Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial.

BACKGROUND: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer. METHODS: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849. FINDINGS: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths. INTERPRETATION: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state. FUNDING: FKD Therapies Oy.

Novel Opiate-Free Anesthetic Technique for Major Urologic Procedures.

OBJECTIVES: We postulated that an opiate-free (OF) general anesthesia (GA) technique could adequately control a patient's pain without adversely affecting recovery. We compared patients undergoing major urologic procedures with and without opiate-based GA. METHODS: A propensity-matched analysis was performed comparing hospital length of stay, postoperative nausea and vomiting, ileus occurrence, postanesthesia care unit, and total opiate consumption, as well as sedation and hemodynamic variables. The data are expressed as medians and were analyzed with the Wilcoxon rank-sum test. P < 0.05 indicate statistical significance. RESULTS: In total, 166 patients were evaluated in both the OF group and the opiate-based treatment group. American Society of Anesthesiologists classification and age were comparable, with most surgeries being laparoscopic and confined to the bladder, kidney, and prostate gland. The median opiate consumption in morphine equivalents in the postanesthesia care unit was 7.7 mg (range 5-11.7 mg) for the OF cohort versus 11.7 mg (range 5-17.3 mg) for the control group (P < 0.001). Similarly, the median total postoperative opiate consumption in morphine equivalents was 23.9 mg (range 13.8-42.4 mg) for the OF group compared with 32.1 mg (range 17.38-57.51 mg) for the control group (P = 0.0081). The median hospital length of stay for the OF group was 1.4 days (range 1.2-2.3 days) versus 1.3 days (range 1.2-2.4 days) for the control group (P = 0.8466). CONCLUSIONS: There was a statistically significant difference in opiate consumption postoperatively for patients who underwent an OF technique compared with a conventional opiate-based technique. This technique appears to be a possible alternative approach, without any apparent untoward consequences during admission.

Evaluation of the Fluorescence In Situ Hybridization Test to Predict Recurrence and/or Progression of Disease after bacillus Calmette-Guérin for Primary High Grade Nonmuscle Invasive Bladder Cancer: Results from a Prospective Multicenter Trial.

PURPOSE: Single center studies have shown that positive UroVysion® fluorescence in situ hybridization results were associated with recurrence of nonmuscle invasive bladder cancer treated with intravesical bacillus Calmette-Guérin. Our goal was to validate these findings. MATERIALS AND METHODS: We performed a prospective, multicenter diagnostic trial to determine whether the fluorescence in situ hybridization test could predict recurrence or progression in patients with primary high grade nonmuscle invasive bladder cancer who were scheduled to receive bacillus Calmette-Guérin. Fluorescence in situ hybridization testing was performed prior to the first bacillus Calmette-Guérin instillation, prior to the sixth instillation and at 3-month cystoscopy. The performance of fluorescence in situ hybridization was evaluated. RESULTS: A total of 150 patients were enrolled in analysis, including 68 with Ta disease, 41 with T1 disease, 26 with carcinoma in situ alone and 15 with papillary carcinoma plus carcinoma in situ. At 9 months of followup there were 46 events, including 37 recurrences and 9 progressions. For events with positive fluorescence in situ hybridization findings the HR was 2.59 (95% CI 1.42-4.73) for the baseline test, 1.94 (95% CI 1.04-3.59) for the 6-week test and 3.22 (95% CI 1.65-6.27) at 3 months. Patients with positive results at baseline, 6 weeks and 3 months had events 55% of the time and patients with negative results at each time point had no event 76% of the time. CONCLUSIONS: The study validated that a positive UroVysion fluorescence in situ hybridization test was associated with a 3.3-fold increased risk of recurrence. The test may be useful to risk stratify patients entering clinical trials in whom induction therapy fails. However, using the test to change management decisions is limited due to the discordance between results and outcomes as well as the variance of tests results with time.

Morbidity, mortality and temporal trends in the surgical management of retroperitoneal sarcoma: An ACS-NSQIP follow up analysis.

