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.

A comparison of energy expenditure and perceived exertion between standard axillary crutches, knee scooters, and a hands-free crutch.

BACKGROUND: Ambulation using standard axillary crutches (SACs) is associated with increased energy expenditure (EE) and decreased ability to perform activities of daily living (ADLs). Using a hands-free crutch (HFC) displays potential for easier completion of ADLs and reduction in energy requirements. OBJECTIVES: To determine if a HFC elicits lower EE and heart rate (HR), improvement in performance of ADLs, and decreased rating of perceived exertion (RPE) compared to common ambulatory devices. DESIGN: A randomized crossover-controlled trial. SETTING: University community. PARTICIPANTS: Twenty healthy college students. MAIN OUTCOME MEASURES: Participants completed a 6-minute walk test at 50 m/min, an ADLs course, and a two-flight stair climb with SACs, HFC, knee scooter (KS), and unassisted ambulation (UA). The order of trial conditions was randomized. EE, HR, time to complete ADLs course and stair climb, and RPE during each condition were obtained. One-way analyses of variance were performed to compare EE, HR response, and RPE between the assistive devices and UA. RESULTS: In all outcomes UA resulted in lower EE, HR, and RPE compared to all the assistive devices (p < .05). For the ADLs course, EE was the same for the three assistive devices, whereas HR was significantly lower for HFC compared to SACs and KS (p < .05). RPE for HFC and KS was lower than SACs (p < .05). For the 6MWT, each device significantly differed from the other devices for EE, HR, and RPE, with KS eliciting the lowest values, followed by HFC. For the stair climbing task, HFC elicited lower EE, HR, and RPE than SACs. Fourteen participants indicated their overall preference for HFCs. CONCLUSIONS: In individuals prescribed weight-bearing restrictions, using a HFC may offer an easier and more preferred alternative to more commonly used SACs during ambulation, stair climbing, and other ADLs.

The 17-Gene Genomic Prostate Score Assay Is Prognostic for Biochemical Failure in Men With Localized Prostate Cancer After Radiation Therapy at a Community Cancer Center.

Purpose: The objective of this study was to assess the association between the Oncotype DX Genomic Prostate Score (GPS) assay and long-term outcomes in men with localized prostate cancer (PCa) after radiation therapy (RT). We hypothesized that the GPS assay is prognostic for biochemical failure (BCF), along with distant metastasis (DM) and PCa-specific mortality in patients with PCa receiving RT. Methods and Materials: We retrospectively studied men with localized PCa treated with definitive RT at Georgia Urology from 2010 to 2016. The primary objective was to assess the association between GPS results and time to BCF per the Phoenix criteria; we also assessed time to DM and PCa-specific mortality. We used Cox proportional hazards regression models for all analyses, with clinicopathologic covariates determined a priori for multivariable modeling. Results: A total of 450 patients (median age, 65 years; 35% Black) met eligibility criteria. There was a strong univariable association between GPS result and time to BCF (hazard ratio [HR] per 20-unit increase = 3.08; 95% confidence interval [CI], 2.11-4.46; P < .001), which persisted after adjusting for clinicopathologic characteristics in multivariable analyses. We also observed this association for time to DM (HR = 5.19; 95% CI, 3.06-8.77; P < .001) and PCa-specific mortality (HR = 13.07; 95% CI, 4.42-49.39; P < .001). Race was not a predictor of time to BCF or DM, and the GPS assay was strongly prognostic for all endpoints in Black and White patients. Conclusions: In a community-based cohort, the GPS assay was strongly prognostic for time to BCF as well as long-term outcomes in men treated with RT for localized PCa.

Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non-muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial.

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec.

Personalizing Localized Prostate Cancer: Validation of a Combined Clinical Cell-cycle Risk (CCR) Score Threshold for Prognosticating Benefit From Multimodality Therapy.

