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Background Treatment options for metastatic renal cell carcinoma (mRCC) include cytoreductive nephrectomy (CN) and systemic therapy (ST). Results from the CARMENA and SURTIME trials suggest that CN before ST may not be the optimal treatment strategy for mRCC. Objective To use real-world data to evaluate and compare outcomes for patients with mRCC who underwent CN before, after, or without ST to those patients who only received ST. Design, setting, and participants The Canadian Kidney Cancer information system (CKCis) database was used to identify patients diagnosed with mRCC between January 2011 and April 2020. Only patients with synchronous disease, treated within 12 mo from their initial RCC diagnosis, with International Metastatic Renal Cell Carcinoma Database Consortium intermediate/high risk, and confirmed RCC histology were included. Outcome measurements and statistical analysis Patients were classified into four groups according to the initial treatment received for mRCC. Inverse probability of treatment weighting using propensity scores was used to balance the treatment groups. Cox proportional hazards models were used to assess the impact of CN after adjusting for potential confounding variables in the weighted cohorts. Results and limitations A total of 788 patients were included in the study cohort. Of these 383 patients underwent CN before ST, 73 underwent CN after ST, 80 underwent CN only, and 252 patients received ST only. The median patient age was 63 yr and 73% of the cohort were men. In weighted analysis, the groups undergoing CN before ST (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.52–0.82) and CN after ST (HR 0.41, 95% CI 0.28–0.60) both had better survival compared to the ST only group. No survival benefit was observed for CN only compared to ST only, or for CN before ST compared to CN after ST. Conclusions We evaluated the association between different sequences of treatment with CN and survival in patients with mRCC using CKCis real world data. The results demonstrate that the selected patients who undergo CN, whether performed before or after ST, have an associated improvement in survival. Patient summary Two of the treatment options for metastatic kidney cancer are surgery and systemic therapy (chemotherapy or immunotherapy). We used data from the Canadian Kidney Cancer information system to determine whether there are differences in survival according to the sequencing of these treatments. Patients who had both surgery and systemic therapy, regardless of which treatment was first, had better survival than patients who only received systemic therapy.

To determine the correlation between ultrasound (US), cross-sectional imaging, and pathological renal mass sizes.Between January 2011 and January 2021, a cohort of patients from 14 academic institutions who had an US and cross-sectional imaging within 8 weeks of each other and within 6 months of surgery were identified. A second cohort of patients with small renal masses (≤4 cm) who had US and cross-sectional imaging within 8 weeks of each other were also examined, regardless of their treatment modality. Correlation coefficients, Bland-Altman plots, and sensitivity tables were generated.A total of 1464 patients were included in the surgical cohort and 1582 patients (1921 imaging pairs) were included in the small renal mass (SRM) cohort. Pearson correlation coefficients between computed tomography (CT)/magnetic resonance imaging (MRI) and pathologic size was 0.93 (P.0001) and between US and pathological size was 0.90 (P.0001). The correlation between US and CT/MRI was 0.93 (P.0001). Bland-Altman plots demonstrated a greater agreement for smaller renal masses. For the SRM cohort when comparing US to CT/MRI, 1441 (75%) SRM measurements were within 0.5 cm and only 149 (7.8%) were greater than 1 cm in difference. Subgroup analysis demonstrated that correlation between US and CT/MRI for SRMs were higher in patients with lower body mass index.There is a strong correlation between US and cross-sectional imaging in 75% of patients at baseline imaging. Our study provides support for utilization of US for active surveillance.

To characterize proportion of patients receiving adrenalectomy, adrenal involvement prevalence and oncologic outcomes of routine adrenalectomy in contemporary practice. Ipsilateral adrenalectomy was once standard during radical nephrectomy. However, benefit of routine adrenalectomy has been questioned because adrenal involvement of renal cell carcinoma (RCC) is low.All patients receiving radical nephrectomy in the Canadian Kidney Cancer information system, a collaborative prospective cohort populated by 14 major Canadian centers, between January 2011 to February 2020 were included. Patients were excluded if they had non-RCC histology, multiple tumors, contralateral tumors, metastatic disease or previous history of RCC. Patient demographic, clinical, and surgical information were summarized and compared. Cox-proportional hazards was used for multivariable analysis.During study period, 2759 patients received radical nephrectomy, of these, 831(30.1%) had concomitant adrenalectomy. Pathological adrenal involvement was identified in 102 (3.7%overall; 12.3%of adrenalectomy). Median follow-up was 21.6months (Interquartile range 7.0-46.5). Patients with adrenalectomy had higher venous tumor thrombus (30.3% vs 9.6%; P.0001), higher T stage (71.1% vs 43.4% pT3/4; P.0001), lymph node metastases (17.6% vs 10.7%; P = .0035), Fuhrman grades (71.4% of Fuhrman grades 3/4 vs 56.2%; P.0001) and increased proportion of clear cell histology (79.3% vs 74.5%; P = .0074) compared to the no adrenalectomy group. Adrenalectomy patients had higher risk of recurrence (HR 1.23; 95% CI 1.04-1.47; P = .019) and no difference in survival (HR 1.09, 95% CI 0.86-1.38, P = .48).Adrenalectomy is not associated with better oncological outcome of recurrence/survival. Adrenalectomy should be reserved for patients with radiographic adrenal involvement and/or intra-operative adrenal involvement.