BACKGROUND: Calls for multivisceral resection (MVR) of retroperitoneal sarcoma (RPS) are increasing, although the risks and benefits remain controversial. We sought to analyze current 30-day morbidity and mortality rates, and trends in utilization of MVR in a national database. METHODS: Overall morbidity, severe morbidity, mortality rates, and temporal trends were analyzed utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). RESULTS: From 2012 to 2015, a total of 564 patients underwent RPS resection with 233 patients (41%) undergoing MVR. The MVR group had a higher rate of preoperative weight loss and larger tumors overall. When comparing MVR to non-MVR, there was no significant difference in overall morbidity (22% vs 17%, P = .13), severe morbidity (11% vs 8%, P = .18), or mortality (<1% vs 2%, P = .25). On multivariate analysis, MVR was not associated with increased overall morbidity or severe morbidity. Mortality rates were too low for meaningful statistical analysis. Annual rates of MVR ranged from 37% to 46% with no significant change over time (P = .47). RESULTS: Short-term morbidity and mortality rates after MVR for RPS remain acceptable, but rates of MVR show little change over time in NSQIP hospitals. Concerns about increased morbidity and mortality should not be viewed as a contraindication to wider implementation of MVR for RPS.

Ex-vivo donor partial nephrectomy at the time of donor-directed renal transplantation.

The outcome of nephron-sparing surgical management of small renal masses is generally favorable, specifically in terms of long term renal function, overall survival, and oncologic outcomes. Given the overall prognosis and renal function preservation, transplantation of kidneys with small renal masses has increasingly been accepted as a donor option for renal transplantation. We present a case of an incidental renal mass on preoperative donor transplant evaluation and subsequent ex-vivo donor partial nephrectomy at the time of renal transplantation.

Isolated adrenal metastectomy has a low morbidity rate irrespective of performing surgical sub-specialty.

INTRODUCTION: There has been growing use of adrenalectomy as a potentially curative treatment option for patients with oligometastatic disease to the adrenal gland. We sought to compare the perioperative outcomes of patients undergoing isolated adrenalectomy in the setting of disseminated cancer using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Furthermore, we examined the impact of performing surgical sub-specialty on outcomes. MATERIALS AND METHODS: Data from the ACS-NSQIP database was obtained for patients between 2011 and 2016 who underwent adrenalectomy. Patients were stratified by the presence or absence of disseminated cancer. Univariate and multivariate regression analyses were performed to test for an association between the presence or absence of disseminated cancer and perioperative outcomes. The relationship between performing specialist and outcomes was also compared. RESULTS: A total of 4,207 patients were identified, with 270 (6.4%) in the disseminated cancer group. There was no significant difference in perioperative outcomes between patients with disseminated cancer and without disseminated cancer. On multivariate analysis, neither the presence of disseminated cancer (p = 0.47) nor the surgical sub-specialty performing adrenalectomy (p = 0.52) were associated with an increased risk postoperative morbidity or mortality. Of note, there was a statistically significant increase in the number of adrenalectomies performed by urologists in the setting of disseminated cancer (19.3% versus 10.4%, p < 0.01). CONCLUSIONS: Patients undergoing adrenalectomy in the setting of disseminated cancer did not have significantly worse perioperative outcomes compared to patients undergoing adrenalectomy for other indications. The adverse perioperative event rate was similar whether the operation was performed by a urologist or a general surgeon.

A randomized, controlled trial for transurethral treatment of bladder tumors using PlasmaButton vaporization electrode or monopolar loop electrocautery.

INTRODUCTION: The use of an electrocautery device (monopolar loop) for patients undergoing transurethral resection of bladder tumors (TURBT) is standard of care. The aim of this study is to establish non-inferiority of complication rates for a bipolar energy device, the PK PlasmaButton (PK Button), when compared to the monopolar loop. MATERIALS AND METHODS: Seventy-eight subjects (41 monopolar loop and 37 PK Button), were enrolled in a single-center, prospective, randomized study with cystoscopically detected bladder tumors that were judged endoscopically resectable with only one trip into the operating room. Intra and postoperative data on complication rates, operative time, catheterization time and disease recurrence rates at 3 month follow up were collected. RESULTS: Overall complication rates after TURBT with the monopolar loop or PK Button were similar, (56% versus 38% respectively, p = 0.107), however there were more bladder perforations in the monopolar loop arm compared to the PK Button arm (12.2% versus 0%, respectively, p = 0.028). There was no difference in overall operative time (p = 0.170), catheterization time (p = 0.709) and disease recurrence (p = 0.199). CONCLUSION: The results of this study demonstrated no difference between the monopolar loop and PK Button in regard to overall complications; however, there was a higher rate of bladder perforation with monopolar TURBT. PK Button vaporization for bladder tumors represents a promising alternative to traditional monopolar TURBT without compromising short term (3 month) cancer recurrence rates.

