bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating therapeutic bladder cancer trial disparities in race/ethnicity.
Authors: Iyer Ishaan , Zhang Sylvia , Borno Hala 
Published: February 2022

446 Background: Racial clinical trial disparities in bladder cancer outcomes remains a critical problem in the United States. This study sought to examine representation by race and sex among therapeutic bladder cancer clinical trials that informs the standard of care in bladder cancer management. Methods: Published clinical trial data that inform clinical management were identified from the National Comprehensive Cancer Network guidelines and by clinician input from 2009 to 2021. The characteristics of participants, including sex and race, were collected. Clinical trials were categorized by clinical setting: metastatic bladder cancer (MBC), muscle invasive bladder cancer (MIBC), and non-muscle invasive (NMIBC). Bladder cancer incidence by race were collected from the Surveillance, Epidemiology, and End Results (SEER) Program. SEER incidence data by race was compared to the racial/ethnic breakdown of bladder cancer clinical trial participants and evaluated using hypothesis testing (chi-square). Results: A total of 28 clinical trials were assessed, with a pooled sample of 8003 participants. race was reported for 1786 participants. A total of 17 clinical trials did not report race. The population data from SEER details bladder cancer distributions as 89.52% White, 5.80% Black, 0.33% American Indian/Alaska Native, and 4.36% Asian or Pacific Islander. Chi-square analysis demonstrated significant differences in racial representation for MBC (p< 0.0001) and NMIBC (p=0.0423) settings. No significant differences were observed in the MIBC (p= 0.1954) setting. Conclusions: This study observed that the distributions of race in MBC and NMIBC clinical trials are different from that of the population affected by bladder cancer. It is imperative for therapeutic cancer clinical trials to achieve adequate representation to ensure standard of care therapies in bladder cancer management benefits all.[Table: see text]
Identification of muscle-invasion status in bladder cancer patients using natural language processing and machine learning.
Authors: Yang Ruixin , Zhu Di , Howard Lauren , De Hoedt Amanda M. , Klaassen Zachary William Abraham , Freedland Stephen J. , Williams Stephen B. 
Published: February 2022

447 Background: Mortality from bladder cancer (BC) increases exponentially once it invades the muscle. At the population level, accurate delineation of these patients is challenging. Methods: To develop and validate a natural language processing (NLP) model for automatically identifying muscle-invasive BC (MIBC) patients, aiding in population-based BC research. All patients with a CPT code for transurethral resection of bladder tumor (TURBT) (N = 76,060) were selected from the Department of Veterans Affairs (VA) Corporate Data Warehouse 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 (500 patients) and validation (100 patients). Muscle-invasion (yes/no), unknown, or no cancer, were confirmed by detailed chart review of pathology notes. The NLP performance was assessed by calculating the sensitivity, positive predictive value (PPV), and overall accuracy at the individual note and patient levels. Results: In the validation cohort, the NLP model had overall accuracy of 88% and 92% at the note and patient levels. Specifically, PPV and specificity for predicting muscle-invasion on note level were 83% and 70%, respectively. The model classified non-muscle invasive BC (NMIBC) with 98% sensitivity at both the note and patient levels. Although the sensitivity for MIBC was 70% for note-level determination, the sensitivity was 86% when evaluated at the patient level. 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. The NLP model was able to identify invasion status for 96% TURBT patients at the population level. Inherent limitations include relatively small training set given the size of the VA population. Conclusions: This NLP model for identifying muscle-invasion at the population level had high accuracy. The NLP model may be a practical and accurate tool for efficiently identifying BC invasion status and may potentially aid in population-based BC research in the VA.
Effect of neoadjuvant chemotherapy (NAC) on patient preferences for adjuvant treatment in muscle-invasive urothelial carcinoma (MIUC): A multi-country discrete choice experiment (DCE).
Authors: Broughton Edward I , Steinberg Gary D. , Harrison Michael Roger , Braverman Julia , Jaffe Dena H. , Will Oliver , Senglaub Steven S. , King-Concialdi Kristen , Beusterien Kathleen 
Published: February 2022

