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Introduction: Preoperative coagulation screening for patients without bleeding disorders remains controversial. The combinatorial risk of INR, aPTT, and platelet count (PLT) abnormalities leading to bleeding requiring transfusion is not known in these patients. We examined the association between abnormal coagulation profile and the risk of transfusion following common elective surgery in patients without bleeding disorders. Study Design and Methods: We utilized the National Surgical Quality Improvement Program (NSQIP) database from 2004 to 2018 to identify patients without a history of bleeding disorders undergoing common 23 major elective procedures across 10 specialties. Multivariable logistic regression was used to assess the association between coagulation profile and bleeding requiring packed red blood cell transfusion intra−/post‐operatively. Results: Of the 672,075 patients meeting inclusion criteria, 53.7% presented with normal coagulation profile preoperatively. Overall, 12.2% (n = 82,368) received transfusion. In the setting of normal aPTT/PLT, both Equivocal INR of 1.1–1.5 (aOR 1.41, 95% CI 1.38–1.44) and Abnormal INR of >1.5 (aOR 1.81, 95% CI 1.71–1.93) were significantly associated with an increased risk of transfusion. Equivocal (60–70) and Abnormal (>70) aPTT with normal INR/PLT did not demonstrate a comparable risk of transfusion. We observed a synergistic effect of combinatorial lab abnormalities on the risk of transfusion when both Abnormal INR/aPTT and Low PLT of <100,000 were present (aOR 5.18, 95% CI 3.04–8.84), compared to the effect of Abnormal INR/aPTT and normal/elevated PLT (aOR 1.90, 95% CI 1.48–2.45). Discussion: The preoperative presence of abnormal findings in INR or PLT was significantly associated with the risk of bleeding requiring transfusion during intraoperative and postoperative periods. See editorial on page 2155–2157, in this issue [ABSTRACT FROM AUTHOR]

Background: Aging may detrimentally affect cognitive and motor function. However, age is also associated with experience, and how these factors interplay and affect outcomes following surgery is unclear. We sought to evaluate the effect of surgeon age on postoperative outcomes in patients undergoing common surgical procedures.Methods: We performed a retrospective cohort study of patients undergoing 1 of 25 common surgical procedures in Ontario, Canada, from 2007 to 2015. We evaluated the association between surgeon age and a composite outcome of death, readmission and complications. We used generalized estimating equations for analysis, accounting for relevant patient-, procedure-, surgeon- and hospital-level factors.Results: We found 1 159 676 eligible patients who were treated by 3314 surgeons and ranged in age from 27 to 81 years. Modelled as a continuous variable, a 10-year increase in surgeon age was associated with a 5% relative decreased odds of the composite outcome (adjusted odds ratio [OR] 0.95, 95% confidence interval [CI] 0.92 to 0.98, p = 0.002). Considered dichotomously, patients receiving treatment from surgeons who were older than 65 years of age had a 7% lower odds of adverse outcomes (adjusted OR 0.93, 95% CI 0.88-0.97, p = 0.03; crude absolute difference = 3.1%).Interpretation: We found that increasing surgeon age was associated with decreasing rates of postoperative death, readmission and complications in a nearly linear fashion after accounting for patient-, procedure-, surgeon- and hospital-level factors. Further evaluation of the mechanisms underlying these findings may help to improve patient safety and outcomes, and inform policy about maintenance of certification and retirement age for surgeons. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between local treatment modality, surgery or radiotherapy, and non-prostate cancer and cardiovascular mortality in patients treated for nonmetastatic prostate cancer, given the high competing risk of mortality in this population.Methods: We performed a population-based, retrospective cohort study of men treated for nonmetastatic prostate cancer in Ontario, Canada, from 2002 to 2009. Patients treated with surgery and radiotherapy were matched on demographics, comorbidity, and cardiovascular risk factors. The primary outcome was non-prostate cancer mortality. Outcomes were compared using the Fine and Gray subdistribution method with generalized estimating equations. We used a previously published technique to quantify the prevalence and strength of residual confounding necessary to account for observed results.Results: We examined 5393 pairs of matched men. The 10-year cumulative incidence of non-prostate cancer mortality was higher among patients who underwent radiotherapy (12%) than surgery (8%; adjusted subdistribution hazard ratio [HR] 1.57, 95% confidence interval 1.35-1.83). Patients treated with radiotherapy also had an increased risk of cardiovascular mortality (adjusted HR 1.74, 95% confidence interval 1.27-2.37). Hypothetical residual confounders would have to be both strongly associated with non-prostate cancer mortality (HRs > 2.5) and have highly differential prevalence to nullify the observed effect.Conclusion: Among patients carefully matched on cardiovascular risk factors, those treated with radiotherapy had an increased risk of non-prostate cancer mortality and cardiovascular disease. Because of the observational nature of the data, the potential for confounding remains. The magnitude and prevalence of potential residual confounders required to account for differences in treatment effects for prostate cancer was quantified. [ABSTRACT FROM AUTHOR]

Objective: To assess the toxicity and effectiveness of contemporary metastatic castrate-resistant prostate cancer (mCRPC) treatments at a population level, among all patients in Ontario particularly treated with newer agents, including abiraterone, enzalutamide, docetaxel, and cabazitaxel.Methods: We performed a population-based, retrospective cohort study of 2439 men aged ≥65 years treated for mCRPC with abiraterone, enzalutamide, docetaxel, or cabazitaxel from 2003 to 2015 in Ontario, Canada. Our primary outcome was treatment-related toxicity, defined as hospitalizations and emergency room (ER) visits during mCRPC treatment. Based on toxicity profiles identified during phase III trials, we further identified specific treatment-related toxicity. We calculated hazard ratios (HRs) using multivariable Cox proportional hazards models with time-varying exposures.Results: Abiraterone and enzalutamide exposure were not associated with any-cause (P = .19 and .52, respectively) or treatment-related (P = .45 and .64, respectively) toxicities. In contrast, docetaxel exposure was associated with an increased risk of any-cause (HR 1.29, 95% confidence interval [CI] 1.15-1.44) and treatment-related (HR 1.52, 95% CI 1.33-1.74) toxicities. Cabazitaxel exposure was associated with a significant risk of treatment-related toxicity (HR 5.94, 95% CI 1.87-18.92) but not any-cause toxicity (HR 2.37, 95% CI 0.59-9.63).Conclusion: Among patients with mCRPC, we failed to show any increased risk of hospitalizations and ER visits for treatment-related complications for abiraterone or enzalutamide. In contrast, treatment with intravenous chemotherapeutic agents was associated with an increased risk of hospitalizations and ER visits to manage these complications. [ABSTRACT FROM AUTHOR]

Introduction: We sought to determine whether patients undergoing radical prostatectomy (RP) in the context of disseminated cancer have higher 30-day complications. Methods: We conducted a retrospective cohort study of the National Surgical Quality Improvement Program (NSQIP) database. Men undergoing RP (from January 1, 2005 to December 31, 2014) for prostate cancer were identified and stratified by presence (n=97) or absence (n=27 868) of disseminated cancer. The primary outcome was major complications (death, re-operation, cardiac or neurologic events) within 30 days of surgery. Secondary outcomes included pulmonary, infectious, venous thromboembolic, and bleeding complications; prolonged length of stay; and concomitant procedures (bowel-related, cystectomy, urinary diversion, and major ureteric reconstruction). Odds ratios (OR) for each complication were calculated using univariable logistic regression. Results: We did not identify a difference in major complication rates (OR 2.26, 95% confidence interval [Cl] 0.71-7.1 6). Patients with disseminated cancer had increased risk of venous thromboembolic events (OR 3.30, 95% Cl 1.04-10.48) and transfusion (OR 2.45, 95% 0 1.18-5.05), but similar odds of pulmonary and infectious complications and length of stay. Bowel procedures were rare, however, a significantly higher proportion of patients with disseminated cancer required bowel procedures (2.1% vs. 0.3%; p=0.03). Patients with disseminated cancer undergoing RP had greater comorbidities and higher predicted probability of morbidity and mortality. This study is limited by its retrospective design, lack of cancer-specific variables, and prostatectomyspecific complications. Conclusions: RP in the context of disseminated cancer may be associated with increased perioperative complications. Caution should be exercised in embarking on this practice outside of clinical trials. [ABSTRACT FROM AUTHOR]

