARC versus ORC in a multicenter contemporary retrospective cohort of patients. DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter study included patients with bladder cancer treated with radical cystectomy at 10 academic centers between 2000 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Intraoperative outcomes including blood loss and operative time as well as postoperative outcomes including time to discharge, complication, readmission, reoperation, and mortality rates at 30 and 90 d were assessed. Multiple imputation and inverse probability of treatment weighting (IPTW) were used. IPTW-multivariable-adjusted regression and logistic analyses were performed to evaluate the associations of RARC versus ORC with perioperative outcomes at 30 and 90 d. RESULTS AND LIMITATIONS: Overall, 1887 patients (1197 RARC and 690 ORC) were included in the study. After IPTW-adjusted analysis, no differences between the groups in terms of preoperative characteristics were observed. RARC was associated with lower blood loss (p<0.001), shorter length of stay (p<0.001), and longer operative time (p=0.007). On IPTW-adjusted multivariable logistic regression analyses, no differences in terms of 30- and 90-d complications, reoperation, and mortality rates were observed. RARC was independently associated with a higher readmission rate at both 30 and 90 d. Limitations are mainly related to the retrospective nature of the study. CONCLUSIONS: While RARC was associated with less blood loss and shorter hospital stay, it also led to longer operation times and more readmissions. There were no differences in 30- and 90-d complications. Because there are no apparent differences in safety between ORC and RARC in expert centers, differences in oncologic and cost-effectiveness outcomes are likely to drive decision making regarding RARC utilization. PATIENT SUMMARY: In this study we investigated the differences between RARC and ORC in terms of perioperative outcomes. We found no difference in early and late complications. We concluded that, to date, differences in oncologic and cost-effectiveness outcomes should drive decision making regarding RARC utilization.

Open Versus Robotic Cystectomy: A Propensity Score Matched Analysis Comparing Survival Outcomes.

BACKGROUND: To assess the differential effect of robotic assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) on survival outcomes in matched analyses performed on a large multicentric cohort. METHODS: The study included 9757 patients with urothelial bladder cancer (BCa) treated in a consecutive manner at each of 25 institutions. All patients underwent radical cystectomy with bilateral pelvic lymphadenectomy. To adjust for potential selection bias, propensity score matching 2:1 was performed with two ORC patients matched to one RARC patient. The propensity-matched cohort included 1374 patients. Multivariable competing risk analyses accounting for death of other causes, tested association of surgical technique with recurrence and cancer specific mortality (CSM), before and after propensity score matching. RESULTS: Overall, 767 (7.8%) patients underwent RARC and 8990 (92.2%) ORC. The median follow-up before and after propensity matching was 81 and 102 months, respectively. In the overall population, the 3-year recurrence rates and CSM were 37% vs. 26% and 34% vs. 24% for ORC vs. RARC (all p values > 0.1), respectively. On multivariable Cox regression analyses, RARC and ORC had similar recurrence and CSM rates before and after matching (all p values > 0.1). CONCLUSIONS: Patients treated with RARC and ORC have similar survival outcomes. This data is helpful in consulting patients until long term survival outcomes of level one evidence is available.

Propensity-score-matched comparison of soft tissue surgical margins status between open and robotic-assisted radical cystectomy.

INTRODUCTION: The use of robotic-assisted radical cystectomy (RARC) is becoming more widespread. While its safety is accepted, its oncological efficacy as compared to the current standard, open radical cystectomy (ORC), remains debatable. MATERIALS AND METHODS: The aim of this study is to compare the rates of positive soft tissue surgical margins (STSM), between patients treated with RARC or ORC, using a large contemporaneous collaborative database. We included 2,536 patients with urothelial carcinoma of the bladder treated at 26 institutions. A propensity-score matching 1:1 was performed with 3 ORC patients matched to 1 RARC patient. The final cohort included 1,614 patients. Uni- and multivariable logistic regression analyses tested the impact of surgical technique on STSM status, before and after propensity-score matching. RESULTS: Overall, 870 (34%) patients underwent RARC and 1,666 (66%) ORC. The overall STSM rate was 11%; 10% in the ORC group and 13% in the RARC group. Within the propensity-score-matched cohort, the positive STSM rate were 14% and 13% in the ORC and RARC group, respectively (P = 0.1). In multivariable analysis, after propensity match RARC approach was not associated with the risk of a positive STSM (P = 0.1). These results were confirmed in the subgroup of patients with pathologic non-organ-confined or organ-confined diseases. CONCLUSIONS: While treatment with RARC is associated with a higher absolute rate of STSM, the difference did not remain after adjustment for the effects of other established prognostic factors. Results from ongoing trials are awaited to assess the validity of these findings.