There are conflicting reports regarding radical cystectomy complication risk from obesity subcategories, and a BMI threshold below which complication risk is notably reduced is undefined. A BMI threshold may be helpful in prehabilitation to aid patient counseling and inform weight loss strategies to potentially mitigate obesity-associated complication risk. This study aims to identify such a threshold and further investigate the association between BMI subcategories and perioperative complications from radical cystectomy.Data were extracted from the Canadian Bladder Cancer Information System, a prospective registry across 14 academic centers. Five hundred and eighty-nine patients were analyzed. Perioperative (≤90 days) complications were compared between BMI subcategories. Unconditional multivariable logistic regression and cubic spline analysis were performed to determine the association between BMI and complication risk and identify a BMI threshold.Perioperative complications were reported in 51 (30%), 97 (43%), and 85 (43%) normal, overweight, and obese patients (Complication risk from radical cystectomy is independently associated with BMI. Both overweight and obese patients are at increased risk compared to normal BMI patients. A BMI threshold of 34 kg/m

Purpose To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC). Materials and methods We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age. Results pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6–37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p p = 0.002) compared to those with luminal papillary subtype. Conclusions While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

Objective: To evaluate the role of incomplete metastasectomy (IM) for patients with metastatic renal cell carcinoma (mRCC) on overall survival (OS) and time to introduction of first-line systemic therapy. Methodology: Patients diagnosed with mRCC between Jan 2011 and Apr 2019 in 16 centers were selected from the Canadian Kidney Cancer information system database. We included mRCC patients who had prior nephrectomy and had received an IM (resection of at least 1 metastasis) or no metastasectomy (NM). A propensity score matching was performed to minimize selection bias. Cox proportional hazards analysis was used to assess the impact of the metastasectomy while adjusting for potential confounders. OS was assessed by Kaplan-Meier analysis. Results: A total of 138 patients with mRCC underwent IM, while 1221 patients did not. On multivariate analysis, IM did not improve OS (hazard ratio [HR] 0.96, 95% CI 0.63 to 1.45, P = 0.836) However, subgroup analyses revealed IM improved OS compared with NM when lungs were the only site involved (median time to OS not reached versus 66 months, respectively; P = 0.014). Additionally, lung metastasectomy delayed the systemic therapy compared with NM (median 41 and 13 months, respectively, P = 0.014). IM of endocrine organs (thyroid, pancreas, adrenals) or bone metastases did not impact OS. Conclusion: The role of IM for mRCC is limited. Incomplete resection of lung metastases was associated with improved OS and delayed time to introduction of systemic therapy when lungs were the sole location of metastatic disease. Despite case-matching, unknown unadjusted confounders may explain the relationship between IM and survival in this analysis.

IntroductionNon-muscle invasive bladder cancer (NMIBC) accounts for about 75% of newly diagnosed bladder cancers. The treatment for NMIBC involves surgical removal of the tumour followed by 6 weekly instillations of immunotherapy or chemotherapy directly into the bladder (ie, intravesical therapy). NMIBC has a high rate of recurrence (31%–78%) and progression (15%). Moreover, bladder cancer and its treatment may affect patient functioning and quality of life. Exercise is a safe and effective intervention for many patient with cancer groups, however, no studies have examined exercise during intravesical therapy for NMIBC. The primary objective of the Bladder cancer and exeRcise trAining during intraVesical thErapy (BRAVE) trial is to examine the safety and feasibility of an exercise intervention in patients with bladder cancer undergoing intravesical therapy. The secondary objectives are to investigate the preliminary efficacy of exercise on health-related fitness and patient-reported outcomes; examine the social cognitive predictors of exercise adherence; and explore the potential effects of exercise on tumour recurrence and progression.Methods and analysisBRAVE is a phase II randomised controlled trial that aims to include 66 patients with NMIBC scheduled to receive intravesical therapy. Participants will be randomly assigned to the exercise intervention or usual care. The intervention consists of three supervised, high-intensity interval training sessions per week for 12 weeks. Feasibility will be evaluated by eligibility, recruitment, adherence and attrition rates. Preliminary efficacy will focus on changes in cardiorespiratory fitness and patient-reported outcomes from baseline (prior to intravesical therapy) to pre-cystoscopy (3 months). Cancer outcomes will be tracked at 3 months, and 1-year follow-up by cystoscopy. Analysis of covariance will compare between-group differences at post-intervention (pre-cystoscopy) for all health-related fitness and patient-reported outcomes.Ethics and disseminationThe study was approved by the Health Research Ethics Board of Alberta-Cancer Committee (#20–0184). Dissemination will include publication and presentations at scientific conferences and public channels.Trial registration numberNCT04593862; Pre-results.

INTRODUCTION AND OBJECTIVE:Surgical morbidity after radical cystectomy (RC) is significant, particularly in patients with an above-normal body mass index (BMI). Prehabilitation is a multi-modal, pr...

ObjectivesRectus sheath blocks are an established option for analgesia following abdominal surgery, but pharmacokinetic data are limited. This study sought to characterise the absorption of lidocaine injectate and the pharmacokinetics of lidocaine after rectus sheath injection.MethodsBilateral rectus sheath single-injection blocks were given to 10 patients undergoing general or urological surgery. Afterwards, serial lidocaine serum levels and ultrasound measurements of the rectus sheath injectate reservoir were collected.Key findingsInjectate within the rectus sheath was visible with ultrasound up to 12 h after injection. However, the rate of drug absorption exceeded that of injectate disappearance. Peak serum concentration occurred within 30 min with average peak concentrations of 1.65 μg/ml. Lidocaine clearance was lower than reported in young healthy subjects. The body mass index positively correlated with lidocaine terminal phase half-life, and clearance negatively correlated with age.ConclusionsThe study provides the first data describing lidocaine pharmacokinetics after rectus sheath injection. Peak serum concentrations transiently achieved systemic levels associated with pain relief after a single bolus injection. The data from this study could be used to develop a regime using single shot rectus sheath blockade with a bolus of lidocaine followed by infusion using bilateral rectus sheath catheters.

Introduction: The impact of paraneoplastic syndromes (PNS) on survival in patients with renal cell carcinoma (RCC) is uncertain. This study was conducted to analyze the association of PNS with recurrence and survival of patients with non-metastatic RCC undergoing nephrectomy. Methods: The Canadian Kidney Cancer information system is a multi-institutional cohort of patients started in January 2011. Patients with nephrectomy for non-metastatic RCC were identified. PNS included anemia, polycythemia, hypercalcemia, and weight loss. Associations between PNS and recurrence or death were assessed using Kaplan-Meier curves and multivariable analysis. Results: Of 4337 patients, 1314 (30.3%) had evidence of one or more PNS. Patients with PNS, were older, had higher comorbidity, and had more advanced clinical and pathological tumor characteristics as compared to patients without PNS (all p

Objective To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC). Methods Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses. Results A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75–1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71–1.58, P = 0.77). Conclusion Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage.

INTRODUCTION AND OBJECTIVE:Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard and recommended treatment for clinical T2-T4aN0M0 bladder cancer. Howev...