Comparison of common risk stratification indices to predict outcomes among stage IV cancer patients with bowel obstruction undergoing surgery.

BACKGROUND AND OBJECTIVES: Among patients with disseminated malignancy (DMa), bowel obstruction is common with high operative morbidity. Since preoperative risk stratification is critical, we sought to compare three standard risk indices, the American Society of Anesthesiology (ASA) classification, Charlson comorbidity index (CCI), and modified frailty index (mFI). METHODS: We identified 1928 DMa patients with bowel obstruction who underwent an abdominal operation from 2007 to 2012 American College of Surgeons National Surgical Quality Improvement Program. Multivariate analyses assessed predictors of prolonged length of stay (LOS), 30-day serious morbidity and mortality. Receiver operating characteristics' areas under the curves (AUCs) for risk indices scores and 30-day mortality were assessed. RESULTS: Serious morbidity and mortality rates were 20.4% and 14.8%. ASA and CCI did not predict serious morbidity or prolonged LOS, but were predictors of mortality. The mFI did not predict prolonged LOS, but did predict serious morbidity and mortality. Subgroup analyses showed similar results. There were no significant differences between ASA, CCI, and mFI AUCs for mortality. CONCLUSIONS: ASA, CCI, and mFI are limited in their ability to predict postoperative adverse events among DMa patients undergoing surgery for bowel obstruction. These data suggest that a more tailored preoperative risk stratification tool would improve treatment planning.

The modified frailty index to predict morbidity and mortality for retroperitoneal sarcoma resections.

BACKGROUND: The modified frailty index (mFI) is an important method to risk-stratify surgical patients and has been validated for general surgery and selected surgical subspecialties. However, there are currently no data assessing the efficacy of the mFI to predict acute morbidity and mortality in patients undergoing surgery for retroperitoneal sarcoma. METHODS: Using the American College of Surgeons' National Surgical Quality Improvement Program from 2007 to 2012, we performed a retrospective analysis of patients with a diagnosis of primary malignant retroperitoneal neoplasm who underwent surgical resection. The mFI was calculated according to standard published methods. Univariate and multivariate statistical analyses including χ2 and logistic regression were used to identify predictors of 30-d overall morbidity, 30-d severe morbidity (Clavien III/IV), and 30-d mortality. RESULTS: We identified 846 patients with the diagnosis of primary malignant retroperitoneal neoplasm who underwent surgical resection. The distribution mFI scores was 0 (48.5%) or 1 (36.3%), with only 4.5% of patients presenting with a score ≥3. Rates of 30-d overall morbidity, serious morbidity, and mortality were 22.6%, 12.9%, and 1.2%, respectively. Only selected mFI scores were associated with serious morbidity and overall morbidity on multivariate analysis (P < 0.05), and mFI did not predict 30-d mortality (P > 0.05). CONCLUSIONS: Our data demonstrate that the majority of patients undergoing retroperitoneal sarcoma resections have few, if any, comorbidities. The mFI was a limited predictor of overall and serious complications and was not a significant predictor of mortality. Better discriminators of preoperative risk stratification may be needed for this patient population.

A case report of a renal diffuse B-cell lymphoma.

Diffuse large B-cell lymphomas (DLBCL) are the most common lymphomas worldwide. They also appear to be the most common primary retroperitoneal lymphomas, but this presentation is relatively uncommon in the literature. Retroperitoneal masses, including lymphomas, often present with nonspecific symptoms and laboratory values, necessitating radiographic assessment and consideration of mass biopsy prior to the initiation of treatment. Here we present a case of a primary retroperitoneal DLBCL as well as a review of the clinical presentation, imaging findings, and differential diagnosis of such tumors.

Utility of Prostate Cancer Screening in Kidney Transplant Candidates.