Objective To assess the utility of routine frozen section analysis of ureters at the time of radical cystectomy ( RC) for urothelial cancer ( UC), and the long-term outcomes of adverse ureteric pathology. Patients and Methods Pathological data on 2 047 patients undergoing RC for UC with routine frozen section analysis of ureters (January 1971 to December 2009) were analysed. Univariate and multivariable logistic and Cox proportional hazards models were used to determine the risk of upper tract UC ( UTUC) recurrence, local recurrence and overall survival in those identified as having adverse pathology (severe atypia/carcinoma in situ [ CIS] or UC) at time of frozen section analysis. Results Adverse pathology was identified by frozen section analysis in 178 patients (8.6%). Frozen section analysis was found to have poor sensitivity in identifying adverse pathology (59.1%), which was improved in patients with preoperative CIS (68.0%). After a median (interquartile range) follow-up of 12.4 (1.9-10.1) years, 28 patients (1.4%) developed UTUC recurrence. There were no uretero-enteric anastomotic recurrences. Adverse pathology on frozen section analysis was associated with UTUC recurrence on univariate analysis (hazard ratio [ HR] 6.2, 95% confidence interval [ CI] 2.9-13.5), but 15/28 patients (54%) with UTUC recurrence had benign ureteric frozen section analysis on initial sectioning. Adverse pathology on frozen section analysis was not independently associated with the risk of local recurrence ( HR 1.08, 95% CI 0.61-1.89) or overall survival ( HR 1.12, 95% CI 0.94-1.35) in multivariate models. Conclusions Ureteric frozen section analysis has poor sensitivity and may be marginally improved in pre-existing CIS. UTUC recurrence is rare and can occur despite negative frozen section analysis. Our data question the utility of routine frozen section analysis of the distal ureteric margin at the time of RC. [ABSTRACT FROM AUTHOR]

Background Intracorporeal orthotopic neobladder (iONB) creation following robotic radical cystectomy is an emerging procedure and robust functional data are required. Objective To evaluate urodynamic features of iONB and bladder cancer–specific and general health-related quality-of-life (HRQOL) outcomes. Design, setting, and participants We retrospectively assessed 28 men who underwent iONB creation (January 2012 to October 2013) and compared results to a previously characterized cohort of 79 of open ONB procedures. Outcome measurements and statistical analysis iONB pressure-volume properties were characterized using multichannel urodynamics (UDS). The Bladder Cancer Index (BCI) questionnaire, modified with mucus- and pad-related questions, and the Short Form Health Survey (SF-36) were used to evaluate urinary function and HRQOL. ONB cohorts were compared for functional outcomes and BCI score. Multivariable linear regression was used to assess predictors of BCI score. Results and limitations The median follow-up was 9.4 mo for the iONB and 62.1 mo for the open ONB group ( p < 0.0001); ≥2-yr follow-up had been completed for one (4%) patient in the iONB group compared to 75 (95%) patients in the open ONB group ( p < 0.0001). In UDS tests, the iONB group had minimal postvoid residual volume, normal compliance, and a mean capacity of 514 cm 3 (range 339–1001). BCI mean scores for urinary function ( p = 0.58) and urinary bother ( p = 0.31) were comparable between the groups. The surgical approach was not associated with the BCI score on multivariable analysis. Rates of 24-h pad use were comparable between iONB and open ONB groups (pad-free 17% vs 19%; ≤2 pads 84% vs 79%), as reflected by total pad usage ( p = 0.1); pad size and daytime wetness were worse in the iONB group. The clean intermittent catheterization rate was 10.7% in the iONB and 6.3% in the open ONB group. Limitations include the retrospective comparison, small number of patients and short follow-up for the iONB group. Conclusions iONB had adequate UDS characteristics and comparable bladder cancer–specific HRQOL scores to open ONB. However, pad size and daytime wetness were worse for iONB, albeit over significantly shorter follow-up. Patient summary We demonstrate that the volumetric and pressure characteristics are acceptable for a neobladder created using an entirely robot-assisted laparoscopic technique after bladder removal for cancer. Urinary function and quality-of-life outcomes related to the robotic technique were compared to those for neobladders created via an open surgical technique. We found that urinary function and bother indices were comparable; however, the robotic group required larger incontinence pads that were wetter during the daytime. This may be explained by the significantly shorter duration of recovery after surgery in the robotic group. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the clinical and pathologic staging of patients with urothelial carcinoma (UC) in bladder diverticula (BD) after undergoing radical cystectomy (RC) and determine the impact of UCBD on recurrence and survival. Methods: We reviewed our institutional database of patients who underwent RC for UC (1971-2009). Outcomes were compared between patients with and without UCBD. Kaplan-Meier curves estimated recurrence-free survival (RFS) and overall survival (OS). Multivariable Cox regression evaluated associations between UCBD and survival. Results: Inclusion criteria were met in 1991 patients. UCBD was seen in 77 (4 %) patients and occurred exclusively in men (mean age 68 ± 8.5 years). The highest pathologic stage tumor was found in the BD in 44 (57 %) of these patients. Pathologic upstaging was more common with UCBD compared with UC not in BD (48 vs. 39 %, p = 0.031). On univariate analysis, no differences in RFS or OS were observed comparing patients with or without UCBD stratified by clinically organ-confined (≤T2) and extravesical (>T2) disease. On multivariable analysis, the presence of UCBD was not associated with differences in RFS (HR 0.92, 95 % CI 0.59-1.42, p = 0.69) or OS (HR 0.98, 95 % CI 0.74-1.31, p = 0.92). Conclusion: Upstaging was common in patients with UCBD, observed in almost half of the patients. There were no differences in RFS or OS after RC when comparing patients with or without UC in a diverticulum stratified by stage. [ABSTRACT FROM AUTHOR]

Background Anatomic partial nephrectomy (PN) techniques aim to decrease or eliminate global renal ischemia. Objective To report the technical feasibility of completely unclamped “minimal-margin” robotic PN. We also illustrate the stepwise evolution of anatomic PN surgery with related outcomes data. Design, setting, and participants This study was a retrospective analysis of 179 contemporary patients undergoing anatomic PN at a tertiary academic institution between October 2009 and February 2013. Consecutive consented patients were grouped into three cohorts: group 1, with superselective clamping and developmental-curve experience ( n = 70); group 2, with superselective clamping and mature experience ( n = 60); and group 3, which had completely unclamped, minimal-margin PN ( n = 49). Surgical procedure Patients in groups 1 and 2 underwent superselective tumor-specific devascularization, whereas patients in group 3 underwent completely unclamped minimal-margin PN adjacent to the tumor edge, a technique that takes advantage of the radially oriented intrarenal architecture and anatomy. Outcome measurements and statistical analysis Primary outcomes assessed the technical feasibility of robotic, completely unclamped, minimal-margin PN; short-term changes in estimated glomerular filtration rate (eGFR); and development of new-onset chronic kidney disease (CKD) stage >3. Secondary outcome measures included perioperative variables, 30-d complications, and histopathologic outcomes. Results and limitations Demographic data were similar among groups. For similarly sized tumors ( p = 0.13), percentage of kidney preserved was greater ( p = 0.047) and margin width was narrower ( p = 0.0004) in group 3. In addition, group 3 had less blood loss (200, 225, and 150 ml; p = 0.04), lower transfusion rates (21%, 23%, and 4%; p = 0.008), and shorter hospital stay ( p = 0.006), whereas operative time and 30-d complication rates were similar. At 1-mo postoperatively, median percentage reduction in eGFR was similar (7.6%, 0%, and 3.0%; p = 0.53); however, new-onset CKD stage >3 occurred less frequently in group 3 (23%, 10%, and 2%; p = 0.003). Study limitations included retrospective analysis, small sample size, and short follow-up. Conclusions We developed an anatomically based technique of robotic, unclamped, minimal-margin PN. This evolution from selective clamped to unclamped PN may further optimize functional outcomes but requires external validation and longer follow-up. Patient summary The technical evolution of partial nephrectomy surgery is aimed at eliminating global renal damage from the cessation of blood flow. An unclamped minimal-margin technique is described and may offer renal functional advantage but requires long-term follow-up and validation at other institutions. [ABSTRACT FROM AUTHOR]

