Predicting Response to Intravesical BCG in High-Risk NMIBC Using an Artificial Intelligence-Powered Pathology Assay: Development and Validation in an International 12-Center Cohort.

PURPOSE: There are few markers to identify those likely to recur or progress after treatment with intravesical bacillus Calmette-Guérin (BCG). We developed and validated artificial intelligence-based histologic assays that extract interpretable features from transurethral resection of bladder tumor digitized pathology images to predict risk of recurrence, progression, development of BCG-unresponsive disease, and cystectomy. MATERIALS AND METHODS: Pre-BCG resection-derived whole-slide images and clinical data were obtained for high-risk NMIBC cases treated with BCG from 12 centers and were analyzed through a segmentation and feature extraction pipeline. Features associated with clinical outcomes were defined and tested on independent development and validation cohorts. Cases were classified into high or low risk for recurrence, progression, BCG-unresponsive disease, and cystectomy. RESULTS: Nine hundred forty-four cases (development: 303, validation: 641, median follow-up: 36 months) representative of the intended use population were included (high-grade Ta: 34.1%, high-grade T1: 54.8%; carcinoma in situ only: 11.1%, any carcinoma in situ: 31.4%). In the validation cohort, "high recurrence risk" cases had inferior high-grade recurrence-free survival vs "low recurrence risk" cases (HR, 2.08, P < .0001). "High progression risk" patients had poorer progression-free survival (HR, 3.87, P < .001) and higher risk of cystectomy (HR, 3.35, P < .001) than "low progression risk" patients. Cases harboring the BCG-unresponsive disease signature had a shorter time to development of BCG-unresponsive disease than cases without the signature (HR, 2.31, P < .0001). AI assays provided predictive information beyond clinicopathologic factors. CONCLUSIONS: We developed and validated AI-based histologic assays that identify high-risk NMIBC cases at higher risk of recurrence, progression, BCG-unresponsive disease, and cystectomy, potentially aiding clinical decision making.

National Surgical Quality Improvement Program audit of contemporary perioperative care for radical cystectomy.

OBJECTIVE: To examine the impact of increased compliance to contemporary perioperative care measures, as outlined by enhanced recover after surgery (ERAS) guidelines, among patients undergoing radical cystectomy (RC). PATIENTS AND METHODS: From the National Surgical Quality Improvement Program database we captured patients undergoing RC between 2019 and 2021. We identified five perioperative care measures: regional anaesthesia block, thromboembolism prophylaxis, ≤24 h perioperative antibiotic administration, absence of bowel preparation, and early oral diet. We stratified patients by the number of measures utilised (one to five). Statistical endpoints included 30-day complications, hospital length of stay (LOS), readmissions, and optimal RC outcome. Optimal RC outcome was defined as absence of any postoperative complication, re-operation, prolonged LOS (75th percentile, 8 days) with no readmission. Multivariable regressions with Bonferroni correction were performed to assess the association between use of contemporary perioperative care measures and outcomes. RESULTS: Of the 3702 patients who underwent RC, 73 (2%), 417 (11%), 1010 (27%), 1454 (39%), and 748 (20%) received one, two, three, four, and five interventions, respectively. On multivariable analysis, increased perioperative care measures were associated with lower odds of any complication (odds ratio [OR] 0.66, 99% confidence interval [CI] 0.6-0.73), and shorter LOS (ß -0.82, 99% CI -0.99 to -0.65). Furthermore, patients with increased compliance to contemporary care measures had increased odds of an optimal outcome (OR 1.38, 99% CI 1.26-1.51). CONCLUSIONS: Among the measures we assessed, greater adherence yielded improved postoperative outcomes among patients undergoing RC. Our work supports the efficacy of ERAS protocols in reducing the morbidity associated with RC.

Long-term outcomes of bladder-sparing therapy vs radical cystectomy in BCG-unresponsive non-muscle-invasive bladder cancer.