INTRODUCTION: The combined clinical cell-cycle risk (CCR) score is a validated model that combines the cell-cycle progression (CCP) score with the University of California San Francisco Cancer of the Prostate Risk Assessment (CAPRA) score. This score determines the risk of progressive disease for men with prostate cancer. Here, we further validate the prognostic ability of the CCR score and evaluate its ability to help determine which patients may safely forgo multimodality therapy. PATIENTS AND METHODS: We evaluated the CCR and a CCR-based multimodality threshold (2.112) in a retrospective, multi-institutional cohort of men with National Comprehensive Cancer Network intermediate- or high-risk localized disease (N = 718). These men received single or multimodality therapy (androgen deprivation with radiation [RT], or surgery with adjuvant RT or hormones). RESULTS: CCR score prognosticated metastasis for single-modality therapy, as a continuous variable (hazard ratio, 3.97; 95% confidence interval [CI], 2.61-6.06) and when dichotomized at the threshold (hazard ratio, 15.90; 95% CI, 5.43-46.52). The 10-year Kaplan-Meier risk for those receiving single-modality (RT or surgical) therapy with CCR scores below and above the threshold for single-modality treatment was 4.3% (95% CI, 1.0%-17.1%) and 20.4% (95% CI, 13.2%-30.7%), respectively. Using the threshold, 27% of men with newly diagnosed high-risk and 73% with unfavorable intermediate-risk disease could avoid multimodality therapy. CONCLUSIONS: Patients with CCR scores below the multimodality threshold (2.112) may safely forgo multimodality therapy. The CCR score can be used as a decision aid to counsel men whether or not single-modality therapy would be sufficient for their intermediate- or high-risk prostate cancer.

A Contemporary Analysis of the 30-day Morbidity and Mortality Associated With Cytoreductive Nephrectomy.

OBJECTIVE: To examine the rates of adverse surgical outcomes in patients undergoing cytoreductive nephrectomy (CN) compared to patients undergoing radical nephrectomy in the nonmetastatic setting using a large administrative database. METHODS: Patients in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) who underwent a radical nephrectomy between 2011 and 2016 were included. Patients were stratified by the preoperative variable of presence or absence of metastatic cancer. Perioperative outcomes were compared. A multivariable logistic regression analysis was performed to test the association between patients with metastatic cancer and perioperative morbidity and 30-day mortality. RESULTS: There were 15,869 total patients included in this analysis of whom 1322 (8%) patients had metastatic cancer. Of the entire cohort, the majority of patients were over 60 years old (58%) and 9621 (61%) were male. Seventy-three of the patients were Caucasian. Patients with metastatic cancer had more minor (P< .01) and major (P< .01) complications, a higher rate of reoperation (P< .01), and a higher rate of unplanned readmissions (P< .01). Finally, the cohort with metastatic cancer had a higher rate of postoperative 30-day mortality (P< .01) than patients without metastatic cancer. CONCLUSION: Patients undergoing a CN have significantly worse perioperative outcomes than patients undergoing a radical nephrectomy without evidence of metastases. Careful surgical risk stratification and appropriate patient counseling should be undertaken when selecting candidates for CN.

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.

Modified Frailty Index Predicts Postoperative Outcomes in Patients Undergoing Radical Pelvic Surgery.

Patients undergoing radical pelvic surgery such as proctectomy or radical cystectomy are at risk of experiencing a variety of complications. Frailty renders patients vulnerable to adverse events. We hypothesize that frailty measured preoperatively using a validated scoring system correlates with increased likelihood of experiencing Clavien-Dindo grade IV complications and 30-day mortality and may be used as a predictive model for patients preoperatively. The NSQIP database was queried for patients who underwent proctectomy or radical cystectomy from 2008 to 2012. Preoperative frailty was calculated using the 11-point modified frailty index (MFI). Patients were scored based on the presence of indicators and categorized into two groups (<3 or ≥3). Major postoperative morbidities and mortality were identified and analyzed in each group. 10,048 proctectomy and cystectomy patients were identified. The MFI was found to be predictive of both 30-day mortality (P < 0.0001) and Clavien-Dindo grade IV complications (P < 0.0001). Receiver operating characteristic analysis demonstrated improved discriminative power of the MFI with the addition of American Society of Anesthesiologists class for both prediction of complications and 30-day mortality. An MFI score of ≥3 is predictive of postoperative morbidity and mortality. Providers should be encouraged to calculate frailty preoperatively to predict adverse outcomes.

