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Purpose: Understanding treatment patterns and effectiveness for patients with metastatic prostate cancer (mPCa) is dependent on accurate assessment of metastatic status. The objective was to develop a natural language processing (NLP) model for identifying patients with mPCa and evaluate the model's performance against chart-reviewed data and an International Classification of Diseases (ICD) 9/10 code-based method., Methods: In total, 139,057 radiology reports on 6,211 unique patients from the Department of Veterans Affairs were used. The gold standard was metastases by detailed chart review of radiology reports. NLP performance was assessed by sensitivity, specificity, positive predictive value, negative predictive value, and date of metastases detection. Receiver operating characteristic curves was used to assess model performance., Results: When compared with chart review, the NLP model had high sensitivity and specificity (85% and 96%, respectively). The NLP model was able to predict patient-level metastasis status with a sensitivity of 91% and specificity of 81%, whereas sensitivity and specificity using ICD9/10 billing codes were 73% and 86%, respectively. For the NLP model, date of metastases detection was exactly concordant and within < 1 week in 55% and 58% of patients, compared with 8% and 17%, respectively, using the ICD9/10 billing codes method. The area under the curve for the NLP model was 0.911. A limitation is the NLP model was developed on the basis of a subset of patients with mPCa and may not be generalizable to all patients with mPCa., Conclusion: This population-level NLP model for identifying patients with mPCa was more accurate than using ICD9/10 billing codes when compared with chart-reviewed data. Upon further validation, this model may allow for efficient population-level identification of patients with mPCa.

Context: Randomized controlled trials (RCTs) have shown that addition of docetaxel or androgen receptor axis-targeted therapy (ARAT) to androgen deprivation therapy (ADT) or addition of ARAT to ADT and docetaxel improves overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC). However, it is unknown whether docetaxel, when given as part of triplet therapy, has an independent OS benefit., Objective: To compare the efficacy of ADT plus ARAT with the triplet of ADT, ARAT, and docetaxel through a network meta-analysis (NMA) of RCTs in mHSPC., Evidence Acquisition: Bibliographic databases and conference proceedings were searched in March 2022 for RCTs that evaluated the addition of docetaxel, ARAT, or both to ADT in mHSPC. The primary endpoint was OS. Standard random-effect NMA and Bayesian analyses were performed to compare ADT plus ARAT with triplet therapy., Evidence Synthesis: Eleven RCTs (n = 11 546) were eligible. Compared with ADT plus ARAT, the triplet had a nonsignificant OS benefit (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.68-1.16), while ADT plus docetaxel (HR 1.16 [0.94-1.43]) and ADT alone (HR 1.46 [1.30-1.64]) had an increased risk of death. By P-score ordering, the triplet was the most effective treatment strategy (P score = 0.936) followed by ADT plus ARAT (P score = 0.704). The triplet had a 77% likelihood of being the best treatment strategy compared with a 23% likelihood for ADT plus ARAT., Conclusions: The triplet of ADT, ARAT, and docetaxel was the highest ranked treatment strategy, but it did not confer a statistically significant OS benefit over ADT plus ARAT. This NMA provides the highest-level comparative evidence for these treatment approaches in the initial management of mHSPC., Patient Summary: We synthesized the available evidence from clinical trials conducted in newly diagnosed metastatic prostate cancer to compare the survival of patients receiving triplet therapy (androgen receptor axis-targeted therapy [ARAT], androgen deprivation therapy [ADT], and docetaxel) with those receiving only ARAT and ADT. We conclude that the triplet is a somewhat more effective treatment approach., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

We conducted a cross-sectional analysis of ClinicalTrials.gov-registered oncology randomized controlled trials between September 2019 and December 2021 to identify predictors of trial suspensions. The dataset included 1,183 oncology trials, of which 384 (32.5%) were suspended. COVID-19 accounted for 47 (12.2%) suspensions. Trials that were single center- or US-based had higher odds of COVID-19 (ORs: 3.85 and 2.48, 95% CIs: 1.60-11.50 and 1.28-4.93, respectively) or any-reason suspensions (ORs: 2.33 and 2.04, 95% CIs: 1.46-3.45 and 1.40-2.76, respectively). Phase two (OR 1.27), three (OR 6.45) and four trials (OR 11.5) had increased odds of COVID-19 suspensions, compared to phase one trials.

Introduction: Radium-223 was approved for metastatic castration-resistant prostate cancer based on the ALSYMPCA trial. We characterize radium-223 treatment patterns and overall survival (OS) in a large equal access health system., Methods: We identified all men within the Veterans Affairs (VA) Healthcare System who received radium-223 between January 2013 and September 2017. Patients were followed until death or last followup. We abstracted all treatments received prior to radium; no treatments after radium were abstracted. Our primary aim was understanding practice patterns, and secondary outcome was the association between treatment pattern and OS measured using Cox models., Results: We identified 318 bone metastatic castration-resistant prostate cancer patients who received radium-223 within the VA Healthcare System. Of these patients 277 (87%) died during followup. The 5 predominant treatment patterns that encompassed 88% of patients (279/318) were 1) androgen receptor-targeted agent (ARTA)-radium, 2) docetaxel-ARTA-radium, 3) ARTA-docetaxel-radium, 4) docetaxel-ARTA-cabazitaxel-radium and 5) radium alone. Median OS was 11 months (95% CI 9.7-12.5). Men who received ARTA-docetaxel-radium had the worst survival. All other treatments had similar outcomes. Only 42% of patients completed the full 6 injections; 25% received only 1 or 2 injections., Conclusions: We identified the most common radium-223 treatment patterns and their association with OS within the VA population. The better survival in ALSYMPCA (14.9 months) vs our study (11 months) along with 58% of patients not receiving the full radium-223 course suggests radium is being used later in the disease course in the real world in a more heterogeneous population.

