Cost of Bladder Cancer Care: A Single-center Comparison of Radical Cystectomy and Trimodal Therapy.

INTRODUCTION: Radical cystectomy and trimodal therapy are both accepted options in the management of muscle-invasive bladder cancer. As such, we sought to evaluate the micro-level costs associated with both modalities. METHODS: All patients undergoing trimodal therapy or radical cystectomy for primary treatment of urothelial muscle-invasive bladder cancer at a single academic center between 2008 and 2012 were included. Direct costs associated with each phase of a patient's clinical course were collected from the hospital's financial department, and physician costs were calculated based on the provincial fee schedule. Costs of radiation treatments were derived from previously published literature. RESULTS: A total of 137 patients were included. The mean (±SD) patient age was 69 (±12) years. Overall, 89 (65%) patients underwent radical cystectomy and 48 (35%) were treated with trimodal therapy. The radical cystectomy group had higher rates of cT3/T4 compared to those in the trimodal therapy group (51% vs 26%, P < .001). The median cost in the treatment phase for radical cystectomy was $30,577 (IQR: $23,908-$38,837) vs $18,979 ($17,271-$23,519) for trimodal therapy (P < .001). There was no significant difference between treatment groups with respect to cost of diagnosis or workup. However, the cost of follow-up care was numerically higher for patients undergoing trimodal therapy compared to radical cystectomy ($3,096/y vs $1,974/y, P = .09). CONCLUSIONS: In appropriately selected patients with muscle-invasive bladder cancer trimodal therapy costs are not prohibitive and are lower than in radical cystectomy. With increasing follow-up time after primary treatment, the cost difference between modalities may be mitigated by the need for bladder surveillance and salvage therapy in the trimodal therapy cohort.

Robotic Versus Open Cystectomy for Bladder Cancer: Synthesizing the Data from Current Systematic Reviews and Meta-Analyses.

This is a summary of existing systematic reviews comparing robotic assisted radical cystectomy (RARC) with open radical cystectomy (ORC). Our aim was to compare operative approaches with respect to perioperative, postoperative, oncologic, and health-related quality of life (QOL) outcomes. We performed a systematic review of MEDLINE, Medline-in-Process and Medline Epubs Ahead of Print, and the Cochrane Library on 22 February 2022. We included reviews of adult patients with bladder cancer undergoing RARC or ORC for muscle invasive or high-risk non-muscle invasive bladder cancer. Nonrandomized studies were excluded to minimize confounding and selection bias. The GRADE approach was used to determine the confidence in estimates. We assessed the quality of identified systematic reviews using AMSTAR 2 checklist. Six well-conducted, systematic reviews and meta-analyses were included. RARC was consistently associated with lower estimated blood loss (EBL) and transfusion rates, and longer operative time. There was inconsistent evidence for the impact of RARC on hospital length of stay (LOS). There was no significant difference in overall complication rate or major complication rate, or oncologic outcomes between groups. Comparison of QOL outcomes between studies was limited by statistical and methodological heterogeneity. RARC is associated with improvement in EBL and transfusion risk. There does not appear to be differences in oncologic outcomes or complications between approaches. Prospective studies are needed to assess the impact of diversion type, technique, and recovery pathways on patient outcomes and to assess the impact of operative approach on cost and patient-reported QOL.

Prevalence and Natural History of Non-metastatic Castrate Resistant Prostate Cancer: A Population-Based Analysis.

PURPOSE: To determine the prevalence and natural history of nmCRPC prior to the adoption of novel androgen receptor axis-targeting therapies(ARAT). MATERIALS AND METHODS: This was a retrospective population-based cohort study of men with nmCRPC in Ontario, Canada between January 2007-March 2018. Patients with prostate cancer, castrate level of testosterone(<1.7nmol/L) and a PSA>2.0ng/mL with a subsequent rise>25% from the nadir, and without metastasis were included. Annual prevalence of nmCRPC was calculated. Crude time from nmCRPC to metastasis and all-cause death are presented as medians with interquartile range(IQR). Predictors of time from nmCRPC to death were compared using univariable and multivariable cox proportional hazard models. RESULTS: We identified 2045 patients with nmCRPC. Median age was 79(IQR:72-84). 984 patients(48.1%) received upfront hormonal therapy while 583(28.5%) received initial radiotherapy and 478(23.4%) underwent radical prostatectomy. Median time from primary treatment to nmCRPC was 6 years(IQR:3-10). The average annual prevalence of nmCRPC was 8% among men receiving ADT. Crude median time from nmCRPC to death was 37.6 months(IQR:22.1-55.4). Median time from nmCRPC to metastasis and metastasis to death was 20.0 and 8.3 months, respectively. Patients who had primary surgery experienced longer crude survival. Older patients, patients who had a higher PSA at nmCRPC, and patients with grade group 4 to 5 disease had a shorter time from nmCRPC to death. CONCLUSION: This is the largest population-level analysis of the prevalence and natural history of nmCRPC. The current study can be used as a historical cohort to compare how novel imaging modalities and ARAT impact prevalence and disease trajectory over time.