Background Renal tumor biopsies (RTB) have been proposed as a means to diminish overtreatment of small renal masses. A potential concern of RTB is tumor seeding along the biopsy tract leading to worse clinical outcomes. Objectives To evaluate whether RTB was associated with greater upstaging to pT3a compared to patients without a biopsy and to determine if pathologic upstaging affects the risk of recurrence. Design, setting and participants The Canadian Kidney Cancer information system was used to identify patients who underwent radical or partial nephrectomy for malignant renal tumors ≤ 4cm (cT1a) between January 1, 2011 and July 2, 2019. Intervention RTB prior to nephrectomy or nephrectomy without biopsy. Outcomes measurements and statistical analysis Upstaging to pT3a and cancer recurrence were compared between subjects that had a RTB compared to those who did not. A multivariable analysis was used to evaluate factors associated with disease upstaging and recurrence. Results and limitations The cohort consisted of 1993 cT1a patients, followed for a median of 17.5 months. Of these patients, 502 (25%) had a preoperative RTB. There was no difference in the proportion with tumor upstaging to pT3a between patients that had RTB compared to those who did not (7.2% vs. 6.3%; P = 0.5). On multivariable analysis, RTB was not associated with pathological upstaging (Odds Ratio 0.90; 95% Confidence Interval 0.61–1.34) or recurrence (Odds Ratio 1.04; 95% Confidence Interval 0.57–1.89). The main limitation is that the study is underpowered to detect small differences between groups. Conclusions In this large, multi-institution cohort, RTB was not associated with increased risk of tumor upstaging or recurrence. Hence, tumor tract seeding, although possible, should not be a clinical deterrent to using RTBs as a means of personalizing renal masses management and diminishing overtreatment. Patient summary Recent evidence suggests that tumor seeding following RTB may be more common than initially perceived. Our results have demonstrated that RTB was not associated with an increased risk of tumor upstaging or disease recurrence.

The “trifecta” is a summary measure of outcome after partial nephrectomy (PN) that encompasses three parameters: negative surgical margin, ≤ 10% decrease in post-operative estimated glomerular filtration rate (eGFR) and absence of urological complications. We assessed trifecta rates in patients undergoing open (OPN), laparoscopic (LPN), and robotic PN (RPN) for a clinical T1 renal mass (≤ 7 cm). Clinical and pathologic parameters were extracted from the prospectively maintained Canadian Kidney Cancer Information System for patients treated between January 2011 and October 2018. Comparisons between groups were made using Kruskal–Wallis test for continuous variables and Chi-squared independence test for categorical variables. Multivariable analysis was performed to identify predictors of each component of the trifecta and the trifecta itself. Of 1708 total patients, 746 underwent OPN, 678 LPN, and 284 RPN for a T1 renal mass. A ‘trifecta’ was achieved in 53% OPN, 52% LPN and 47% RPN (p = 0.194). On multivariable analysis, OPN and LPN were associated with less frequent post-operative decline in eGFR and more frequent trifecta when compared to RPN, but there was no difference between OPN and LPN. OPN also predicted a higher rate of negative margins compared to RPN but not LPN. After correction for confounding variables, OPN and LPN were more likely than RPN to achieve the trifecta, which appeared to be due primarily to loss of renal function. No difference was observed between OPN and LPN. Analyses were limited by the lack of nephrometry score.

Background Testicular cancer survivors (TCS) are at increased risk of cancer-related fatigue (CRF), psychosocial impairment, and poor mental health-related quality of life (HRQoL). Here, we examine the effects of high-intensity interval training (HIIT) on patient-reported outcomes (PROs) in TCS. Secondarily, we explore cardiorespiratory fitness as a mediator of intervention effects and select baseline characteristics as moderators of intervention effects. Methods TCS (n = 63) were randomly assigned to 12 weeks of supervised HIIT or usual care (UC). PROs included CRF, depression, anxiety, stress, self-esteem, sleep quality, and HRQoL assessed at baseline, post-intervention, and 3-month follow-up. Results TCS (median 7 years postdiagnosis) completed 99% of training sessions and achieved 98% of target training intensity. ANCOVA revealed that, compared to UC, HIIT significantly improved post-intervention CRF (p = 0.003), self-esteem (p = 0.029), and multiple HRQoL domains (ps ≤ 0.05). Effects on CRF (p = 0.031) and vitality (p = 0.015) persisted at 3-month follow-up. Cardiorespiratory fitness changes mediated CRF and HRQoL improvements. CRF effects were larger for TCS with an inactive lifestyle, lower fitness, higher testosterone, and clinical fatigue at baseline. Conclusions HIIT significantly improves CRF and HRQoL in TCS. Mediation by cardiorespiratory fitness and moderation by clinical characteristics suggests opportunities for targeted exercise interventions to optimise PROs in TCS.

Purpose The prognostic significance of level of venous tumor thrombus (VTT) extension in patients with non-metastatic renal cell carcinoma (RCC) has been controversial. The aim of this study was to examine the prognostic significance of VTT extent in patients who underwent surgery for non-metastatic RCC. Materials and Methods The Canadian Kidney Cancer information system database was used to identify patients who underwent surgery for non-metastatic RCC and VTT from January 2011 to December 2019. Association between VTT level and recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) was examined. Univariable and multivariable analyses were performed to estimate predictors of survival. Results Out of 6,340 patients during the study period, 228 patients (3.6%) had VTT. VTT was level 0 in 84 (37%), level I to II in 112 (49%), and level III to IV in 33 (14%) patients as per the Mayo Clinic classification. Median age was 65.4 years (interquartile range [IQR] 57.6–72.2) and 169 (74.1%) were male. After a median follow-up of 21.2 months, VTT level did not significantly impact the RFS, CSS, or OS. For VTT level 0, I to II, and III to IV, there was no significant difference in estimated 5-year RFS (31%, 23%, and 30.5%; P > 0.05), CSS (70%, 69%, and 55%; P > 0.05) and OS (64%, 66%, and 50%; P > 0.05). Adjusting for known prognostic factors, thrombus level was not associated with risk of recurrence or death. Conclusion In a large, multi-institutional cohort of patients undergoing surgery for non-metastatic RCC with tumor thrombus, thrombus extent was not independently associated with recurrence or death.

