bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive value of dynamic changes in ctDNA and baseline biomarkers with neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial.
Authors: Young Matthew Nicholas , Szabados Bernadett , Assaf Zoe , Jackson-Spence Francesca , Nally Elizabeth , Wells Connor , Suárez Cristina , Castellano Daniel , Powles Thomas , Banchereau Romain 
Published: January 2024

534 Background: Circulating tumour DNA (ctDNA) is being explored in the neoadjuvant setting in multiple prospective trials. Dynamic changes may be a surrogate marker of pathological complete response. ABACUS was a multi-centre, single-arm phase II trial investigating two cycles of atezolizumab before cystectomy in patients with muscle-invasive urothelial cancer who were ineligible for or refused neoadjuvant cisplatin-based chemotherapy (NCT02662309). Results of primary and secondary endpoints have been previously published. Here we perform exploratory biomarker analysis using different definitions of ctDNA response and assess correlation with tissue response at time of cystectomy in the ABACUS trial. We also assess how these definitions of response correlate with baseline biomarker expression. Methods: Patients with baseline PDL-1, CD8, TMB and sequential ctDNA measurements (baseline and at cystectomy) were included. ctDNA analysis was performed using the Signatera assay, PD-L1 positivity was defined as ≥5% of immune cell staining, TMB was assessed using the FoundationOne CDx assay and CD8 measurement was performed via immunohistochemistry analyses. Two definitions of ctDNA response were used—ctDNA clearance and a 50% reduction (or greater) in ctDNA variant allele frequency (VAF). Results were correlated with pathological complete response (pCR) rate at time of cystectomy and relapse-free survival. Results: The 2-yr DFS and OS rates in ABACUS were 68% and 77%, respectively (N=95). 40 patients had sequential DNA analysis. 43% (17/40) had pathological complete response and 20% (8/40) experienced relapse. 63% (25/40) patients were ctDNA+ at baseline, with 40% (10/25) having ctDNA response of 50% VAF reduction and 8% (3/40) achieving ctDNA clearance. 30% (3/10) of patients who had VAF reduction experienced relapse and 40% (4/10) achieved pCR. All patients with ctDNA clearance achieved pCR none relapsed. There was no association between VAF reduction of 50% and tissue response (pCR) (p=0.24). Additional analysis showed no association between a ctDNA reduction of 75% (rather than 50%) and pCR (p=0.24). Baseline PDL-1, TMB and not predictive of pathological complete response (p=0.18, p=0.77, p=0.10, respectively) or ctDNA response (p=0.54, p=0.77, p=0.74) to neoadjuvant atezolizumab. There was no difference in relapse rates between ctDNA/PD-L1+ve vs ctDNA+ve/PD-L1-ve patients (16% vs 16%, respectively). Conclusions: ctDNA clearance is rare but appears more accurate than 50% reduction in VAF to predict response/relapse. This is relevant for ongoing neoadjuvant trials planning to use this as an endpoint. Combining immune tissue based biomarkers with ctDNA does not appear to improve biomarker accuracy.
Outcomes in patients (pts) with advanced urothelial carcinoma (aUC) treated with enfortumab vedotin (EV) after switch maintenance avelumab (MAv) in the UNITE study.
Authors: Nizam Amanda , Jindal Tanya , Jiang Cindy Y. , Alhalabi Omar , Bakaloudi Dimitra Rafailia , Talukder Rafee , Davidsohn Matthew P. , Nguyen Charles B , Oh Eugene , Taylor Amy K , Lemke Emily , Kilari Deepak , Hoimes Christopher J. , Emamekhoo Hamid , Gupta Shilpa , Bellmunt Joaquim , Grivas Petros , Campbell Matthew T , Alva Ajjai Shivaram , Koshkin Vadim S 
Published: January 2024