Prostate MRI versus PSA screening for prostate cancer detection (the MVP Study): a randomised clinical trial.

OBJECTIVES: Our objective was to compare prostate cancer detection rates between patients undergoing serum prostate-specific antigen (PSA) vs magnetic resonance imaging (MRI) for prostate cancer screening. DESIGN: Phase III open-label randomised controlled trial. SETTING: Single tertiary cancer centre in Toronto, Canada. PARTICIPANTS: Men 50 years of age and older with no history of PSA screening for ≥3 years, a negative digital rectal exam and no prior prostate biopsy. INTERVENTIONS: Patients were recommended to undergo a prostate biopsy if their PSA was ≥2.6 ng/mL (PSA arm) or if they had a PIRADS score of 4 or 5 (MRI arm). Patients underwent an end-of-study PSA in the MRI arm. PRIMARY AND SECONDARY OUTCOME MEASURES: Adenocarcinoma on prostate biopsy. Prostate biopsy rates and the presence of clinically significant prostate cancer were also compared. RESULTS: A total of 525 patients were randomised, with 266 in the PSA arm and 248 in the MRI arm. Due to challenges with accrual and study execution during the COVID-19 pandemic, the study was terminated early. In the PSA arm, 48 patients had an abnormal PSA and 28 (58%) agreed to undergo a prostate biopsy. In the MRI arm, 25 patients had a PIRADS score of 4 or 5 and 24 (96%) agreed to undergo a biopsy. The relative risk for MRI to recommend a prostate biopsy was 0.52 (95% CI 0.33 to 0.82, p=0.005), compared with PSA. The cancer detection rate for patients in the PSA arm was 29% (8 of 28) vs 63% (15 of 24, p=0.019) in the MRI arm, with a higher proportion of clinically significant cancer detected in the MRI arm (73% vs 50%). The relative risk for detecting cancer and clinically significant with MRI compared with PSA was 1.89 (95% CI 0.82 to 4.38, p=0.14) and 2.77 (95% CI 0.89 to 8.59, p=0.07), respectively. CONCLUSIONS: Prostate MRI as a stand-alone screening test reduced the rate of prostate biopsy. The number of clinically significant cancers detected was higher in the MRI arm, but this did not reach statistical significance. Due to early termination, the study was underpowered. More patients were willing to follow recommendations for prostate biopsy based on MRI results. TRIAL REGISTRATION NUMBER: NCT02799303.

A Retrospective Look at Term Outcomes After Definitive Surgical Repair for Traumatic Pelvic Fracture Urethral Injuries - Does Initial Management Make a Difference?

OBJECTIVE: To compare the long-term outcomes of initial management of pelvic fracture urethral injury (PFUI) in a large cohort of trauma patients undergoing urethral reconstruction. MATERIALS AND METHODS: 119 patients underwent urethral reconstruction by a single surgeon for PFUI at our center between 1998-2018. We compared initial PFUI management - primary realignment vs suprapubic tube (SPT) insertion alone. Multivariable Cox proportional hazard analysis was used to assess the association between primary intervention and the risk of having a complication. RESULTS: PFUI was initially managed with primary realignment (57%) or SPT alone (43%). Ultimately, all patients underwent a primary perineal urethral anastomosis after a median of 7 months (IQR: 5-14). Overall, 27 patients (23%) had 1 or more long-term complications after a median 25 months (IQR:7-66), including urethral stricture, de novo erectile dysfunction, and urinary incontinence. On multivariable analysis, initial PFUI management did not predict for complications. CONCLUSION: No difference was found in long-term outcomes after urethral reconstruction when comparing initial PFUI management of primary realignment vs SPT insertion.

Trimodal therapy vs. radical cystectomy for muscle-invasive bladder cancer: A Markov microsimulation model.

