Transcriptomic Heterogeneity of Expansile Cribriform and Other Gleason Pattern 4 Prostate Cancer Subtypes.

BACKGROUND: Prostate cancers featuring an expansile cribriform (EC) pattern are associated with worse clinical outcomes following radical prostatectomy (RP). However, studies of the genomic characteristics of Gleason pattern 4 subtypes are limited. OBJECTIVE: To explore transcriptomic characteristics and heterogeneity within Gleason pattern 4 subtypes (fused/poorly formed, glomeruloid, small cribriform, EC/intraductal carcinoma [IDC]) and the association with biochemical recurrence (BCR)-free survival. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study including 165 men with grade group 2-4 prostate cancer who underwent RP at a single academic institution (2016-2020) and Decipher testing of the RP specimen. Patients with Gleason pattern 5 were excluded. IDC and EC patterns were grouped. Median follow-up was 2.5 yr after RP for patients without BCR. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Prompted by heterogeneity within pattern 4 subtypes identified via exploratory analyses, we investigated transcriptomic consensus clusters using partitioning around medoids and hallmark gene set scores. The primary clinical outcome was BCR, defined as two consecutive prostate-specific antigen measurements >0.2 ng/ml at least 8 wk after RP, or any additional treatment. Multivariable Cox proportional-hazards models were used to determine factors associated with BCR-free survival. RESULTS AND LIMITATIONS: In this cohort, 99/165 patients (60%) had EC and 67 experienced BCR. Exploratory analyses and clustering demonstrated transcriptomic heterogeneity within each Gleason pattern 4 subtype. In the multivariable model controlled for pattern 4 subtype, margin status, Cancer of the Prostate Risk Assessment Post-Surgical score, and Decipher score, a newly identified steroid hormone-driven cluster (hazard ratio 2.35 95% confidence interval 1.01-5.47) was associated with worse BCR-free survival. The study is limited by intermediate follow-up, no validation cohort, and lack of accounting for intratumoral and intraprostatic heterogeneity. CONCLUSIONS: Transcriptomic heterogeneity was present within and across each Gleason pattern 4 subtype, demonstrating there is additional biologic diversity not captured by histologic subtypes. This heterogeneity can be used to develop novel signatures and to classify transcriptomic subtypes, which may help in refining risk stratification following RP to further guide decision-making on adjuvant and salvage treatments. PATIENT SUMMARY: We studied prostatectomy specimens and found that tumors with similar microscopic appearance can have genetic differences that may help to predict outcomes after prostatectomy for prostate cancer. Our results demonstrate that further gene expression analysis of prostate cancer subtypes may improve risk stratification after prostatectomy. Future studies are needed to develop novel gene expression signatures and validate these findings in independent sets of patients.

Readmissions trends following radical cystectomy for bladder cancer unchanged in the era of enhanced recovery after surgery (ERAS) protocols.

PURPOSE: To provide nationally representative estimates of contemporary trends in readmission rates, readmission location (index vs. nonindex hospital), and causes of readmission following radical cystectomy (RC) in the era of enhanced recovery after surgery (ERAS) protocol implementation. MATERIALS AND METHODS: Patients with bladder cancer who underwent RC were identified in the Nationwide Readmissions Database (2016-2019). Yearly trends in 30-day and 90-day readmission rates and readmission causes were assessed in the whole cohort and subset of patients who underwent RC at high volume centers (>22 RCs/year). Multivariable logistic regression was used to determine predictors of index readmission, nonindex readmission, death during readmission, and experiencing a second readmission. RESULTS: Among the 20,957 RC patients, the 30-day and 90-day readmission rates were 23.5% (n = 4,931) and 39.1% (n = 7,987), respectively. For 90-day readmissions, 27.6% (n = 2,206) were to nonindex hospitals. During the study period, there was no significant change in the yearly 30-day or 90-day readmission rates and percentage of readmissions to nonindex hospitals (all p > 0.05). This was also true in the subset of patients who underwent RC at high volume centers. The only significant change in causes of readmission during the study period was wound readmissions (2.7% in 2016 vs. 5.1% of readmissions in 2019, p = 0.02). CONCLUSIONS: During the era of ERAS protocol implementation, in this nationally representative study, most causes of readmission and both 30 and 90-day readmission rates were unchanged, even at high volume RC centers. Moving forward, novel interventions are needed which focus on the postdischarge recovery period to help decrease readmission rates following RC.