Objective The location of positive lymph nodes (LNs) is important for bladder cancer staging. Little is known regarding the impact of perivesical (PV) lymph node (PVLN) involvement on survival. This study characterized PVLN identified after radical cystectomy (RC) and analyzed their impact on recurrence and survival. Materials and methods We reviewed our institutional review board–approved database including all patients who underwent RC with pelvic lymphadenectomy for curative intent for urothelial carcinoma. Clinical and pathologic data were obtained. Patients were analyzed in groups according to the location of positive LNs: PV+/other LN (ON)+, PV+/ON−, and PV−/ON+. Kaplan-Meier curves were used to estimate recurrence-free survival (RFS) and overall survival (OS). Multivariable Cox regression (including pathologic T category, number of positive LNs, highest level of positive LNs, chemotherapy, and margin status) was performed to evaluate associations between PVLN status and survival. Results In total, 2,017 patients met inclusion criteria and 465 (23%) were LN+. PVLNs were identified in 936 patients (47%), positive in 197 patients (10%), and represented isolated LN+disease in 101 patients (5%). On univariate analysis, RFS and OS were significantly worse in the PV+/ON+group compared with the PV+/ON− and PV−/ON+ groups. There were no significant differences in RFS or OS between the PV+/ON− and PV−/ON+ groups. On multivariable analysis, PV+/ON+disease was independently associated with worse RFS and OS when compared with PV−/ON+ disease. Conclusions PVLNs were identified in a significant number of patients after RC. Positive PVLN, when in combination with other positive LNs, portends worse survival even when correcting for the number of positive nodes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether hormonal markers predict erectile dysfunction (ED) and symptoms of T deficiency syndrome (TDS), which are commonly found in the population of infertile men. Design: Retrospective study utilizing a prospectively maintained infertility database. Setting: A tertiary referral center. Patient(s): A total of 1,750 of 2,783 men presenting for evaluation of infertility between 1995 and 2010 completed validated questionnaires. Intervention(s): Androgen Deficiency in the Aging Male (ADAM) and Sexual Health Inventory for Men questionnaires were administered. Baseline risk factors for ED and TDS were also measured. Subjects underwent serum hormone evaluation for total T, calculated bioavailable T, sex hormone–binding globulin, E2, LH, FSH, and PRL. Main Outcome Measure(s): Multivariable logistic regression modeling was used to determine the significance of hormonal markers in predicting ED (Sexual Health Inventory for Men score <22) and/or a positive ADAM score. Result(s): The prevalence of ED and a positive response to the ADAM questionnaire were 30.5% and 45.2%, respectively, in this population (mean age, 36 years). Low serum T (total T < 10 nmol/L) was found in 29.4%. Neither T nor bioavailable T was significantly associated with the symptoms of ED or TDS on multivariable regression analysis. Conclusion(s): Erectile dysfunction and TDS in young, infertile men seem to be unrelated to hormone changes. [Copyright &y& Elsevier]

Background: We describe the practice variability of CUA (Canadian Urological Association) members and factors which predict these patterns for common stone scenarios. Methods: We asked 308 English- and 52 French-speaking CUA members to complete online surveys in their respective languages. We collected demographic information on fellowship training, shock wave lithotripsy (SWL) access, academic setting and whether they are at a hospital with regionalized surgical services. Respondents indicated their actual as well as ideal treatment for scenarios of renal, proximal and distal ureteric calculi . Results: In total, 131 urologists responded (36% response rate), all of whom treated urolithiasis. Of this number, 17% had endourology fellowship training, 76% had access to SWL, 42% were at an academic institution and 66% were at institutions with regionalized surgical services. Actual and ideal treatment modalities selected for symptomatic, distal and proximal ureteric stones (4, 8, 14 mm) were consistent with published guidelines. There were discrepancies between the use of ureteroscopy and SWL in actual versus ideal scenarios. Actual and ideal practices were congruent for proximal ureteric stones and asymptomatic renal calculi. In multivariate analysis, respondents were less likely to perform ureteroscopy on proximal 4- and 8-mm stones if they were at a hospital with regionalized surgical services (OR: 0.097; 95% Cl: O.Dl-0.76, p = 0.03 and OR: 0.330; 95% Cl: 0.1 3-0.83, p = 0.02). Interpretation: There is clinical variability in the management of urolithiasis in Canada; however, management approaches fall within published guidelines. Type of hospital and access to operating room resources may affect treatment modality selection. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint-inhibitor (ICI)-based therapy is the standard of care for first-line treatment of metastatic renal cell carcinoma (mRCC). It is unclear whether prior removal of the primary tumor influences the efficacy of these treatments. We performed a systematic review and meta-analysis of studies of first-line ICI in mRCC to determine whether the efficacy of ICI-therapy, compared to sunitinib, is altered based on receipt of prior nephrectomy.Methods: We systematically reviewed studies indexed in MEDLINE (PubMed), Embase, and Scopus and conference abstracts from relevant medical societies as of August 2020 to identify randomized clinical trials assessing first-line immunotherapy-based regimes in mRCC. Studies were included if overall survival (OS) and progression-free survival (PFS) outcomes were reported with data stratified by nephrectomy status. We pooled hazard ratios (HRs) stratified by nephrectomy status and performed random effects meta-analysis to assess the null hypothesis of no difference in the survival advantage of immunotherapy-based regimes based on nephrectomy status, while accounting for study level correlations.Results: Among 6 randomized clinical trials involving 5,121 patients, 3,968 (77%) had undergone prior nephrectomy. We found an overall survival benefit for immunotherapy-based regimes, compared to sunitinib, among both patients who had undergone nephrectomy (HR 0.75, 95% CI 0.63 -0.88) and those who had not (HR 0.74, 95% CI 0.59 -0.92), without evidence of difference based on nephrectomy history (P = 0.70; I2 = 36%). Results assessing PFS were similar (P = 0.45, I2 = 0%).Conclusions: These clinical data suggest that prior nephrectomy does not affect the efficacy of ICI-based regimens in mRCC relative to sunitinib. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions Androgen‐deprivation therapy (ADT) remains a cornerstone in treatment for patients with advanced prostate cancer. ADT is associated with several adverse effects, including osteoporosis, metabolic syndrome, and cardiovascular events, leading to guidelines recommending routine testing to monitor for these toxicities. There is a lack of data assessing adherence to these recommendations.The authors conducted a retrospective cohort study using administrative data from Ontario, Canada between 2008 and 2021. They identified all older men (aged 65 years and older) who received ADT for prostate cancer using comprehensive provincial health databases. The primary outcomes were the use of testing for lipids, dysglycemia (glucose), bone health serum, and bone density between 6 weeks before and 1 year after the initiation of ADT.In total, 29,097 patients were examined, of whom 52.8% were prescribed ADT by urologists, 37.9% were prescribed ADT by radiation oncologists, 2.8% were prescribed ADT by medical oncologists, and 2.4% were prescribed ADT by other physicians. Adherence to guidelines was low: only 21.3% of patients received a bone density scan, 41.2% underwent bone health–related serum tests, 51.3% completed a lipid profile, and 65.9% underwent dysglycemia testing within 1 year of diagnosis. Overall, only 11.9% of patients received all of the recommended investigations. Adherence to testing did not appear to improve over time (2008–2021) or with guideline publication. Patient (age) and physician (specialty) factors had important associations with adherence to testing.Most patients receiving ADT for prostate cancer do not receive recommended testing to monitor for treatment‐related toxicity. Further study is required to address barriers to therapeutic monitoring of men on ADT and to reduce treatment‐associated adverse events. [ABSTRACT FROM AUTHOR]

The article focuses on the aspects of selecting treatment for men with prostate cancer considering age and comorbidity factors. Topics discussed include the analysis of the survival and mortality of the patients considering their age, the study which reveals the significant of insulin therapy for type 2 diabetes on preventing curative treatment following prostate cancer diagnosis, and the comparison of the mortality rate between prostate cancer and diabetic men.

The article discusses the treatment of metastatic renal-cell carcinoma using the model of the Bayesian approach. It reports that the network meta-analysis revealed that the use of cabozantinib was associated with the longest progression-free survival. The use of pembrolizumab plus axitinib and avelumab plus axitinib also have likelihoods of long progression-free survival in the treatment.