Purpose: To systematically review the literature to investigate racial disparities among bladder cancer clinical trial enrollees., Methods: A systematic review was conducted using Ovid, MEDLINE® to identify clinical trials between 1970 and 2020. Articles were reviewed and were included if they assessed race in their outcomes reporting among bladder cancer patients enrolled in clinical trials. The review was conducted in accordance with the PRISMA statement., Results: We identified 544 clinical trials meeting our initial search criteria, with only 24 (4.4%) studies reporting racial demographic data. Enrollees were largely Caucasian (81-98%), with a strikingly small proportion of enrolled patients consisting of African-Americans (2-8%) and Hispanics (2-5%). Only one of the studies reported results on the efficacy and safety/tolerability of the tested treatment separately for racial groups and performed analyses stratified by race., Conclusion: Race is poorly studied in bladder cancer clinical trials. Trial cohorts may not reflect multicultural populations. The potential association between race and efficacy, safety or tolerability of the tested interventions is unknown. Given the up to twofold increase in bladder cancer-specific death among African-Americans, further research is needed to address the impact of race in clinical trials, while encompassing socioeconomic factors and disease risk factor exposures., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: The aim of this study was to examine the effect of surgeon-anesthesiologist sex discordance on postoperative outcomes., Summary Background Data: Optimal surgical outcomes depend on teamwork, with surgeons and anesthesiologists forming two key components. There are sex and sex-based differences in interpersonal communication and medical practice which may contribute to patients' perioperative outcomes., Methods: We performed a population-based, retrospective cohort study among adult patients undergoing 1 of 25 common elective or emergent surgical procedures from 2007 to 2019 in Ontario, Canada. We assessed the association between differences in sex between surgeon and anesthesiologists (sex discordance) on the primary endpoint of adverse postoperative outcome, defined as death, readmission, or complication within 30 days following surgery using generalized estimating equations., Results: Among 1,165,711 patients treated by 3006 surgeons and 1477 anesthesiologists, 791,819 patients were treated by sex concordant teams (male surgeon/male anesthesiologist: 747,327 and female surgeon/female anesthesiologist: 44,492), whereas 373,892 were sex discordant (male surgeon/female anesthesiologist: 267,330 and female surgeon/male anesthesiologist: 106,562). Overall, 12.3% of patients experienced >1 adverse postoperative outcomes of whom 1.3% died. Sex discordance between surgeon and anesthesiologist was not associated with a significant increased likelihood of composite adverse postoperative outcomes (adjusted odds ratio 1.00, 95% confidence interval 0.97-1.03)., Conclusions: We did not demonstrate an association between intraoperative surgeon and anesthesiologist sex discordance on adverse postoperative outcomes in a large patient cohort. Patients, clinicians, and administrators may be reassured that physician sex discordance in operating room teams is unlikely to clinically meaningfully affect patient outcomes after surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Several studies have assessed the negative effect of the COVID-19 pandemic on cancer screening and diagnosis rates. However, this has not been evaluated for prostate biopsy and prostate cancer (PC) diagnosis in an equal-access health care system., Objective: To determine the association of the pandemic with prostate biopsy and PC diagnosis rates among Black vs White patients in the Veterans Affairs Health Care System (VAHCS)., Design, Setting, and Participants: This cohort study included a retrospective analysis of all prostate biopsies performed on patients in the VAHCS without a preexisting PC diagnosis between January 2018 and March 2021. The base population included all living male patients who had at least 1 visit to the VAHCS during the 3 years prior to each month of the study., Exposure: The COVID-19 pandemic., Main Outcomes and Measures: The main outcomes were the number of prostate biopsies and PC diagnoses by month. The influence of the pandemic on prostate biopsy volume and the incidence of PC diagnoses was modeled using an interrupted time-series analysis. Poisson generalized linear models were fitted to project the expected number of prostate biopsies and PC diagnoses had there been no pandemic interruption. Additional models were used to test for differences by race., Results: Prior to the pandemic (January 2018 through February 2020), monthly biopsy numbers among 51 606 included men ranged between 1230 and 1695, of which 56% to 60% of results were positive for PC. The estimated number of missed PC diagnoses from March 2020 through March 2021 ranged from 97 cases (October 2020: 752 cases expected, 655 cases observed) to 573 cases (April 2020: 794 cases expected, 221 cases observed). Prior to the pandemic, biopsy rates were statistically significantly higher among Black vs White men (incidence rate ratio, 2.25; 95% CI, 2.06-2.46; P < .001). There was no change in biopsy rates associated with race at the onset of the pandemic nor during the recovery period from March 2020 to March 2021. Similar trends were observed for PC diagnosis rates., Conclusions and Relevance: Results of this cohort study demonstrate that during the COVID-19 pandemic, prostate biopsy and PC diagnosis rates decreased, particularly during the peak of the pandemic. However, there were no statistically significant changes in rates by race.

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 surgery for primary 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 criteria. 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., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: This was a secondary analysis aiming to assess whether hydrophilic or hydrophobic statins have a differential effect on urinary retention (UR) and lower urinary tract symptoms (LUTS) in men following a prostate biopsy (PBx), who were at risk for prostate cancer development., Methods: This was a population-based cohort study with data incorporated from the Institute for Clinical and Evaluative Sciences database to identify all Ontarian men aged 66 and above with a history of a single negative PBx between 1994 and 2016, with no drug prescription history of any of several putative chemo-preventative medications (statins, proton pump inhibitors, five-alpha-reductase inhibitors, and alpha-blockers). Multivariable Cox regression models with time-dependent covariates were used to assess the association of hydrophilic and hydrophobic statins with UR and LUTS within 30 days of a PBx. All models were adjusted for other known putative chemopreventive medications, age, rurality, pharmacologically treated diabetes, comorbidity score, and study inclusion year., Results: Overall, 21 512 men were included, with a median followup time of 9.4 years (interquartile range [IQR] 5.4-13.4 years). Hydrophobic and hydrophilic statins were initiated by 30.7% and 19.6% of men, respectively, after the first negative PBx. UR and LUTS were experienced by 2.2% and 10% of men, respectively. Cox models demonstrated hydrophilic statins were associated with a lower risk of UR (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.38-0.83, p=0.0038) and LUTS (HR 0.86, 95% CI 0.76-0.98, p=0.022), while no such association was shown for hydrophobic statins., Conclusions: Initiation of hydrophilic statins in men older than 66 appears to be inversely associated with the risk of UR and LUTS within 30 days of a PBx.

Purpose: We aimed to compare patient-reported mental health outcomes for men undergoing treatment for localized prostate cancer longitudinally over 5 years., Materials and Methods: We conducted a prospective population-based analysis using the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study. Patient-reported depressive symptoms (Centers for Epidemiologic Studies Depression [CES-D]) and domains of the Medical Outcomes Study 36-item Short Form survey evaluating emotional well-being and energy/fatigue were assessed through 5 years after treatment with surgery, radiotherapy (with or without androgen deprivation therapy) and active surveillance. Regression models were adjusted for outcome-specific baseline function, demographic and clinicopathological characteristics, and treatment approach., Results: A total of 2,742 men (median [quartiles] age 64 [59-70]) met inclusion criteria. Baseline depressive symptoms, as measured by the CES-D, were low (median 4, quartiles 1-8) without differences between groups. We found no effect of treatment modality on depressive symptoms (p=0.78), though older age, poorer health, being unmarried and baseline CES-D score were associated with declines in mental health. There was no clinically meaningful association between treatment modality and scores for either emotional well-being (p=0.81) or energy/fatigue (p=0.054)., Conclusions: This prospective, population-based cohort study of men with localized prostate cancer showed no clinically important differences in mental health outcomes including depressive symptoms, emotional well-being, and energy/fatigue according to the treatment received (surgery, radiotherapy, or surveillance). However, we identified a number of characteristics associated with worse mental health outcomes including: older age, poorer health, being unmarried, and baseline CES-D score which may allow for early identification of patients most at risk of these outcomes following treatment.