INTRODUCTION: Radical cystectomy (RC) is the historic gold standard treatment for muscle-invasive bladder cancer (MIBC), but trimodal therapy (TMT) has emerged as a valid therapeutic option for select patients. Given that prospective clinical trials have been difficult to perform in this area, our aim was to compare these two primary treatment strategies using decision analytic methods. METHOD: A two-dimensional Markov microsimulation model was constructed using TreeAge Pro to compare RC and TMT for patients with newly diagnosed MIBC. A comprehensive literature search was used to populate model probabilities and utilities. Our primary outcome was quality-adjusted life expectancy (QALE). Secondary outcomes included crude life expectancy (LE) and bladder cancer recurrences. The simulated patient for our model was an adult with MIBC (pT2-4 N0 M0) who was a candidate for either RC or TMT. RESULTS: A total of 500 000 patients were simulated. TMT resulted in an estimated mean QALE of 7.48 vs. 7.41 for RC. However, the average LE for patients treated with TMT was lower compared with RC (10.20 vs. 10.74 years). A sensitivity analysis evaluating the impact of age showed that younger patients treated with RC had greater QALE and longer LE than those treated with TMT; inverse findings were observed for elderly patients. Overall, 39.4% of patients treated with TMT experienced a bladder recurrence. CONCLUSIONS: RC results in a longer LE compared to TMT (0.54 years), but with a lower QALE (-0.07 years). The preferred treatment strategy varied with patient age.

Association of Surgeon-Patient Sex Concordance With Postoperative Outcomes.

Importance: Surgeon sex is associated with differential postoperative outcomes, though the mechanism remains unclear. Sex concordance of surgeons and patients may represent a potential mechanism, given prior associations with physician-patient relationships. Objective: To examine the association between surgeon-patient sex discordance and postoperative outcomes. Design, Setting, and Participants: In this population-based, retrospective cohort study, adult patients 18 years and older undergoing one of 21 common elective or emergent surgical procedures in Ontario, Canada, from 2007 to 2019 were analyzed. Data were analyzed from November 2020 to March 2021. Exposures: Surgeon-patient sex concordance (male surgeon with male patient, female surgeon with female patient) or discordance (male surgeon with female patient, female surgeon with male patient), operationalized as a binary (discordant vs concordant) and 4-level categorical variable. Main Outcomes and Measures: Adverse postoperative outcome, defined as death, readmission, or complication within 30-day following surgery. Secondary outcomes assessed each of these metrics individually. Generalized estimating equations with clustering at the level of the surgical procedure were used to account for differences between procedures, and subgroup analyses were performed according to procedure, patient, surgeon, and hospital characteristics. Results: Among 1 320 108 patients treated by 2937 surgeons, 602 560 patients were sex concordant with their surgeon (male surgeon with male patient, 509 634; female surgeon with female patient, 92 926) while 717 548 were sex discordant (male surgeon with female patient, 667 279; female surgeon with male patient, 50 269). A total of 189 390 patients (14.9%) experienced 1 or more adverse postoperative outcomes. Sex discordance between surgeon and patient was associated with a significant increased likelihood of composite adverse postoperative outcomes (adjusted odds ratio [aOR], 1.07; 95% CI, 1.04-1.09), as well as death (aOR, 1.07; 95% CI, 1.02-1.13), and complications (aOR, 1.09; 95% CI, 1.07-1.11) but not readmission (aOR, 1.02; 95% CI, 0.98-1.07). While associations were consistent across most subgroups, patient sex significantly modified this association, with worse outcomes for female patients treated by male surgeons (compared with female patients treated by female surgeons: aOR, 1.15; 95% CI, 1.10-1.20) but not male patients treated by female surgeons (compared with male patients treated by male surgeons: aOR, 0.99; 95% CI, 0.95-1.03) (P for interaction = .004). Conclusions and Relevance: In this study, sex discordance between surgeons and patients negatively affected outcomes following common procedures. Subgroup analyses demonstrate that this is driven by worse outcomes among female patients treated by male surgeons. Further work should seek to understand the underlying mechanism.

Association between chronic bladder catheterisation and bladder cancer incidence and mortality: a population-based retrospective cohort study in Ontario, Canada.