Gleason Grade 1 Prostate Cancer Volume at Biopsy Is Associated With Upgrading but Not Adverse Pathology or Recurrence After Radical Prostatectomy: Results From a Large Institutional Cohort.

PURPOSE: Clinical guidelines suggest that for low-grade, clinically localized prostate cancer, patients with higher volume of disease at diagnosis may benefit from definitive therapy, although the data remain unclear. Our objective was to determine associations between low-grade prostate cancer volume and outcomes in men managed with primary radical prostatectomy. MATERIALS AND METHODS: Men with cT1-2N0/xM0/x prostate cancer, prostate specific antigen at diagnosis <10 ng/mL, and Gleason grade group 1 pathology on diagnostic biopsy managed with primary radical prostatectomy were included. Outcomes were pathological upgrade at radical prostatectomy (≥Gleason grade group 2), University of California, San Francisco adverse pathology at radical prostatectomy (≥Gleason grade group 3, pT3/4, or pN1), alternate adverse pathology at radical prostatectomy (≥Gleason grade group 3, ≥pT3b, or pN1), and recurrence (biochemical failure with 2 prostate specific antigen ≥0.2 ng/mL or salvage treatment). Multivariable logistic regression models were used to estimate associations between percentage of positive cores and risk of upgrade and adverse pathology at radical prostatectomy. Multivariable Cox proportional hazards regression models were used to estimate associations between percentage of positive cores and hazard of recurrence after radical prostatectomy. RESULTS: A total of 1,029 men met inclusion criteria. Multivariable logistic regression models demonstrated significant associations between percentage of positive cores and pathological upgrade (OR 1.31, 95% CI 1.1-1.57, P < .01), but not University of California, San Francisco adverse pathology at radical prostatectomy (P = .84); percentage of positive cores was negatively associated with alternate adverse pathology (OR 0.67, 95% CI 0.48-0.93, P = .02). Multivariable Cox regression models demonstrated no association between percentage of positive cores and hazard of recurrence after radical prostatectomy (P = .11). CONCLUSIONS: In men with Gleason grade group 1 prostate cancer, tumor volume may be associated with upgrading at radical prostatectomy, but not more clinically significant outcomes of adverse pathology or recurrence.

The Natural History of Untreated Biopsy Grade Group Progression and Delayed Definitive Treatment for Men on Active Surveillance for Early-Stage Prostate Cancer.

PURPOSE: For men with clinically localized prostate cancer outcomes of continuing active surveillance (AS) after biopsy progression are not well understood. We aim to determine the impact of continuing AS and delayed definitive treatment after biopsy progression on oncologic outcomes. MATERIALS AND METHODS: Participants in our prospective AS cohort (1990-2018) diagnosed with grade group (GG) 1, localized prostate cancer, with prostate specific antigen <20 who were subsequently upgraded to ≥GG2, and underwent further surveillance (biopsy/imaging/prostate specific antigen) were identified. Patients were stratified by post-progression followup into 3 groups: continue AS untreated, pursue early radical prostatectomy (RP) ≤6 months, or undergo late RP within 6 months to 5 years of progression. Patients receiving other treatments were excluded. We compared characteristics between groups and examined the associations of early vs late RP with risk of adverse pathology (AP) at RP and recurrence-free survival (RFS) after RP. RESULTS: Of 531 patients with biopsy progression and further surveillance 214 (40%) remained untreated, 192 (36%) pursued early RP and 125 (24%) underwent late RP. Among patients who underwent early vs late RP, there was no difference in GG (p=0.15) or AP (55% vs 53%, p=0.74) rate at RP, or 3-year RFS (80% vs 87%, log-rank p=0.64) after RP. In multivariable models, only Cancer of Prostate Risk Assessment post-surgical score was associated with risk of RFS (HR=1.42 per point, 95% CI 1.24-1.64). CONCLUSIONS: Among patients continuing AS after biopsy progression, 60% underwent surgery within 5 years. Delayed surgery after progression was not associated with higher risk of AP or RFS. This suggests select patients may be able to safely delay treatment after progression.