OBJECTIVE: To quantify the oncological risks of bladder-sparing therapy (BST) in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) compared to upfront radical cystectomy (RC). PATIENTS AND METHODS: Pre-specified data elements were collected from retrospective cohorts of patients with BCG-unresponsive NMIBC from 10 international sites. After Institutional Review Board approval, patients were included if they had BCG-unresponsive NMIBC meeting United States Food and Drug Administration criteria. Oncological outcomes were collected following upfront RC or BST. BST regimens included re-resection or surveillance only, repeat BCG, intravesical chemotherapy, systemic immunotherapy, and clinical trials. RESULTS: Among 578 patients, 28% underwent upfront RC and 72% received BST. The median (interquartile range) follow-up was 50 (20-69) months. There were no statistically significant differences in metastasis-free survival, cancer-specific survival, or overall survival between treatment groups. In the BST group, high-grade recurrence rates were 37% and 52% at 12 and 24 months and progression to MIBC was observed in 7% and 13% at 12 and 24 months, respectively. RC was performed in 31.7% in the BST group and nodal disease was found in 13% compared with 4% in upfront RC (P = 0.030). CONCLUSION: In a selected cohort of patients, initial BST offers comparable survival outcomes to upfront RC in the intermediate term. Rates of recurrence and progression increase over time especially in patients treated with additional lines of BST.

The role of radical cystectomy and lymphadenectomy in the management of bladder cancer with clinically positive lymph node involvement.

PURPOSE OF REVIEW: The role of radical cystectomy and pelvic lymph node dissection in muscle-invasive bladder cancer (MIBC) with clinically positive lymph nodes is debated. This review examines the role of surgery in treating patients with clinical N1 and more advanced nodal involvement (N2-N3) within a multimodal treatment approach. RECENT FINDINGS: For clinical N1 disease, guidelines typically recommend neoadjuvant chemotherapy followed by surgery. However, for N2-N3 disease, guidelines vary. Advances in diagnostics, systemic therapies, and surgical recovery have improved the prognosis for these patients. Research is increasingly identifying MIBC patients, including those with positive nodes, who may achieve complete pathologic response and long-term survival, supporting the role of surgery even in advanced nodal stages. SUMMARY: Managing MIBC with clinically positive lymph nodes, especially in N2-N3 disease, requires a tailored approach. While neoadjuvant chemotherapy followed by radical cystectomy is standard for N1 disease, the role of surgery in advanced nodal stages is growing because of better patient selection and treatment strategies. Emerging evidence suggests that consolidative surgery may improve outcomes in these complex cases.

Sequential Intravesical Valrubicin and Docetaxel for the Salvage Treatment of Non-Muscle-Invasive Bladder Cancer.

PURPOSE: Intravesical gemcitabine-docetaxel has emerged as an efficacious and well-tolerated salvage therapy for non-muscle-invasive bladder cancer. However, further rescue therapies are needed for subsequent recurrences or intolerance, particularly when cystectomy is refused or precluded. Valrubicin is a U.S. Food and Drug Administration-approved agent for bacillus Calmette-Guérin unresponsive disease, yet as monotherapy has demonstrated poor efficacy. We report our experience with sequential intravesical valrubicin and docetaxel as a rescue therapy for non-muscle-invasive bladder cancer. MATERIALS AND METHODS: We retrospectively identified all patients with recurrent non-muscle-invasive bladder cancer treated with valrubicin and docetaxel between April 2013 and June 2021. Patients received weekly sequential intravesical instillations of 800 mg valrubicin and 37.5 mg docetaxel for 6 weeks. If disease-free at first follow-up, monthly maintenance of 2 years was initiated. The primary outcome was recurrence-free survival, assessed using the Kaplan-Meier method. RESULTS: The analysis included 75 patients with median follow-up of 21 months (IQR: 13-37). Twelve patients with low-grade disease had a 73% recurrence-free survival at 2 years. Sixty-three patients with recurrent high-grade disease had a 38% 2-year high-grade recurrence-free survival. Forty-two (56%) patients had carcinoma in situ present; recurrence-free survival was similar for those with and without carcinoma in situ (P = .63). Two patients died of metastatic bladder cancer while 10 underwent cystectomy. Among patients with high-grade disease, overall, cancer-specific, and cystectomy-free survivals were 87%, 96%, and 84% at 2 years, respectively. Adverse events included bladder spasms (n = 18), urinary frequency (n = 10), and dysuria (n = 8). Two patients could not tolerate valrubicin and docetaxel induction. CONCLUSIONS: In a heavily pretreated population, our results suggest valrubicin and docetaxel is an effective rescue treatment for patients with recurrent non-muscle-invasive bladder cancer. Further prospective evaluation is needed.