OBJECTIVES: To compare the risk of bladder cancer and bladder cancer mortality among patients with chronic bladder catheterisation (indwelling or intermittent) to patients from the general population. DESIGN: Retrospective cohort study. SETTING: Population-based study in Ontario, Canada between 2003 and 2018. PARTICIPANTS: Adult patients 18-90 years of age with chronic bladder catheterisation were hard matched to patients from the general population without a history of bladder catheterisation. INTERVENTIONS: The presence of a chronic catheter was defined as a minimum of two physician encounters for bladder catheterisation, suprapubic tube insertion or home care for catheter care separated by at least 28 days. Urinary tract infection (UTI) rates were collected. MAIN OUTCOME MEASURES: Bladder cancer and bladder cancer-specific mortality after a 1-year lag period were compared between groups. RESULTS: We identified 36 903 patients with chronic catheterisation matched to 110 709 patients without a history of catheterisation. Patients were followed for a median of 8.8 years (IQR: 5.2-11.9 years). The median age was 62 years (IQR: 50-71) and 52% were female. More patients in the catheter group developed bladder cancer (393 (1.1%) vs 304 (0.3%),p<0.001). There were 106 (0.3%) bladder cancer deaths in the catheter group and 59 (0.1%) in the comparison group (p<0.001). Chronic catheterisation (adjusted subdistribution HR (sdHR)=4.80, 95% CI: 4.26 to 5.42,p<0.001) and the number of UTIs (adjusted sdHR=1.04 per UTI, 95% CI: 1.04 to 1.05,p<0.001) were independent predictors of bladder cancer. The relative rate of bladder cancer-specific death was more than eightfold higher among patients with chronic catheterisation (adjusted sdHR=8.68, 95% CI: 6.97 to 10.81,p<0.001). Subgroup analysis among patients with neurogenic bladder and bladder calculi similarly revealed an increased risk of bladder cancer diagnosis and mortality. Bladder cancer risk was highest among patients in the two longest catheter duration quintiles (2.9-5.9 and 5.9-15.5 years). CONCLUSIONS: This is the first study to quantify the increase in bladder cancer incidence and mortality in a large, diverse cohort of patients with chronic indwelling or intermittent bladder catheterisation. The risk was highest among patients with a chronic catheter beyond 2.9 years.

Assessment of gender representation in clinical trials leading to FDA approval for oncology therapeutics between 2014 and 2019: A systematic review-based cohort study.

BACKGROUND: Ensuring representative data accrual in clinical trials is important to safeguard the generalizability of results and to minimize disparities in care. This study's goal was to evaluate differences in gender representation in trials leading to US Food and Drug Administration (FDA) cancer drug approvals. METHODS: An observational study was conducted from January 2014 to April 2019 using PubMed and the National Institutes of Health trials registry for primary trial reports. The National Cancer Institute's Surveillance, Epidemiology, and End Results program and US Census were consulted for national cancer incidence. The outcome was an enrollment incidence disparity (EID), which was calculated as the difference between male and female trial enrollment and national incidence, with positive values representing male overrepresentation. RESULTS: There were 149 clinical trials with 59,988 participants-60.3% and 39.7% were male and female, respectively-leading to 127 oncology drug approvals. The US incidence rates were 55.4% for men versus 44.6% for women. Gender representation varied by specific tumor type. Most notably, women were underrepresented in thyroid cancer (EID, +27.4%), whereas men were underrepresented in soft tissue cancer (EID, -26.1%). Overall, women were underrepresented when compared with expected incidence (EID, +4.9%; 42% of trials). CONCLUSIONS: For many specific tumor types, women are underrepresented in clinical trials leading to FDA oncology drug approvals. It is critical to better align clinical trial cohort demographics and the populations to which these data will be extrapolated. LAY SUMMARY: This study assesses whether gender disparities exist in clinical trials leading to US Food and Drug Administration (FDA) cancer drug approvals. From January 2014 to April 2019, 149 clinical trials leading to FDA oncology drug approvals showed 60.3% and 39.7% of the enrollees were male and female, respectively. Gender representation varied by specific tumor when compared with the expected incidence rate of cancer in the United States, although women were more often underrepresented. Increased efforts are needed with regard to ensuring equitable representation in oncology clinical trials.

Women as Authors of Randomized Controlled Trials of Minimally Invasive Surgery: Systematic Review and Meta-Analysis of 3 Decades of Trials.

BACKGROUND: Female authorship opportunities have lagged behind those of their male counterparts, with gender disparities most prominent in surgical specialties. Our objective was to determine trends of female first, last, and first or last authorships across time and surgical specialties and whether female first or last authorship was associated with journal impact factor. STUDY DESIGN: A systematic review of EMBASE (OvidSP), MEDLINE (OvidSP), and Cochrane (Wiley) databases from inception to December 22, 2017 was performed to identify all randomized controlled trials evaluating minimally invasive surgery vs classical surgical techniques. The primary end point was female first, last, and first or last authorship, with gender determined via an online search strategy and verified via Genderize.io. Secondary end point was journal impact factor, recorded from Clarivate Analytics InCites. RESULTS: There were 9,321 articles identified and 489 met our inclusion/exclusion criteria. Sixty-eight (13.9%) first and 60 (12.3%) last female authors were identified. A positive linear trend for female first (R2 = 0.35, Cochran-Armitage test for trend, p < 0.001), last (R2 = 0.30, p < 0.001), and first or last authorships (R2 = 0.40, p < 0.001) over time was identified. This trend was observed across surgical specialties except for orthopaedics. The highest calculated percentages of female first, last, and first or last authorships by the year 2017 were seen in obstetrics and gynecology (33.8%, 32.0%, and 43.8%, respectively), all significantly lower than the corresponding percentage of the female obstetrics and gynecology workforce in 2017 (57.0%). Neither female first nor last authorship positions were associated with journal impact factor. CONCLUSIONS: A significant increase in female first and last authorship in randomized controlled trials of minimally invasive surgical techniques in the last 3 decades has been observed, but continued efforts to bridge this gender gap are sorely needed.