Utility of Blue Light Cystoscopy for Post-bacillus Calmette-Guérin Bladder Cancer Recurrence Detection: Implications for Clinical Trial Recruitment and Study Comparisons.

PURPOSE: The utility of blue light cystoscopy (BLC) in patients receiving bacillus Calmette-Guérin (BCG) during post-treatment cystoscopy is not well understood. Our objective was to determine if BLC improves recurrence detection in patients with non-muscle invasive bladder cancer (NMIBC) undergoing BCG. MATERIALS AND METHODS: Using the prospective multi-institutional Cysview® Registry (2014-2019), patients with NMIBC who received BCG within 1 year prior to BLC were identified. Primary outcomes were recurrences and whether lesions were detected on white light cystoscopy (WLC), BLC or both. We calculated the percentage of cystoscopies with recurrences that were missed with WLC alone. The cystoscopy-level BLC false-positive rate was the proportion of cystoscopies with biopsies only due to BLC suspicious lesions without recurrence. RESULTS: Of 1,703 BLCs, 282 cystoscopies were in the analytic cohort. The overall recurrence rate was 45.0% (127). With only WLC, 13% (16/127) of recurrences would have been missed as 5.7% (16/282) of cystoscopies performed had recurrence only identified with BLC. Among 16 patients with recurrence missed with WLC, 88% (14) had carcinoma in situ. The cystoscopy-level BLC false-positive rate was 5% (15). CONCLUSIONS: BLC helped detect recurrences after recent BCG that would have been missed with WLC alone. Providers should consider BLC for high-risk patients undergoing BCG and should discuss the risk of false-positives with these patients. As clinical trials of novel therapies for BCG-unresponsive disease increase and there are no clear guidelines on BLC use for post-treatment cystoscopies, it is important to consider how variable BLC use could affect enrollment in and comparisons of these studies.

Lipid-Lowering Drug Use and Cancer Incidence and Mortality in the ARIC Study.

Background: Lipid-lowering drugs, particularly statins, are associated with reduced incidence of certain cancers in some studies. Associations with cancer mortality are not well studied, and whether associations are similar across race is unknown. Methods: We conducted a prospective analysis of 12 997 cancer-free participants in the Atherosclerosis Risk in Communities Study who were never users at visit 1 (1987-1989). Ever use, duration of use, and age at first use were modeled as time-dependent variables using Cox regression to estimate associations with total, obesity- and smoking-associated, bladder, breast, colorectal, lung, and prostate cancer incidence and mortality. Results: We ascertained 3869 cancer cases and 1661 cancer deaths in 237 999 or more person-years. At 6 years of follow-up, 70.8% of lipid-lowering drug use was a statin. Compared with never use, ever use was associated with lower total, obesity- and smoking-associated cancer mortality and with colorectal cancer mortality (hazard ratio [HR] = 0.50, 95% confidence interval [CI] = 0.32 to 0.79) and incidence (HR = 0.69, 95% CI = 0.53 to 0.92). Inverse associations were consistent by sex and race. Shorter-term use was associated with bladder cancer incidence in men (<10 years: HR = 1.67, 95% CI = 1.02 to 2.73). First use at age 60 years or older was inversely associated with: total mortality, obesity- and smoking-associated mortality, and colorectal cancer mortality; and total incidence, obesity- and smoking-associated incidence, and breast, colorectal, and prostate cancer incidence. Conclusions: This study provides additional evidence for inverse associations between lipid-lowering drug use and cancer incidence and mortality but a positive association with bladder cancer incidence in men. Evaluation of the impact of chemoprevention strategies that include lipid-lowering drugs on population-level cancer burden is needed.

Evaluation of the Cancer of Bladder Risk Assessment (COBRA) Score in the Cancer Genome Atlas (TCGA) Bladder Cancer Cohort.