537 Background: MAv is approved in pts with aUC without progression (PD) on 1L platinum-based therapy (PBT). As pts in the pivotal EV trials had not received MAv after PBT, data on outcomes with EV post-MAv are limited. We examined outcomes with EV post-MAv in the multicenter retrospective UNITE study. We hypothesized that outcomes would be similar to published EV data. Methods: Pts who received sequential PBT, MAv, then EV monotherapy were included. Investigator-assessed observed response rate (ORR) was assessed for evaluable pts with scans after ≥ 1 cycle EV using χ2 test and logistic regression. Progression-free and overall survival (PFS, OS) were measured from EV start and assessed using ΚΜ method and Cox proportional hazards model. Results: Among 633 pts at 16 US sites, 49 received PBT and MAv then EV. Median age 72; 63% men; 96% Caucasian; 82% ECOG PS 0/1, 71% lower tract tumor; 65% pure urothelial histology; 71% visceral or bone mets; 33% Bellmunt score (BS) 2-3. In terms of PBT, 67% had cisplatin-based (cis); 26% carboplatin-based (carbo); 6% both cis- and carbo-based therapy. Best response to PBT was CR/PR/SD for 12% / 59% / 29% pts, respectively. Median time from PBT start to EV start was 8.5 months (mo) (3.9-21.2). Median follow up from EV start was 8.5 mo (95%CI 6.7-15.0). ORR to EV was 54%; median PFS and OS were 7.0 mo (95%CI 5.8-13.3) and 13.3 mo (95%CI 10.8-NR). Median PFS2 measured from PBT start until PD after starting EV or death was 17.5 mo (95%CI 15.2-22.5). Median OS from PBT start was 22.5 mo (95%CI 18.6-NR); 29% of pts remained on EV at data cutoff; 43% received subsequent therapy (Tx) after EV with median time to next therapy 6.4 mo (1.8-15.9). Outcomes did not differ among subgroups, except for improved PFS and OS in pts with BS 0-1 vs BS 2-3 (Table). Conclusions: Pts with aUC treated with EV after MAv had outcomes consistent with data for EV in PBT- and checkpoint inhibitor-refractory aUC. These data support the use of EV as third-line Tx after progression on MAv but should be validated in larger cohorts. [Table: see text]
Cost-effectiveness-analysis of different treatment modalities in bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NIMBC).
Authors: Rieger Constantin , Schluechtermann Joerg , Storz Enno , Pfister David A. , Heidenreich Axel 
Published: January 2024

556 Background: Elaborate treatment and repetitive surveillance makes bladder cancer to the most expensive cancer type over the lifetime of a patient with a peak in non-muscle invasive bladder cancer. Radical cystectomy (RC) as the Standard of Care in BCG unresponsive NMIBC is associated with a significant health-related quality-of-life burden (QALY). Gemcitabine/Docetaxel, Pembrolizumab or Hyperthermic Intravesical Chemotherapy (HIVEC) have recently been published as salvage treatment options trying to increase the rate of bladder preservation. Methods: We developed a Markov model from a payer´s perspective with the clinical data of single-arm studies for BCG unresponsive NMIBC (Gemcitabine/Docetaxel and Pembrolizumab) and our clinical data for patients receiving HIVEC (n=29) as intravesical salvage-chemotherapy. Costs were simulated with a non-commercial DRG-grouper, utilities were derived from comparable cost-effectiveness studies. We used a Monte-Carlo Simulation to identify the optimal treatment, comparing the incremental cost effectiveness ratios (ICER) in consideration of a willingness-to pay of 50.000 Euro/QALY. Results: Over a horizon of 10 years, Gemcitabine/Docetaxel, HIVEC and Pembrolizumab were associated with costs of 48.353 64.438 and 204.580 Euro, and QALY´s of 6.16, 6.48 and 6.00, resulting in an ICER of 26.482, 42.567 and 184.533 Euro in comparison to RC (costs: 21.871 Euro; QALY: 5.01). Monte-Carlo Simulation has identified HIVEC as the treatment of choice in the assumption of a WTP of <50.000 Euro. QALY gains in Gemcitabine/Docetaxel and especially HIVEC were mainly driven by bladder preservation and the low rate of progression. Conclusions: Considering a WTP of <50.000 Euro / QALY, Gemcitabine/Docetaxel and HIVEC are highly cost-effective therapy options in BCG unresponsive bladder cancer, while RC remains the cheapest option. At its current price, Pembrolizumab is only cost-effective with a price reduction of 70%.
Evaluating outcomes of sacituzumab govitecan (SG) in patients with urothelial cancer (UC), previously treated with enfortumab vedotin (EV).
Authors: Vlachou Evangelia , Johnson Burles Avner , Hahn Noah M. , Rourke Kelli , McConkey David James , Hoffman-Censits Jean H. 
Published: January 2024