Objectives: To determine the geographic distribution of muscle-invasive bladder cancer mortality according to race in the United States (US). African Americans (AAs) have up to two times the risk of bladder cancer mortality compared to Caucasians. Bladder cancer mortality increases exponentially once it invades the muscle. Geographic heterogeneity in bladder cancer mortality according to race remains to be determined., Design: Analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data for 6,044 patients aged 66-85 diagnosed with clinical stage T2-T4 N0M0 bladder cancer from 1 January 2002 to 31 December 2011. Fine and Gray-competing risks regression models were used to assess the association of race with bladder cancer-specific mortality (BCSM) according to tumor registry., Results: Out of 6,044 patients, 5,408 (89.5%) were Caucasian, 352 (5.82%) were non-Hispanic AA, 85 (1.4%) were Hispanic, and 199 (3.29%) were other. Of the 18 registries, AAs with bladder cancer were largely concentrated in Louisiana (19%), New Jersey (17.9%), and Georgia (17.6%). New Jersey was the only registry where AAs had increased risk of BCSM than Caucasians and only for stage T2 disease: (AHR, 1.74; 95% CI 1.22-2.47, p = 0.002). According to treatment, AAs in New Jersey had worse BCSM than Caucasians when they underwent radical cystectomy (AHR, 2.05; 95% CI 1.26-3.35, p = 0.0039) and radiotherapy or chemotherapy alone (AHR, 1.55; 95% CI 1.03-2.35, p = 0.0367)., Conclusions: We observed geographic variation in bladder cancer mortality which impacted only one registry with one of the largest population of AAs. These findings support further investigation into the social determinants of race (i.e., socioeconomic status and distance to healthcare facility) and culturally centered healthcare decision making which may drive these results., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Enrolment of racial/ethnic minorities in randomized controlled trials (RCTs) has historically been poor, despite efforts at improving access to RCTs. Under-representation of racial/ethnic minorities limits the external validity and generalizability of trials. Our objective was to determine to what extent are published RCTs of minimally invasive surgical techniques reporting the racial composition of their study cohorts and to describe the racial composition of patients enrolled in these trials, where data were available., Methods: EMBASE (OvidSP®), MEDLINE (OvidSP®), and Cochrane (Wiley®) databases were systematically searched from inception to December 22, 2017 to identify all RCTs comparing minimally invasive and classical surgical techniques. The Mann-Kendall trend test was used to evaluate reporting trends over the study period. Predictors of racial reporting were evaluated using logistic regression analyses., Results: Our search strategy yielded 9,321 references of which 496 RCTs met our inclusion/exclusion criteria. Racial information was reported in 20 (4.03%) studies. There was no significant improvement in racial reporting over the study period (p for trend = 0.31). Of the 17 different patient populations accounting for the 20 RCTs, 14 (82.4%) originated from the USA. Multicenter RCTs had significantly increased likelihood of reporting racial composition of the patient cohort (odds ratio 5.10, p = 0.025). White/Caucasian patients accounted for 84.5% of the pooled patient population, with Black/African American, Asian and Latin/Hispanic patients accounting for 7.9%, 1.2%, and 2.1%, respectively., Conclusions: Among RCTs assessing minimally invasive surgical techniques over the past 30 years, data on included patients' race is poorly reported. In addition to important efforts to improve access to clinical trials for racial and ethnic minorities, efforts aimed at improving reporting and transparency of surgical RCTs are sorely needed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: There are limited data regarding the effect of treatment delays on important long-term outcomes among men with intermediate/high-risk prostate cancer (PC)., Materials and Methods: We identified 3,962 men with intermediate/high-risk disease from the SEARCH cohort treated with radical prostatectomy (RP) from 1988 to 2018. Cox proportional hazard models assessed the association between time from biopsy to RP (up to 1 year) and time to castration-resistant PC (CRPC), metastasis and all-cause mortality. Interaction terms were used to test for effect modification by risk group., Results: Of the 3,962 men, 167 developed CRPC, 248 developed metastases and 884 died after a median followup of 85 months. Longer delays between biopsy and RP were associated with a decreased risk of CRPC (adjusted HR=0.88, 95% CI: 0.80-0.98, p=0.02), independent of D'Amico risk group (interaction p >0.05). In men with intermediate and high-risk disease, we found no statistically significant association between length of time to RP and risk of developing metastases (p=0.5 and 0.9, respectively) or all-cause mortality (p=0.1 and 0.1, respectively)., Conclusions: Among men with intermediate and high-risk PC, we found no statistically significant increased risk of adverse long-term outcomes, including CRPC, metastasis and death, for men who had treatment delays up to 1 year following PC diagnosis.

Shared decision-making (SDM) is a hallmark of patient-centred care that uses informed consent to help guide patients with making complex health-care decisions. In SDM, patients and providers work together to determine the best course of action based on both the current available evidence and the patient's values and preferences. SDM not only provides a framework for the legal and ethical obligations providers need to fulfil for informed consent, but also leads to improved knowledge of treatment options and satisfaction of decision-making for patients. Tools such as decision aids have been developed to support SDM for complex decisions. Several decision aids are available for use in the field of urology and female pelvic medicine and reconstructive surgery, but these decision aids are also associated with barriers to SDM implementation including patient, provider and systematic challenges. However, solutions to such barriers to SDM include continued development of SDM tools to improve patient engagement, expand training of providers in SDM communication models and a process to encourage implementation of SDM., (© 2021. Springer Nature Limited.)