OBJECTIVE: To evaluate the Cancer of the Bladder Risk Assessment (COBRA) score in The Cancer Genome Atlas (TCGA) bladder cancer cohort. Second, to investigate the utility of the COBRA score within each bladder cancer molecular subtype following radical cystectomy (RC) and determine if it can help identify candidates for adjuvant therapies and clinical trials. METHODS: Among the TCGA bladder cancer cohort (n = 412), RC pathology reports were reviewed to calculate COBRA scores. Kaplan-Meier survival curves along with univariable and multivariable Cox proportional hazard models were used to determine the clinical utility of the COBRA score to predict overall survival (OS) within the overall cohort and within each molecular subtype (if n>30 within subtype). RESULTS: In the analytic cohort (n = 273) there was a median follow-up of 18 months. Higher COBRA score was associated with significant increased risk of death in both univariable (HR = 1.52 per point [PP] 95% CI [1.32, 1.75)] and multivariable models (HR = 1.54 PP 95% CI [1.32, 1.79]). This remained true in multivariable models stratified by molecular subtype for basal (HR = 1.37 PP 95% CI [1.07, 1.74]), luminal infiltrated (HR = 1.70 PP 95% CI [1.10, 2.64]), and luminal papillary (HR = 1.62 PP 95% CI [1.28, 2.06]) tumors. CONCLUSION: Our findings validate the COBRA score in the TCGA bladder cancer cohort. This suggests the COBRA score can be used in conjunction with molecular subtyping information to help guide clinical decision-making following RC to improve risk stratification and allow for earlier identification of candidates for adjuvant therapies and clinical trials.

Live Renal Ultrasonography Facilitates Double-J Ureteral Stent Insertion at the Bedside: A Pilot Study for the COVID-19 Era.

Objectives: To investigate the feasibility and efficacy of live renal ultrasonography to guide Double-J ureteral stent placement at the bedside. Patients and Methods: Between April 12 and June 5, 2020, patients presenting with acute ureteral obstruction requiring decompression were prospectively selected for ultrasound-guided bedside ureteral stent placement. During stent placement, upper tract access confirmed using ultrasound with or without retrograde injection of ultrasound contrast before Double-J stent insertion. A postprocedural abdominal X-ray was obtained for stent position confirmation. Results: Eight patients (four men and four women) were offered bedside ultrasound-guided ureteral stent placement, and all eight consented to proceed. Stents were placed in seven of eight patients. One patient had an impacted ureterovesical junction stone and stricture requiring ureteroscopy and laser lithotripsy in the operating room. All patients tolerated procedures without immediate complications. Conclusion: Live renal ultrasonography can facilitate a high success rate for bedside ureteral stent placement outside the operating room. This approach is an attractive alternative to fluoroscopy-guided stent placement in the operating room and is of particular value in the COVID-19 era when judicious use of these resources is salient.

Urethral Defect in Setting of Recurrent Urethral Foreign Body Insertion.

We present a case of recurrent episodes of foreign body insertion into the urethra, ultimately resulting in urethral defect at the penoscrotal junction. We have decided against treating the urethral defect as it facilitates nonoperative retrieval of the urethral foreign bodies. We present our experience and rationale for the clinical management of this complex patient.

A Nationally Representative Study of Nonindex Hospital Readmissions following Radical Prostatectomy: Implications for Bundled Payment Models.

PURPOSE: Implementing episode based payment models requires a detailed understanding of health care utilization throughout the 90-day postoperative episode. This includes nonindex hospital readmissions, which currently do not exist for patients treated with radical prostatectomy. We compared the causes, costs and predictors of index vs nonindex hospital readmissions after radical prostatectomy. MATERIALS AND METHODS: We identified patients with prostate cancer who underwent radical prostatectomy from 2010 to 2014 in the Nationwide Readmissions Database. Sociodemographic factors, hospital costs and causes of 90-day readmissions were compared between index and nonindex hospital readmissions. Multivariable regression models were used to determine whether nonindex readmissions were more costly than index readmission for several causes of readmission and also to identify predictors of nonindex readmissions. RESULTS: Of the 214,473 patients treated with radical prostatectomy 12,316 (5.7%) experienced a 90-day readmission and 4,283 (30.6%) had a nonindex readmission. Nonindex readmissions were more likely for complications which were cardiovascular specific (16.6% vs 10.3%) and nonradical prostatectomy specific (49.4% vs 32.8%, each p <0.01). On multivariable modeling readmission costs were significantly higher for nonindex vs index readmissions ($10,751 vs $10,113, p <0.01). Cardiovascular and electrolyte related nonindex readmissions ($12,995 vs $10,108, p <0.001, and $4,962 vs $3,179, p=0.01, respectively) were more expensive. Nonindex hospital readmission predictors included minimally invasive radical prostatectomy (OR 1.28, 95% CI 1.03-1.58), radical prostatectomy done at a high volume institution (OR 2.02, 95% CI 1.41-2.89) and residence in a more rural location (less than 50,000 population OR 1.68, 95% CI 1.21-2.35). CONCLUSIONS: In this nationally representative study nonindex hospital readmissions were associated with higher readmission costs, which were driven by differences in a small subset of readmissions. The benefits of undergoing radical prostatectomy at a high volume center should be carefully balanced with the increased odds of nonindex hospital readmissions and higher costs associated with such centers as regionalization continues.