Re-operation within 30 days of radical cystectomy: Identifying high-risk patients and complications using American College of Surgeons National Surgical Quality Improvement Program database.

INTRODUCTION: Radical cystectomy (RC) is a highly morbid procedure, with 30-day complication rates approaching 31%. Our objective was to determine risk factors for re-operation within 30 days following a RC for non-metastatic bladder cancer. METHODS: We included all patients who underwent a RC for non-metastatic bladder cancer using The American College of Surgeons National Surgical Quality Improvement Program database between January 1, 2007 and December 31, 2014. Logistic regression analyses were used to evaluate predictors of re-operation. RESULTS: A total of 2608 patients were included; 5.8% of patients underwent re-operation within 30 days. On multivariable analysis, increasing body mass index (BMI) (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.01-1.07), African American race (vs. Caucasian OR 2.29, 95% CI 1.21-4.34), and history of chronic obstructive pulmonary disease (COPD) (OR 2.33, 95% CI 1.45-3.74) were significant predictors of re-operation within 30 days of RC. Urinary diversion type (ileal conduit vs. continent) and history of chemotherapy or radiotherapy within 30 days prior to RC were not. Patients who underwent re-operation within this timeframe had a significantly higher mortality rate (4.0% vs. 1.6%) and were more likely to experience cardiac (7.2% vs. 1.9%), pulmonary (23.0% vs. 3.0%), neurological (2.0% vs. 0.49%), and venous thromboembolic events (10.5% vs. 5.4%), as well as infectious complications (64.5% vs. 24.1%), with a significantly longer hospital length of stay (16.5 vs. 7.0 days). CONCLUSIONS: Recognizing increasing BMI, COPD, and African American race as risk factors for re-operation within 30 days of RC will allow urologists to preoperatively identify such high-risk patients and prompt them to adopt more aggressive approaches to minimize postoperative surgical complications.

Does prophylactic ureteric stenting at the time of colorectal surgery reduce the risk of ureteric injury? A systematic review and meta-analysis.

AIM: Cystoscopic placement of ureteric stents during colorectal surgery (CRS) may aid in the intraoperative identification of the ureters and thus prevent ureteric injury, but may also be associated with prolonged operating time, increased cost and adverse events. No formal recommendations exist regarding the use of ureteric stents prior to CRS. Our aim was to determine the effect of prophylactic ureteric stent insertion on the risk of ureteric injury among adult patients undergoing CRS. METHOD: A systematic search using the Ovid platform was completed. The primary outcome was risk of ureteric injury. Secondary outcomes included the risk of acute kidney injury (AKI), urinary tract infection (UTI), sepsis, length of stay (LOS) and mortality. The Paule-Mandel pooling and a random effects model was used to produce odds ratios (ORs) with 95% confidence intervals (CIs) for binary outcomes. Standardized mean differences (MD) were reported for continuous variables. Analyses were completed using R3.5. RESULTS: Nine retrospective cohort studies evaluating 98 507 patients were included. The incidence of ureteric injury was 0.6%. Overall, 5.1% of patients underwent ureteric stenting. There was no change in the odds of ureteric injury among stented patients compared with controls (OR 1.30, 95% CI 0.39-4.29, I2  = 25%). Operating time was significantly longer (MD 49.3 min, 95% CI 35.3-63.4, I2  = 96%) in the intervention group. There was no difference in rates of AKI, UTI, sepsis, LOS or mortality between groups. CONCLUSION: Given the retrospective nature of the identified studies, the benefit of prophylactic ureteric stenting remains uncertain. Prophylactic ureteric stenting was not associated with increased patient morbidity but did significantly increase operating time.