Background Androgen-deprivation therapy (ADT) has been associated with cardiovascular risk factors and the development of cardiovascular disease in men with metastatic prostate cancer. We sought to examine the effect of ADT on nonprostate cancer mortality among patients with nonmetastatic prostate cancer. Methods We performed a population-based, retrospective cohort study of men aged 66 years and older treated with surgery or radiotherapy for nonmetastatic prostate cancer in Ontario, Canada from 2002 to 2009 using administrative datasets (including the Ontario Cancer Registry, Ontario Drug Benefit, and Ontario Health Insurance Plan). Analysis was performed between September 2016 and April 2017. ADT exposure was operationalized as a time-varying binary and cumulative dose exposure. Primary and secondary outcomes were nonprostate cancer mortality and cardiovascular mortality, respectively. The Fine and Gray subdistribution method with generalized estimating equations was used to calculate subdistribution hazard ratios (sdHR), while accounting for competing risks. Results We examined 20,651 men treated for nonmetastatic prostate cancer. Median follow-up was 7.4 years and median ADT exposure was 6.4 months. ADT was not significantly associated with nonprostate cancer mortality (sdHR = 0.75, 95% CI: 0.37–1.50) or cardiovascular mortality (sdHR = 1.16, 95% CI: 0.37–3.63) when operationalized as a binary time-varying exposure. Similar results were obtained when we examined ADT cumulative dose exposure. Conclusions ADT is not associated with nonprostate cancer mortality or cardiovascular mortality in a large, population-based cohort of older men with localized prostate cancer treated by surgery or radiation therapy. [ABSTRACT FROM AUTHOR]

Background: Androgen-deprivation therapy (ADT) has been associated with cardiovascular risk factors and the development of cardiovascular disease in men with metastatic prostate cancer. We sought to examine the effect of ADT on nonprostate cancer mortality among patients with nonmetastatic prostate cancer.Methods: We performed a population-based, retrospective cohort study of men aged 66 years and older treated with surgery or radiotherapy for nonmetastatic prostate cancer in Ontario, Canada from 2002 to 2009 using administrative datasets (including the Ontario Cancer Registry, Ontario Drug Benefit, and Ontario Health Insurance Plan). Analysis was performed between September 2016 and April 2017. ADT exposure was operationalized as a time-varying binary and cumulative dose exposure. Primary and secondary outcomes were nonprostate cancer mortality and cardiovascular mortality, respectively. The Fine and Gray subdistribution method with generalized estimating equations was used to calculate subdistribution hazard ratios (sdHR), while accounting for competing risks.Results: We examined 20,651 men treated for nonmetastatic prostate cancer. Median follow-up was 7.4 years and median ADT exposure was 6.4 months. ADT was not significantly associated with nonprostate cancer mortality (sdHR = 0.75, 95% CI: 0.37-1.50) or cardiovascular mortality (sdHR = 1.16, 95% CI: 0.37-3.63) when operationalized as a binary time-varying exposure. Similar results were obtained when we examined ADT cumulative dose exposure.Conclusions: ADT is not associated with nonprostate cancer mortality or cardiovascular mortality in a large, population-based cohort of older men with localized prostate cancer treated by surgery or radiation therapy. [ABSTRACT FROM AUTHOR]

Introduction: Radical cystectomy is a highly morbid procedure with 30-day perioperative complication rates approaching 50%. Our objective was to determine the effect of patients' body mass index (BMI) on perioperative outcomes following radical cystectomy for bladder cancer. Methods: We identified 3930 eligible patients who underwent radical cystectomy for nonmetastatic bladder cancer using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. The primary exposure was preoperative BMI, categorically operationalized in four strata according to the World Health Organization criteria: <18.5 kg/m², 18.5-25 kg/m², 25-30 kg/m², and >30 kg/m². Our primary outcome was major perioperative complication comprising mortality, reoperation, cardiac event, or neurological event. Results: BMI was significantly associated with rates of major complications (p=0.003): major complications were experienced by 17.0% of patients with BMI <18.5 kg/m², 7.8% of patients with BMI 18.5-25 kg/m², 7.9% of patients with BMI 25-30 kg/m², and 10.8% of patient with BMI >30 kg/m². Following multivariable adjustment for relevant demographic, comorbidity, and treatment factors, compared to patients with BMI 18.5-25 kg/m², patients with BMI <18.5 kg/m² (odds ratio [OR] 2.28; 95% confidence interval [CI] 1.07-4.78) and BMI >30 kg/m² (OR 1.59;95% CI 1.17-2.16) were significantly more likely to experience a major complication in the 30 days following cystectomy. Among the secondary outcomes, significant differences were identified in rates of pulmonary complications (p=0.003), infectious complications (p<0.001), bleeding requiring transfusion (p=0.01), and length of stay (p=0.001). Conclusions: Patients who are outside of a normal BMI range are more likely to experience major complications following radical cystectomy for bladder cancer. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Elective pelvic nodal irradiation for patients with muscle-invasive bladder cancer (MIBC) undergoing trimodal therapy (TMT) is controversial. In patients with node-negative (N0) MIBC, the benefit of elective whole-pelvis concurrent chemoradiation (WP-CCR) compared to bladder-only (BO)-CCR has not been demonstrated. Using realworld data from the National Cancer Database (NCDB), we sought to compare the overall survival (OS) between BO-CCR and WP-CCR for MIBC. METHODS: Using the 2020 NCDB Participant User File, we identified cases of MIBC diagnosed between 2017 and 2019. We selected patients with clinical T2-T4aN0M0 disease receiving CCR as first-line treatment. CCR was defined as transurethral resection of bladder tumor followed by =40 Gy radiation to the bladder with concurrent single- or multiple-agent chemotherapy. Based on elective nodal irradiation status, patients were stratified as having received BO-CCR vs. WP-CCR. OS analysis was performed using summary three-month conditional landmark, inverse probability treatment weighting (IPTW)-adjusted Kaplan-Meier estimates, and Cox regression. RESULTS: A total of 604 patients receiving CCR for MIBC were identified: 367 (60.8%) BO-CCR and 237 (39.2%) WP-CCR. Before IPTW, the groups were imbalanced in terms of baseline characteristics. The median followup of the weighted population was 42.3 months (interquartile range 18.1-49.1 months). In IPTW-adjusted Cox proportional hazards regression analysis, WP-CCR was associated with a significant OS benefit compared to BO-CCR (adjusted hazard ratio 0.72, 95% confidence interval 0.54-0.96, p=0.026). CONCLUSIONS: In the setting of CCR for N0 MIBC, this retrospective NCDB analysis revealed that WP-CCR was associated with a benefit in OS compared to BO-CCR. [ABSTRACT FROM AUTHOR]

Surgical patients can be discharged to a variety of facilities which vary widely in intensity of care. Postoperative readmissions have been found to be more strongly associated with post-discharge events than pre-discharge complications, indicating the importance of discharge destination. We sought to evaluate the association between discharge destination and 30-day outcomes. A retrospective cohort study was conducted using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Patients were dichotomized based on discharge destination: home versus non-home. The main outcome of interest was 30-day unplanned readmission. The secondary outcomes included post-discharge pulmonary, infectious, thromboembolic, and bleeding complications, as well as death. In this cohort study of over 1.5 million patients undergoing common surgical procedures across eight surgical specialties, we found non-home discharge to be associated with adverse 30-day post-operative outcomes, namely, unplanned readmissions, post-discharge pulmonary, infectious, thromboembolic, and bleeding complications, as well as death. Non-home discharge is associated with worse 30-day outcomes among patients undergoing common surgical procedures. Patients and caregivers should be counseled regarding discharge destination, as non-home discharge is associated with adverse post-operative outcomes. [ABSTRACT FROM AUTHOR]

Introduction: While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the magnitude differs based on disease indication and concurrent steroid administration. Methods: We performed a systematic review and meta-analysis of phase II/III RCTs of AA in APC published as of August 11, 2020. Primary outcomes examined were all-and high-grade (grade = 3) hypokalemia and fluid retention, and secondary outcomes included hypertension and cardiac events. We performed random effects meta-analysis comparing intervention (AA + steroid) and control (placebo ± steroid), stratified by treatment indication and whether patients received steroids. Results: Among 2,739 abstracts, we included 6 relevant studies encompassing 5901 patients. Hypokalemia and fluid retention were observed more frequently among patients receiving AA (odds ratio [OR] 3.10 [95% CI 1.69-5.67] and 1.41 [95% CI 1.19-1.66]). This was modified by whether patients in the control received steroids: trials where control patients did not demonstrated a larger association between AA and hypokalemia (OR 6.88 [95% CI 1.48-2.36] versus OR 1.86 [95% CI 4.97-9.54], P < .0001) and hypertension (OR 2.53 [95% CI 1.91-3.36] vs. OR 1.55 [95% CI 1.17-2.04], P = .1) than those where steroids were administered. We observed heterogeneity due to indication: there were greater effects on hypokalemia (P < 0001), hypertension (P = .03), and cardiac disorders (P = .01) among patients treated for mHSPC than mCRPC. Conclusions: The magnitude of cardiotoxicity with AA differs based on trial design and disease indication. These data are valuable in treatment decisions and highlight utilization of appropriate data for counseling. [ABSTRACT FROM AUTHOR]