Analysis of the prognostic utility of the cell cycle progression (CCP) score generated from needle biopsy in men treated with definitive therapy.

BACKGROUND: Accurate risk stratification can help guide appropriate treatment decisions in men with localized prostate cancer. Here, we evaluated the independent ability of the molecular cell cycle progression (CCP) score and the combined cell-cycle clinical risk (CCR) score to predict 10-year risk of progression to metastatic disease in a large, pooled analysis of men with definitively treated prostate cancer. METHODS: The pooled analysis included 1,062 patients from four institutions (Martini Clinic, Durham VA Medical Center, Intermountain Healthcare, Ochsner Clinic) treated definitively for localized prostate cancer by either radical prostatectomy or radiotherapy (brachytherapy or external beam radiotherapy ± hormone therapy). The CCP score was determined using the RNA expression of 46 genes from archival formalin-fixed paraffin-embedded biopsy tissue. The CCR score was calculated using a predefined linear combination of the CCP score and the Cancer of the Prostate Risk Assessment (CAPRA) score. The scores were evaluated for association with 10-year risk of metastatic disease following definitive therapy after adjusting for other clinical variables. RESULTS: The CCP score was strongly associated with 10-year risk of metastatic disease in multivariable analysis [Hazard Ratio per unit score = 2.21; 95% confidence interval (CI) 1.64, 2.98; p = 1.9 × 10-6] after adjusting for CAPRA, treatment type, and cohort. CCR was also highly prognostic (Hazard Ratio per unit score = 4.00; 95% CI 2.95, 5.42; p = 6.3 × 10-21). There was no evidence of interaction between CCP or CCR and cohort (p = 0.79 and p = 0.86, respectively) or treatment type (p = 0.55 and p = 0.78, respectively). Observed patient CCR-based predicted risks for metastatic disease by 10 years ranged from 0.1 to 99.4%, (IQR 0.7%, 4.6%). CONCLUSIONS: Both CCP and CCR scores provided independent prognostic information for predicting progression to metastatic disease after both surgery and radiation. These results further demonstrate their potential use as a risk stratification tool in patients with newly-diagnosed prostate cancer.

Adrenalectomy: should urologists not be doing more?

PURPOSE: Adrenalectomy is an operation performed by both urologists and general surgeons; however, the majority are performed by general surgeons. We investigated whether there was a difference in outcomes based on surgical specialty performing the procedure. If no differences exist, an argument can be made that urologists should be doing more adrenalectomies. METHODS: The National Surgical Quality Improvement Project (NSQIP) Participant Use File (PUF) was queried to extract all cases of adrenalectomies performed from 2011 to 2015. Current Procedural Technology (CPT) codes 60540 and 60650 were used. The data were stratified by surgical specialty performing the adrenalectomy (urology or general surgery). Our outcomes of interest included post-surgical complications, reoperations, 30-day readmission, mortality, and hospital length of stay. RESULTS: A total of 3358 patients who underwent adrenalectomy between 2011 and 2015 were included. General surgeons performed 90% of these (n = 3012) and urologists performed 10% (n = 334). Differences in number of post-surgical complications, length of stay, rate of reoperation, 30-day readmission, and mortality were not statistically significant between general surgeons and urologists (p = 0.76, p = 0.29, p = 0.37, p = 0.98, and p = 0.59, respectively). Small complication rates disallowed multivariable analyses, but unadjusted rates for reoperation, presence of any post-operative complication, readmission within 30 days, and mortality were similar between specialties. CONCLUSIONS: Surgical specialty did not make a difference in outcomes for patients undergoing adrenalectomy, despite a large disparity in the number of procedures performed by general surgeons versus urologists. Urologists should continue performing adrenalectomies and, given their familiarity with the retroperitoneum, perhaps perform more than is the current trend.