Neoadjuvant Versus Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A Microsimulation Model.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is clinically understudied, and there are no definitive recommendations regarding timing of perioperative chemotherapy. The objective of this study was to compare 3 treatment pathways in UTUC: nephroureterectomy (NU) alone, neoadjuvant chemotherapy (NAC), and adjuvant chemotherapy (AC) using a microsimulation model. PATIENTS AND METHODS: An individual-level state transition model was constructed using TreeAgePro software to compare treatment strategies for patients with newly diagnosed UTUC. The base case was that of a 70-year-old patient with a radiographically localized upper tract tumor. Primary outcome was quality-adjusted life expectancy. Secondary outcomes included crude overall survival, rates of adverse events, and bladder cancer diagnoses. RESULTS: A total of 100,000 patients were simulated. NAC was preferred, with an estimated quality-adjusted life expectancy of 7.50 years versus 6.79 years with NU alone and 7.23 years with AC. Median crude overall survival was 123 months with NAC, 96 months with NU only, and 111 months with AC. Overall, 40.0% of patients in the AC group with invasive pathology completed chemotherapy. In the NAC group, 83.3% of patients completed chemotherapy. In the NAC group, 37.5% of patients experienced an adverse chemotherapy event compared to 15.1% of patients in the AC group. Bladder cancer recurrence rates were 64.9%, 65.9%, and 67.4% over the patient's lifetime for the NU, NAC, and AC strategies, respectively. CONCLUSION: This study supports the increased use of NAC in UTUC until robust randomized trials are completed. The ultimate choice should be based on patient and tumor factors.

Assessment of Secondary Sarcomas Among Patients With Cancer of the Abdomen or Pelvis Who Received Combinations of Surgery, Radiation, and Chemotherapy vs Surgery Alone.

Importance: The association of radiation and chemotherapy with the development of secondary sarcoma is known, but the contemporary risk has not been well characterized for patients with cancers of the abdomen and pelvis. Objective: To compare the risk of secondary sarcoma among patients treated with combinations of surgery, radiation, or chemotherapy with patients treated with surgery alone and the general population. Design, Setting, and Participants: This population-based cohort study included 173 580 patients in Ontario, Canada, with nonmetastatic cancer of the prostate, bladder, colon, rectum or anus, cervix, uterus, or testis. Patients were enrolled from January 1, 2002, to January 31, 2017. Data analysis was conducted from March 1, 2019, to January 31, 2020. Exposures: Treatment combinations of radiation, chemotherapy, and surgery. Main Outcome and Measures: Diagnosis of sarcoma based on histologic codes from the Ontario Cancer Registry. Time to sarcoma was compared using a cause-specific proportional hazard model. Results: Of 173 580 patients, most were men (125 080 [72.1%]), and the largest group was aged between 60 and 69 years (58 346 [33.6%]). Most patients had genitourinary cancer (86 235 [51.4%]) or colorectal cancer (69 241 [39.9%]). Overall, 64 301 (37.1%) received surgery alone, 51 220 (29.5%) received radiation alone, 15 624 (9.0%) were treated with radiation and chemotherapy, 15 252 (8.8%) received radiation with surgery, and 11 822 (6.8%) received all 3 treatments. A total of 332 patients (0.2%) had sarcomas develop during a median (interquartile range) follow-up of 5.7 (2.2-8.9) years. The incidence of sarcoma was 0.3% among those who underwent radiation alone (138 of 51 220) and radiation with chemotherapy (40 of 15 624), 0.2% among those who received radiation and surgery (36 of 15 252) and all 3 modalities (25 of 11 822), and 0.1% among those who received surgery with chemotherapy (13 of 14 861) and surgery alone (80 of 64 801). Compared with a reference group of patients who had surgery alone, the greatest risk of sarcoma was found among patients who underwent a combination of radiation and chemotherapy (cause-specific relative hazard [csRH], 4.07; 95% CI, 2.75-6.01; P < .001), followed by patients who had radiation alone (csRH, 2.35; 95% CI, 1.77-3.12; P < .001), radiation with surgery (csRH, 2.33; 95% CI, 1.57-3.46; P < .001), and all 3 modalities (csRH, 2.27; 95% CI, 1.44-3.58; P < .001). In the general population, 7987 events occurred during 46 554 803 person-years (17.2 events per 100 000 person-years). The standardized incidence ratio for sarcoma among patients treated with radiation compared with the general population was 2.41 (95% CI, 1.57-3.69; 41.3 events per 100 000 person-years). The annual number of cases of sarcoma increased from 2009 (15 per 100 000 persons) to 2016 (32 per 100 000 persons), but the annual rate did not change during the study period. Conclusions and Relevance: In this cohort study, patients treated with radiation or chemotherapy for abdominopelvic cancers had an increased rate of sarcoma. Although the absolute rate is low, patients and physicians should be aware of this increased risk of developing sarcoma.