Unplanned Conversion From Partial to Radical Nephrectomy: An Analysis of Incidence, Etiology, and Risk Factors.

PURPOSE: Conversions from partial to radical nephrectomy are uncommon and reports on this topic are rare. In this study we present a detailed analysis of conversions from partial to radical nephrectomy in a single-institutional contemporary experience and provide an analysis of preoperative risk factors. MATERIALS AND METHODS: Patients who underwent converted (cases) and completed (controls) partial nephrectomy from 2000 to 2015 were matched 1:1 for analysis. Perioperative imaging was reviewed and RENAL (for radius, exophytic/endophytic properties, anterior/posterior descriptor, and location relative to the polar line) nephrometry scores were calculated. Reasons for conversions were abstracted from operative reports. Multivariable conditional logistic regression analyses were used to assess preoperative risk factors for conversion. RESULTS: A total of 168 cases (6.1% of all partial nephrectomies) were identified and matched on tumor size, year of surgery, and surgical approach to 168 controls. Conversion rates decreased from 13% in 2000-2003 to 4% in 2012-2015. Oncologic considerations, such as concern for upstaging and positive margins, were the most cited (56%) reasons for conversion. On multivariable analyses, male sex (odds ratio 2.34; P = .03), Charlson score (odds ratio per 1-unit increase: 1.28; P = .03), posterior and middle (on anteroposterior axis) location (reference: anterior, odds ratio 2.83, P = .02 and odds ratio 6.38, P < .001, respectively) and hilar location (reference: peripheral/central, odds ratio 5.61; P < .001) were associated with increased odds of conversion. CONCLUSIONS: Rates of conversion from partial to radical nephrectomy in our experience were low and decreased over time. Preoperative characteristics such as hilar, posterior, and middle locations were significantly associated with conversions after controlling for tumor size, and offer guidance for operative planning and patient counseling.

Sequential Intravesical Gemcitabine and Docetaxel for bacillus Calmette-Guérin-Naïve High-Risk Nonmuscle-Invasive Bladder Cancer.

PURPOSE: Bacillus Calmette-Guérin (BCG) is currently recommended as adjuvant therapy following complete transurethral resection of bladder tumor for high-risk nonmuscle-invasive bladder cancer (NMIBC). In response to the BCG shortage, gemcitabine plus docetaxel (Gem/Doce) has been utilized at our institution in the BCG-naïve setting. We report the outcomes of patients with high-risk BCG-naïve NMIBC treated with Gem/Doce. MATERIALS AND METHODS: We retrospectively reviewed patients with BCG-naïve high-risk NMIBC treated with Gem/Doce from May 2013 through April 2021. Patients received 6 weekly intravesical instillations of sequential 1 gm gemcitabine and 37.5 mg docetaxel after complete transurethral resection of bladder tumor. Monthly maintenance of 2 years was initiated if disease-free at first followup. The primary outcome was recurrence-free survival. Survival was assessed with the Kaplan-Meier method, indexed from the first Gem/Doce instillation. Adverse events were reported using CTCAE (Common Terminology Criteria for Adverse Events) v5 (National Cancer Institute, Bethesda, Maryland). Differences were assessed with the log-rank test. RESULTS: There were 107 patients with a median followup of 15 months included in the analysis. Patients had high-risk characteristics including 47 with any carcinoma in situ and 55 with T1 disease. Recurrence-free survival was 89%, 85% and 82% at 6, 12 and 24 months, respectively. Recurrence rates were similar between patients with or without carcinoma in situ (p=0.42). No patient had disease progression or died of bladder cancer. One patient underwent cystectomy due to end-stage lower urinary tract symptoms. Overall survival was 84% at 24 months. There were 92 adverse events (1 ≥grade 3), and 4 (4%) patients were unable to receive a full induction course. CONCLUSIONS: Gem/Doce is an effective and well-tolerated therapy for BCG-naïve NMIBC. Further investigation is warranted.

Cost-Effectiveness Analysis of Pembrolizumab for Bacillus Calmette-Guérin-Unresponsive Carcinoma In Situ of the Bladder.