567 Background: SG is an antibody drug conjugate (ADC) FDA approved for treatment refractory UC with Response Rate (RR) of 27%. Many patients (pts) receive SG after disease progression (PD) on EV, another ADC commonly used in earlier lines of therapy. In the TROPHY study, 10/113 pts treated with SG received prior EV and RR was similar to that of the entire cohort. We present a real-world experience in pts treated with SG after EV. Methods: In this retrospective analysis, pts with aUC treated with SG following EV at Johns Hopkins were identified. Demographic and treatment details were extracted by chart review. RR [Complete Response (CR) + Partial Response (PR)] with 95% Confidence Interval (95%CI) were compared between pts who did and did not have response to EV and between subgroups of interest using the χ2 test. Response to EV was defined as physician-assessed CR or PR. Cox proportional hazard model analysis was used for comparing progression free (PFS) and overall (OS) survival for SG between groups. Results: 23 pts were identified, including 10 (43.5%) females and 19 (82.6%) white. Median age was 71.8 years (range: 46.3, 85.4). Primary tumor location was upper tract for 11 (47.8%) pts, lower tract for 11 (47.8%) and 1 pt had tumor in both sites. 11 (47.8%) pts had liver metastasis present at SG initiation. SG was 3rd line treatment for 5 (21.7%) pts and ≥ 4th line for 18 (78.3%). 4 (17.4%) pts had tumors with variant histology. RR for the entire cohort was 17.4%. Reason for discontinuation was PD in 16 (69.6%) pts and toxicity/functional decline in 7 (30.4%). The table summarizes RR in different subgroups. Median PFS for SG was 2.63 months among EV responders and 1.35 months for non-responders [Hazard Ratio (HR): 0.31, 95%CI: 0.12, 0.83, P = 0.02]. Median OS for SG was 5.36 months in EV responders and 5.78 months in non-responders (HR: 0.82, 95%CI: 0.27, 2.46, P= 0.7). No PFS or OS difference was found between subgroups: Upper vs lower tract primary tumor, liver metastasis presence vs absence, variant histology vs pure UC, estimated glomerular filtration rate (eGFR) ≥ 30 mL/min vs < 30. The small sample precluded multivariable analysis. Conclusions: To our knowledge this is the largest real-world cohort of pts with UC treated with SG post EV. A trend towards improved RR and PFS for SG was noted among EV responders. In our analysis clinical outcomes remained consistently similar across all subgroups, including pts with known poor prognosis risk factors. [Table: see text]
Experiences of patients with bladder cancer: A comparison of urban and rural areas.
Authors: Makaroff Lydia , Filicevas Alex , Hensley Patrick J. , Kamat Ashish M. 
Published: January 2024

568 Background: Bladder cancer patients encounter unique challenges and advantages in urban and rural environments, significantly influencing their path from diagnosis to treatment. While numerous studies explore bladder cancer from clinical and therapeutic perspectives, there is a noticeable gap in research addressing patients' experiences based on geographical locale. This study aims to bridge this gap by offering a comparative analysis of urban versus rural experiences. Methods: The World Bladder Cancer Patient Coalition and IQVIA formulated an online survey, designed to capture the multifaceted experiences of bladder cancer patients. Available in various languages, the survey was accessible from October 2021 to February 2022. Responses underwent systematic analysis, with parameters including gender, time since diagnosis, age, region, and disease stage, forming the sub-analytical categories. Results: We received a total of 1,198 responses from 45 countries. Key findings are summarized in the table, highlighting the comparative experiences of urban and rural patients. Conclusions: Significant disparities emerge between urban and rural bladder cancer patients. Rural patients particularly face prolonged diagnosis times, less clear communication from healthcare providers, and experience greater challenges in accessing treatment. These findings underscore the need for a re-evaluation of communication strategies and healthcare infrastructure, especially in rural areas. This research serves as a stepping stone for further investigations aimed at fostering a more patient-centric approach to bladder cancer care. Limitations to consider involve the inherent biases of online survey distribution and the possibility of certain regions being underrepresented. [Table: see text]
Effect of body mass index (BMI) on efficacy of immune checkpoint inhibitors (ICIs) in patients with metastatic urothelial carcinoma (mUC) in a real-world setting.
Authors: Lynn David , Hobeika Charbel , Patgunarajah Ubenthira , Dawsey Scott , Pramod Nikhil , Wei Wei , Nair Monica , Maroli Kimberly , Martin Allison , Ornstein Moshe Chaim , Wee Christopher Eing , Gilligan Timothy D. , Nizam Amanda , Bonham Amanda , Mian Omar Y. , Pavicic Paul G. , Diaz-Montero C. Marcela , Gupta Shilpa 
Published: January 2024