Background: Recent reports with a small number of patients showed an association of red blood cell distribution width (RDW) with prostate cancer (PCa) progression., Objective: To investigate whether preoperative RDW can serve as a prognostic marker in patients with PCa undergoing radical prostatectomy (RP) in a large, equal access, and diverse patient cohort., Design Setting and Participants: Data were retrospectively collected on 4756 men treated with RP at eight Veteran Affairs medical centers within the Shared Equal Access Regional Cancer Hospital (SEARCH) database from 1999 through 2017., Outcome Measurements and Statistical Analysis: Biochemical recurrence (BCR) was the primary outcome, while metastasis, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) were secondary outcomes., Results and Limitations: The mean (standard deviation) age was 62 yr (6.1), and 1589 (33%) men were black. The median (interquartile range) follow-up was 82 mo (46-127). Preoperative RDW either as a continuous variable or when stratified by quartiles was not associated with BCR. Likewise, preoperative RDW was not associated with metastases or PCSM. However, higher RDW was significantly associated with higher ACM, both as a continuous variable ( p < 0.001) and when stratified by quartiles in univariable and multivariable models ( p < 0.001). RDW was found to be correlated with D'Amico risk classification of PCa. Study limitations include its retrospective nature and lack of data regarding advanced PCa., Conclusions: Preoperative RDW was not associated with PCa outcomes in men treated with RP but was associated with ACM. While RDW may be a biomarker of overall health, it is not a biomarker for PCa outcomes. These results emphasize the importance of diverse, larger sized studies in genitourinary cancer research., Patient Summary: Prostate cancer includes a wide spectrum of diseases with different genetic, pathological, and oncological behaviors. Red blood cell distribution width is helpful in predicting the overall survival for a localized prostate cancer patient, and hence, it can help inform personalized treatment decisions and operative care.

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.

Background: Challenges in identifying microsatellite instability (MSI)/mismatch repair (MMR)-tested colorectal carcinoma (CRC) patients in electronic health records have led to gaps in the understanding of MSI-high/deficient mismatch repair prevalence. Methods: An algorithm to identify MSI-/MMR-tested Veterans Affairs patients was developed and an observational study of adult CRC patients with MSI/MMR testing from 2010 to 2018 was undertaken. Results: An optimized model to identify MSI-/MMR-tested patients yielded high positive predictive value (89.0%) and specificity (97.8%). The authors observed MSI-high/deficient mismatch repair CRC in 54 of 291 patients (18.6%); highest frequencies were observed in stages II (25.9%) and III (22.6%) and lowest in stage IV (5.8%). Conclusions: In this real-world study, the authors proposed a novel method of identifying MSI-/MMR-tested patients. Further validation and refinement of this model, and study in a larger CRC cohort, is warranted.

Background: Surgical resection of oligometastatic disease has been shown to be associated with an improved survival in other malignancies, though its role is not established in metastatic urothelial carcinoma (mUC). We sought to examine utilization trends of metastasectomy in mUC and associated outcomes using the NCDB database., Methods: We queried the NCDB from 2004 to 2016 for patients with metastatic urothelial carcinoma who had undergone metastasectomy. The annual utilization trend of metastasectomy was evaluated by linear regression. We compared overall survival (OS) between propensity score matched patients who had undergone metastasectomy and those who had not using two-sided log-rank and Cox regression models. We also performed sensitivity analyses on subcohorts of mUC., Results: The utilization rate of metastasectomy in mUC was 7% and did not change significantly over time. Patients who received metastasectomy on average were younger, had >cT3 disease, had radical surgery to the primary tumor, and received systemic therapy. After propensity score matching, metastasectomy was not associated with an OS benefit for mUC patients (HR, 0.94; 95% CI, 0.83 to 1.07; P=0.38). Stratified subgroup analysis based on systemic therapy, radical surgery to primary tumor, clinical N stage, and primary location of disease did not show an OS benefit of metastasectomy., Conclusion: Metastasectomy is uncommonly used, though utilization has persisted over more than a decade. Despite selection biases and residual confounding favoring patients undergoing metastasectomy, we found similar OS among these individuals and those who did not undergo metastasectomy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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; I 2  = 36%). Results assessing PFS were similar (P = 0.45, I 2  = 0%)., Conclusions: These clinical data suggest that prior nephrectomy does not affect the efficacy of ICI-based regimens in mRCC relative to sunitinib., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Mortality from bladder cancer (BC) increases exponentially once it invades the muscle, with inherent challenges delineating at the population level. We sought to develop and validate a natural language processing (NLP) model for automatically identifying patients with muscle-invasive bladder cancer (MIBC)., Methods: All patients with a Current Procedural Terminology code for transurethral resection of bladder tumor (TURBT; n = 76,060) were selected from the Department of Veterans Affairs (VA) database. A sample of 600 patients (with 2,337 full-text notes) who had TURBT and confirmed pathology results were selected for NLP model development and validation. The NLP performance was assessed by calculating the sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and overall accuracy at the individual note and patient levels., Results: In the validation cohort, the NLP model had average overall accuracies of 94% and 96% at the note and patient levels. Specifically, the F1 score and overall accuracy for predicting muscle invasion at the patient level were 0.87% and 96%, respectively. The model classified nonmuscle-invasive bladder cancer (NMIBC) with overall accuracies of 90% and 93% at the note and patient levels. When applying the model to 71,200 patients VA-wide, the model classified 13,642 (19%) as having MIBC and 47,595 (66%) as NMIBC and was able to identify invasion status for 96% of patients with TURBT at the population level. Inherent limitations include a relatively small training set, given the size of the VA population., Conclusion: This NLP model, with high accuracy, may be a practical tool for efficiently identifying BC invasion status and aid in population-based BC research., Competing Interests: Ruixin YangResearch Funding: Janssen, Merck Lauren E. HowardResearch Funding: Bayer (Inst), Merck (Inst), Ferring (Inst), MDxHealth (Inst), Sanofi (Inst), Diasorin (Inst), Myriad Genetics (Inst), LungLife AI (Inst) Amanda De HoedtStock and Other Ownership Interests: Myovant SciencesResearch Funding: Bayer (Inst), Ferring (Inst), Merck (Inst), Janssen (Inst), MDxHealth (Inst), Sanofi (Inst), Diasorin (Inst), Myriad Genetics (Inst), LungLife AI (Inst), Pfizer (Inst), Blue Earth Diagnostics (Inst) Florian R. SchroeckOther Relationship: Sesen Bio Zachary KlaassenHonoraria: Pfizer/Astellas, BayerConsulting or Advisory Role: Sesen Bio Stephen J. FreedlandEmployment: Genomic Health (I)Consulting or Advisory Role: Astellas Pharma, Janssen Biotech, Dendreon, Bayer, Pfizer, Ferring, AstraZeneca, Sanofi, Myovant Sciences, Clovis Oncology, Merck, Exact SciencesSpeakers' Bureau: Sanofi, AstraZenecaResearch Funding: Bayer (Inst), Janssen Biotech (Inst), Myriad Genetics (Inst), GenomeDx (Inst), Progenika (Inst), MDxHealth (Inst), OPKO Diagnostics (Inst), Diasorin, MerckTravel, Accommodations, Expenses: Sanofi Stephen B. WilliamsConsulting or Advisory Role: Taris BioMedical (Inst), Photocure, UroTodayTravel, Accommodations, Expenses: JanssenNo other potential conflicts of interest were reported.