454 Background: Patient preference is an important factor in selecting appropriate treatment choices. Although underutilized, the standard of care for MIUC is with NAC, whereas evidence for adjuvant therapy is less clear. With the introduction of novel adjuvant treatments such as immune checkpoint inhibitors, treatment options are expected to expand. This study examines whether preferences for adjuvant therapy is impacted in MIUC patients receiving NAC. Methods: A cross-sectional, web-based survey included patients ≥ 18 years old who self-reported being diagnosed with MIUC and underwent radical cystectomy or nephroureterectomy without recurrence. Patients were recruited from the US, UK, Canada, France, and Germany (May–Sep 2021). A DCE using 2 adjuvant treatment profiles included 8 attributes: cancer-free survival, overall survival (OS), hypothyroidism requiring life-long hormone therapy, risk of a serious adverse event (requiring medical intervention/possible hospitalization), nausea, fatigue, diarrhea, and a dosing regimen (frequency of treatment and monitoring); an opt-out option of no treatment was also shown. Patients were grouped according to self-reported receipt of NAC. Descriptive statistics and hierarchical Bayesian logistic model with estimated preference weights were used. Relative importance estimates (mean ± standard error), or how much the attribute ranges accounted for the variation in preferences, were computed for each attribute. Bivariate comparisons used t-tests. Results: This interim analysis identified 205 patients (70.7% of target sample; US, n = 99; Germany, n = 60; UK, n = 31; Canada, n = 14; France, n = 1). Of 82 patients (40.0%) receiving NAC, 32.7% were patients > 65 years and 55.1% were male; receipt of NAC did not differ by age ( P = 0.248) or sex ( P = 0.731). Patients were willing to accept increased risk in toxicities for increased treatment efficacy. Specifically, mean relative importance of treatment attributes showed that difference in median OS (25 months compared to 78 months) was most important (34.6% ± 1.6), although less so for those who did not receive NAC (30.2% ± 2.4 vs 37.5% ± 2.0; P = 0.022). Patients chose an adjuvant treatment option over ‘no treatment’ 91% of the time, with similar findings by NAC status. Conclusions: Preliminary data indicates that receipt of NAC impacts preferences for adjuvant treatment attributes. However, regardless of these attributes, patients still preferred adjuvant treatment over none. These results suggest that providing standard of care NAC does not reduce patient preference for adjuvant therapy; rather, patient preferences for adjuvant treatment attributes vary by treatment history, with implications for improving quality of care and outcomes.
Long-term cost comparisons of radical cystectomy versus trimodal therapy for muscle-invasive bladder cancer.
Authors: Golla Vishnukamal , Shan Yong , Farran Elias Joseph , Vu Kevin , Stewart Courtney A. , Khaki Ali Raza , Keegan Kirk A. , Kamat Ashish M. , Tyler Douglas S. , Freedland Stephen J. , Williams Stephen B. 
Published: February 2022

455 Background: Earlier studies on the cost of muscle-invasive bladder cancer treatments are limited to short-term periods of cost. Our study objective is to compare the 2- and 5-year costs associated with trimodal therapy (TMT) versus radical cystectomy (RC) benchmarked against costs for patients who received no curative treatment. Methods: This cohort study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Medicare expenditures were summed from inpatient, outpatient, and physician services within 2 and 5 years of diagnosis to determine total costs Total Medicare costs at 2-and 5-years following TMT versus RC were compared using inverse probability of treatment-weighted (IPTW) propensity score models. Results: A total of 2,537 patients aged 66-85 years diagnosed with clinical stage T2-4a muscle-invasive bladder cancer from January 1, 2002 through December 31, 2009. Total median costs for patients that received no definitive/systemic treatments (RC, TMT, radiotherapy alone, or chemotherapy alone) were $73,780 vs. $88,275 at 2-and 5-years respectively. Total median costs were significantly higher for TMT than RC at 2-years ($372,839 vs. $191,363, p<0.001) and 5-years ($424,570 vs. $253,651, p<0.001), respectively. TMT had higher outpatient median costs than RC (2-yr: $318,221 vs. $100,900; 5-yr: $367,092 vs. $146,561) with significantly higher costs largely associated with radiology, medications, pathology/laboratory, and other professional services. Conclusions: TMT vs. RC was associated with higher long-term costs among patients with muscle-invasive bladder cancer largely driven by outpatient expenditures. Reduction in costs associated with radiology, medications, pathology/laboratory, and other professional services may improve the value of TMT.[Table: see text]
Contemporary treatment and survival differences in patients with urothelial versus nonurothelial bladder and upper tract carcinomas: Analyses from the National Cancer Database (NCDB).
Authors: Aragon-Ching Jeanny B. , Wang Hongkun 
Published: February 2022