PURPOSE: Patients with bacillus Calmette-Guérin-unresponsive carcinoma in situ are treated with radical cystectomy or salvage intravesical chemotherapy. Recently, pembrolizumab was approved for bacillus Calmette-Guérin-unresponsive carcinoma in situ. MATERIALS AND METHODS: We used a decision-analytic Markov model to compare pembrolizumab, salvage intravesical chemotherapy (with gemcitabine-docetaxel induction+monthly maintenance) and radical cystectomy for patients with bacillus Calmette-Guérin-unresponsive carcinoma in situ who are radical cystectomy candidates (index patient 1) or are unwilling/unable to undergo radical cystectomy (index patient 2). The model used a U.S. Medicare perspective with a 5-year time horizon. One-way and probabilistic sensitivity analyses were performed. Incremental cost-effectiveness ratios were compared using a willingness to pay threshold of $100,000/quality-adjusted life year. RESULTS: For index patient 1, pembrolizumab was not cost-effective relative to radical cystectomy (incremental cost-effectiveness ratios $1,403,008/quality-adjusted life year) or salvage intravesical chemotherapy (incremental cost-effectiveness ratios $2,011,923/quality-adjusted life year). One-way sensitivity analysis revealed that pembrolizumab only became cost-effective relative to radical cystectomy with a >93% price reduction. Relative to radical cystectomy, salvage intravesical chemotherapy was cost-effective for time horizons <5 years and nearly cost-effective at 5 years (incremental cost-effectiveness ratios $118,324/quality-adjusted life year). One-way sensitivity analysis revealed that salvage intravesical chemotherapy became cost-effective relative to radical cystectomy if risk of recurrence or metastasis at 2 years was less than 55% or 5.9%, respectively. For index patient 2, pembrolizumab required >90% price reduction to be cost-effective (incremental cost-effectiveness ratios $1,073,240/quality-adjusted life year). Pembrolizumab was cost-effective in 0% of 100,000 microsimulations in probabilistic sensitivity analyses for both index patients. CONCLUSIONS: At its current price, pembrolizumab is not cost-effective for bacillus Calmette-Guérin-unresponsive carcinoma in situ relative to radical cystectomy or salvage intravesical chemotherapy. Although gemcitabine-docetaxel is not cost-effective relative to radical cystectomy at 5 years, further studies may validate its cost-effectiveness if recurrence and metastasis thresholds are met.

The current landscape of salvage therapies for patients with bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer.

PURPOSE OF REVIEW: Although radical cystectomy represents the gold standard treatment for patients with high-risk nonmuscle invasive bladder cancer (NMIBC) whose disease does not respond to bacillus Calmette-Guérin (BCG), many patients are unable or unwilling to undergo surgery. The need remains for effective bladder-preserving therapies. This review aims to describe existing treatments, contemporary research in this field and ongoing trials of salvage therapies for patients with BCG-unresponsive NMIBC. RECENT FINDINGS: Intravesical chemotherapy has been utilized frequently in this setting. Emerging data on combination regimens such as intravesical gemcitabine and docetaxel and intravesical cabazitaxel, gemcitabine and cisplatin are promising; nevertheless, larger, prospective trials are needed. Meanwhile, the intravenous checkpoint inhibitor pembrolizumab was recently FDA-approved for patients BCG-unresponsive NMIBC. Encouraging clinical trial results for intravesical nadofaragene firadenovec, oportuzumab monatox and ALT-803 + BCG have been released, while data from trials of other treatment strategies, including novel chemotherapy and drug delivery, augmented BCG immunotherapy, adenoviral and gene therapy, targeted therapy, and combination systemic immunotherapy with intravesical agents, are eagerly awaited. SUMMARY: Several novel salvage therapies offer promise for patients with BCG-unresponsive NMIBC. Patient selection, efficacy, safety, cost and ease of administration must be carefully considered to determine the optimal treatment approach.

Partial versus radical nephrectomy in clinical T2 renal masses.