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 &lt;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.

Importance: Treatment-related regret is an integrative, patient-centered measure that accounts for morbidity, oncologic outcomes, and anxiety associated with prostate cancer diagnosis and treatment., Objective: To assess the association between treatment approach, functional outcomes, and patient expectations and treatment-related regret among patients with localized prostate cancer., Design, Setting, and Participants: This population-based, prospective cohort study used 5 Surveillance, Epidemiology, and End Results (SEER)-based registries in the Comparative Effectiveness Analysis of Surgery and Radiation cohort. Participants included men with clinically localized prostate cancer from January 1, 2011, to December 31, 2012. Data were analyzed from August 2, 2020, to March 1, 2021., Exposures: Prostate cancer treatments included surgery, radiotherapy, and active surveillance., Main Outcomes and Measures: Patient-reported treatment-related regret using validated metrics. Regression models were adjusted for demographic and clinicopathologic characteristics, treatment approach, and patient-reported functional outcomes., Results: Among the 2072 men included in the analysis (median age, 64 [IQR, 59-69] years), treatment-related regret at 5 years after diagnosis was reported in 183 patients (16%) undergoing surgery, 76 (11%) undergoing radiotherapy, and 20 (7%) undergoing active surveillance. Compared with active surveillance and adjusting for baseline differences, active treatment was associated with an increased likelihood of regret for those undergoing surgery (adjusted odds ratio [aOR], 2.40 [95% CI, 1.44-4.01]) but not radiotherapy (aOR, 1.53 [95% CI, 0.88-2.66]). When mediation by patient-reported functional outcomes was considered, treatment modality was not independently associated with regret. Sexual dysfunction, but not other patient-reported functional outcomes, was significantly associated with regret (aOR for change in sexual function from baseline, 0.65 [95% CI, 0.52-0.81]). Subjective patient-perceived treatment efficacy (aOR, 5.40 [95% CI, 2.15-13.56]) and adverse effects (aOR, 5.83 [95% CI, 3.97-8.58]), compared with patient expectations before treatment, were associated with treatment-related regret. Other patient characteristics at the time of treatment decision-making, including participatory decision-making tool scores (aOR, 0.80 [95% CI, 0.69-0.92]), social support (aOR, 0.78 [95% CI, 0.67-0.90]), and age (aOR, 0.78 [95% CI, 0.62-0.97]), were significantly associated with regret. Results were comparable when assessing regret at 3 years rather than 5 years., Conclusions and Relevance: The findings of this cohort study suggest that more than 1 in 10 patients with localized prostate cancer experience treatment-related regret. The rates of regret appear to differ between treatment approaches in a manner that is mediated by functional outcomes and patient expectations. Treatment preparedness that focuses on expectations and treatment toxicity and is delivered in the context of shared decision-making should be the subject of future research to examine whether it can reduce regret.

Purpose of Review: The purpose of this review is to describe the causes, management, and clinical outcomes associated with cachexia and related components including sarcopenia, among patients with bladder cancer (BCa)., Recent Findings: Cachexia in patients with BCa is associated with poorer outcomes after radical cystectomy (RC), radiation, and chemotherapy. Nutritional supplements and novel pharmaceutical agents including magnolol, flucoidan and Anamorelin are currently undergoing investigation for their potential use in BCa patients with cachexia., Summary: Cachexia is a hypercatabolic state thought to be caused by an immune-regulated release of cytokines and disruptions of molecular pathways within the tumor microenvironment and systemically. Nutritional deficiencies in patients with BCa also contribute to cachexia and sarcopenia. Patients with BCa -related cachexia and sarcopenia experience worse survival and therapeutic outcomes after RC, chemotherapy, and radiation therapy. Patients with cachexia also experience more postoperative complications after RC. The management of cachexia in patients with BCa remains challenging and requires timely identification, and multidisciplinary management including nutritional supplementation, physical therapy, palliative care, and pharmacological agents. Clinical trials and human studies are still required to determine which pharmacological agents are optimal for BCa cachexia., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Financial toxicity is an underappreciated component of cancer survivorship. Treatment-specific out-of-pocket costs for patients undergoing localized prostate cancer treatment have not, to date, been described and may influence patient's decision making., Methods: We performed a retrospective cohort study among commercially-insured patients in the United States with incident prostate cancer from 2013 to 2018. We captured out-of-pocket and total costs in the year following diagnosis and compared these between patients receiving radical prostatectomy, radiotherapy, and no local treatment using propensity-score weighting adjusting for patient demographics and pre-diagnosis health utilization costs., Results: Among 30,360 included men [median age 59 years, 83% Charlson score 0], 15,854 underwent surgery, 5,265 radiotherapy, and 9,241 no local therapy in the year following diagnosis. In the 6-months preceding diagnosis, median overall and out-of-pocket health care costs were $2022 (interquartile range $3778) and $466 (interquartile range $781), respectively. Following propensity-score weighting, out-of-pocket costs were significantly lower for patients who received no active treatment (adjusted cost $1746, 95% confidence interval [CI] $1704-1788), followed by those who underwent surgery ($2983, 95% CI $2832-3142, P < 0.001), and those who underwent radiation ($3139, 95% CI $2939-3353, P < 0.001) in the 6-months following diagnosis. Similar patterns were seen with out-of-pocket costs 6 to 12 months following index, with overall costs, and with costs attributable to inpatient, outpatient medical, and outpatient pharmacy services., Conclusions: Among commercially insured men with incident prostate cancer, active treatment with surgery or radiotherapy was associated with significantly higher out-of-pocket costs versus those who received no treatment, with little difference observed between treatment approaches., Competing Interests: Conflict of interest The authors attest they have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to describe bladder cancer outcomes as a function of race among patients with high-risk non-muscle-invasive bladder cancer (NMIBC) in an equal-access setting., Methods: A total of 412 patients with high-risk NMIBC who received bacille Calmette-Guérin (BCG) from January 1, 2010, to December 31, 2015, were assessed. The authors used the Kaplan-Meier method to estimate event-free survival and Cox regression to determine the association between race and recurrence, progression, disease-specific, and overall survival outcomes., Results: A total of 372 patients who had complete data were included in the analysis; 48 (13%) and 324 (87%) were Black and White, respectively. There was no difference in age, sex, smoking status, or Charlson Comorbidity Index by race. White patients had a higher socioeconomic status with a greater percentage of patients living above the poverty level in comparison with Black patients (median, 85% vs 77%; P < .001). A total of 360 patients (97%) received adequate induction BCG, and 145 patients (39%) received adequate maintenance BCG therapy. There was no significant difference in rates of adequate induction or maintenance BCG therapy according to race. There was no significant difference in recurrence (hazard ratio [HR], 1.53; 95% confidence interval [CI], 0.64-3.63), progression (HR, 0.77; 95% CI, 0.33-1.82), bladder cancer-specific survival (HR, 1.01; 95% CI, 0.30-3.46), or overall survival (HR, 0.97; 95% CI, 0.56-1.66) according to Black race versus White race., Conclusions: In this small study from an equal-access setting, there was no difference in the receipt of BCG or any differences in bladder cancer outcomes according to race., (© 2021 American Cancer Society.)