463 Background: Non-urothelial bladder and upper tract cancers are known to have worse prognosis than urothelial cancers. Further descriptive analyses of patterns of demographic presentation, stage, metastases and response to chemotherapy and immunotherapy are explored through the NCDB database. Methods: The primary objective of this retrospective review is to evaluate trends and differences between upper tract urothelial cancers (UTUC) versus non-urothelial (nUTUC) histologies (squamous, sarcomatoid, small cell or neuroendocrine, adenocarcinoma) and bladder urothelial cancer (UC) and bladder non-urothelial cancer (nUC) and compare the demographics, disease characteristics, treatment, incidence of stage and survival according to NCDB. Results: Data from diagnosis in year 2004 – 2017 were extracted from the NCDB. A total of 649939 cases of whom 630423 were urothelial and 19516 were non-urothelial for both bladder and upper tract cancers were identified. More men were diagnosed with urothelial carcinoma, UTUC (62%) and bladder UC (75%). The median age was similar for both groups, 71.4 years (UC) and 70.1 years (nUC). Majority were Caucasian at 91.6% (UC) and 85.7% (nUC) while African-American patients consisted of 5.26% in the UC and 10.8% in the nUC cohorts. Primary surgery occurred more frequently in the UC cohort (94.7%) compared to the nUC (87%). More patients were diagnosed with stage IV cancer in the nUC group (21.9%) compared to UC at 4.6%, and overall survival was slightly worse with nUC for stage IV cancers with median OS of 7.92 mos (CI, (7.75, 8.08) for UC vs 6.14 mos (CI, (5.78, 6.47) nUC; logrank p = < 0.001, although the biggest numeric difference was in the stage 0 and stage I patients with mOS of 110.13 mos (CI, 109.44, 110.82) versus 46.09 mos (CI, 42.09, 50.66), p < 0.001. Use of chemotherapy resulted in improved overall survival in the UC group with mOS of 73.53 mos (CI, 72.61, 74.41) compared to nUC at 17.28 mos (CI, (16.59, 17.87), p < 0.0001 and use of immunotherapy similarly yielded improvement in the UC group with mOS of 115.98 mos (CI, 114.33- 117.65) compared to nUC at 64.49 mos (CI, 45.67, 88.51); p < 0.0001. Conclusions: Urothelial cancer of both bladder and upper tract origin compared to non-urothelial cancers tend to have better prognosis in both presentation at diagnosis and with early stage cancers as well as treatment in advanced stages with chemotherapy or immunotherapy, highlighting the need for better therapeutic strategies for non-urothelial cancers.
Regional trends in the cost of transurethral bladder tumor resection in the outpatient and physician office setting.
Authors: Kokkotos Fotios , Buser Hannah , An Aimee , Ferrara Katherine 
Published: February 2022