Screening recommendations for prostate cancer remain controversial, and no specific guidelines exist for screening in renal transplant candidates. To examine whether the use of prostate-specific antigen (PSA)-based screening in patients with ESRD affects time to transplantation and transplant outcomes, we retrospectively analyzed 3782 male patients ≥18 years of age undergoing primary renal transplant evaluation during a 10-year period. Patients were grouped by age per American Urological Association screening guidelines: group 1, patients <55 years; group 2, patients 55-69 years; and group 3, patients >69 years. A positive screening test result was defined as a PSA level >4 ng/ml. We used univariate analysis and Cox proportional hazards models to identify the independent effect of screening on transplant waiting times, patient survival, and graft survival. Screening was performed in 63.6% of candidates, and 1198 candidates (31.7%) received kidney transplants. PSA screening was not associated with improved patient survival after transplantation (P=0.24). However, it did increase the time to listing and transplantation for candidates in groups 1 and 2 who had a positive screening result (P<0.05). Furthermore, compared with candidates who were not screened, PSA-screened candidates had a reduced likelihood of receiving a transplant regardless of the screening outcome (P<0.001). These data strongly suggest that PSA screening for prostate cancer may be more harmful than protective in renal transplant candidates because it does not appear to confer a survival benefit to these candidates and may delay listing and decrease transplantation rates.

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.

Microscopic haematuria at time of diagnosis is associated with lower disease stage in patients with newly diagnosed bladder cancer.

OBJECTIVES: To determine whether the severity of haematuria (microscopic or gross) at diagnosis influences the disease stage at presentation in patients diagnosed with bladder cancer. PATIENTS AND METHODS: We conducted a multi-institutional observational cohort study of patients who were newly diagnosed with bladder cancer between August 1999 and May 2012. We reviewed the degree of haematuria, demographic information, clinical and social history, imaging, and pathology. The association of haematuria severity with incident tumour stage and grade was evaluated using logistic regression. RESULTS: Patients diagnosed with bladder cancer presented with gross haematuria (GH; 1 083, 78.3%), microscopic haematuria (MH; 189, 13.7%) or without haematuria (112, 8.1%). High-grade disease was found in 64% and 57.1% of patients presenting with GH and MH, respectively, and severity of haematuria was not associated with higher grade disease. Stage of disease at diagnosis for patients presenting with MH was Ta/carcinoma in situ (CIS) in 68.8%, T1 in 19.6%, and ≥T2 in 11.6%. Stage of disease at diagnosis for patients presenting with GH was Ta/CIS in 55.9%, T1 in 19.6%, and ≥T2 in 17.9%. On multivariate analyses, GH was independently associated with ≥T2 disease at diagnosis (odds ratio 1.69, 95% confidence interval 1.05-2.71, P = 0.03). CONCLUSIONS: Among patients with newly diagnosed bladder cancer, presentation with GH is associated with a more advanced pathological stage. Earlier detection of disease, before development of GH, could influence survival in patients with bladder cancer. Type of haematuria at presentation does not impact grade of disease.

Surgical Apgar Score predicts an increased risk of major complications and death after renal mass excision.

PURPOSE: Tailoring perioperative management to minimize the postoperative complication rates depends on reliable prognostication of patients most at risk. The Surgical Apgar Score is an objective measure of the operative course validated to predict major complications and death after general/vascular surgery. We assessed the ability of the Surgical Apgar Score to identify patients most at risk for postoperative morbidity and mortality after renal mass excision. MATERIALS AND METHODS: Data for 886 patients undergoing renal mass excision via radical or partial nephrectomy from 2010 to 2013 were extracted from a prospectively collected database. The Surgical Apgar Score was calculated using electronic anesthesia records. Major postoperative complications, readmission and reoperation within 30 days of surgery as well as 90-day mortality were examined. RESULTS: Overall 13.2% of patients experienced major postoperative complications at 30 days. Clavien grade I, II, III, IV and V complications were experienced by 1.7%, 2.9%, 5.8%, 1.9% and 0.9%, respectively. The 90-day all cause mortality rate was 1.4%. The Surgical Apgar Score was significantly lower in patients experiencing major complications (mean 7.3 vs 7.8, p=0.004) and death (6.3 vs 7.7, p=0.03). Patients with a Surgical Apgar Score of 4 or less were 3.7 times more likely to experience a major complication (p=0.01) and 24 times more likely to die within 90 days of surgery (p=0.0007) compared to patients with a Surgical Apgar Score greater than 8. CONCLUSIONS: The Surgical Apgar Score is an easily collected metric that can identify patients at higher risk for major complications and death after renal mass excision. A prospective trial to help further delineate the optimal use of this tool in an adjusted perioperative management approach with patients undergoing renal mass excision is warranted.

Variation in performance of candidate surgical quality measures for muscle-invasive bladder cancer by hospital type.