Aim: While high estimated glomerular filtration rate (eGFR) has been associated with increased overall mortality, its effect on postoperative outcomes is relatively understudied. We sought to investigate the association between high eGFR and 30‐day postoperative outcomes using a multi‐specialty surgical cohort. Methods: Using the National Surgical Quality Improvement Program database, we selected adult for whom eGFR could be calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration equation. Based on sex‐specific distributions of eGFR stratified by age quintiles, we classified patients into low (<5th percentile), normal (5–95th percentile) and high eGFR (>95th percentile). The primary outcome was a composite of any 30‐day major adverse outcomes, including: death, reoperation, cardiac arrest, myocardial infarction and stroke. Secondary outcomes included 30‐day infectious complications, venous thromboembolism (VTE), bleeding requiring transfusion, prolonged length of stay and unplanned readmission. After matching for demographic differences, comorbidity burden and operative characteristics, logistic regression models were used to evaluate the association between extremes of eGFR and the outcomes of interest. Results: Of 1 668 447 patients, 84 115 (5.07%) had a high eGFR. High eGFR was not associated with major adverse outcomes (odds ratio [OR] 1.00 [95% confidence interval (CI): 0.97, 1.03]); however, it was associated with reoperation (OR 1.04 [95% CI: 1.00,1.08]), infectious complications (OR 1.14 [95% CI: 1.11, 1.16]), VTE (OR 1.15 [95% CI: 1.09, 1.22]) and prolonged length of stay (OR 1.19 [95% CI: 1.16, 1.21]). Conclusion: Our findings support an association between high eGFR and adverse 30‐day postoperative outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To synthesise available data regarding the disease‐free survival (DFS) benefit of adjuvant immune checkpoint inhibitors (ICIs) for patients with renal cell carcinoma (RCC) and evaluate the overall safety profile of ICIs in this setting. Materials and Methods: We utilised PubMed, Embase, and relevant conference proceedings to identify phase III randomised controlled trials comparing adjuvant ICIs vs placebo/observation for RCC. The primary outcome of interest was DFS. Variables for subgroup analyses were programmed death‐ligand 1 (PD‐L1) expression, sarcomatoid features, nephrectomy type, and disease‐risk category. Secondary outcomes included Grade ≥3 adverse events (AEs), immune‐related AEs, and treatment discontinuation due to AEs. All outcomes were analysed using random‐effects models owing to inter‐study heterogeneity. Results: Among the four included studies, one demonstrated a significant DFS benefit. There was considerable clinical and statistical heterogeneity (I2 = 64%) due to differences in inclusion criteria and interventions. While pooled results across the four studies did not demonstrate a significant benefit in DFS overall (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.69–1.04) there was significant benefit among patients with positive PD‐L1 expression (HR 0.72, 95% CI 0.55–0.94) and sarcomatoid features (HR 0.59, 95% CI 0.38–0.91). Conclusion: The evidence base to date regarding ICIs as adjuvant therapy in RCC is mixed – conclusions are limited by considerable heterogeneity between studies. However, pooled analyses suggest that patients with positive PD‐L1 expression or sarcomatoid features are most likely to benefit from adjuvant immunotherapy. [ABSTRACT FROM AUTHOR]

The current standard of care for muscle-invasive bladder cancer is neoadjuvant chemotherapy followed by radical cystectomy with lymph node dissection. Although this treatment provides therapeutic benefit, it is associated with notable morbidity. Bladder sparing techniques, such as concurrent chemo-radiation, are less invasive and prioritize organ preservation in individuals with invasive bladder cancer and offer comparable disease control. High-dose-rate brachytherapy is an emerging paradigm in the management of muscle-invasive bladder cancer. During high-dose-rate brachytherapy, radioactive sources are introduced to the area of the primary tumor through specialized catheters. The specific placement of brachytherapy catheters results in heightened effectiveness of the radiation treatment with less radiation damage to surrounding structures. For bladder-sparing therapies such as brachytherapy to rival radical cystectomy, these techniques need to be refined further by radiation oncologists. One such modality for developing and practicing these techniques is the use of cadaveric models in innovation-focused clinical training facilities, which provide a simulated sterile surgical environment without the concern for extending intraoperative time. The objective of this technical note is to demonstrate how clinical training facilities such as the Houston Methodist Institute for Technology, Innovation & Education are ideal for the development, testing, and training of novel brachytherapy techniques using cadaveric models. By utilizing a network of similarly innovative training centers, research and development of brachytherapy techniques can be expedited, and novel bladder-sparing treatment methods can be implemented as the standard of care for bladder cancer. [ABSTRACT FROM AUTHOR]

Introduction: There are no meta-analyses of randomized controlled trials (RCTs) comparing open radical cystectomy (ORC) with robot-assisted radical cystectomy (RARC), inclusive of both intracorporeal (iRARC) and extracorporeal (hybrid RARC, hRARC) urinary reconstruction. Methods: MEDLINE, Embase, Scopus, the International Clinical Trials Registry Platform and ClinicalTrials.gov registries were searched in May 2022. Outcomes of interest included recurrence-or progression-free survival (RFS/PFS), margin status and lymph node yield, mean estimated blood loss (EBL) and operating room time (ORT), hospital length of stay (LOS), 90-day complications and readmissions, and quality of life (QoL). Pairwise meta-analyses and network meta-analyses were performed using random-effects models and Bayesian hierarchical random-effects models, respectively. Results: We found no significant differences between RARC and ORC for oncological and most perioperative outcomes: RFS/PFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.67-1.23); positive surgical margins (odds ratio [OR] 1.05, 95% CI 0.60-1.85); lymph node yield (mean difference [MD] -0.63, 95% CI -2.63-1.37); LOS (MD -0.22, 95% CI -1.10-0.65); overall complications (OR 0.81, 95% CI 0.61-1.07); major complications (OR 0.94, 95% CI 0.69-1.30); readmissions (OR 0.90, 95% CI 0.60-1.35); and QoL (standardized MD -0.02, 95% CI -0.17-0.14). We found significantly lower EBL for RARC compared to ORC (MD -312.61, 95% CI - 447 to -178.22) at the expense of significantly prolonged ORT (MD 82.34 minutes, 95% CI 44.82-119.86). Network meta-analysis did not find significant differences in complications between hRARC and iRARC. Conclusions: This meta-analysis confirms the equivalence of RARC and ORC with respect to oncological outcomes. [ABSTRACT FROM AUTHOR]

Pulse granulomas are uncommon, benign foreign body inflammatory reactions that typically occur in the oral cavity. They are exceedingly rare elsewhere. Here we describe a 35-year-old woman who presented with interstitial cystitis and was found to have an incidental bladder mass. Histological examination of the biopsy revealed a pulse granuloma. The salient histopathologic features include corrugated hyaline rings and amorphous hyaline conglomerations within the connective tissue stroma of the lamina propria, admixed with chronic inflammatory cells with multinucleated foreign-body type giant cells. To our knowledge this is the first reported case of a pulse granuloma in the urinary bladder. [Copyright &y& Elsevier]

Objective: To examine the impact of androgen deprivation therapy (ADT) and primary treatment modality on cardiovascular and skeletal-related events and to investigate potential effect modification in a contemporary cohort of patients treated for clinically localized prostate cancer.Subjects and Methods: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results-Medicare linked databases for men aged 65-79 years who underwent radical prostatectomy or radiotherapy for cT1 or cT2 prostate cancer from 2000 to 2008. We categorized treatment according to primary therapy and receipt of ADT. We described the cumulative incidence of cardiovascular and skeletal-related events.Results: Among 60,156 men, 14,403 underwent surgery and 45,753 underwent radiotherapy. Median follow-up was 6.0 years. After adjusting for baseline differences, treatments with radiotherapy (adjusted hazard ratios [aHR] 1.16-1.28, P <.0001-.04) and ADT (aHR 1.18-1.32, P <.0001-.008) were each independently associated with increased risk of coronary heart disease, sudden cardiac death, fracture, and fracture requiring hospitalization. Radiotherapy was associated with an increased risk of myocardial infarction (aHR 1.20, P = .02), whereas ADT was not (P = .5). We did not identify a significant statistical interaction between primary and hormonal treatment.Conclusion: Care for cardiovascular and skeletal-related events is an important part of the survivorship phase for a significant proportion of patients with localized prostate cancer. Increasing use of ADT for patients with localized disease undergoing radiotherapy and the observed higher prevalence of these events in these patients should be considered when discussing the risks and benefits of treatment for localized prostate cancer and when formulating a survivorship plan. [ABSTRACT FROM AUTHOR]