Introduction: Current guidelines support active surveillance (AS) for select patients with favorable intermediate risk (FIR) prostate cancer (CaP). A significant proportion of FIR CaP patients undergoing surgical treatment are found to have evidence of adverse pathology. Our objective was to determine the incidence and predictors of pathologic upgrading in FIR AS patients undergoing radical prostatectomy., Materials and Methods: The Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting (WW) database was used to identify men younger than 80 years with National Comprehensive Cancer Network FIR CaP initially opting for AS and/or WW between 2010 and 2015 and subsequently underwent radical prostatectomy at least one year following diagnosis. Patients were assigned into one of three subgroups based on their intermediate risk factor: Gleason Score 7(3 + 4) (Group 1), prostate specific antigen level of 10-20 ng/ml (Group 2), and cT2b-c (Group 3). Pathologic upgrading was present in Group 1 if pathologic GS was 7 (4 + 3) or worse. For patients in Groups 2 and 3, upgrading occurred if pathologic GS was 7 (3 + 4) or worse. Oncologic and sociodemographic predictors of pathologic upgrading were evaluated univariable and multivariable logistic regression analysis., Results: 18,760 patients were identified. Pathologic upgrading occurred in 138 (13.3%), 59 (25.0%), and 8,011 (45.8%) patients in groups 1, 2, and 3 respectively. Pathologic downgrading occurred in 226 (21.7%) patients in group 1. Significant predictors of pathologic upgrading on multivariable analysis included older age at diagnosis: 70 to 79 vs. 40 to 49 years (Groups 1 and 3, P < 0.05), a more recent diagnosis: 2014 to2015 vs. 2010-2011 (Groups 2 and 3, P < 0.005), higher volume disease: 37.5% to 49.9% vs. 0% to 12.4% (Groups 2 and 3, P < 0.005), and clinically palpable disease (Groups 1 and 2, P < 0.05). Additional risk factors for upgrading included uninsured or Medicaid status, diagnosis in a Western region (Group 2), African American ethnicity and higher socioeconomic status (Group 3) CONCLUSIONS: FIR CaP is a clinically heterogeneous risk group with incidence of pathologic upgrading ranging from 13.3% in those with GS 7 (3 + 4) to 45.8% in those with cT2b-c disease. Risk of pathologic upgrading in FIR CaP patients initially managed with AS and/or WW is significantly associated with multiple patient-level oncologic and sociodemographic variables., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) and cancer often occur in the same individuals, in part due to the shared risk factors such as obesity. Obesity promotes adipose inflammation, which is pathogenically linked to both cardiovascular disease and cancer. Compared with Caucasians, the prevalence of obesity is significantly higher in African Americans (AA), who exhibit more pronounced inflammation and, in turn, suffer from a higher burden of CVD and cancer-related mortality. The mechanisms that underlie this association among obesity, inflammation, and the bidirectional risk of CVD and cancer, particularly in AA, remain to be determined. Socio-economic disparities such as lack of access to healthy and affordable food may promote obesity and exacerbate hypertension and other CVD risk factors in AA. In turn, the resulting pro-inflammatory milieu contributes to the higher burden of CVD and cancer in AA. Additionally, biological factors that regulate systemic inflammation may be contributory. Mutations in atypical chemokine receptor 1 (ACKR1), otherwise known as the Duffy antigen receptor for chemokines (DARC), confer protection against malaria. Many AAs carry a mutation in the gene encoding this receptor, resulting in loss of its expression. ACKR1 functions as a decoy chemokine receptor, thus dampening chemokine receptor activation and inflammation. Published and preliminary data in humans and mice genetically deficient in ACKR1 suggest that this common gene mutation may contribute to ethnic susceptibility to obesity-related disease, CVD, and cancer. In this narrative review, we present the evidence regarding obesity-related disparities in the bidirectional risk of CVD and cancer and also discuss the potential association of gene polymorphisms in AAs with emphasis on ACKR1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Guha, Wang, Harris, Nelson, Stepp, Klaassen, Raval, Cortes, Coughlin, Bogdanov, Moore, Desai, Miller, Lu, Kim and Weintraub.)

Public reporting of consultant/staff urologist outcomes must rely on commonly performed procedures, accurate data input, and adequate funding. Precautions must be taken to ensure that this information is utilised in the best interests of informing the public and surgeons., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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., (© 2021 American Cancer Society.)