571 Background: There is emerging data on the role of BMI and outcomes of ICIs in various solid tumors, with underweight pts having worse outcomes to ICIs. The effect of BMI on efficacy of ICIs in pts with mUC is not clear. Methods: We identified 335 adult pts with mUC at the Cleveland Clinic treated who received >/= 2 cycles of ICI with pembrolizumab (P) or atezolizumab (A) between 2015 and 2023. Patient characteristics including age, sex, race, primary site (bladder vs upper tract UC (UTUC)), tumor histology and pre-ICI treatment NLR values were collected. BMI was calculated and values were collected and compared to assess impact on overall (OS) and progression free survival (PFS) after ICI start date. BMI was broken down into four categories: underweight (BMI less than 18.5 kg/m2), normal weight (BMI between 18.5 and 24.9 kg/m2), obese (BMI 30 kg/m2 or greater) and overweight (BMI between 25 and 29.9 kg/m2). OS and PFS were estimated by Kaplan Meier method and compared using log rank test. Results: Median age of pts was 73 yrs (35-95) and 254 (76%) pts were males. 247 (74%) received P, 88 (26%) received A. We found that underweight pts had significantly worse OS compared to normal or higher BMI (2.32 vs 13.08 mos; p=0.001) as well a significantly worse PFS (1.61 vs 4.75 mos; p=0.02) (Table). Conclusions: In our large real-world cohort of pts with mUC receiving ICI, we report for the first time the effect of BMI on outcomes with ICI. Further prospective studies are warranted. [Table: see text]
Comparative cost-effectiveness of trimodal therapy and radical cystectomy for management of muscle-invasive bladder cancer.
Authors: Joyce Daniel D. , Wymer Kevin , Boorjian Stephen A. , Gore John L. , Khaki Ali Raza , Raldow Ann Caroline , Williams Stephen B. , Smith Angela B. , Sharma Vidit 
Published: January 2024

572 Background: Bladder preservation with trimodal therapy (TMT), which consists of maximal transurethral resection of bladder tumors followed by chemoradiation, is now included in guidelines with radical cystectomy (RC) as options for definitive management of muscle-invasive bladder cancer (MIBC). Prospective randomized controlled trial data to help guide treatment selection are lacking, and prior efforts to bridge this knowledge gap have failed primarily due to poor accrual. A recent retrospective analysis comparing TMT to RC reported similar oncologic outcomes between these treatments when performed in highly selected patients. However, treatment toxicities and costs vary significantly between these management options. To investigate the impact of these outcomes on relative treatment value, we evaluated the comparative cost-effectiveness of TMT and RC for treatment of MIBC. Methods: Cost-effectiveness was compared between TMT and RC for patients with a solitary, muscle-invasive tumor less than 7cm, no or unilateral hydronephrosis, limited carcinoma in situ, and adequate bladder function (criteria utilized in a recent retrospective comparative series) using a microsimulation model with a 5-year horizon from a Medicare payer perspective. Additionally, a 10-year lifetime horizon was evaluated to better understand the impact of long-term outcome uncertainty on cost-effectiveness. Based on recently published multicenter retrospective propensity score matched data, metastatic progression and survival probabilities were assumed to be equivalent between treatments. Utility values and additional probabilities, including both short and long-term treatment toxicities, were obtained from published literature. Primary outcomes of interest included effectiveness measured in quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER) using a willingness-to-pay threshold of $100,000/QALY. One-way and probabilistic sensitivity analyses were performed to assess the robustness of the model. Results: At 5 years, the average cost was $32,286.35 higher for TMT versus RC. The average QALYs were 3.88 and 3.96 for RC and TMT respectively. TMT was not cost-effective at 5-year (ICER: $379,917.21/QALY) or 10-year (ICER: $222,704.78/QALY) time horizons. On one-way sensitivity analyses, TMT would become cost effective if: 1) TMT costs were less than $16,152; or 2) TMT resulted in a 13.3% improvement in metastasis free survival relative to RC. Conclusions: Although it resulted in similar quality and duration of life, TMT was not cost-effective relative to RC at 5 and 10 years given higher treatment costs. These findings support the role of both TMT and RC in management of MIBC and highlight the need for continued efforts to reduce healthcare costs associated with TMT.
Outcomes with neoadjuvant chemotherapy in bladder-preserving treatment for MIBC.
Authors: Glover Michael , Ewongwo Agnes , Usoz Melissa , Kornberg Zachary , Bagshaw Hilary , Shah Jay Bakul , Shah Sumit , Qian Yushen 
Published: January 2024