Ileal ureter formation has been found to be a suitable treatment option for long, chronic ureteral strictures not amendable to less invasive forms of repair. Minimally invasive surgical techniques for this condition have been investigated. We report the first series of robotic completely intracorporeal ileal ureter using a four-arm robotic technique. Three patients underwent this procedure, including one patient with a solitary kidney. All procedures were performed effectively with a median operative time of 450 minutes (range: 420-540) and median estimated blood loss of 100 mL (range: 50-200). Postoperatively, one patient suffered volvulus and subsequent necrosis of small bowel and ileal ureter, which required re-operation and small bowel resection, including the ileal ureter. The other two patients report no surgical complications to date. This early series represents preliminary technical procedure feasibility. Further experience is necessary. [ABSTRACT FROM AUTHOR]

To evaluate the association between surgical modality (RARC vs. ORC) and the risk of 30-day complications. We utilized the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) Cystectomy-Targeted database from 2019 to 2021. The primary outcome was a composite of major complications including 30-day mortality, reoperation, cardiac events, and stroke. Secondary outcomes included individual major and cystectomy-specific complications. Propensity score matching (PSM) was employed to minimize inherent differences within our cohort. We performed logistic regression to assess the association between outcomes of interest and operative modality. We found no difference between operative modality and the primary outcome, however, RARC was associated with a 70% lower risk of 30-day mortality (OR 0.30, 95% CI 0.13-0.70) and had favorable outcomes with respect to respiratory, deep venous thrombosis, wound complications, and length of stay. Limitations are related to residual confounding given the observational methodology. RARC was associated with reduced risk of multiple 30-day complications, including mortality, as well as organ system and cystectomy-specific outcomes. These data support the clinical benefit of increased adoption of RARC. [ABSTRACT FROM AUTHOR]

• Metastatic urothelial carcinoma of the bladder can be treated with chemoimmunotherapy. • Comorbid and elderly patients receive first-line immunotherapy more often. • Chemoimmunotherapy combination treatment is higher in academic centers. • Combination therapy showed improved survival compared to chemo- or immunotherapy. First-line systemic therapy for metastatic urothelial carcinoma of the bladder (mUC) consists of platinum-based chemotherapy in most patients and PD1/L1 inhibitors in selected patients. Multiple combination chemoimmunotherapy trials failed to show a clear benefit over chemotherapy alone. We used real-world data to evaluate clinical and sociodemographic factors associated with receipt of first-line chemotherapy, immunotherapy, or combination chemoimmunotherapy treatment for metastatic bladder cancer and examined differences in overall survival (OS). We used the National Cancer Database to identify patients with stage IV mUC diagnosed between 2014 and 2018, who were treated with first-line immunotherapy, chemotherapy, or combination treatment. We performed multivariable logistic regression modeling to determine factors associated with treatment receipt Adjusted Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression were used to evaluate the association between treatment and OS. In our cohort of 4,169 patients, multivariable analysis identified increasing age (RRR: 1.07, 95%CI, 1.06–1.08) and comorbidity burden (, as independent predictors of receiving immunotherapy. Treatment at an academic facility was associated with increased likelihood of combination treatment (RRR: 1.29, 95%CI, 1.01–1.65). After IPTW, we found that combination therapy (hazard ratio [HR]: 0.72; 95%CI, 0.62–0.83) was associated with improved survival compared to chemotherapy. Patients with older age and more comorbidities were more likely to receive immunotherapy than chemotherapy for first-line treatment of metastatic urothelial carcinoma of the bladder. Utilization of chemoimmunotherapy was observed to be higher in academic centers and was associated with improved survival compared to chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Given the low incidence of urachal carcinoma of the bladder (UCB), there is limited published data from contemporary population‐based cohorts. This study aimed to describe demographic, clinicopathological features, and survival outcomes of patients diagnosed with UCB. Methods: The National Cancer Database (2004–2016) was queried for UCB patients. Descriptive analyses characterized demographics and clinicopathologic features. We assessed 5‐year overall survival (OS) rates of the entire cohort and subgroups of localized/locally advanced and metastatic disease. We utilized Cox proportional hazards models to assess the association between covariates of interest and all‐cause mortality and to examine the impact of surgical technique and chemotherapy. Results: We identified 841 patients with UCB. The most common histologic subtype was non‐mucinous adenocarcinoma (39.6%). Approximately 50% had ≥cT2 disease, and 14.3% were metastatic at diagnosis. Altogether, partial cystectomy (60%) was most performed, and lymph node dissection was performed in 377 patients (44.8%), with specific temporal increase in utilization over the study period (p < 0.001). Overall, median OS was 59 months, and 5‐year OS was 49%. In patients with localized/locally advanced disease, we found no association between partial and radical cystectomy (Hazards ratio [HR] 1.75; 95% CI 0.72–4.3) as well as receipt of perioperative chemotherapy (HR 1.97, 95% CI 0.79–4.90) and outcomes. Lastly, receipt of systemic therapy was not associated with survival benefit (HR 0.785, 95% CI 0.37–1.65) in metastatic disease cohort. Conclusion: This large population‐based cohort provides insight into the surgical management and systemic therapy, without clear evidence on the association of chemotherapy and survival in the perioperative and metastatic setting. [ABSTRACT FROM AUTHOR]

While studies have demonstrated an association between preoperative hypoalbuminemia and adverse clinical outcomes, the optimal serum albumin threshold for risk-stratification in the broader surgical population remains poorly defined. We sought define the optimal threshold of preoperative serum albumin concentration for risk-stratification of adverse post-operative outcomes. Using the American College of Surgeons National Surgical Quality Improvement Program Database, we identified 842,672 patients that had undergone a common surgical procedure in one of eight surgical specialties. An optimal serum albumin concentration threshold for risk-stratification was determined using receiver-operating characteristic analysis. Multivariable logistic regression analysis was used to evaluate the odds of adverse surgical events; a priori defined subgroup analyses were performed. A serum albumin threshold of 3.4 g/dL optimally predicted adverse surgical outcomes in the broader cohort. After multivariable analysis, patients with hypoalbuminemia had increased odds of death within 30 days of surgery (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.94–2.08). Hypoalbuminemia was associated with greater odds of primary adverse events among patients with disseminated cancer (OR 2.03, 95% CI 1.88–2.20) compared to patients without disseminated cancer (OR 1.47, 95% CI 1.44–1.51). The standard clinical threshold for hypoalbuminemia is the optimal threshold for preoperative risk assessment. [ABSTRACT FROM AUTHOR]

Pelvic lymph node dissection (PLND) is a fundamental component in the management of muscle-invasive bladder cancer (MIBC). Currently, there are no available tools to intra-operatively reliably target and identify lymph nodes which may have metastasis; therefore, a template-based PLND of lymph node landing zones must be performed. Prior studies in animal models have mapped lymph node drainage from the bladder using fluorescent molecules. Hexaminolevulinate HCl dye is a candidate for the proposed application In this study, given its fluorescent properties and ability to differentiate between normal urothelial cells and urothelial carcinoma. This is an investigator-initiated, single-institution, single-arm prospective study to determine the feasibility and safety of Hexaminolevulinate HCl administration into the bladder prior to robotic assisted radical cystectomy (RARC) and assessing for the presence of fluorescence in the lymph node regions and at the surgical margin via blue light laparoscopy. The study will recruit 10 patients with MIBC and either imaging-confirmed cN1 disease or higher risk for nodal metastasis with ≥ cT3 disease. Patients will receive intravesical instillation of Hexaminolevulinate HCl prior to the standard of care: RARC and PLND. The surgeon's subjective assessment of fluorescence during blue light intra-abdominal laparoscopy will be recorded. The obturator node packet will undergo: 1) standard pathologic analysis for nodal metastasis, 2) analysis under epifluorescent microscopy to assess for microscopic fluorescence and 3) ex vivo staining in Hexaminolevulinate HCl dye followed by epifluorescent microscopy. Enrollment opened on December 1, 2022. Results: Conclusions: [ABSTRACT FROM AUTHOR]

Introduction: Limited evidence exists on the comparative effectiveness of local treatments for prostate cancer (PCa) due to the lack of generalizability. Using granular national data, we sought to examine the association between radical prostatectomy (RP) and intensity-modulated radiation therapy (IMRT) treatment and survival. Methods: Records were abstracted for localized PCa cases diagnosed in 2004 across seven state registries to identify patients undergoing RP (n=3019) or IMRT (n=667). Comorbidity was assessed by the Adult Comorbidity Evaluation-27 (ACE-27). Propensity score matching (PSM) was used to balance covariates between treatment groups. All-cause and PCa-specific mortality were primary endpoints. A subgroup analysis of patients with high-risk PCa (RP, n=89; IMRT, n=95) was conducted. Results: Following PSM, matched patients (n=502 pairs) treated with either RP or IMRT were well-balanced with respect to covariates. With a median followup of 10.5 years (interquartile range [IQR] 9.9-11.0), the 11-year overall survival (OS) was 71.2% (95% confidence interval [CI] 66.9-75.8) for RP and 62.3% (95% CI 57.4-67.6) for IMRT. IMRT was associated with a 41% increased risk of all-cause mortality (hazard ratio [HR] 1.41, 95% CI 1.13-1.76) but not PCa-specific mortality (HR 1.75, 95% CI 0.84-3.64), as compared to RP. In patients with highrisk PCa, IMRT, as compared to RP, was not associated with statistically significant difference in all-cause (HR 1.53, 95% CI 0.97-2.42) or PCa-specific mortality (HR 1.92, 95% CI 0.69-5.36). Conclusions: Despite a low mortality rate at 10 years and possible residual confounding, we found a significantly increased risk of all-cause mortality, but no PCa-specific mortality associated with IMRT as compared to RP in this population-based study. [ABSTRACT FROM AUTHOR]