OBJECTIVE: To report perioperative, renal functional and oncologic outcomes for patients undergoing partial or radical nephrectomy for cT2 renal masses. METHODS: Retrospective review of patients who underwent partial (n = 72) or radical nephrectomy (n = 379) for cT2 renal masses from 2000 to 2016. After propensity adjustment using inverse probability weighting, the following were compared by surgery (partial or radical nephrectomy): complications, renal function measured by estimated glomerular filtration rate as continuous and as <60 mL/min/1.73 m2 at 1 and 3 years postoperatively and overall, metastases-free survival and cancer-specific survival in patients with renal cell carcinoma. RESULTS: After propensity adjustment, clinical and radiographic features were well-balanced between groups. Overall and severe complications were more common for partial compared with radical nephrectomy, although not statistically significant (19 vs 13%, P = 0.14 and 4 vs 2%, P = 0.3, respectively). Estimated glomerular filtration rate change at 1 and 3 years was more pronounced in radical compared with partial nephrectomy (median -16 vs -5 and -14 vs -2, respectively, P < 0.001). A greater proportion of radical nephrectomy patients had an estimated glomerular filtration rate <60 at 1 and 3 years (55 vs 17% and 48 vs 17%, respectively, P < 0.01). In renal cell carcinoma patients, overall, metastases-free and cancer-specific survival were not significantly different between groups (median survivor follow up 7.1 years, interquartile range 3.6-11.4). CONCLUSIONS: Partial nephrectomy appears to be a relatively safe and a potentially effective treatment for cT2 renal masses, conferring better renal functional preservation compared with radical nephrectomy. These data support continued use of partial nephrectomy for renal masses >7 cm in appropriately selected patients.

Cost-Effectiveness of Maintenance bacillus Calmette-Guérin for Intermediate and High Risk Nonmuscle Invasive Bladder Cancer.

PURPOSE: While guidelines support the use of maintenance bacillus Calmette-Guérin for patients with intermediate and high risk nonmuscle invasive bladder cancer, in an era of bacillus Calmette-Guérin shortage we explored the cost-effectiveness of maintenance bacillus Calmette-Guérin. MATERIALS AND METHODS: A Markov model compared the cost-effectiveness of maintenance bacillus Calmette-Guérin to surveillance after induction bacillus Calmette-Guérin for intermediate/high risk nonmuscle invasive bladder cancer from a U.S. Medicare perspective. Five-year oncologic outcomes, toxicity rates and utility values were extracted from the literature. Univariable and multivariable sensitivity analyses were conducted. A willingness to pay threshold of $100,000 per quality adjusted life year was considered cost-effective. RESULTS: At 5 years mean costs per patient were $14,858 and $13,973 for maintenance bacillus Calmette-Guérin and surveillance, respectively, with quality adjusted life years of 4.046 for both, making surveillance the dominant strategy. On sensitivity analysis full dose and 1/3 dose maintenance bacillus Calmette-Guérin became cost-effective if the absolute reduction in 5-year progression was greater than 2.1% and greater than 0.76%, respectively. On further sensitivity analysis full dose and 1/3 dose maintenance bacillus Calmette-Guérin became cost-effective when maintenance bacillus Calmette-Guérin toxicity equaled surveillance toxicity. In multivariable sensitivity analyses using 100,000 Monte-Carlo microsimulations, full dose and 1/3 dose maintenance bacillus Calmette-Guérin was cost-effective in 17% and 39% of microsimulations, respectively. CONCLUSIONS: Neither full dose nor 1/3 dose maintenance bacillus Calmette-Guérin appears cost-effective for the entire population of patients with intermediate/high risk nonmuscle invasive bladder cancer. These data support prioritizing maintenance bacillus Calmette-Guérin for the subset of patients with high risk nonmuscle invasive bladder cancer most likely to experience progression, in particular those who tolerated induction bacillus Calmette-Guérin well. Overall, our findings support the American Urological Association policy statement to allocate bacillus Calmette-Guérin for induction rather than maintenance therapy during times of bacillus Calmette-Guérin shortage.

Biomarkers Implicated in Lower Urinary Tract Symptoms: Systematic Review and Pathway Analyses.