Cost-Benefit Analysis of a Support Program for Nursing Staff.

OBJECTIVES: A peer-support program called Resilience In Stressful Events (RISE) was designed to help hospital staff cope with stressful patient-related events. The aim of this study was to evaluate the impact of the RISE program by conducting an economic evaluation of its cost benefit. METHODS: A Markov model with a 1-year time horizon was developed to compare the cost benefit with and without the RISE program from a provider (hospital) perspective. Nursing staff who used the RISE program between 2015 and 2016 at a 1000-bed, private hospital in the United States were included in the analysis. The cost of running the RISE program, nurse turnover, and nurse time off were modeled. Data on costs were obtained from literature review and hospital data. Probabilities of quitting or taking time off with or without the RISE program were estimated using survey data. Net monetary benefit (NMB) and budget impact of having the RISE program were computed to determine cost benefit to the hospital. RESULTS: Expected model results of the RISE program found a net monetary benefit savings of US $22,576.05 per nurse who initiated a RISE call. These savings were determined to be 99.9% consistent on the basis of a probabilistic sensitivity analysis. The budget impact analysis revealed that a hospital could save US $1.81 million each year because of the RISE program. CONCLUSIONS: The RISE program resulted in substantial cost savings to the hospital. Hospitals should be encouraged by these findings to implement institution-wide support programs for medical staff, based on a high demand for this type of service and the potential for cost savings.

Prognostic implications of prostatic urethral involvement in non-muscle-invasive bladder cancer.

PURPOSE: Non-muscle-invasive bladder cancer involving the prostatic urethra is associated with pathologic upstaging and shorter survival. We investigated the survival impact of prostatic urethral involvement in non-muscle-invasive patients who are not upstaged at cystectomy. METHODS: From 2000 to 2016, 177 male patients underwent cystectomy for high-risk non-muscle-invasive bladder cancer and remained pT1, pTis, or pTa, and N0 on final pathology; 63 (35.6%) patients had prostatic urethral involvement and 114 (64.4%) did not. Prostatic involvement was non-invasive (Ta or Tis) in 56 (88.9%) patients and superficially invasive (T1) in 7 (11.1%) patients. No patient had stromal invasion. Log-rank and Cox regression analyses were used to evaluate survival. RESULTS: Compared to patients without prostatic urethral involvement, patients with involvement were more likely to have received intravesical therapy (84.6% vs. 64.4%, p < 0.01), have multifocal tumor (90.8% vs. 51.7%, p < 0.01), and have positive urethral margins (7.7% vs. 0%, p < 0.01) and ureteral margins (18.5% vs. 5.1%, p < 0.01). Log-rank comparison showed inferior recurrence-free, cancer-specific, and overall survival in patients with prostatic involvement (p = 0.01, p = 0.03, p < 0.01). Patients with prostatic urethral involvement were more likely to experience recurrence in the urinary tract (p < 0.01). On Cox regression, prostatic urethral involvement was an independent predictor of overall mortality (HR = 2.08, p < 0.01). CONCLUSIONS: Prostatic urethral involvement is associated with inferior survival in patients who undergo cystectomy for non-muscle-invasive bladder cancer and remain pT1, pTis, or pTa on final pathology. Prostatic urethral involvement is thus an adverse pathologic feature independent of its association with upstaging.