Preoperative Incidence of Deep Venous Thrombosis in Patients With Bladder Cancer Undergoing Radical Cystectomy.

OBJECTIVE: To determine the preoperative incidence of subclinical lower-extremity deep vein thrombosis (DVT), as well as to evaluate the utility of preoperative DVT screening in patients with bladder cancer before undergoing radical cystectomy. MATERIALS AND METHODS: Beginning in 2014, we prospectively instituted a policy of obtaining a screening lower-extremity duplex ultrasound on all patients within 7 days before undergoing radical cystectomy. We reviewed the electronic medical records of all patients at our institution who underwent radical cystectomy for bladder cancer from January 2012 through December 2015. The screened group (n = 65) underwent preoperative screening; the historical control group (n = 78) did not. Primary outcome was a lower-extremity duplex ultrasound positive screening. Secondary outcome measures included the development of symptomatic venous thromboembolism (VTE) postoperatively, and the rate and severity of complications. RESULTS: DVT was identified in 13.9% of patients before undergoing cystectomy. Univariate analysis demonstrated an increased risk of subclinical DVT in patients who were exposed to neoadjuvant chemotherapy (35.3% vs 5.1%, P = .008). Postoperatively, there was a nonsignificant trend of lower DVT rate in the screened group compared to historical control. Overall complication rate and severity were similar between the groups. CONCLUSION: Subclinical DVT is present in a significant number of pre-cystectomy patients, especially those exposed to neoadjuvant chemotherapy. Ultrasound screening in patients before undergoing radical cystectomy may identify opportunities for early intervention to reduce morbidity and mortality associated with perioperative DVT or venous thromboembolism in the cystectomy population.

Extended outpatient chemoprophylaxis reduces venous thromboembolism after radical cystectomy.

PURPOSE: Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism, is a common cause of morbidity and mortality after radical cystectomy. The purpose of our study was to evaluate the utility of extended outpatient chemoprophylaxis against VTE after radical cystectomy-with a focus on any reduction in the incidence of VTE, including DVT and pulmonary embolism. MATERIALS AND METHODS: Beginning in April 2013, we prospectively instituted a policy of extending inpatient VTE prophylaxis with subcutaneous heparin/enoxaparin for 30 days postoperatively. For this study, we reviewed the electronic medical records of all patients who underwent radical cystectomy at our institution from January 2012 through December 2015. The experimental group (n = 79) received extended outpatient chemoprophylaxis against VTE; the control group (n = 51) received no chemoprophylaxis after discharge. The primary outcome was the 90-day incidence of VTE. The secondary outcomes included the overall complication rate, the hemorrhagic complication rate, as well as the rate of readmission within 30 days of hospital discharge. RESULTS: The experimental group experienced a significantly lower rate of DVT (5.06%), assessed as of 90 days postoperatively, than the control group (17.6%): a relative risk reduction of 71.3% (P = 0.021). We found no significant differences in secondary outcomes between the 2 groups, including the overall complication rate (54.4% vs. 68.6%), the hemorrhagic complication rate (3.7% vs. 2.0%), and the readmission rate (21.5% vs. 29.4%). CONCLUSION: Extended outpatient chemoprophylaxis significantly reduced the incidence of VTE.

Racial Disparities in Surgical Outcomes Among Males Following Major Urologic Cancer Surgery.

INTRODUCTION: Disparities in healthcare outcomes between races have been extensively described; however, studies fail to characterize the contribution of differences in distribution of covariates between groups and the impact of discrimination. This study aims to characterize the degree to which clinicodemographic factors and unmeasured confounders are contributing to any observed disparities between non-Hispanic white and black males on surgical outcomes after major urologic cancer surgery. METHODS: Non-Hispanic white and black males undergoing radical cystectomy, nephrectomy, or prostatectomy for cancer in the American College of Surgeons National Surgical Quality Improvement Program database from 2007 to 2016 were included in this analysis. The outcome of interest was Clavien III-V complications. Analysis was conducted in 2017 using the Peters-Belson method to compare the disparity in outcomes while adjusting for 13 important demographic and clinical characteristics. RESULTS: Of the 15,693 cases included with complete data, 13.0% (n=2,040) were black. There was a significantly increased rate of unadjusted Clavien III and V complications between white versus black males for radical cystectomy (21.9% vs 10.1%, p=0.005); nephrectomy (6.4% vs 3.9%, p=0.028); and radical prostatectomy (2.3% vs 1.6%, p=0.046). Adjusting for differences in age, BMI, American Society of Anesthesiologists score, functional status, smoking history, and comorbidities including diabetes, chronic obstructive pulmonary disease, heart failure, renal failure, bleeding disorder, steroid use, unintentional weight loss, and hypertension between the groups could not explain the disparity in complications after radical cystectomy; the unexplained discrepancy was an absolute excess of 11.8% (p=0.01) in black males. There was an unexplained excess of complications in black males undergoing radical prostatectomy and nephrectomy but neither reached statistical significance. CONCLUSIONS: Black males undergoing radical cystectomy for cancer experienced higher complication rates than white males. Unexplained differences between the black and white males significantly contributed to the disparity in outcomes, which suggests that unmeasured factors, such as the quality of surgical or perioperative care, are playing a considerable role in the observed inequality. SUPPLEMENT INFORMATION: This article is part of a supplement entitled African American Men's Health: Research, Practice, and Policy Implications, which is sponsored by the National Institutes of Health.

