bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncologic outcomes in patients with residual invasive upper tract urothelial carcinoma following neoadjuvant chemotherapy.
Authors: Fletcher Sean A. , Pallauf Maximilian , Watts Emelia K. , Lombardo Kara A. , Campbell Jack A. , Mari Andrea , Rouprêt Morgan , Boorjian Stephen A. , Djaladat Hooman , Kikuchi Eiji , Soria Francesco , Rink Michael , Raman Jay D. , Abdollah Firas , Ploussard Guillaume , Hoffman-Censits Jean H. , McConkey David James , Shariat Shahrokh F. , Pradere Benjamin , Singla Nirmish 
Published: March 2023

475 Background: Emerging evidence supports use of neoadjuvant chemotherapy (NAC) prior to radical nephroureterectomy (RNU) for appropriately selected patients with upper tract urothelial carcinoma (UTUC). However, oncologic outcomes have not been well characterized for patients with residual muscle-invasive disease after NAC. Methods: We used a multi-institutional cohort from 24 centers in the U.S., Europe, and Japan to retrospectively identify patients who underwent RNU for UTUC from 1985-2022 and had high-grade muscle-invasive disease. We stratified the cohort based on receipt of NAC (>ypT2 vs. >pT2). Exclusion criteria included receipt of adjuvant chemotherapy, concurrent cystectomy with RNU, and distant metastatic disease. Baseline characteristics were compared between groups. Kaplan-Meier survival analysis with log-rank test was used to compare differences in recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS). Multivariable Cox regression and Fine-Gray competing risk regression were used to determine predictors of these outcomes. Results: A total of 1,233 patients were included, 62 of whom received NAC prior to RNU. A platinum-based regimen was used in 90% of NAC recipients, and the median number of cycles administered was 4 (IQR: 3-5). Median follow-up time among all patients was 22 months (IQR: 8-47 mo.). NAC recipients were more likely to have pathologic node positivity (35% vs. 13%) and less likely to have positive tumor margins (8% vs. 28%). On Kaplan-Meier analysis, NAC recipients with residual >ypT2 disease had poorer outcomes than those with >pT2 disease (2-year RFS [NAC vs. no NAC]: 52% vs. 80%, p<0.001; 2-year OS: 60% vs. 78%, p=0.003; 2-year CSS: 61% vs. 86%, p<0.001). Multivariable analyses also showed a statistically significant association between residual muscle-invasive disease after NAC and poorer RFS, OS, and CSS (Table). Conclusions: NAC recipients with >ypT2 disease at RNU after exhibit poorer outcomes than stage-matched chemotherapy naïve counterparts. This may reflect effects of occult micrometastatic disease or chemoresistant primary tumors in non-responders. Our data highlight the need to improve prospective identification of candidates most likely to respond to NAC prior to RNU for UTUC in order to maximize its therapeutic benefit. [Table: see text]
Chemotherapy, immunotherapy, or combination first-line treatment for metastatic urothelial carcinoma of the bladder: A large real-world experience.
Authors: Ranganathan Sanjana , Riveros Carlos , Xu Jiaqiong , Geng Michael , Huang Emily , Anis Maryam , Muhammad Taliah , Zhang Jun , Efstathiou Eleni , Wallis Christopher J.D. , Sonpavde Guru P. , Satkunasivam Raj 
Published: March 2023