Impact of intravesical therapy for non-muscle invasive bladder cancer on the accuracy of urine cytology.

PURPOSE: Urine cytology remains an essential diagnostic tool in the surveillance of patients with non-muscle invasive bladder cancer (NMIBC). The correlation of urine cytology with biopsy specimens to determine its accuracy following induction intravesical therapy has not been investigated. METHODS: A retrospective review was performed of patients who underwent intravesical therapy for biopsy-proven non-muscle invasive disease between 2013 and 2016 at our institution. All patients uniformly underwent cytology and systematic bladder biopsies in the operating room within 12 weeks following intravesical therapy. The accuracy of urinary cytology in predicting high-grade disease recurrence following intravesical therapy was confirmed by correlating cytology results to post-treatment systematic biopsies, regardless of endoscopic findings. Only patients with complete information regarding urine cytology and pathologic biopsy results, both pre- and post-intravesical therapy, were included. RESULTS: 90 cytology samples following intravesical therapy were analyzed from 76 patients who met inclusion criteria. 72 (80.0%) and 18 (20.0%) of the samples were collected from patients initially treated for high- and low-grade disease, respectively. Fifty-six (62.2%) specimens were obtained from patients following induction of bacillus Calmette-Guerin (BCG) therapy; the remainder were from patients treated with intravesical gemcitabine/docetaxel, mitomycin, or BCG/interferon. For patients treated with BCG, cytology was positive for high-grade disease in 8/15 patients with high-grade pathology on follow-up biopsy, thus demonstrating a sensitivity of 53% (95% CI 27-79%), specificity of 95% (95% CI 84-99%), positive predictive value of 80% (95% CI 44-98%), and negative predictive value of 85% (95% CI 71-94%). If cytologic interpretation was broadened to include high-grade and "suspicious for high-grade" findings, sensitivity increased to 67% (95% CI 38-88%) and specificity decreased to 88% (95% CI 74-96%). CONCLUSIONS: While urinary cytology maintains a high specificity following intravesical therapy, it demonstrates a low sensitivity for potentially aggressive high-grade urothelial carcinoma. Further evaluation of more effective, clinic-based enhanced cystoscopy techniques and biomarkers is warranted to better identify patients at risk for disease recurrence following BCG therapy.

Factors associated with red blood cell, platelet, and plasma transfusions among inpatient hospitalizations: a nationally representative study in the United States.

BACKGROUND: Demographic and hospital-level factors associated with red blood cell (RBC), plasma, and platelet transfusions in hospitalized patients across the U.S. are not well characterized. METHODS: We conducted a retrospective analysis of the National Inpatient Sample (2014). The unit of analysis was a hospitalization; sampling weights were applied to generate nationally-representative estimates. The primary outcome was having ≥ 1 RBC transfusion procedure; plasma and platelet transfusions were similarly assessed as secondary outcomes. For each component, factors associated with transfusion were measured using adjusted prevalence ratios (adjPR) and 95% confidence intervals (95% CI) estimated by multivariable Poisson regression. RESULTS: The prevalence of RBC, plasma, and platelet transfusion was 5.8%, 0.9%, and 0.7%, respectively. RBC transfusions were associated with older age (≥ 65 vs. < 18 years; adjPR = 1.80; 95% CI = 1.66-1.96), female sex (adjPR = 1.13; 95% CI = 1.12-1.14), minority race/ethnic status, and hospitalizations in rural hospitals compared to urban teaching hospitals. Prevalence of RBC transfusion was lower among hospitalizations in the Midwest compared to the Northeast (adjPR = 0.73; 95% CI = 0.67-0.80). All components were more likely to be transfused in patients with a primary hematologic diagnosis, patients with a higher number of total diagnoses, patients who experienced a higher number of other procedures, and patients who eventually died in the hospital. In contrast to RBC transfusions, prevalence of platelet transfusion was greater in urban teaching hospitals (vs. rural; adjPR = 1.71; 95% CI = 1.49-1.98) and lower in blacks (vs. whites; adjPR = 0.80; 95% CI = 0.76-0.85). CONCLUSIONS: Nationally, there is heterogeneity in factors associated with transfusion between each blood component, including by hospital type and location. This variability presents patient blood management programs with potential opportunities to reduce transfusions.