PURPOSE: Lower urinary tract symptoms are prevalent and burdensome, yet methods to enhance diagnosis and appropriately guide therapies are lacking. We systematically reviewed the literature for human studies of biomarkers associated with lower urinary tract symptoms. MATERIALS AND METHODS: PubMed®, EMBASE® and Web of Science® were searched from inception to February 13, 2018. Articles were included if they were in English, performed in benign urological populations without neurological disorders or interstitial cystitis/bladder pain syndrome, and assessed a biomarker's association with or ability to predict specific lower urinary tract symptoms or urological conditions. Bioinformatic pathway analyses were conducted to determine whether individual biomarkers associated with symptoms are present in unifying pathways. RESULTS: Of 6,150 citations identified 125 met the inclusion criteria. Most studies (93.6%) assessed biomarkers at 1 time point and were cross-sectional in nature. Few studies adjusted for potentially confounding clinical variables or assessed biomarkers in an individual over time. No individual biomarkers are currently validated as diagnostic tools for lower urinary tract symptoms. Compared to controls, pathway analyses identified multiple immune response pathways that were enriched in overactive bladder syndrome and cell migration/cytoskeleton remodeling pathways that were enriched in female stress incontinence. CONCLUSIONS: Major deficiencies in the existing biomarker literature include poor reproducibility of laboratory data, unclear classification of patients with lower urinary tract symptoms and lack of adjustment for clinical covariates. Despite these limitations we identified multiple putative pathways in which panels of biological markers need further research.

Current Clinical Trials in Non-muscle-Invasive Bladder Cancer: Heightened Need in an Era of Chronic BCG Shortage.

PURPOSE OF REVIEW: BCG is the gold standard agent used in high-risk non-muscle-invasive bladder cancer (NMIBC) that is amenable to bladder sparing management. However, recent BCG shortages appear to be a chronic problem. There are limited effective intravesical options in lieu of BCG or in patients in whom BCG is not effective. This review aims to highlight emerging bladder sparing therapies and trials for NMIBC. RECENT FINDINGS: Patients with high-risk NMIBC who do not respond to BCG are at increased risk for progression and death from bladder cancer. There are a variety of clinical trials exploring different therapeutic approaches including checkpoint inhibition, novel chemotherapy and drug delivery, viral and gene therapy, vaccines, and targeted therapy. In the era of limited supply of BCG, there is a need for both effective first-line alternatives as and options for patients who do not respond to BCG. Fortunately, there are a variety of active trials and mechanisms exploring these areas aggressively.

The Relationship between Sleep Disorders and Lower Urinary Tract Symptoms: Results from the NHANES.

PURPOSE: It is well established that sleep disorders are associated with the nocturia prevalence in men. While previous literature supports that patients with sleep disorders are at increased risk for nocturia, the risk of daytime lower urinary tract symptoms has not been well established. MATERIALS AND METHODS: We examined the NHANES (National Health and Nutrition Examination Survey) database between 2006 and 2008. Men older than 40 years who completed the sleep, prostate and kidney questionnaires were included in study. The presence of lower urinary tract symptoms was defined as 2 or more symptoms, including hesitancy, incomplete emptying and/or nocturia. Multivariable models using logistic regression were constructed to compare groups of men with and without a sleep disorder. RESULTS: Of the 3,071 men who completed all survey questions 270 (8.8%) reported a sleep disorder. Men with a sleep disorder had a significantly higher body mass index (30.8 vs 27.4 kg/m2), a greater likelihood of reporting diabetes (20.3% vs 10.2%) and more comorbidities (72.6% vs 45.2%, all p <0.01) than men without a sleep disorder. Multivariable logistic regressions demonstrated that men with a sleep disorder were more likely to report nocturia (OR 1.23), 2 or more lower urinary tract symptoms (OR 1.12) and daytime lower urinary tract symptoms (OR 1.27, all p <0.01). CONCLUSIONS: Sleep disorders are associated with an increased risk of nocturia and daytime lower urinary tract symptoms independent of body mass index, diabetes and an increased number of comorbidities. Based on the current data clinicians should consider assessing lower urinary tract symptoms in men with a sleep disorder since intervention could improve lower urinary tract symptoms and sleep disorders as well as daytime urinary symptoms.

Reclassification of prostate cancer risk using sequentially identified SNPs: Results from the REDUCE trial.