Key Points Question Does the implementation of multiple Enhanced Recovery After Surgery (ERAS) pathways across 1 health care system affect ERAS guideline adherence, length of stay, complications, readmissions, and mortality? Findings In this quality improvement study, comparison of pre-post–ERAS cohorts found that pathway implementation was associated with increased guideline adherence, from 52% to 76%; decreased unadjusted length of stay, from a mean of 9.4 to 7.8 days; and decreased adjusted length of stay by 0.71 days, with no differences in serious complications or 30-day mortality. Meaning These results suggest that implementation of multiple ERAS pathways could provide system-level improvement in ERAS guidelines adherence and length of stay., Importance Engaging multidisciplinary care teams in surgical practice is important for the improvement of surgical outcomes. Objective To evaluate the association of multiple Enhanced Recovery After Surgery (ERAS) pathways with ERAS guideline adherence and outcomes. Design, Setting, and Participants This quality improvement study compared a pre-ERAS cohort (2013-2017) with a post-ERAS cohort (2014-2018). All patients were from Alberta Health Services in Alberta, Canada, and had available ERAS and up to 1-year postsurgery administrative data. Data collected included age, sex, body mass index, tobacco and alcohol use, diabetes, comorbidity index, and surgical characteristics. Data analysis was performed from May 7, 2020, to February 1, 2021. Interventions Implementation of 5 ERAS pathways (colorectal, liver, pancreas, gynecologic oncology, and radical cystectomy) across 9 sites. Main Outcomes and Measures Adherence to ERAS guidelines was measured by the percentage of patients whose care met the common ERAS pathway care element criteria. Surgical procedures were grouped by complexity; complications were classified by severity. Outcome measures for the pre-post–ERAS cohorts included length of stay (LOS), readmission, complications, and mortality. Results A total of 7757 patients participated in the study, including 984 in the pre-ERAS cohort (median [interquartile range] age, 62 [53-71] years; 526 [53.5%] female) and 6773 in the post-ERAS cohort (median [interquartile range] age, 62 [53-71] years; 3470 [51.2%] male). In the total cohort, care-element adherence improved from 52% to 76% (P, This quality improvement study evaluates the implementation of Enhanced Recovery After Surgery pathways to examine the association with guideline adherence, length of stay, complications, readmissions, and mortality.

The role of renal tumor biopsy (RTB) in the management of small renal masses (SRMs) is progressively being recognized as a tool to decrease overtreatment. While an increasing number of studies assessing its role in diagnostics are becoming available, RTB remains variably used amongst urologists. Many patient-, tumor-, and institution-related factors may influence urologists on whether to perform a RTB to help guide management.We aimed at identifying factors associated with the use of RTB for localized SRMs within a number of centers contributing data to the Canadian Kidney Cancer information system.We identified 3,838 patients diagnosed with a localized SRM (≤4 cm) between January 2011 and December 2018. Patients were stratified based on whether a RTB was performed prior to the primary therapeutic intervention. Factors associated with use of RTB were assessed using univariable and multivariable logistic regression models.A total of 993 patients (25.9%) underwent an RTB. There was an overall increase in RTB use over time (P0.001), with patients diagnosed between 2015 and 2018 undergoing more RTB than patients diagnosed between 2011 and 2014 (29.8% vs. 22.2%, respectively; P0.001). Patients managed in centers with the highest patient-volume had RTB more frequently than patients managed in low-volume centers. On multivariable analysis, increasing year of diagnosis was significantly associated with more RTB use. Patients treated with surgery underwent RTB statistically less often than patients undergoing thermal ablation (P0.001) or managed with active surveillance (P0.001). Larger SRMs were associated with more RTB use in patients on active surveillance (P = 0.009), but with less RTB in patients undergoing surgery (P = 0.045).This large multicenter cohort study reveals an increasing adoption and overall use of RTB amongst Canadian urologists. Patients managed in high-volume centers and those undergoing non-surgical management were associated with greater use of RTB. Tumor size was also associated with RTB use. This study highlights the influence that physician perceptions and clinical factors may have in the decision to use RTB prior to initiating a therapeutic approach.

Objectives To determine the association between lymph node dissection (LND) at the time of radical nephrectomy and survival in a large, multi-institutional cohort using a propensity score matching design. Subjects and Methods The Canadian Kidney Cancer information system was used to identify patients undergoing radical nephrectomy for nonmetastatic renal cell carcinoma. Associations between LND with overall survival , recurrence free survival and cancer specific survival were determined using various propensity score techniques in the overall cohort and in patients with varying probabilities of pN1. Cox models were used to determine association of lymph node removed with outcomes. Results Of the 2,699 eligible patients, 812 (30%) underwent LND. Of the LND patients, 88 (10.8%) had nodal metastases. There was no association between LND and improved overall survival, recurrence free survival or cancer specific survival using various propensity score techniques (stratification by propensity score quintile, matched pairs, inverse treatment probability weighting and adjusted for propensity score quintile). There was no association between LND and a therapeutic benefit in patients with increased threshold probabilities of nodal metastases. Increased number of lymph nodes removed was not associated with improved survival outcomes. Conclusions LND at the time of radical nephrectomy for renal cell carcinoma is not associated with improved outcomes. There was no benefit in patients at high risk for nodal metastases, and the number of nodes removed did not correlate with survival. Further studies are needed to determine which high risk patients may benefit from LND.