We examined the survival benefit of perioperative chemotherapy in men treated with radical surgery for primary urethral urothelial carcinoma (UUC). 191 men with UCC were identified within the National Cancer Database. We demonstrated that neoadjuvant chemotherapy was associated with improved survival compared to no chemotherapy or adjuvant chemotherapy. Introduction: The treatment landscape in invasive primary carcinoma of the urethra of urothelial histology closely aligns that of locally advanced urothelial carcinoma of the bladder. The survival benefit of perioperative chemotherapy for men undergoing radical surger y for primar y urethral urothelial carcinoma (UUC) has not yet been well-elucidated. Patients and Methods: Using the National Cancer Database (NCDB), we identified men diagnosed with non-metastatic invasive UUC (T2-4 N0-2 M0) from 2004 to 2016 treated with radical extirpative surgery. We compared OS between patients who had received peri-operative neoadjuvant (NAC) or adjuvant (AC) chemotherapy and those who had not using Kaplan-Meier curves and multivariable Cox proportional hazards regression model. Results: A total of 191 patients met inclusion cr iter ia. 113 patients (59.2%) did not receive chemotherapy, while 39 (20.4%) and 39 (20.4%) received NAC and AC, respectively. Median follow-up was 28.0 months. Upon multivariable analysis, receipt of NAC (HR 0.50, 95% CI 0.28-0.91, P = .02) decreased the risk of all-cause mortality, while receipt of AC (HR 0.76, 95% CI 0.41-1.41) was not significantly associated with an OS benefit, as compared to no chemotherapy. Conclusion: Our study is the first to evaluate treatment specific outcomes in male patients with primary carcinoma of the urethra. We observed that neoadjuvant chemotherapy in men with UUC was associated with OS benefit. The utilization of NAC may improve survival, consistent with urothelial carcinoma of the bladder. [ABSTRACT FROM AUTHOR]

Introduction: Active surveillance (AS) is increasingly used for favorable intermediate-risk (FIR) prostate cancer (PCa). Our objective was to determine oncological and sociodemographic predictors of deferred definitive therapy and decision for radical prostatectomy (RP) vs. radiotherapy (RT). Methods: The Surveillance, Epidemiology, and End Results (SEER) Prostate with Watchful Waiting database was used to identify all FIR PCa diagnosed between 2010 and 2015 opting for AS for at least one year following diagnosis. We sought to determine predictors of treatment and treatment type using multivariable logistic regression. Results: A total of 20 334 patients were identified. An annual decrease in incident FIR patients managed initially with AS between 2010 (4061) and 2015 (2947) was noted (p for trend <0.001); 17 895 (88.0%) patients underwent deferred RP and/or RT. Patients with higher baseline cancer volume and clinical stage were significantly more likely to discontinue AS. Patients of higher socioeconomic status were more likely to undergo deferred therapy, with increased odds for RT over RP. African American patients had lower odds of undergoing definitive intervention (odds ratio 0.83, p=0.030) and were significantly more likely to opt for XRT. Oncological characteristics leading to FIR classification influenced treatment choice at the time of deferred intervention: RT was treatment of choice in 86.3% and 86.0% of Gleason group 2 and prostate-specific antigen 10-20 FIR patients, respectively; 96.1% of treated cT2b-c FIR patients opted for RP. Conclusions: Most FIR PCa patients initially managed with AS eventually undergo deferred definitive therapy, with choice of treatment significantly influenced by patients' baseline oncological and sociodemographic characteristics. [ABSTRACT FROM AUTHOR]

Introduction: Shared decision-making is widely recommended when men are considering prostate cancer screening with prostate-specific antigen (PSA). The role of patients' trust in cancer information from their physician in such decisions is unknown. Methods: We identified male respondents ≥18 years of age from the Health Information National Trends Survey, a population-based survey of people living in the U.S. (2011-014). We assessed the association between degree of trust in cancer information from respondent's physician with patient-reported receipt of PSA screening and patient-reported discussion of PSA screening with their physician. Results: Among 5069 eligible respondents, 3606 (71.1%) men reported trusting cancer information from their physician "a lot," 1186 (23.4%) "somewhat," 219 (4.3%) "a little," and 58 (1.1%) "not at all." A total of 2655 (52.4%) men reported receiving PSA screening. The degree of trust an individual had in his physician for cancer information was strongly associated with his likelihood of having received PSA screening (ptrend <0.0001) (54.9% "a lot" vs. 27.6% "not at all"). These findings persisted after multivariable regression. Similarly, men who had high levels of trust in their physician were more likely to have discussed PSA screening with a strong trend across strata (ptrend <0.0001). Conclusions: The level of trust an individual has in cancer information from his physician is strongly associated with his likelihood of discussing and undergoing PSA screening. As rationale, implementation of PSA screening requires shared decision-making, and the level of trust an individual has in his physician has important implications for dissemination of PSA screening guidelines. [ABSTRACT FROM AUTHOR]

Context In the last decade, there has been a proliferation of treatment options for metastatic renal cell carcinoma (mRCC). However, direct comparative data are lacking for most of these agents. Objective To indirectly compare the efficacy and safety of systemic therapies used in the first-line treatment of mRCC. Evidence acquisition Medline, EMBASE, Web of Science, and Scopus databases were searched using the OvidSP platform for studies indexed from database inception to October 23, 2017. Abstracts of conferences of relevant medical societies were included, and the systematic search was supplemented by hand search. For the systematic review, we identified any parallel-group randomized controlled trials assessing first-line systemic therapy. For network meta-analysis, we limited these to a clinically-relevant network based on standard practice patterns. Progression-free survival (PFS) was the primary outcome. Overall survival (OS) and grade 3 and 4 adverse events (AEs) were secondary outcomes. Evidence synthesis In total, 37 trials reporting on 13 128 patients were included in the systematic review. The network meta-analysis comprised 10 trials reporting on 4819 patients. For PFS (10 trials, 4819 patients), there was a high likelihood (SUCRA 91%) that cabozantinib was the preferred treatment. For OS (5 trials, 3379 patients), there was a 48% chance that nivolumab plus ipilimumab was the preferred option. There was a 67% likelihood that nivolumab plus ipilimumab was the best tolerated regime with respect to AEs. Conclusions Cabozantinib and nivolumab plus ipilimumab are likely to be the preferred first-line agents for treating mRCC; however, direct comparative studies are warranted. These findings may provide guidance to patients and clinicians when making treatment decisions and may help inform future direct comparative trials. Patient summary There are many treatment options for patients diagnosed with metastatic renal cell carcinoma. We indirectly compared the available options and found that cabozantinib and nivolumab plus ipilimumab are likely to be preferable choices as the first-line treatment in this situation. [ABSTRACT FROM AUTHOR]