Rates of primary and secondary treatments for patients on active surveillance for localized prostate cancer-A population-based cohort study.

BACKGROUND: The rate of primary and secondary treatment while on active surveillance (AS) for localized prostate cancer at the general population level is unknown. Our objective was to determine the patterns of secondary treatments after primary surgery or radiation for patients who undergo AS. METHODS: This was a population-based retrospective cohort study of men aged 50-80 years old in Ontario, Canada, between 2008 and 2016. We identified 26 742 patients with prostate cancer, a Gleason grade score ≤7, and an index prostate-specific antigen ≤10 ng/mL. Patients were categorized as undergoing AS with or without delayed primary treatment (DT; treatment >6 months after diagnosis) versus immediate treatment (IT; treatment ≤6 months). Patients receiving DT and IT were propensity score matched and the rate of secondary treatment (surgery or radiation ± androgen deprivation treatment) was compared using Cox proportional hazards models. RESULTS: We identified 10 214 patients who underwent AS and 11 884 patients who underwent IT. Among patients undergoing AS, 3724 (36.5%) eventually underwent DT and among them, 406 (10.9%) underwent secondary treatment. The median time to DT was 1.2 years (IQR 0.5-8.1 years). The relative rate of undergoing secondary treatment was similar in the DT vs IT group (HR 0.92; 95% CI: 0.79-1.08). The risk of death in the DT group was higher compared to patients who did not undergo treatment (HR 1.23, 95% CI: 1.01-1.49). CONCLUSIONS: Among patients with localized prostate cancer on AS, one third undergo DT. The rate of secondary treatment was similar between the DT and IT groups. Patients in the DT group may experience a higher risk of mortality compared to those who remained on AS.

A Systematic Review and Network Meta-analysis of Novel Androgen Receptor Inhibitors in Non-metastatic Castration-resistant Prostate Cancer.

BACKGROUND: Among men with high-risk non-metastatic castrate-resistant prostate cancer (nmCRPC), we used network meta-analysis to compare non-steroidal anti-androgens (NSAAs) and stratified class-level meta-analysis to identify subgroups with particular benefit from NSAAs with androgen deprivation therapy versus androgen deprivation therapy alone. MATERIALS AND METHODS: We performed a systematic review of phase III parallel-group randomized controlled trials in adult men with nmCRPC. Primary outcome was metastasis-free survival (MFS). Secondary outcomes included overall survival (OS), prostate-specific antigen (PSA) progression-free survival (PFS), and rates of grade 3 to 4 adverse events (AEs). We assessed class-level effects using random effects models; effect modification owing to subgroup effects using random-effects models to pool study-level differences; and comparative outcomes between agents using fixed-effect network models in a Bayesian framework. RESULTS: Three randomized controlled trials were identified. Pooled MFS, PSA-PFS, and OS were significantly greater with NSAA versus placebo (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.25-0.41; HR, 0.08; 95% CI, 0.05-0.13; and HR, 0.74; 95% CI, 0.61-0.90, respectively). Subgroup analysis demonstrated a greater benefit with NSAAs in men with Eastern Cooperative Oncology Group performance status 0 (HR, 0.30; 95% CI, 0.24-0.38) versus 1 (HR, 0.45; 95% CI, 0.36-0.56; P = .005), but no difference owing to PSA doubling time (P = .43) or use of osteoclast targeting therapy (P = .77). Bayesian analysis showed apalutamide and enzalutamide had a 56% and 44% likelihood of maximizing MFS, respectively, with subgroup analysis demonstrating these agents were preferred regardless of PSA doubling time and performance status. There was a 44%, 41%, and 15% likelihood that apalutamide, darolutamide and enzalutamide offered the greatest OS benefit, respectively. Grade 3 to 4 AEs were more common with NSAAs (odds ratio [OR], 1.47; 95% CI, 1.27-1.71) and there was a 61% chance that darolutamide was preferred. CONCLUSIONS: NSAAs improve survival in high-risk nmCRPC. Apalutamide and enzalutamide may result in improved oncologic outcomes. Darolutamide may result in fewer AEs. Phase IV data are needed to validate these findings.

Abiraterone vs. docetaxel for metastatic hormone-sensitive prostate cancer: A microsimulation model.