477 Background: First-line therapy for metastatic urothelial carcinoma of the bladder (mUC) consists of platinum-based chemotherapy in most patients and PD1/L1 inhibitors in selected patients. Multiple combination chemo-immunotherapy trials failed to show a clear benefit over chemotherapy alone. We sought to use real-world data to evaluate clinical and sociodemographic factors associated with receipt of first-line chemotherapy, immunotherapy or combination chemo-immunotherapy treatment for metastatic bladder cancer and examined differences in overall survival (OS). Methods: We used the National Cancer Database to identify patients with stage IV UCB diagnosed between 2014 and 2018, who were treated with first-line immunotherapy, chemotherapy, or combination treatment. We performed multivariable logistic regression modeling to determine factors associated with treatment receipt. An extension of inverse probability treatment weighting (IPTW) obtained from multinomial logistic regression was used to balance clinical and sociodemographic differences between treatment groups. Adjusted Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression were used to evaluate the association between treatment and OS. Results: A total of 4,169 patients were identified in the cohort; 3,255 (78.1%) were treated with chemotherapy, 601 (14.4%) with immunotherapy, and 313 (7.5%) with combination treatment. Multivariable analysis identified increasing age (RRR: 1.07, 95% CI, 1.06-1.08), comorbidity burden (Charlson-Deyo 2, RRR: 1.65, 95% CI, 1.21-2.24 and Charlson-Deyo 3, RRR: 2.11; 95% CI, 1.51-2.93), and treatment at an academic facility (RRR: 1.26; 95% CI, 1.03-1.53) as independent predictors of receiving immunotherapy. Treatment at an academic facility (RRR: 1.29, 95% CI, 1.01-1.65) was associated with receipt of combination treatment. After IPTW, we found that combination therapy (hazard ratio [HR]: 0.72; 95% CI, 0.62-0.83), but not immunotherapy alone, was associated with improved survival compared to chemotherapy. These data are limited by inability to determine platinum eligibility, and residual confounding. Conclusions: Patients with older age and more comorbidities were more likely to receive immunotherapy than chemotherapy for first-line treatment of metastatic urothelial carcinoma of the bladder. Modest real-world utilization of chemo-immunotherapy was observed to be higher in academic centers and was associated with improved survival compared to chemotherapy. The study is limited by retrospective design; prospective data are necessary to identify patients who may benefit from combination chemo-immunotherapy.
Economic impact of bladder cancer (BC) in the United States (US).
Authors: Clark Otavio , Sarmento Tulio , Eccleston Anthony , Brinkmann Julia , Picoli Renato , Daliparthi Vamsi , Voss Jorine , Chandrasekar Sanjana , Thompson Allison , Chang Jane 
Published: March 2023

479 Background: Incidence and mortality for BC has changed very little over the past 20 years. Approximately 40% of patients with high-risk non-muscle invasive BC eventually recur/progress. It is important to understand the economic impact of disease recurrence/progression in BC. Methods: An economic model was constructed to calculate the number of patients receiving each treatment modality at every stage of disease and their respective costs. Epidemiological data was based on the CancerMPact Patient Metrics (PM) database, and treatment modality data retrieved from CMP Treatment Architecture (TA), 2021 version. Resource utilization and costs were obtained from the medical literature and public data sources. Only direct costs were considered. Results: There were an estimated 83,532 newly diagnosed BC patients of all stages in 2021 with a projected total cost of treatment of $2,584,783,728. Average cost per patient varied from $19,521 (stage 0a) to $169,533 (metastatic disease) (Table). Cost profile differed substantially among the stages of disease. For the 75,760 patients that were expected to have a recurrence in 2021, an additional cost of $3,953,096,316 was estimated at an average cost per patient of $52,179. The expected total cost to treat newly diagnosed and newly recurrent patients is reported in this model, with the total cost in 2021 estimated to exceed $6.5 billion. Conclusions: Treatment and resource costs increase for BC as the disease recurs/progresses. More effective treatments earlier in the disease setting to delay recurrence/progression may reduce the economic burden associated with BC. [Table: see text]
Impact of 68Ga-PSMA PET/CT in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide.
Authors: Altavilla Amelia , Caroli Paola , Giunta Emilio Francesco , Scarpi Emanuela , Rossetti Virginia , Casadei Chiara , Lolli Cristian , Schepisi Giuseppe , Bleve Sara , Cursano Maria Concetta , Gasperoni Lorenzo , Matteucci Federica , De Giorgi Ugo 
Published: March 2023