Hospitalisation and readmission costs after radical cystectomy in a nationally representative sample: does urinary reconstruction matter?

OBJECTIVE: To investigate the impact of continent urinary diversion on readmissions and hospital costs in a nationally representative sample of radical cystectomies (RCs) performed in the USA. PATIENTS AND METHODS: The 2010-2014 Nationwide Readmissions Database was queried for patients with a diagnosis of bladder cancer who underwent RC. We identified patients undergoing continent (neobladder or continent cutaneous reservoir) or incontinent (ileal conduit) diversions. Multivariable logistic regression models were used to identify predictors of 90-day readmission, prolonged length of stay, and total hospital costs. RESULTS: Amongst 21 126 patients identified, 19 437 (92.0%) underwent incontinent diversion and 1 689 (8.0%) had a continent diversion created. Continent diversion patients were younger, healthier, and treated at high-volume metropolitan centres. Continent diversions resulted in fewer in-hospital complications (37.3% vs 42.5%, P = 0.02) but led to more 90-day readmissions (46.5% vs 39.6%, P = 0.004). In addition, continent diversion patients were more often readmitted for infectious complications (38.7% vs 29.4%, P = 0.004) and genitourinary complications (18.5% vs 13.0%, P = 0.01). On multivariable logistic regression, patients with a continent diversion were more likely to be readmitted within 90 days (odds ratio [OR] 1.55, 95% confidence interval [CI]: 1.28, 1.88) and have increased hospital costs during initial hospitalisation (OR 1.99, 95% CI: 1.52, 2.61). Continent diversion led to a $4 617 (American dollars) increase in initial hospital costs ($36 640 vs $32 023, P < 0.001), which was maintained at 30 days ($48 621 vs $44 231, P < 0.001) and at 90 days ($56 380 vs $52 820, P < 0.001). CONCLUSION: In a nationally representative sample of RCs performed in the USA, continent urinary diversion led to more frequent readmissions and increased hospital costs. Interventions designed to address specific outpatient issues with continent diversions can potentially lead to a significant decrease in readmissions and associated hospital costs.

Oncological Outcomes of Sequential Intravesical Gemcitabine and Docetaxel in Patients with Non-Muscle Invasive Bladder Cancer.

BACKGROUND: Bacillus Calmette-Guérin (BCG) unresponsive/relapsing patients with non-muscle invasive bladder cancer (NMIBC) who prefer bladder preservation over radical cystectomy (RC) or those who do not qualify for surgery may be offered intravesical therapies. Gemcitabine (GEM) combined with Docetaxel (DOCE) has been offered at Johns Hopkins Hospital (JHH). OBJECTIVE: To evaluate experience with GEM/DOCE, to confirm safety of the regimen, to identify populations that may benefit most, and to consider the appropriate endpoints for judging efficacy of second line therapies. METHODS: Thirty-three patients who received full induction GEM/DOCE since 2011, per the protocol adapted from U. Iowa, were identified and characterized. Multivariable logistic regression was used to determine factors associated with recurrence. Cox proportional hazard models evaluated risk factors for disease-free survival (DFS) and high-grade recurrence-free survival (HG-RFS). RESULTS: There were no serious adverse effects of therapy. Across all patients, median follow-up time was 18.6 months with a median DFS of 6.5 months, 42% 1-year, and 24% 2-year DFS. Median HG-RFS was 17.1 months with 56% 1-year and 42% 2-year HG-RFS. Among patients initially presenting with HG-NMIBC, 46% (13/28) had HG recurrence. BCG unresponsive/relapsing patients (N = 25) displayed 49% 1-year HG-RFS and 34% 2-year HG-RFS. In total, there were 5 LG and 16 HG recurrences, with 5 progressions and 8 cystectomies among these. CONCLUSIONS: GEM/DOCE is a well-tolerated therapy that deserves further study as an alternative to immediate RC for highly selected patients with HG-NMIBC. BCG naïve patients responded more effectively than BCG unresponsive/relapsing patients. As anticipated, GEM/DOCE efficacy was improved for HG only patients.