5080 Background: Men with prostate cancer (PCa) undergoing active surveillance (AS) are at increased risks of cardiovascular death and disease progression. Any intervention that can address these issues during AS would be highly beneficial. Clinical and preclinical studies have demonstrated the benefits of exercise to improve cardiovascular health in cancer patients and suggested the potential role of exercise in suppressing PCa progression in men with PCa undergoing AS. Therefore, the purpose of this study was to investigate the effects of exercise on cardiorespiratory fitness and biochemical progress of PCa in men with PCa on AS. Methods: The Exercise During Active Surveillance for Prostate Cancer (ERASE) Trial was a single-centre, two-armed, randomized controlled trial in Edmonton, Canada. 52 men with localized PCa who were undergoing AS were randomized to high-intensity interval training (HIIT; n = 26) or usual care (UC; n = 26). The HIIT group performed thrice-weekly, supervised, aerobic HIIT on a treadmill at 85-95% of peak cardiorespiratory fitness (VO2peak) for 12 weeks. The primary outcome was VO2peak, and the secondary and exploratory outcomes included biochemical progression of PCa (prostate-specific antigen [PSA]), PSA kinetics, and growth of prostate cancer cell line LNCaP. Results: 46/52 participants (88%) completed the postintervention VO2peak assessment and adherence to HIIT was 96%. Compared to UC, HIIT significantly improved VO2peak (adjusted between-group mean difference, 1.6 ml·kg-1·min-1; 95% confidence interval [CI], 0.3 to 2.9; p= 0.014). HIIT also significantly reduced PSA level (adjusted between-group mean difference, -1.1 ug/L; 95% CI, -2.1 to 0.0; p= 0.043) and PSA velocity ( p= 0.040), and suppressed LNCaP cell growth ( p =0.024). No significant differences were found in PSA doubling time ( p= 0.10) and testosterone ( p= 0.24). Conclusions: The ERASE Trial is the first randomized controlled trial to demonstrate the impact of HIIT exercise for improving physical fitness and inhibiting biochemical progression of PCa in men with localized PCa on AS. Our findings suggest that supervised aerobic HIIT may be a promising intervention in this clinical setting. Larger-scale randomized controlled trials are warranted to determine if improvements in physical fitness and PCa-related markers translate into improved long-term clinical outcomes in these men such as disease progression, receipt of radical treatments, posttreatment complications, and survival. Clinical trial information: NCT03203460.

BACKGROUND Testicular cancer survivors (TCS) have an increased risk of treatment-related cardiovascular disease (CVD), which may limit their overall survival. We evaluated the effects of high-intensity aerobic interval training (HIIT) on traditional and novel CVD risk factors and surrogate markers of mortality in a population-based sample of TCS. METHODS This phase 2 trial (ClinicalTrials.gov identifier NCT02459132) randomly assigned 63 TCS to usual care (UC) or 12 weeks of supervised HIIT (ie, alternating periods of vigorous-intensity and light-intensity aerobic exercise). The primary outcome was peak aerobic fitness (VO2peak) assessed via a treadmill-based maximal cardiorespiratory exercise test. Secondary endpoints included CVD risk (eg, Framingham Risk Score), arterial health, parasympathetic nervous system function, and blood-based biomarkers. RESULTS Postintervention VO2peak data were obtained for 61 participants (97%). HIIT participants attended 99% of the exercise sessions and achieved 98% of the target exercise intensity. Analysis of covariance demonstrated that HIIT was superior to UC for improving VO2peak (adjusted between-group mean difference, 3.7 mL O2/kg/min; 95% confidence interval, 2.4-5.1 [P

Active surveillance instead of active treatment (at) is preferred for patients with low-risk prostate cancer (lr-pca), but practice varies widely. We conducted a population-based study to assess the proportion of patients who underwent at between January 2011 and December 2014, and to evaluate factors associated with at. The provincial cancer registry was linked to administrative health datasets to identify patients with lr-pca and to acquire demographic, tumour, and treatment data. The primary outcome was receipt of at during the first 12 months after diagnosis, defined as any receipt of external-beam radiotherapy, brachytherapy, radical prostatectomy, cryotherapy, or androgen deprivation. Univariate and multivariate logistic regression were used to analyze the correlation between patient and tumour factors and at. Of 1565 patients with lr-pca, 554 (35.4%) underwent at within 12 months of diagnosis. Radical prostatectomy was the most common treatment (58%), followed by brachytherapy (29.6%). Younger age [odds ratio (or) 0.92, 95% confidence interval (ci): 0.91 to 0.94], lower score (&ge, 3) on the Charlson comorbidity index (OR: 0.36, 95% ci: 0.19 to 0.68), T2 stage (or: 3.05, 95% ci: 2.03 to 4.58), higher prostate-specific antigen (psa) at diagnosis (or: 1.13, 95% ci: 1.06 to 1.21), radiation oncologist consultation (or: 3.35, 95% ci: 2.55 to 4.39), and earlier diagnosis year (2012 or: 0.46, 95% ci: 0.34 to 0.63, 2013 or: 0.45, 95% ci: 0.32 to 0.63, 2014 or: 0.33, 95% ci: 0.23 to 0.47) were associated with a higher probability of at. This contemporary population-based study demonstrates that approximately one third of patients with lr-pca undergo at. Patients of younger age, with less comorbidity, a higher tumour stage, higher psa, earlier year of diagnosis, and radiation oncologist consultation were more likely to undergo at. Further investigation is needed to identify strategies that could minimize overtreatment.

The choice of urinary diversion at cystectomy is a life altering decision. Patient decision aids are clinical tools that promote shared decision making by providing information about management options and helping patients communicate their values. We sought to develop and evaluate a patient decision aid for individuals undergoing cystectomy with urinary diversion.We used the IPDAS (International Patient Decision Aids Standards) to guide a systematic development process. A literature review was performed to determine urinary diversion options and the incidence of outcomes. We created a prototype using the Ottawa Decision Support Framework. A 10-question survey was used to assess patient decision aid acceptability among patients, allied health professionals and urologists. The primary outcome was acceptability of the patient decision aid.Ileal conduit and orthotopic neobladder were included as primary urinary diversion options because they had the most evidence and are most commonly performed. Continent cutaneous diversion was identified as an alternative option. Outcomes specific to ileal conduit were stomal stenosis and parastomal hernia. Outcomes specific to neobladder were daytime and nighttime urinary incontinence and urinary retention. Acceptability testing was completed by 8 urologists, 9 patients and 1 advanced practice nurse. Of the respondents 94% reported that the language was appropriate, 94% reported that the length was adequate and 83% reported that option presentation was balanced. The patient decision aid met all 6 IPDAS defining criteria, all 6 certification criteria and 21 of 23 quality criteria.We created a novel patient decision aid to improve the quality of decisions made by patients when deciding among urinary diversion options. Effectiveness testing will be performed prospectively.