577 Background: Trimodality bladder preservation is an acceptable alternative to radical cystectomy (RC) for muscle invasive bladder cancer (MIBC). Multiple retrospective studies have reported similar disease control rates and overall survival rates with chemoradiation (CRT), but the benefit of neoadjuvant chemotherapy (NAC) prior to CRT is not established. This study investigates the outcomes of CRT with or without NAC for management of MIBC. Methods: Retrospective analysis of 135 adult patients with muscle invasive bladder cancer evaluated in the Department of Radiation Oncology over 7 years (2016-2022). Patients were excluded if they did not receive NAC or if they underwent RC. Patients were treated with NAC followed by CRT. Overall survival (OS), progression-free survival (PFS), and metastasis-free survival (MFS) were calculated using Kaplan-Meier methods. Follow-up was censored at 36 months after treatment. Differences in survival outcomes by completion of status of NAC were analyzed using log-rank tests. All survival analyses were performed in SAS version 9.4. Results: Of the 135 evaluated patients, 38 were treated with NAC followed by CRT. The 24-month OS, PFS, and MFS were 76% [95% CI 62-92%], 60% [95% CI 46-79%], and 72% [95% CI 58-90%] respectively. The 24-month PFS in patients who received a full course of NAC was 66.0% [95% CI 50-87%]) and 38.0% [95 CI 15-92%] in those who did not complete NAC regimen. Overall PFS was significantly higher in the NAC cohort (log-rank p=0.03). There was no significant difference in OS between patients who completed prescribed course of NAC versus those who did not (log-rank p=0.48). Treatment was overall well tolerated with 28.2% of grade 2 or higher RT toxicity. Conclusions: NAC prior to CRT achieved excellent short term disease-free and survival outcomes in patients with non-metastatic MIBC. This analysis is limited by its retrospective nature but suggests that completion of NAC prior to CRT may be associated with lower rates of disease recurrence. [Table: see text]
Development of a novel machine learning-based predictive risk calculator for radical cystectomy.
Authors: Rajagopalan Aravind , Chua Kevin J. , Patel Hiren V. , Pfail John , Kaldany Alain , Fu Melinda , Elsamra Sammy , Jang Thomas L. , Pitt Henry , Ghodoussipour Saum 
Published: January 2024

578 Background: Radical cystectomy (RC) is a standard treatment for patients with muscle invasive and certain high-risk non-invasive bladder cancers. Existing clinical risk calculators based for RC on standard regression methods have demonstrated poor, inaccurate predictions of post-operative risks and adverse outcomes. We aimed to build a risk calculator using novel machine learning methods to predict complication rates and other outcomes based on clinical characteristics of patients undergoing RC. Methods: Patients who had an RC for bladder cancer between 2019 and 2021 were pulled from the National Surgical Quality Improvement Database. Potential predictors included clinically meaningful characteristics such as patient demographics, pre-operative labs, comorbidities, pre-operative bowel and antibiotic preparations, and prior treatment history, as well as cystectomy-specific characteristics such as diversion type and surgical approach. Outcomes included risk of any complication, infectious complication, mortality, and readmissions. Logistic regression, random forest, and support vector machine algorithms were used to build predictive models. Models were optimized assessed with area under the ROC curve (AUROC) and average precision (AP). Results: 8,936 patients were included in the sample dataset. Random forest classifiers outperformed other models for predicting risk of any complication (AUROC = 0.662; AP = 0.66), infectious complication (AUROC = 0.615; AP = 0.20), and mortality (AUROC = 0.603; AP = 0.03). The logistic regression model best predicted readmissions (AUROC = 0.587; AP = 0.26). Top predictors of complication risk included operation time, glomerular filtration rate, and type of procedure (robotic vs. open). Infectious complication was best predicted by wound classification and diversion type, mortality was best predicted by BMI and operation time, and readmissions was predicted most by pre-existing renal failure and emergent cases. Conclusions: Machine learning-based risk calculators were more effective in predicting morbidity and mortality after RC compared to more standard predictive algorithms. Machine learning algorithms therefore demonstrate greater predictive potential when given a wide range of clinical characteristics. [Table: see text]