Context Randomized clinical trials have recently examined the benefit of adding docetaxel or abiraterone to androgen deprivation therapy (ADT) in hormone-naïve advanced prostate cancer (PCa). Objective To perform a systematic review and network meta-analysis of randomized clinical trials, indirectly evaluating overall survival (OS) for men treated with abiraterone acetate plus prednisone/prednisolone with ADT (Abi-ADT) versus docetaxel with ADT (Doce-ADT) in hormone-naïve high-risk and metastatic PCa. Evidence acquisition Medline, Embase, Web of Science, Scopus, and Clinicaltrials.gov databases were searched in August 2017. We pooled results using the inverse variance technique and random-effects models. The Bucher technique for indirect treatment comparison was used to compare Abi-ADT with Doce-ADT. A priori subgroup and sensitivity analyses were performed. Evidence synthesis Overall, 6067 patients from five trials were included: 1181 (19.5%) patients who received Doce-ADT, 1557 (25.7%) patients who received Abi-ADT, and 3329 (54.9%) patients who received ADT-alone. There was a total of 1921 deaths: 391 in the Doce-ADT group, 353 in the Abi-ADT group, and 1177 in the ADT-only group. The pooled hazard ratio (HR) for OS was 0.75 (95% confidence interval [CI]: 0.63–0.91, I 2 = 51%, 3 trials, 2951 patients) for Doce-ADT versus ADT-alone and 0.63 (95% CI: 0.55–0.72, I 2 = 0%, 2 trials, 3116 patients) for Abi-ADT versus ADT-alone. The indirect comparison of Abi-ADT to Doce-ADT demonstrated no statistically significant difference in OS between these approaches (HR: 0.84, 95% CI: 0.67–1.06). Findings were similar in various a priori subset analyses, including patients with metastatic disease. Bayesian analyses demonstrated comparable results (HR: 0.83, 95% CI: 0.63–1.16). Despite the lack of statistical significance, Surface Under the Cumulative Ranking Analysis demonstrated an 89% probability that Abi-ADT was preferred. Conclusions We did not identify a significant difference in OS between Abi-ADT and Doce-ADT for men with hormone-naïve high-risk or metastatic PCa, although Bayesian analysis demonstrates a high likelihood that Abi-ADT was preferred. Patient summary We synthesized the evidence available from studies examining the administration of docetaxel or abiraterone in combination with hormonal therapy for patients with newly diagnosed, advanced prostate cancer. While these studies did not directly compare these agents, we used methodological techniques to indirectly compare them and found no significant difference in overall survival. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to determine the personal practices of urologists, radiation oncologists, and medical oncologists regarding prostate cancer screening and treatment using the physician surrogate method, which seeks to identify acceptable healthcare interventions by ascertaining interventions physicians select for themselves. Methods: A hierarchical, contingent survey was developed through a consensus involving urologists, medical oncologists, and radiation oncologists. It was piloted at the University of Toronto and then circulated to urologists, radiation oncologists, and medical oncologists through professional medical societies in the U.S., Canada, Central and South America, Australia, and New Zealand. The primary outcome was physicians' personal choices regarding prostatespecific antigen (PSA) screening and the secondary outcome was treatment selection among those diagnosed with prostate cancer. Results: A total of 869 respondents provided consent and completed the survey. Of these, there were 719 urologists, 89 radiation oncologists, nine medical oncologists, and 53 undisclosed specialists. Most (784 of 869 respondents; 90%) endorsed past or future screening for themselves (among male physicians) or for relatives (among female physicians). Among urologists and radiation oncologists making prostate cancer treatment decisions, there was a significant correlation between physician specialty and the treatment selected (Phi coefficient=0.61; p=0.001). Conclusions: Physicians who routinely treat prostate cancer are likely to undertake prostate cancer screening themselves or recommend it for immediate family members. Treatment choice is influenced by the well-recognized specialty bias. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury (PNI) is a rare but preventable complication of surgery. We sought to assess whether the use of minimally invasive surgery (MIS) affects the occurrence of PNI. Using the American College of Surgeons National Surgical Quality Improvement Program database, we examined rates of PNI among patients undergoing appendectomy, hysterectomy, colectomy, or radical prostatectomy between 2005 and 2012. We assessed the effect of MIS, as compared with open surgery, on PNI occurrence using logistic regression. Among 297,532 patients, of whom 175,884 (59.1%) underwent MIS, the rate of PNI was 0.03 per cent. Forty-four patients treated using MIS had PNI (0.03%) as compared with 63 who underwent open surgery (0.05%; P = 0.0002). There was a significant decrease in the proportion of surgeries resulting in PNI (P < 0.0001) over time. In univariate analysis, MIS was associated with a decreased occurrence of PNI (odds ratio 0.48, 95% confidence interval 0.33-0.71), but this became nonsignificant on multivariable analysis (odds ratio 0.71, 95% confidence interval 0.47-1.09). Increased operative time and smoking status were the only factors independently associated with an increased risk of PNI on multivariable analysis. MIS techniques during common abdominal-pelvic surgeries do not appear to increase the risk of PNI. Prolonged operative time and smoking are independently associated with an increased risk of PNI. Quality improvement initiatives to increase awareness of PNI and identify patients at increased risk of this preventable complication should be considered. [ABSTRACT FROM AUTHOR]

Introduction: We sought to examine the relationship between preoperative platelet to white blood cell ratio (PLT/WBC), a hematological marker of the systemic inflammatory response, and postoperative infectious complications following radical nephrectomy for localized renal cell carcinoma. Methods: We performed a retrospective cohort study of patients treated with radical nephrectomy for localized kidney cancer between January 1, 2005 and December 31, 2014 (n=6235) using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Univariate and multivariate analyses were used to assess the association between PLT/WBC ratio and 30-day infectious complications, including surgical site infection, urinary tract infection (UTI), pneumonia, and sepsis. Secondarily, we examined major complications and bleeding requiring transfusion. Results: A lower PLT/WBC ratio was associated with an increased risk of sepsis, pneumonia, and UTI rates (p<0.05 for all). Furthermore, there was a significant trend of decreasing rates of sepsis and pneumonia with increasing PLT/WBC ratio across quintiles (p<0.05 for all). On multivariate analysis, patients with the lowest PLT/WBC ratios (Quintile 1) had a two-fold risk of having a postoperative infectious complication compared to patients in the highest quintile (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.42-2.86; p<0.0001). Patients in Quintile 5 had a higher risk of requiring blood transfusion than those in Quintiles 2-4 (p<0.05 for all). Conclusions: The PLT/WBC ratio represents a widely available and novel index to predict risk of infectious and bleeding complications in patients undergoing radical nephrectomy. External validation is required and the biological underpinning of this phenomenon requires further study. [ABSTRACT FROM AUTHOR]

Importance: Antithrombotic medications are among the most commonly prescribed medications.Objective: To characterize rates of hematuria-related complications among patients taking antithrombotic medications.Design, Setting, and Participants: Population-based, retrospective cohort study including all citizens in Ontario, Canada, aged 66 years and older between 2002 and 2014. The final follow-up date was December 31, 2014.Exposures: Receipt of an oral anticoagulant or antiplatelet medication.Main Outcomes and Measures: Hematuria-related complications, defined as emergency department visit, hospitalization, or a urologic procedure to investigate or manage gross hematuria.Results: Among 2 518 064 patients, 808 897 (mean [SD] age, 72.1 [6.8] years; 428 531 [53%] women) received at least 1 prescription for an antithrombotic agent over the study period. Over a median follow-up of 7.3 years, the rates of hematuria-related complications were 123.95 events per 1000 person-years among patients actively exposed to antithrombotic agents vs 80.17 events per 1000 person-years among patients not exposed to these drugs (difference, 43.8; 95% CI, 43.0-44.6; P < .001, and incidence rate ratio [IRR], 1.44; 95% CI, 1.42-1.46). The rates of complications among exposed vs unexposed patients (80.17 events/1000 person-years) were 105.78 for urologic procedures (difference, 33.5; 95% CI, 32.8-34.3; P < .001, and IRR, 1.37; 95% CI, 1.36-1.39), 11.12 for hospitalizations (difference, 5.7; 95% CI, 5.5-5.9; P < .001, and IRR, 2.03; 95% CI, 2.00-2.06), and 7.05 for emergency department visits (difference, 4.5; 95% CI, 4.3-4.7; P < .001, and IRR, 2.80; 95% CI, 2.74-2.86). Compared with patients who were unexposed to thrombotic agents, the rates of hematuria-related complications were 191.61 events per 1000 person-years (difference, 117.3; 95% CI, 112.8-121.8) for those exposed to both an anticoagulant and antiplatelet agent (IRR, 10.48; 95% CI, 8.16-13.45), 140.92 (difference, 57.7; 95% CI, 56.9-58.4) for those exposed to anticoagulants (IRR, 1.55; 95% CI, 1.52-1.59), and 110.72 (difference, 26.5; 95% CI, 25.9-27.0) for those exposed to antiplatelet agents (IRR, 1.31; 95% CI, 1.29-1.33). Patients exposed to antithrombotic agents, compared with patients not exposed to these drugs, were more likely to be diagnosed as having bladder cancer within 6 months (0.70% vs 0.38%; odds ratio, 1.85; 95% CI, 1.79-1.92).Conclusions and Relevance: Among older adults in Ontario, Canada, use of antithrombotic medications, compared with nonuse of these medications, was significantly associated with higher rates of hematuria-related complications (including emergency department visits, hospitalizations, and urologic procedures to manage gross hematuria). [ABSTRACT FROM AUTHOR]