INTRODUCTION AND OBJECTIVES:We conducted a whole human genome short hairpin RNA (shRNA) screen on highly motile human squamous cell carcinoma (Hep3) cells and identified a panel of novel functional...

INTRODUCTION AND OBJECTIVES:Metastatic RCC is incurable, and the current therapeutic paradigm is centered around controlling the disease burden to prolong overall survival. We conducted a whole hum...

Introduction The neutrophil-to-lymphocyte ratio (NLR) is an attractive marker because it is derived from routine bloodwork. NLR has shown promise as a prognostic factor in muscle invasive bladder cancer (MIBC) but its value in patients receiving neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is not yet established. Since NLR is related to an oncogenic environment and poor antitumor host response, we hypothesized that a high NLR would be associated with a poor response to NAC and would remain a poor prognostic indicator in patients receiving NAC. Methods A retrospective analysis was performed on patients with nonmetastatic MIBC (cT2-4aN0M0) who received NAC prior to RC between 2000 and 2013 at 1 of 19 centers across Europe and North America. The pre-NAC NLR was used to split patients into a low (NLR ≤ 3) and high (NLR > 3) group. Demographic and clinical parameters were compared between the groups using Student's t test, chi-squared, or Fisher's exact test. Putative risk factors for disease-specific and overall survival were analyzed using Cox regression, while predictors of response to NAC (defined as absence of MIBC in RC specimen) were investigated using logistic regression. Results Data were available for 340 patients (199 NLR ≤ 3, 141 NLR > 3). Other than age and rate of lymphovascular invasion, demographic and pretreatment characteristics did not differ significantly. More patients in the NLR > 3 group had residual MIBC after NAC than the NLR ≤ 3 group (70.8% vs. 58.3%, P = 0.049). NLR was the only significant predictor of response (odds ratio: 0.36, P = 0.003) in logistic regression. NLR was a significant risk factor for both disease-specific (hazard ratio (HR): 2.4, P = 0.006) and overall survival (HR:1.8, P = 0.02). Conclusion NLR > 3 was associated with a decreased response to NAC and shorter disease-specific and overall survival. This suggests that NLR is a simple tool that can aid in MIBC risk stratification in clinical practice.

To evaluate outcomes of surgically treated patients with clinically localized papillary renal cell carcinoma (RCC) and determine if papillary RCC subtype is associated with recurrence and survival.This is a historical cohort study using the prospectively maintained Canadian Kidney Cancer Information System database between January 2011 and September 2018. All patients underwent partial or radical nephrectomy. Patient, tumor, treatment, and outcomes were compared between papillary RCC type 2 and type 1 cohorts.During the study period, 509 patients had clinically localized papillary RCC type 2 (n = 172) or type 1 (n = 337) histology. Sex, race, and comorbidities were similar between groups. Pathologic stage (pT3 or pT4), nuclear grade (3 or 4), and tumor diameter were higher in the type 2 papillary RCC cohort (P0.0001). A greater proportion of type 2 papillary RCC patients received radical nephrectomy (42.4% vs. 24.6%, P0.0001). More type 2 papillary RCC patients underwent lymph node dissection (19.6% vs. 5.5%, P0.0001) and had lymph node metastases removed during surgery (6.4% vs. 0.6%, P= 0.103). Overall, adjusting for age, grade, pathologic stage, positive nodes, and tumor size, type 2 papillary RCC had worse outcomes compared to type 1, as demonstrated by elevated all-cause mortality (hazard ratio = 7.7 [95% confidence interval: 2.0-28.9]), P=0.0027) and worse recurrence-free survival (hazard ratio = 8.2 [95% confidence interval: 3.6-19.0], P0.0001).Patients with clinically localized type 2 papillary RCC present with higher risk disease and have worse prognosis compared to patients with clinically localized type 1 papillary RCC. To the best of our knowledge, this is the largest cohort study comparing papillary RCC subtypes.

PurposeThe Alberta Prostate Cancer Research Initiative (APCaRI) Registry and Biorepository was established in 2014 by the APCaRI to facilitate the collection of clinical and patient-reported data, biospecimen, to measure prostate cancer outcomes and to support the development and clinical translation of innovative technologies to better diagnose and predict outcomes for patients with prostate cancer.ParticipantsMen suspected with prostate cancer and referred to Urology centres in Alberta were enrolled in the APCaRI 01 study, while men with a prior prostate cancer diagnosis participated in the APCaRI 03 study from 1 July 2014 to 30 June 2019. The APCaRI Registry and Biorepository links biospecimens and data from a wide representation of patients drawn from an Alberta population of more than 4 million.Findings to dateFrom 1 July 2014 to 30 June 2019, total APCaRI 01 and 03 study recruitment was 3754 men; 142 (4%) of these men withdrew in full, 65 men (2%) withdrew biospecimens and 123 men (3%) died of any cause. Over this same time, 8677 patient-reported outcome measure (PROM) surveys and 7368 biospecimens were collected and are available from the registry and biorepository, respectively. The data entry error rate was 0.8% and 0.95% for critical and non-critical values, respectively, and 1.8% for patient-reported surveys.Future plansThe APCaRI Registry and Biorepository will collect longitudinal data and PROM surveys until 2024, patient outcomes up to 25 years after recruitment and biospecimen storage for up to 25 years. The APCaRI cohorts will continue to provide data and samples to researchers conducting retrospective studies. The richness of the data and biospecimens will complement many different research questions, ultimately to improve the quality of care for men with prostate cancer.