BACKGROUND: Although the clinical validity of risk-associated single nucleotide polymorphisms (SNPs) for assessment of disease susceptibility has been consistently established, risk reclassification from increasing numbers of implicated risk-associated SNPs raises concern that it is premature for clinical use. Our objective is to assess the degree and impact of risk reclassification with the increasing number of SNPs. METHODS: A total of 3239 patients from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial were included. Four genetic risk scores (GRSs) were calculated based on sets of sequentially discovered prostate cancer (PCa) risk-associated SNPs (17, 34, 51, and 68 SNPs). RESULTS: Pair-wise correlation coefficients between sets of GRSs increased as more SNPs were included in the GRS: 0.80, 0.86, and 0.95 for 17 versus 34 SNPs, 34 versus 51 SNPs, and 51 versus 68 SNPs, respectively. Using a GRS of 1.5 as a cutoff for higher versus lower risk, reclassification rates of PCa risk decreased: 14.11%, 12.04%, and 8.15% for 17 versus 34 SNPs, 34 versus 51 SNPs, and 51 versus 68 SNPs, respectively. Evolving GRSs, nevertheless, provide a tool for further refining risk assessment. When all four sequential GRSs were considered, the detection rates of PCa for men whose GRSs were consistently <1.5, reclassified, and consistently ≥1.5 were 20.8%, 29.67%, and 39.26%, respectively (Ptrend = 1.12 × 10-8 ). In comparison, the detection rates of PCa in men with negative or positive family history were 23.75% and 31.78%, respectively. CONCLUSIONS: Risk assessment using currently available SNPs is justified. Multiple GRS values from evolving sets of SNPs provide a valuable tool for better refining risk.

Non-muscle-invasive bladder cancer: Intravesical treatments beyond Bacille Calmette-Guérin.

An unmet need exists for patients with high-risk non-muscle-invasive bladder cancer for whom bacille Calmette-Guérin (BCG) has failed and who seek further bladder-sparing approaches. This shortcoming poses difficult management dilemmas. This review explores previously investigated first-line intravesical therapies and discusses emerging second-line treatments for the heterogeneous group of patients for whom BCG has failed. The myriad of recently published and ongoing trials assessing novel salvage intravesical treatments offer promise to patients who both seek an effective cure and want to avoid radical surgery. However, these trials must carefully be contextualized by specific patient, tumor, and recurrence characteristics. As data continue to accumulate, there will potentially be a role for these agents as second-line or even first-line intravesical therapies. Cancer 2017;123:390-400. © 2016 American Cancer Society.

Extended Duration Enoxaparin Decreases the Rate of Venous Thromboembolic Events after Radical Cystectomy Compared to Inpatient Only Subcutaneous Heparin.

PURPOSE: Venous thromboembolic events are a significant source of morbidity after radical cystectomy. At our institution subcutaneous heparin was historically given to patients undergoing radical cystectomy immediately before incision and throughout the inpatient stay. In an effort to decrease the overall rate of venous thromboembolism and post-discharge venous thromboembolism, a regimen including extended duration enoxaparin was initiated for patients undergoing radical cystectomy. MATERIALS AND METHODS: In January 2013 thromboprophylaxis was modified for patients undergoing radical cystectomy by replacing a regimen of subcutaneous heparin before induction and then every 8 hours until discharge home with enoxaparin daily for postoperative prophylaxis continued until 28 days after discharge. Data from our institutional radical cystectomy database for patients undergoing surgery from January 2011 to May 2014 were reviewed. The primary outcome was clinically symptomatic postoperative venous thromboembolism. Secondary outcomes included timing of venous thromboembolism and blood transfusions. Multivariate logistic regression was used to control for differences between cohorts. RESULTS: Of the 402 patients 234 underwent radical cystectomy before the change and 168 after. The enoxaparin regimen decreased the rate of venous thromboembolism (12% vs 5%, p=0.024) with the main benefit on post-discharge venous thromboembolism (6% vs 2%, p=0.039). Overall 17 of 37 (46%) venous thromboembolisms occurred after discharge home. Multivariate analysis confirmed that the enoxaparin regimen was independently associated with reduced odds of venous thromboembolism (OR 0.33, 95% CI 0.14-0.76, p=0.009). Intraoperative and postoperative transfusion rates were similar between cohorts. CONCLUSIONS: Thromboprophylaxis with extended duration enoxaparin decreased the rate of venous thromboembolism after radical cystectomy compared to inpatient only subcutaneous heparin with no increased risk of bleeding.