OBJECTIVE: To test the association between hospital type and performance of candidate quality measures for treatment of muscle-invasive bladder cancer (MIBC) using a large national tumour registry. Proposed quality measures include receipt of neoadjuvant chemotherapy, timely treatment, adequate lymph node dissection, and continent urinary diversion. PATIENTS AND METHODS: Using the National Cancer Database, patients with stage ≥II urothelial carcinoma treated with radical cystectomy (RC) from 2003 to 2010 were identified. Hospitals were grouped by type and annual RC volume: community, comprehensive low volume (CLV), comprehensive high volume (CHV), academic low volume (ALV), and academic high volume (AHV) groups. Logistic regression models were used to test the association between hospital group and performance of quality measures, adjusting for year, demographic, and clinical/pathological characteristics; generalised estimating equations were fitted to the models to adjust for clustering at the hospital level. RESULTS: In all, 23 279 patients underwent RC at community (12.4%), comprehensive (CLV 38%, CHV 5%), and academic (ALV 17%, AHV 28%) hospitals. While only 0.8% (175) of patients met all four quality criteria, 61% of patients treated at AHV hospitals met two or more quality metric indicators compared with ALV (45%), CHV (44%), CLV (38%), and community (37%) hospitals (P < 0.001). After adjustment, patients were more likely to receive two or more quality measures when treated at AHV (odds ratio [OR] 2.4, confidence interval [CI] 2.0-2.9), ALV (OR 1.3, CI 1.1-1.6), and CHV (OR 1.3, CI 1.03-1.7) hospitals compared with community hospitals. CONCLUSIONS: Patients undergoing RC at AHV hospitals were more likely to meet quality criteria. However, performance remains low across hospital types, highlighting the opportunity to improve quality of care for MIBC.

Multicenter evaluation of the role of UroVysion FISH assay in surveillance of patients with bladder cancer: does FISH positivity anticipate recurrence?

BACKGROUND: The significance of a positive UroVysion FISH assay is uncertain in patients with normal cystoscopy. This multicenter study evaluates the clinical significance of a positive FISH assay in patients with no visible tumor and excluding those with a positive cytology. METHODS: A multi-institutional, retrospective study of patients with a history of urothelial carcinoma of the bladder identified 664 patients with a FISH assay after excluding those with cystoscopic evidence of a tumor and/or positive cytology. Our primary end point was cancer recurrence, defined by biopsy. Progression was defined as recurrence with a tumor stage ≥T2. Statistical analyses were performed using Fisher's exact test as a one-tailed test and Chi-square test with significance at 0.05, using SPSS(®) version 19.0 (SPSS Inc., Chicago, IL, USA). RESULTS: Of the 664 patients in this study, tumor stage was Ta (363, 55 %), T1 (183, 28 %), and CIS (109, 16 %) and most were high grade (440 pts, 66 %). The median follow-up was 26 months (3-104 months), and 277 (41.7 %) patients were recurred. In patients who were FISH positive, mean time to recurrence was 12.6 months, compared to 17.9 months if FISH negative (p = 0.03). In univariate analysis, atypical cytology, positive FISH, cystoscopic findings (atypical vs. normal), and previous intravesical therapy were associated with recurrence (p < 0.05). On multivariate analysis, pathologic stage, cystoscopic findings, and cytology were independently associated with recurrence (p < 0.05). Progression to ≥T2 disease occurred in 34 (5.1 %) patients in this cohort. On multivariate analysis, only initial T stage and FISH result were found to be independent predictors of progression (p < 0.05). CONCLUSIONS: Patients with a positive FISH and atypical cytology are more likely to recur even in the absence of visible tumor. FISH positivity may portend a higher risk for progression. These findings require prospective validation.

Preoperative quantification of perceptions of surgical frailty.