INTRODUCTION: Our aim was to determine whether androgen deprivation therapy (ADT) with abiraterone acetate (AA) or ADT with docetaxel chemotherapy (DC) resulted in improved quality-adjusted life years (QALYs) among men with de novo metastatic castration-sensitive prostate cancer (mCSPC) and the cost effectiveness of the preferred strategy using decision analytic techniques. METHODS: A microsimulation model with a lifetime time horizon was constructed. Our primary outcome was QALYs. Secondary outcomes included cost, incremental cost effectiveness ratio (ICER), unadjusted overall survival (OS), rates of second- and third-line therapy, and adverse events. A systematic literature review was used to generate probabilities and utilities to populate the model. The base case was a 65-year-old patient with de novo mCSPC. RESULTS: A total of 100 000 microsimulations were generated. Initial AA resulted in a gain of 0.45 QALYs compared to DC (3.36 vs. 2.91 QALYs) with an ICER of $276 251.82 per QALY gained with initial AA therapy. Median crude OS was 51 months with AA and 48 months with DC. Overall, 46.6% and 42.6% of patients received second-line therapy and 8.7% and 7.9% patients received third-line therapy in the AA and DC groups, respectively. Grade 3/4 adverse events were experienced in 17.6% of patients receiving initial AA and 22.3% of patients receiving initial DC. CONCLUSIONS: Although ADT with AA results in a gain in QALYs and crude OS compared to DC, AA therapy is not a cost-effective treatment strategy to apply uniformly to all patients. The availability of AA as a generic medication may help to close this gap. The ultimate choice should be based on patient and tumor factors.

Exploring the patterns of practice and satisfaction among female urologists in Canada.

INTRODUCTION: Our aim was to explore the satisfaction, personal and professional challenges, and practice barriers among female urologists in Canada. METHODS: A literature review was completed to design our survey. Trends with respect to career and personal satisfaction were identified, including academic advancement, mentorship, professional challenges, workplace discrimination, family satisfaction, and remuneration, among others. These key themes were formatted into 44 questions, translated into French, and distributed electronically as a survey to 80 female urology staff across Canada. RESULTS: Sixty (75.0%) women completed the survey. Many had been in practice <5 years (44.1%) and 72.9% completed a fellowship. Overall, 96.6% of women were very or somewhat satisfied with their career. Seeing more time-consuming patients and financial constraints within the healthcare system were the greatest source of dissatisfaction. Two-thirds of respondents reported that they received significant mentorship and 40% found it difficult to find a mentor during their training. Overall, 65.0% experienced gender discrimination, most commonly from a colleague or a patient. Women who practiced in the community were more likely to report experiencing discrimination compared to women practicing in an academic setting (78.1% vs. 51.9%; p=0.034). Mean time for maternity leave was 17.1 (±8.3) weeks, and 30.2% reported a pregnancy-related complication triggered by their work. Overall, 66.1% would choose urology again. CONCLUSIONS: It is important to advocate for the wellness of female urologists. To accomplish this, we need to address the challenges revealed in the survey, including supporting women on maternity leave, improving mentorship, and prioritizing female urology leadership initiatives. We have established a formal circle of support within the urology community in Canada to achieve these goals.

Is There an Association between Urinary Incontinence and Mortality? A Retrospective Cohort Study.

PURPOSE: Previous studies have shown an association between urinary incontinence and increased mortality independently of demographics and health status. However, they do not account for the effect of frailty as a state of vulnerability. We evaluated whether there is an association between urinary incontinence and mortality and, if so, whether adjustment for a frailty index would affect the association. MATERIALS AND METHODS: We performed a cross-sectional study in a nationally representative sample of 2,282 community dwelling individuals 50 years old or older who were surveyed between 2003 and 2006. The study primary outcome was overall survival as reported on December 31, 2011. We used design adjusted Cox proportional hazards regression models to estimate the hazard of mortality associated with urinary incontinence. We adjusted the models for demographics and a validated 45-item frailty index incorporating an accumulation of deficits in the domains of health and independence. RESULTS: Of the individuals 23% reported having urinary incontinence at least a few times per week. Stress urinary incontinence and urge urinary incontinence were associated with a 13.3% (95% CI 7.2-19.7) and 18.4% (95% CI 8.3-29.4) increase in the frailty index, respectively. Without controlling for frailty individuals with urinary incontinence were at higher risk for death (HR 1.39, 95% CI 1.13-1.72). When adjusted for the frailty index, the association between urinary incontinence and mortality was no longer significant (HR 1.10, 95% CI 0.89-1.36). CONCLUSIONS: The association between urinary incontinence and mortality can be understood based on increased frailty in incontinent individuals. Urinary incontinence itself is not independently associated with mortality. In clinical practice these findings underscore the importance of screening for frailty in addition to urinary incontinence.