465 Background: TURBT is the standard surgical procedure for diagnosis, staging, and initial treatment of non-muscle invasive bladder cancer. This study aimed to identify current geographic trends associated with the use and cost of TURBT in Medicare beneficiaries. Methods: The Medicare Limited Data Set 100% sample of outpatient and 5% sample of carrier claims data from Q1 2019 to Q3 2020 was used for analysis. Patients who underwent TURBT were identified using CPT codes (55234, 52235, 52240). An analysis of variance (ANOVA) test was run comparing the difference in average claim payment amount, average beneficiary payment to physician, and average allowed charge amount between each region (West, Midwest, Northeast, and South). If the ANOVA test found a significant difference between regions, a t-test was run for all combinations of regions. Results: In the outpatient setting, we identified a total of 92,938 TURBT procedures between 2019 and Q3 2020, including 23,039 (Midwest), 19,890 (Northeast), 33,379 (South), and 16,630 (West). The average Medicare claim payment amount was $2,755 overall, $2,566 (Midwest), $2,866 (Northeast), $2,497 (South), and $3,092 (West). Beneficiaries paid an average of $605 in the Midwest, $673 in the Northeast, $572 in the South, and $697 in the West. The average total charge was $7,343, $7,189, $8,510, and $10,028 in the Midwest, Northeast, South, and West respectively. In the outpatient setting, there were no statistical differences for any cost related variables between the four regions. In the physician office setting, we identified 8,035 TURBT between 2019 and Q3 2020. There were 1,776, 1,577, 3,153, and 1,529 TURBT procedures in the Midwest, Northeast, South, and West, respectively. The average Medicare claim cost was $383 (Midwest), $372 (Northeast), $423 (South), and $417 (West). The average total allowed charges on the claim was $415 overall, and $392, $404, $430, and $432 in the Midwest, Northeast, South, and West, respectively. There was a significant statistical difference (p = 0.0154) for the average claim payment amount between the South and the Northeast. The two regions differed in average claim payment amount by $51 (95% CI: $15, $87). There was a significant difference in the average allowed charge amount between the South and Midwest (p = 0.019) and the West and Midwest (p = 0.016). Compared to the South, the Midwest had a lower average charge amount by $37 (95% CI: $9, $66). The West had a higher average charge amount than the Midwest by $40 (95% CI: $12, $68). Conclusions: This analysis demonstrated a significant difference in the cost of TURBT between regions in the physician office setting. The South had a significant higher claim payment amount than the Northeast. The allowed charge amount in the physician office setting for the South and the West were significantly higher than the Midwest.
Prospective validation of urine based FGFR screening by Uromonitor within the real-world clinicopathological register trial BRIDGister.
Authors: Wirtz Ralph M. , Veltrup Elke , Prazeres Hugo , Dias Carolina , Hake Roland , Eidt Sebastian , Vinagre Joao , Roggisch Jenny , Koch Stefan , Ecke Thorsten 
Published: February 2022

471 Background: The objective of the present study was to prospectively evaluate FGFR mutation detetion in matched urine and tissue samples from patients suspicious of bladder cancer and undergoing first TURB within the framework of the BRIDGister RealWorld Experience trial. Methods: For this pilot study paraffin fixed pretreatment tissue samples from the first TURB of 48 pts participating in the BRIDGister trial and matched urine samples were prospectively collected and analyzed. RNA from FFPE tissues were extracted by commercial kits and analyzed by Therascreen FGFR IVD kit (Qiagen GmbH, Hilden). In addition urine samples were filtered at local urology and filters were shipped for central extraction of cellular DNA (Uromonitor, Porto). Concordance, Kruskal-Wallis, MannWhitney and Sensitivity/Specificity tests were analyzed by JMP 9.0.0 (SAS software). Results: The pilote cohort of the BRIDGister trial consisted of 47 patients (median age: 77, male 65% vs female 35%) of diverse clinical stages (benign lesions/no tumor 38%, pTa 23%, pT1 20%, pT2 19%) and WHO 1973 grade (G1 11%, G2 43%, G3 23%). Based on FFPE tissue testing using Therascreen FGFR IVD kit 10 out of 47 patients exhibited FGFR alterations (25%), while urine filtering for cellular components and subsequent PCR testing revealed 13 out of 40 matched urine sampels were FGFR positive (33%). Comparison with tissue testing as probable gold standard revealed 100% sensitivity, 90% specificity, 77% PPV, 100% NPV as well as high concordance (kappa 0,82, p < 0,0001). There were 3 patients being FGFR positive for Uromonitor from urine with no mutation found in the corresponding TUR biopsy. Conclusions: Filtering urine for cells and subsequent DNA extraction followed by PCR detection results in highly sensitive mutation testing being feasible with good concordance to matched tissue testing. Prospective testing validated the diagnostic accuracy of the Uromonitor FGFR test in a real world setting.
Distribution of immune-related adverse events (irAEs) across genitourinary (GU) malignancies.
Authors: Mar Nataliya , Slaught Matthew , Kaakour Dalia , Azizi Armon , Valerin Jennifer Brooke 
Published: February 2022