BACKGROUND: Frailty has gained recognition as an objective measure of a patient's physiologic reserve that ideally can replace the subjective biases of surgeons. In this study, we sought to examine the concordance between patient and attending surgeon perceptions of the patient's "fitness" before surgery. We then correlated these ratings with the patient's objective frailty scores. METHODS: Patients were prospectively enrolled from urology, general surgery, and surgical oncology clinics. Patients were asked to rate their ability to withstand the physical stress of the scheduled surgery on a visual analog scale. The operating surgeon then independently rated his assessment of the patient's ability to withstand surgery blinded to the patient's self assessment. RESULTS: A total of 203 patients were included. Median patient age and body mass index were 62 (range = 21-87) years and 28.1 kg/m(2) (18.0-53.1), respectively. The majority of patients were white (67%) and male (60.6%). A patients' self-assessment showed no correlation with their age; however, surgeons' ratings showed a positive correlation with patients' age. Patients' self-rated scores showed a positive correlation with their frailty score, although surgeons' ratings showed a stronger correlation. However, when stratified by age group, the positive correlation and predictive ability were lost (P value = 0.198). CONCLUSIONS: Although age is an established risk factor, our data demonstrate surgeons may place an overreliance on a patient's age in place of an objective measure of physiologic reserve. Conversely, patients tended to overestimate their ability to withstand the stress of surgery, possibly leading to unrealistic expectations of their recovery and outcomes.

Adjunctive use of narrow band imaging during transurethral resection/vaporization of bladder tumors to aid In identifying mucosal and sub-mucosal hypervascularity.

For patients with non-muscle invasive bladder cancer, cystoscopy and transurethral resection/vaporization of the bladder tumor plays an integral role in the treatment of a given patient's bladder cancer. Although considered the current gold standard for tumor detection, traditional or white light cystoscopy has been shown to have its limitations visualizing both small papillary tumors and/or carcinoma in-situ. Current efforts have been directed to closing this gap with data demonstrating that by identifying these previously missed lesions, tumor recurrence and progression rates are reduced, thereby improving patient outcomes. Narrow Band Imaging, which can be used during cystoscopy and transurethral resection/vaporization of bladder tumors, can aid in visualizing mucosal and sub-mucosal hypervascularity--a probable surrogate for malignant lesions--potentially visualizing the boundaries of lesions that may have been missed during white light cystoscopy alone. This technique may produce equivalent visual markers with fewer logistical hurdles than currently available methods. In this article, we detail our technique for the adjunctive use of Narrow Band Imaging during cystoscopy and transurethral resection/vaporization of bladder tumors to aid in visualizing mucosal and sub-mucosal hypervascularity. Although not yet readily adopted, Narrow Band Imaging may be a practical and easy to use adjunct to existing methods in visualizing occult bladder lesions.

The burden of overtreatment: comparison of toxicity between single and combined modality radiation therapy among low risk prostate cancer patients.

INTRODUCTION: To compare radiation related toxicities among men with low risk prostate cancer treated with single or multimodal radiation therapy. MATERIALS AND METHODS: The SEER-Medicare linked database was used to assess the relationship between treatment type and toxicity among men with low risk prostate cancer treated with brachytherapy (BT), external beam radiation therapy (EBRT), or combined therapy between 2004 and 2007. Inverse probability of treatment weighting was utilized to minimize selection bias and control for confounding. Multivariate logistic regression models were used to explore the relationship between treatment and outcomes. RESULTS: Overall 1915 (43.9%), 1893 (43.4%), and 555 (12.7%) patients were treated with EBRT, BT, and combined therapy, respectively. In univariate analyses, combined modality radiation was more toxic than BT alone for GU incontinence (56.76% versus 49.08%), GU obstruction (21.26% versus 19.70%), and erectile dysfunction (22.52% versus 22.24%) (p < 0.01, all comparisons). Compared to EBRT alone, combined modality radiation was more toxic for GI bleeding (7.21% versus 6.21%), GU incontinence (56.76% versus 29.24%), GU obstruction (21.26% versus 14.15%), and erectile dysfunction (22.52% versus 15.35%) (p < 0.01, all comparisons). Among the most frequent radiation toxicity events, the probability of treatment associated toxicity was highest for patients receiving combined modality treatment and lowest for the group treated with EBRT. After multivariate adjustment, EBRT alone demonstrated protective effects against GU obstruction (OR 0.56 [CI 0.50-0.63]), GI bleeding (OR 0.57 [CI 0.48-0.67]), GU incontinence (OR 0.39 [CI 0.36-0.43]), and erectile dysfunction (OR 0.68 [CI 0.61-0.76]) when compared to combined therapy. CONCLUSIONS: The use of combined modality radiation therapy in low risk prostate cancer patients is discordant with clinical guidelines and associated with a significantly increased burden of associated toxicity when compared to EBRT monotherapy. Prudent patient selection and judicious use of combined therapy among men with low risk prostate cancer represents a targetable area to reduce the burden of overtreatment.