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.

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.

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.

Accuracy of the NSQIP risk calculator for predicting complications following adrenalectomy.

PURPOSE: Adrenalectomy is performed to treat functional pathology and remove tumors of malignant concern. The National Surgical Quality Improvement Program (NSQIP) risk calculator predicts 30-day complications and length of stay following index surgical procedures. We assess whether this tool accurately predicts complications following adrenalectomy procedures at a tertiary care academic medical center. METHODS: A retrospective review was performed for all adrenalectomies at a single institution from 2004 to 2016. 197 patients underwent adrenalectomy without concurrent resections. Predicted risk for NSQIP complications was calculated for each patient. The mean predicted and observed risks (%) at 30 days across all patients within each category were determined, and these were compared with two-sided one-sample t tests. RESULTS: Of 197 adrenalectomies, 180 were laparoscopic and 17 were open. For laparoscopic adrenalectomy, ten (5.5%) complications were observed including nine (5%) graded Clavien III or greater. All observed complication rates were significantly different than predicted (p values for all < 0.005). Mean observed length of stay was also significantly less than predicted (1.6 versus 2.1 days, p < 0.001). In the open adrenalectomy subgroup, there were no observed complications with observed mean length of stay equivalent to predicted (5.8 versus 5.3, p = 0.08) without a higher readmission rate (5.9 versus 6.0%). CONCLUSIONS: Statistical differences were noted between the actual complication rates of adrenalectomy versus those predicted by the NSQIP calculator. Certain observed differences may not necessarily have clinical significance. Urology procedure-specific calculators may better refine predictions for sub-specialty procedures with future work requisite to determine performance across all practice settings.

The International Penile Advanced Cancer Trial (InPACT): Rationale and Current Status.

The historic international penile cancer trial InPACT is now open and accruing patients in the UK and USA. The trial is geared to answer important questions for patients with evidence of inguinal lymph node disease at presentation. This clinical trial update provides an overview of the study and progress to date.

Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis.

Cancer patients have poor prognoses when lymph node (LN) involvement is present in both high-grade urothelial cell carcinoma (HG-UCC) of the bladder and colorectal cancer (CRC). More than 50% of patients with muscle-invasive UCC, despite curative therapy for clinically-localized disease, will develop metastases and die within 5 years, and metastatic CRC is a leading cause of cancer-related deaths in the US. Xenograft models that consistently mimic UCC and CRC metastasis seen in patients are needed. This study aims to generate patient-derived orthotopic xenograft (PDOX) models of UCC and CRC for primary tumor growth and spontaneous metastases under the influence of LN stromal cells mimicking the progression of human metastatic diseases for drug screening. Fresh UCC and CRC tumors were obtained from consented patients undergoing resection for HG-UCC and colorectal adenocarcinoma, respectively. Co-inoculated with LN stromal cell (LNSC) analog HK cells, luciferase-tagged UCC cells were intra-vesically (IB) instilled into female non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, and CRC cells were intra-rectally (IR) injected into male NOD/SCID mice. Tumor growth and metastasis were monitored weekly using bioluminescence imaging (BLI). Upon sacrifice, primary tumors and mouse organs were harvested, weighed, and formalin-fixed for Hematoxylin and Eosin and immunohistochemistry staining. In our unique PDOX models, xenograft tumors resemble patient pre-implantation tumors. In the presence of HK cells, both models have high tumor implantation rates measured by BLI and tumor weights, 83.3% for UCC and 96.9% for CRC, and high distant organ metastasis rates (33.3% detected liver or lung metastasis for UCC and 53.1% for CRC). In addition, both models have zero mortality from the procedure. We have established unique, reproducible PDOX models for human HG-UCC and CRC, which allow for tumor formation, growth, and metastasis studies. With these models, testing of novel therapeutic drugs can be performed efficiently and in a clinically-mimetic manner.

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.

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.