We assessed survival dependent on pathological response after neoadjuvant chemotherapy in a large multicenter patient cohort, with a particular focus on the difference between the absence of residual cancer (pT0) and the presence of only nonmuscle invasive residual cancer (pTa, pTis, pT1).We retrospectively reviewed records of patients with urothelial cancer who received neoadjuvant chemotherapy and underwent radical cystectomy at 19 contributing institutions from 2000 to 2013. Patients with cT2-4aN0M0 and eventual pN0 disease were selected for this analysis. Estimated overall survival was compared between patients with pT0 and pTa/Tis/T1 disease. A multivariable Cox proportional hazards regression model for overall survival was generated to evaluate hazard ratios for variables of interest.Of 1,543 patients treated with neoadjuvant chemotherapy and radical cystectomy during the study period 257 had pT0N0 and 207 had pTa/Tis/T1N0 disease. The Kaplan-Meier mean estimates of overall survival for pT0 and pTa/Tis/T1 cases were 186.7 months (95% CI 145.9-227.6, median 241.1) and 138 months (95% CI 118.2-157.8, median 187.4), respectively (p=0.58). In the Cox proportional hazards regression model for overall survival pTa/Tis/T1N0 status (HR 0.36, 95% CI 0.23-0.67) and pT0N0 status (HR 0.28, 95% CI 0.17-0.47) compared to pT2N0 pathology, positive surgical margin (HR 1.75, 95% CI 1.07-2.86), and receiving a methotrexate, vinblastine, doxorubicin and cisplatin regimen compared to an "other" regimen (HR 0.45, 95% CI 0.27-0.76) were predictors of overall survival.pTa/Tis/T1N0 and pT0N0 stage on the final cystectomy specimen are strong predictors of survival in patients treated with neoadjuvant chemotherapy and radical cystectomy. We did not discern a statistically significant difference in overall survival when comparing these 2 end points.

To analyze risk factors for wound-specific complications after bulbar urethroplasty, including the association between incision type and complications.This is a retrospective review of 829 urethroplasties excluding penile strictures, incomplete data sets, and radiation-induced urethral stenosis. Ninety-day wound complications were reported using the modified Clavien-Dindo classification of postoperative complications. Risk factors for wound complications were evaluated using univariable and multivariable analysis: patient age, positive preoperative urine culture, Charlson comorbidity index ≥ 2, diabetes, body mass index ≥ 35, smoking, and incision type (lambda perineal incision [LPI] vs. midline perineal incision [MPI]).Five hundred forty patients met inclusion criteria; 373 patients with an LPI and 167 patients with an MPI. Ninety-day wound complications (any Clavien grade) occurred in 21% of patients. Multivariable analyses indicated that incision type alone was significantly associated with wound complications (multivariable: MPI OR 0.53 (0.34-0.83), P = .01). The majority of complications were Clavien ≤ 2, which occurred in 23.3% (87 patients) of LPIs compared to 11.9% (20 patients) of MPIs (P = .002). The primary difference between the incisions was superficial wound edge separation (LPI 10.7% [40 patients]; MPI 0%, P .0001). Early (6-month) urethroplasty success favored the midline incision (LPI 6.2% vs MPI 0%, P = .0003), implying no obvious technical advantage for the lambda incision. Study limitations include a retrospective design and the use of some patient-reported complication outcomes.An LPI is independently associated with increased 90-day wound complications after urethroplasty, with no identifiable advantage in urethroplasty outcome.

Background Treatment of prostate cancer (PCa) may be improved by identifying biological mechanisms of tumor growth that directly impact clinical disease progression. We investigated whether genes associated with a highly tumorigenic, drug resistant, progenitor phenotype impact PCa biology and recurrence. Methods Radical prostatectomy (RP) specimens (±disease recurrence, N = 276) were analyzed by qRT-PCR to quantify expression of genes associated with self-renewal, drug resistance, and tumorigenicity in prior studies. Associations between gene expression and PCa recurrence were confirmed by bootstrap internal validation and by external validation in independent cohorts (total N = 675) and in silico. siRNA knockdown and lentiviral overexpression were used to determine the effect of gene expression on PCa invasion, proliferation, and tumor growth. Results Four candidate genes were differentially expressed in PCa recurrence. Of these, low AXIN2 expression was internally validated in the discovery cohort. Validation in external cohorts and in silico demonstrated that low AXIN2 was independently associated with more aggressive PCa, biochemical recurrence, and metastasis-free survival after RP. Functionally, siRNA-mediated depletion of AXIN2 significantly increased invasiveness, proliferation, and tumor growth. Conversely, ectopic overexpression of AXIN2 significantly reduced invasiveness, proliferation, and tumor growth. Conclusions Low AXIN2 expression was associated with PCa recurrence after RP in our test population as well as in external validation cohorts, and its expression levels in PCa cells significantly impacted invasiveness, proliferation, and tumor growth. Given these novel roles, further study of AXIN2 in PCa may yield promising new predictive and therapeutic strategies. Prostate © 2016 Wiley Periodicals, Inc.

Microflow cytometry (µFCM) has recently emerged as a viable technology to enumerate and quantify individual EVs from complex biologic fluids. This method is a promising alternative to biopsy collection because it is highly sensitive and allows for longitudinal assessment of patients. EVs are highly abundant and analysis by µFCM allows for sophisticated multiparametric analysis of organ-specific, disease-specific, and outcome-specific proteins, genes, or metabolites. Detection of EVs with µFCM requires very little sample yet provides exceptional specificity and sensitivity for low abundance events. By combining µFCM analysis of EVs with advanced machine learning approaches, we have developed a platform technology called ClarityDX to generate EV fingerprints that significantly improve the diagnosis of diseases such as prostate cancer using a few drops of blood. Here I will discuss the development and clinical validation of new blood tests for prostate cancer that utilize the ClarityDX platform. Prostate cancer is the most commonly diagnosed cancer and the third leading cause of cancer deaths in men. Screening has enabled the early detection of many latent prostate cancers, and it is estimated that up to 50% of new prostate cancer diagnoses detect a tumor that was unlikely to surface clinically in the absence of PSA screening. In the majority of cases, the treatment of indolent cancer causes a patient more harm than good. Consequently, there is an urgent need for a noninvasive test to detect clinically significant prostate cancer, or perhaps even more importantly, to detect metastatic disease. ClarityDX Prostate is a µFCM-based test to predict clinically significant prostate cancer prior to a prostate biopsy. A prospective clinical validation of ClarityDX Prostate was performed in a cohort of 377 Albertan men. The overall average AUC for ClarityDX Prostate in this population was 0.83, which was significantly higher than PSA alone. While PSA alone provided only 17% specificity for aggressive prostate cancer at a 95% sensitivity, ClarityDX Prostate was 56% specific for aggressive prostate cancer. We are now conducting a pivotal clinical validation study, in which up to 2,800 men will be enrolled to assess the performance of ClarityDX Prostate in a “real-world” clinical environment. Overall, we have established a robust µFCM EV platform for the development of novel and clinically viable diagnostic tests. Incorporating ClarityDX Prostate into routine prostate cancer screening could reduce the number of unnecessary biopsies by up to 40%. This abstract is also being presented as Poster B57. Citation Format: John D. Lewis, Robert J. Paproski, Desmond B. Pink, Catalina Vasquez, Eric Hyndman, Adrian Fairey, APCaRI. Detection of EV-based signatures in prostate cancer using microflow cytometry and machine learning [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr PR12.