Objectives: To investigate sociodemographic factors influencing decision of initially active surveillance (AS) prostate cancer (CaP) patients to opt for definitive therapy, and, specifically, choice of radical prostatectomy (RP) versus radiation therapy (XRT)., Methods: The Surveillance, Epidemiology, and End Results (SEER) Prostate with Watchful Waiting database was used to identify AS patients diagnosed with NCCN low-risk CaP between 2010 and 2015. We sought to determine predictors of treatment type using multivariable logistic regression analyses., Results: Out of 32,874 men included, 21,255 (64.7%) underwent delayed treatment, with 3,751 (17.6%) and 17,463 (82.2%) opting for RP and XRT, respectively. Patients who were married (Odds Ratio [OR]: 1.18, P <.001), insured (OR 2.94, P <.001), of higher socioeconomic status (OR 1.67 for highest vs lowest, P <.01), and residing in a Southeastern or Midwestern region (ORs 1.26 and 1.22 vs Northeast, respectively, P <.01) were significantly more likely to undergo definitive intervention. A significant interaction between patient race and marital/socioeconomic statuses on the decision-making process was identified. Decision for XRT (vs RP) was more likely in older (OR 11.6 for 70-79 vs 50-59 years, P <.01), unmarried (OR 1.89, P <.01), African American (OR 1.41, P .018), and higher socioeconomic status (OR 1.54 for highest versus lowest quartile, P <.01) patients., Conclusion: The majority of patients initially treated with AS underwent delayed treatment. After accounting for pathologic characteristics, the interaction of sociodemographic factors including race, socioeconomic status, marital status, insurance status, and region of residence are significantly associated with the likelihood of undergoing definitive therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To characterize the contribution of the extirpative and reconstructive portions of radical cystectomy (RC) to complications rates, and assess differences between urinary diversion (UD) types., Materials and Methods: We conducted a retrospective cohort study comparing patients undergoing UD alone or RC+UD for bladder cancer from 2006 to 2017 using ACS National Surgical Quality Improvement Program database. The primary outcome was major complications, while secondary outcomes included minor complications and prolonged length of stay. Propensity score matching (PSM) was utilized to assess the association between surgical procedure (UD alone or RC+UD) and outcomes, stratified by diversion type. Lastly, we examined differences in complication rates between ileal conduit (IC) vs. continent UD (CUD)., Results: When comparing RC + IC and IC alone, PSM yielded 424 pairs. IC alone had a lower risk of any complication (HR 0.63, 95% CI 0.52-0.75), venous thromboembolism (HR 0.45, 95% CI 0.22-0.91) and bleeding needing transfusion (HR 0.41, 95% CI 0.32-0.52). This trend was also noted when comparing RC + CUD to CUD alone. CUD had higher risk of complications than IC, both with (56.6% vs 52.3%, p = 0.031) and without RC (47.8% vs 35.1%, p=0.062), and a higher risk of infectious complications, both with (30.5% vs 22.7%, p< 0.001) and without RC (34.0% vs 22.0%, p=0.032)., Conclusions: RC+UD, as compared to UD alone, is associated with an increased risk of major complications, including bleeding needing transfusion and venous thromboembolism. Additionally, CUD had a higher risk of post-operative complication than IC., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

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 (R 2  = 0.35, Cochran-Armitage test for trend, p < 0.001), last (R 2  = 0.30, p < 0.001), and first or last authorships (R 2  = 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., (Copyright © 2021 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Cytoreductive nephrectomy (CN) has played a role in treatment of metastatic renal cell carcinoma (mRCC) since trials demonstrated a survival benefit in patients receiving CN with interferon. With the publication of CARMENA, it became clear that the value of CN may depend on the co-therapy administered. We sought to assess the benefit of CN in the era of modern immunotherapy (IO)., Methods: We performed a systematic review to identify studies assessing CN in patients receiving TT or IO. We extracted multivariable-adjusted hazard ratios for the association between CN and overall survival (OS) and performed random effects meta-analysis. We tested for effect modification by systemic therapy approach on the association between CN and OS by pooling the difference in logHR associated with CN for patients treated with TT versus IO., Results: We identified three comparisons assessing CN in patients receiving TT or IO. Pooled analysis indicated improved survival with CN in both the TT (2 cohorts, pooled HR: 0.52, 95% CI 0.46-0.59; I 2  = 80%) and IO era (2 cohorts; pooled HR: 0.28, 95% CI 0.16-0.49; I 2  = 21%), with a stronger association in the IO era (p = 0.01; I 2  = 0%)., Conclusion: In observational datasets, we observed a larger survival benefit to CN in patients treated with IO-based regimens versus those treated with TT-based regimens. While the role of CN for patients receiving TT has recently been questioned, this suggests that the results of CARMENA do not necessarily preclude a benefit to CN when combined with IO-based regimens.

Metastatic prostate cancer is associated with considerable morbidity and mortality. Standard treatment for non-metastatic prostate cancer, to prevent metastatic progression, is androgen deprivation therapy (ADT); however, many patients will eventually develop castration-resistant prostate cancer (CRPC), which can prove challenging to treat. Between the stages of non-metastatic androgen-sensitive disease and metastatic CRPC is an intermediate disease state that has been termed non-metastatic CRPC (nmCRPC), which is a heterogeneous, man-made disease stage that occurs after a patient who has no radiological evidence of metastasis shows evidence of cancer progression even after ADT. Awareness of nmCRPC has risen owing to an increased use of ADT and its eventual failure. Men with nmCRPC are at a high risk of progression to mCRPC, with historically few options to halt this process. However, in the past two decades, multiple therapies have been investigated for the treatment of nmCRPC, including endothelin receptor antagonists and bone-targeted therapies, but none has changed the standard of care. In the past decade, the efficacy of androgen receptor pathway-targeting modalities has been investigated. Three novel nonsteroidal antiandrogen agents for treating high-risk nmCRPC have been investigated; the PROSPER, SPARTAN and ARAMIS trials were phase III, randomized, placebo-controlled clinical trials that investigated the efficacy and safety of enzalutamide, apalutamide and darolutamide, respectively. All three therapeutics showed statistically significant improvements in metastasis-free survival, progression to antineoplastic therapy was lengthened and at final analysis, overall survival was significantly improved. The comparative efficacy and safety of all three agents has not yet been investigated in a comprehensive clinical trial, but approval of these medications by the FDA and other regulatory agencies means that providers now have three effective therapeutic options to augment ADT for patients with nmCRPC.