Current Concepts in the Management of Muscle Invasive Bladder Cancer.

Bladder cancer is the ninth most common cancer in the world. Twenty to twenty-five percent of all newly diagnosed bladder cancers are muscle invasive in nature, and further, 20-25% of patients who are diagnosed with high-risk non-muscle invasive disease will eventually progress to muscle invasive disease in due course of time irrespective of adjuvant intravesical therapies. Availability of newer imaging modalities improves appropriate identification of patients with muscle invasive disease. Radical cystectomy remains the mainstay of treatment for management of muscle invasive disease. Availability of neoadjuvant chemotherapy has improved overall survival. Risk stratification systems are now in consideration to identify patients who benefit maximally from neoadjuvant chemotherapy. Urinary diversion is a major cause of morbidity in these patients, and several strategies are being employed to reduce morbidity. In this article, we review available literature on various aspects of management of muscle invasive disease.

The synergy between ionizing radiation and immunotherapy in the treatment of prostate cancer.

There has been a surge in the use of immunotherapy for genitourinary malignancies. Immunotherapy is an established treatment for metastatic renal cell carcinoma and nonmuscle invasive bladder cancer, but its potential for treating prostate cancer (PCa) remains under investigation. Despite reported survival benefits, no published Phase III PCa trials using immunotherapy only as a treatment has demonstrated direct antitumor effects by reducing prostate-specific antigen levels. Subsequently, the thought of combining immunotherapy with other treatment modalities has gained traction as a way to achieving optimal results. Based on data from other malignancies, it is hypothesized that radiotherapy and immunotherapy can act synergistically to improve outcomes. We will discuss the clinical potential of combining immune-based treatments with radiotherapy as a treatment for advanced PCa.

The current status of immunobased therapies for metastatic renal-cell carcinoma.

The management of metastatic renal-cell carcinoma (mRCC) represents an important clinical challenge. Since being approved in the early 1990s, aspecific immunotherapy has been a mainstay of treatment for mRCC and the only therapy that has demonstrated long-term cures for mRCC. However, in recent times there have been landmark advances made in the field of specific immunotherapy for a number of malignancies, including kidney cancer. This review outlines the range of immunobased agents currently available for the treatment of mRCC.

Development of a Classification Scheme for Examining Adverse Events Associated with Medical Devices, Specifically the DaVinci Surgical System as Reported in the FDA MAUDE Database.

OBJECTIVE: To examine the Manufacturer and User Facility Device Experience Database (MAUDE) database to capture adverse events experienced with the Da Vinci Surgical System. In addition, to design a standardized classification system to categorize the complications and machine failures associated with the device. SUMMARY BACKGROUND DATA: Overall, 1,057,000 DaVinci procedures were performed in the United States between 2009 and 2012. Currently, no system exists for classifying and comparing device-related errors and complications with which to evaluate adverse events associated with the Da Vinci Surgical System. METHODS: The MAUDE database was queried for events reports related to the DaVinci Surgical System between the years 2009 and 2012. A classification system was developed and tested among 14 robotic surgeons to associate a level of severity with each event and its relationship to the DaVinci Surgical System. Events were then classified according to this system and examined by using Chi-square analysis. RESULTS: Two thousand eight hundred thirty-seven events were identified, of which 34% were obstetrics and gynecology (Ob/Gyn); 19%, urology; 11%, other; and 36%, not specified. Our classification system had moderate agreement with a Kappa score of 0.52. Using our classification system, we identified 75% of the events as mild, 18% as moderate, 4% as severe, and 3% as life threatening or resulting in death. Seventy-seven percent were classified as definitely related to the device, 15% as possibly related, and 8% as not related. Urology procedures compared with Ob/Gyn were associated with more severe events (38% vs 26%, p < 0.0001). Energy instruments were associated with less severe events compared with the surgical system (8% vs 87%, p < 0.0001). Events that were definitely associated with the device tended to be less severe (81% vs 19%, p < 0.0001). CONCLUSIONS: Our classification system is a valid tool with moderate inter-rater agreement that can be used to better understand device-related adverse events. The majority of robotic related events were mild but associated with the device.