5530 Background: The accuracy of the extracellular vesicle-fingerprint score (EV-FPS) test to predict clinically significant prostate cancer (PCa; Gleason grade (GG) ≥ 3) from indolent disease (GG ≤ 2) and avoid unnecessary prostate biopsies was determined at the point of prostate biopsy decision. Methods: Clinical data, health information, and blood samples were collected from a prospective validation cohort of 415 men, without prior PCa diagnosis, referred to urology clinics for prostate biopsy or transurethral prostate surgery (June 2014-Dec 2016). The patient’s EV-FPS risk score was calculated by combining machine learning model-analyzed microflow cytometry data from EV biomarkers with logistic regression-analyzed patient-centric clinical features. The plasma-derived EV biomarkers were prostate-specific membrane antigen, polysialic acid and ghrelin-growth hormone receptor. The patient clinical features were; age, ethnicity, PCa family history, PSA levels, abnormal digital rectal examination (DRE) and prior negative prostate biopsy. Together, the biomarkers and clinical features provided specificity for clinically significant PCa. Results: The EV-FPS test identified clinically significant PCa patients with high accuracy (0.81 area under curve) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cut-off after test validation; 95% of the patients with GG ≥ 3 would have been found before biopsy, 35% biopsies would have been avoided and diagnosis of GG ≥ 3 PCa would have been missed in only 5% of the cohort. Conclusions: This minimally invasive EV-FPS test accurately predicted clinically significant PCa in men with high EV-FPS risk scores, high PSA level and/or abnormal DRE. Therefore, men with low EV-FPS risk scores could potentially avoid unnecessary prostate biopsies. Clinical care cut-offs to calculate the number of biopsies that could have been avoided, and the percentage of GG ≥ 1 to GG ≥ 3 PCa that could have had a delayed diagnosis. [Table: see text]

36 Background: Multidisciplinary management improves complex treatment decision making in cancer care but its impact for metastatic castration resistant prostate cancer (M1 CRPC) has not been documented. The Edmonton Prostate Interdisciplinary Cancer Clinic (EPICC) is a multidisciplinary specialized clinic focused on the delivery of novel therapeutics (Androgen Receptor Axis Therapy; ARAT) to men with chemotherapy-naïve M1 CRPC. The objective of the current study was to assess the efficacy of ARAT in the EPICC. Methods: The study was a retrospective quality assurance analysis. Eligible patients had a new diagnosis of chemotherapy-naïve M1 CRPC with minimal symptoms. EPICC patients were assessed and treated by a multidisciplinary cancer control team that included nursing oncology, pharmacy oncology and physician oncology (urologic, medical and radiation). Patients were treated in first line with an ARAT (abiraterone (AA) or enzalutamide (EZ)) from October 2017 to March 2018. The main efficacy outcome was overall survival (OS). The Kaplan-Meier method and Cox regression model were used to analyze survival data. Statistical tests were two-sided (p≤0.05). Results: From October 2017 to March 2018, 160 chemotherapy-naïve M1 CRPC patients were assessed in the EPICC. Median age at EPICC admission was 77 years (range, 54-92 years). Median PSA level at EPICC admission was 26.6 ng/mL (range, 0.1-5000 ng/mL). 84 out of 160 (53%) patients had received prior radical local therapy (RLT) with curative intent. 83 (57%) patients were treated with EZ and 64 (43%) patients were treated AA. Median OS for the entire cohort was 23 months. In multivariable analysis, absence of prior RLT (HR 3.6, 95% CI 1.9 to 6.6, p < 0.001), PSA > 20 ng/mL (HR 3.2, 95% CI 1.4 to 7.2, p = 0.004), and higher ECOG performance status (1 vs 0: HR 2.4, 95% CI 1.3 to 4.4, p = 0.005; 2 versus 0: HR 3.5, 95% CI 1.5 to 8.0, p = 0.003; and 3 versus 0: HR 12.7, 95% CI 2.5 to 63.8, p = 0.002) were independently associated with poorer OS. Conclusions: Multidisciplinary management of chemotherapy-naïve M1 CRPC with ARAT is feasible. Real world efficacy of ARAT in EPICC are similar to data reported in phase 3 trials.

To determine the association of micropapillary urothelial carcinoma (MUC) variant histology with bladder cancer outcomes after radical cystectomy.Information on MUC patients treated with radical cystectomy was obtained from five academic centers. Data on 1,497 patients were assembled in a relational database. Tumor histology was categorized as urothelial carcinoma without any histological variants (UC; n = 1,346) or MUC (n = 151). Univariable and multivariable models were used to analyze associations with recurrence-free (RFS) and overall (OS) survival.Median follow-up was 10.0 and 7.8 years for the UC and MUC groups, respectively. No significant differences were noted between UC and MUC groups with regard to age, gender, clinical disease stage, and administration of neoadjuvant and adjuvant chemotherapy (all, P ≥ 0.10). When compared with UC, presence of MUC was associated with higher pathologic stage (organ-confined, 60% vs. 27%; extravesical, 18% vs. 23%; node-positive, 22% vs. 50%; P0.01) and lymphovascular invasion (29% vs. 58%; P0.01) at cystectomy. In comparison with UC, MUC patients had poorer 5-year RFS (70% vs. 44%; P0.01) and OS (61% vs. 38%; P0.01). However, on multivariable analysis, tumor histology was not independently associated with the risks of recurrence (P = 0.27) or mortality (P = 0.12).This multi-institutional analysis demonstrated that the presence of MUC was associated with locally advanced disease at radical cystectomy. However, clinical outcomes were comparable to those with pure UC after controlling for standard clinicopathologic predictors.