Background: Over 20% of men diagnosed with prostate cancer (PC) are ≥75 yr old. More objective disease-specific indices for predicting outcomes beyond chronological age are necessary., Objective: To analyze age-related differences in clinical-genomic prognostic features of aggressiveness in localized PC., Design, Setting, and Participants: A retrospective multicenter cross-sectional study reported the use of the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) guidelines. Clinical-genomic data of patients who underwent a prostate biopsy or radical prostatectomy (RP) were obtained from the Decipher Genomic Resource Information Database (NCT02609269)., Intervention: Our analyses focused on the 22-gene Decipher genomic classifier (GC) and 50-gene (PAM50) models in the biopsy and RP cohorts stratified by age., Outcome Measurements and Statistical Analysis: The primary endpoint was the impact of age on GC scores and PAM50 molecular subtypes. Prognostic indices including Decipher GC scores, PAM50 molecular subtypes, National Comprehensive Cancer Network risk categories, and ISUP grade groups (IGGs) were stratified by age using multivariable logistic regression analyses., Results and Limitations: Within histological low-risk IGGs, there were a higher proportion of patients with high-risk Decipher biopsy scores with age (age <60 yr: 10.1% IGG 1 and 29.9% IGG 2 vs age ≥80 yr: 22% IGG 1 and 37.7% IGG 2). The prevalence of the adverse phenotype luminal B (PAM50-defined) increased with age (age <60 yr: 22.7% and 40.2% vs age ≥80 yr: 29.7% and 49.1%, in patients with IGG 1 and IGG 2, respectively). In IGGs 3-5, no age differences were observed. Multivariable models demonstrated that each age decile entailed a 19% (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.10-1.29, p < 0.001) and a 10% (OR 1.1, 95% CI 1.05-1.16) increased probability for a high-risk Decipher biopsy and RP score, respectively. Aside from an obvious selection bias, data on race, family history, prostate volume, and long-term follow-up outcomes were unavailable., Conclusions: These data demonstrated that elderly men with favorable pathology (IGG 1-2), might harbor more aggressive disease than younger patients based on validated GC scores., Patient Summary: The presented clinical-genomic data demonstrate that elderly patients with low-risk prostate cancer might harbor more aggressive disease than their younger counterparts. This suggests that standard well-accepted paradigm of elderly prostate cancer patients not being aggressively treated, based solely on their chronological age, might need to be reconsidered., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: A proportion of prostate cancer (PCa) patients initially managed with active surveillance (AS) are upgraded to a higher Gleason score (GS) at the time of radical prostatectomy (RP). Our objective was to determine predictors of upgrading on RP specimens using a national database., Methods: The Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting database was used to identify AS patients diagnosed with very low- or low-risk PCa who underwent delayed RP between 2010 and 2015. The primary outcome was upgrading to GS 7 disease or worse. Logistic regression analyses were used to evaluate demographic and oncological predictors of upgrading on final specimen., Results: A total of 3775 men underwent RP after a period of AS, 3541 (93.8%) of whom were cT2a; 792 (21.0%) patients were upgraded on RP specimen, with 85.4%, 10.6%, and 3.4% upgraded to GS 7(3+4), 7(4+3), and 8 diseases, respectively. On multivariable analysis, higher prostate-specific antigen (PSA) at diagnosis (5-10 vs. 0-2 ng/ml, odd ratio [OR] 2.59, p<0.001) and percent core involvement (80-100% vs. 0-20%, OR 2.52, p=0.003) were significant predictors of upgrading on final RP specimen, whereas higher socioeconomic status predicted lower odds of upgrading (highest vs. lowest quartile OR 0.75, p=0.013)., Conclusions: Higher baseline PSA and percent positive cores involvement are associated with significantly increased risk of upgrading on RP after AS, whereas higher socioeconomic status predicts lower odds of such events. These results may help identify patients at increased risk of adverse pathology on final specimen who may benefit from earlier definitive treatment.

Objectives: To assess whether free PSA ratio (FPSAR) at biochemical recurrence (BCR) can predict metastasis, castrate-resistant prostate cancer (CRPC), and cancer-specific survival (CSS), following therapy for localised disease., Patients and Methods: A single-centre retrospective cohort study (NCT03927287) including a discovery cohort composed of patients with an FPSAR after radical prostatectomy (RP) or radiotherapy (RT) between 2000 and 2017. For validation, an independent Biobank cohort of patients with BCR after RP was tested. Using a defined FPSAR cut-off, the metastasis-free-survival (MFS), CRPC-free survival, and CSS were compared. Multivariable Cox models determined the association between post-treatment FPSAR, metastases, and CRPC., Results: Overall, 822 patients (305 RP- and 363 RT-treated patients and 154 Biobank patients) were analysed. In the RP cohort, a total of 272/305 (89.1%) and 33/305 (10.9%) had a FPSAR test incidentally and reflexively, respectively. In the RT cohort, 155/363 (42.7%) and 208/263 (57.3%) had a FPSAR test incidentally and reflexively, respectively. However, in the prospective Biobank RP cohort, FPSAR testing was done on all samples of patients diagnosed with BCR. A FPSAR cut-off of 0.10 was determined using receiver operating characteristic analyses in both the RP and RT cohorts. A FPSAR of <0.10 resulted in longer median MFS (14.8 vs 9.3 years and 14.8 vs 13 years, respectively), and longer median CRPC-free survival (median not reached vs 9.9 years and 20.7 vs 13.8 years, respectively). Multivariable analyses showed that a FPSAR of ≥0.10 was associated with increased metastasis in the RP cohort (hazard ratio [HR] 1.915, 95% confidence interval [CI] 1.241-2.955) and RT cohort (HR 1.754, 95% CI 1.112-2.769), and increased CRPC in the RP cohort (HR 2.470, 95% CI 1.493-4.088). Findings were validated in the Biobank cohort., Conclusions: A post-treatment FPSAR of ≥0.10 is associated with more aggressive disease, suggesting a potentially novel role for this biomarker., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Objective: Older patients diagnosed with cancer are at increased risk of physical and emotional distress; however, prescription utilization patterns largely remain to be elucidated. Our objective was to comprehensively assess prescription patterns and predictors in older patients with bladder cancer., Methods: A total of 10,516 older patients diagnosed with clinical stage T1-T4a, N0, M0 bladder urothelial carcinoma from 1 January 2008 to 31 December 2012 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare were analyzed. We used multivariable analysis to determine predictors associated with psychotropic prescription rates (one or more). Medication possession ratio (MPR) was used as an index to measure adherence in intervals of 3 months, 6 months, 1 year, and 2 years. Evaluation of psychotropic prescribing patterns and adherence across different drugs and demographic factors was done., Results: Of the 10,516 older patients, 5621 (53%) were prescribed psychotropic drugs following cancer diagnosis. Overall, 3972 (38%) patients had previous psychotropic prescriptions prior to cancer diagnosis, and these patients were much more likely to receive a post-cancer diagnosis prescription. Prescription rates for psychotropic medications were higher among patients with higher stage BC (p < 0.001). Gamma aminobutyric acid modulators/stimulators and serotonin reuptake inhibitors/stimulators were the highest prescribed psychotropic drugs in 21% of all patients. Adherence for all drugs was 32% at 3 months and continued to decrease over time., Conclusion: Over half of the patients received psychotropic prescriptions within 2 years of their cancer diagnosis. Given the chronicity of psychiatric disorders with observed significantly low adherence to medications that warrants an emphasis on prolonged patient monitoring and further investigation., (© 2021 John Wiley & Sons Ltd.)