480 Background: Checkpoint inhibitors (CPIs) targeting PD-1/PD-L1 and CTLA-4 have revolutionized management of GU malignancies. These agents are associated with a unique subset of toxicities that are immune-mediated, with a broad clinical spectrum that may affect any organ. Patients can also experience ³1 irAE involving multiple organ systems. Individual patient susceptibilities and type of CPI used may influence the incidence and type of irAEs that may develop. Wehypothesize that there are also differences in irAEs based on the histologic malignancy subtype. Methods: We performed a retrospective analysis of all patients with GU malignancies who received CPIs at the University of California Irvine using an outpatient oncology pharmacy database. Data was collected from 1/1/2020 to 6/30/2021. Patients were aged ³18 years and had a diagnosis of urothelial carcinoma (UC), renal cell carcinoma (RCC), prostate adenocarcinoma, or penile squamous cell carcinoma. Patients must have received ³1 dose of a CPI agent including ipilimumab (I), nivolumab (N), pembrolizumab (P), atezolizumab (At), avelumab (Av), durvalumab (D), and cemiplimab (C). Results: A total of 128 patients who received 141 unique CPI regimens were included. Documented irAEs were noted in 50.0% of patients and 18.4% had ³1 irAE. A total of 99 unique irAEs were recorded. In those who experienced irAEs, 92.2% of patients received CPIs in the metastatic setting and 7.8% in the adjuvant setting. In those who experienced irAEs, 12.5% of patients received combination CPIs with I+N, while 87.5% received single-agent CPI. In those who experienced irAEs, 46.8% of patients had UC, 50.0% had RCC, 1.6% had prostate cancer, and 1.6% had penile cancer. In those who experienced irAEs, 24.2% had skin rash or pruritis, 23.2% had endocrinopathies, 14.1% had colitis, 13.1% had other toxicity including arthritis, 12.0% had hepatitis, 3.9% had myositis, 2.9% had pneumonitis, 1.9% had neurologic toxicity including myasthenia gravis and encephalitis, 1.9% had carpal tunnel syndrome, 1.9% had nephritis, and 0.9% had autoimmune thrombocytopenia. Various irAEs for UC and RCC are summarized in Table. Conclusions: In this dataset, there were differences in type and incidence of irAEs in patients with UC and RCC, while the sample size was too small to draw conclusions about patients with prostate and penile cancer. Further investigation is needed involving other solid tumor types, including non-GU malignancies, to definitively answer this question.[Table: see text]
BCG efficacy in nonmuscle-invasive bladder cancer after prior radiation treatment for prostate cancer.
Authors: Durant Adri , Chang Yu-Hui , Faraj Kassem , Tyson Mark 
Published: February 2022

482 Background: Prostate radiotherapy is associated with worse oncologic outcomes in patients with bladder cancer. This is thought to be secondary to microvascular damage resulting in propagation of inflammation. There is sparse data on the effect of prior radiotherapy on the efficacy of intravesical Bacillus Calmette-Guerin (BCG) in patients with non-muscle invasive bladder cancer (NMIBC). We sought to evaluate BCG response and outcomes in NMIBC patients who have previously undergone prostate radiotherapy compared to patients with no prior history of pelvic radiotherapy. Methods: This is a retrospective cohort study that includes patients who received intravesical BCG for NMIBC at our institution from 2001 to 2019. Data were collected on patient and pathologic characteristics. Patients were stratified into three cohorts: prior radiotherapy (RT), radical prostatectomy (RP), and no prostate cancer (No PCa). Wilcoxon rank sum test and Chi-squared test were used for comparison between groups. The primary endpoints included recurrence at one-year, progression to MIBC and progression to metastatic disease. Results: In 199 total patients who underwent BCG for NMIBC, 23 had a prior history of radiotherapy treatment for prostate cancer, while 17 underwent prior radical prostatectomy. Overall, 41.2% of patients had recurrence at one year. There was no difference in recurrence at one year between the cohorts: 42.8% No PCa, 29.4% RP and 39.1% RT; p = 0.56. There was also no difference in progression to MIBC (6.9% No PCA, 0% RP, and 8.7% RT) or progression to metastatic disease (6.9% No PCA, 5.9% RP and 4.3% RT) with p = 0.50 and 0.89 respectively. Conclusions: The efficacy of intravesical BCG does not appear to be modified by prior radiation treatment for prostate cancer in patients with NMIBC.[Table: see text]