48 Background: 68Ga prostate specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) is a highly sensitive diagnostic tool to detect prostate metastatic sites even at low levels of Prostate Specific Antigen (PSA). We evaluated the impact of 68Ga-PSMA PET/CT in patients treated with enzalutamide as first-line therapy for mCRPC. Methods: In an observational prospective study, 67 consecutive mCRPC patients were treated with enzalutamide 160 mg once daily in first-line for mCRPC. 68Ga-PSMA PET/CT was performed at baseline, after 3 months, during follow-up and at PSA/clinical progression. Patients were evaluated on a monthly basis for serological PSA response and safety. We measured at baseline the sum of metabolic total volume (SMTV), mean standardized uptake volume (SSUVmean), maximum standardized uptake volume (SSUVmax) and total lesion activity (STLA), which is the product of SMTV and SSUVmean, for a maximum of 20 lesions. These parameters together with baseline PSA level, Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason Score (GS) and age were analyzed by univariate and multivariate Cox regression models as potential predictors of progression-free survival (PFS) and overall survival (OS). Results: At the moment of the present analysis, 58 mCRPC patients were considered fully evaluable. The median age was 75 years (range, 47-91), ECOG PS was 0 in 47 cases (81%), 1-2 in 11 (19%), GS was <8 in 22 (38%), 8-10 in 36 (62%), the median baseline PSA was 2.66 µg/L (range 0.09-197). We observed a median SMTV of 5.73 cm3, median SSUVmax of 44.85, median SSUVmean of 25.80 and median STLA of 59.66. At the median follow-up of 52 months, median PFS was 28.9 months (95% CI 16.3-43.6), median OS was not reached (95% CI 36.8-not reached). In univariate analysis, SSUVmax and STLA were significant for PFS (p=0.015 and p=0.001, respectively) and OS (p=0.026 and p=0.019, respectively), while SSUVmean was significant only for OS (p=0.028). On multivariate analysis, STLA only remained significant for PFS (p<0.001) and OS (p=0.026). Conclusions: The assessment of mCRPC by 68Ga-PSMA PET/CT before starting enzalutamide was associated with longer median PFS and OS compared to prior studies using standard imaging only. STLA, expression of both volume and intensity of 68Ga-PSMA uptake, appeared the strongest parameter able to predict PFS and OS.
Surgery for urologic cancers after SARS-CoV-2 infection: Adverse outcomes and optimal delay.
Authors: Flitcroft Madelyn Anne , Verhagen Nathaniel , Shah Nayan , Johnson Scott , Kothari Anai 
Published: March 2023

484 Background: Perioperative SARS-CoV-2 infection has been associated with increased adverse outcomes. Research conducted early in the COVID-19 pandemic suggested an 8 week delay after SARS-CoV-2 infection prior to undergoing surgery. The aim of this study is to determine if prior COVID-19 infection is an independent risk factor for adverse outcomes following surgery for urologic cancers. A secondary objective was to determine the optimal duration to delay surgery, specifically cystectomy, prostatectomy, or nephrectomy, after COVID-19 infection. Methods: Data from the National COVID Cohort Collaborative (N3C) data enclave was used to conduct this retrospective cross-sectional study. Patients with cancer diagnoses that underwent surgery for urologic cancers after January 2020 were included in the analyses. Urologic surgeries were queried using standard SNOMED concepts corresponding to cystectomy, nephrectomy, and prostatectomy. Patients were assessed for adverse postoperative events that were defined using standard SNOMED clinical concepts. COVID-19 positive patients were identified via the N3C Knowledge Store using positive lab measurement or a positive SARS-CoV-2 diagnosis. Analyses were conducted in the N3C data enclave. Results: The study cohort included 38,974 total patients with 15,216, 14,778, and 8,980, undergoing cystectomy, prostatectomy, and nephrectomy, respectively. 2,807 had a history of COVID-19 infection greater than 20 days prior to surgery. Prior history of COVID-19 was independently associated with adverse outcomes for cystectomy (OR 1.21 [1.03-1.43], p<0.05) and nephrectomy (OR 1.27 [1.06-1.52], p<0.05), but not prostatectomy (OR 1.14 [0.95-1.36]). Multivariable regression assessing time to surgery and risk for any adverse events, did not reveal significant benefit to waiting greater than 20 days after COVID-19 infection to operate. Conclusions: Patients with known prior COVID-19 infection who underwent surgical treatment of urologic cancers experienced increased risk of adverse surgical outcomes. Among this group, those who delayed surgery greater than 20 days after infection did not demonstrate decreased risk of these negative outcomes across the procedures studied. Optimal surgical delay in the treatment of urologic cancers after COVID-19 infection does not appear to be greater than 20 days.
Patient-reported outcomes for patients with locally advanced or metastatic urothelial carcinoma under pembrolizumab: A prospective multicenter observational study.
Authors: Annakib Soufyan , Dibert Bekoy Yona , Chevallier Thierry , Fiteni Frédéric , Houede Nadine 
Published: March 2023

490 Background: Evaluation of Patient-Reported Outcomes (PROs) is a major element used by health authorities for treatment approval. Pembrolizumab is a validated second-line treatment for locally advanced or metastatic urothelial carcinoma (la/mUC). In this real-life study, we aimed to describe la/mUC patients’ health-related quality of life (HRQoL) and patient/clinician-reported symptoms before and after pembrolizumab initiation. Here, we present interim results to assess clinical relevance for further analysis. Methods: A multicenter prospective French study was designed. PROs were assessed before pembrolizumab initiation (baseline) and at each treatment visit for seven timepoints. We report the analyses of the first three timepoints. HRQoL was measured using the European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire-Core 30 (EORTC QLQ-C30) and the EuroQoL 5-dimensions 5-level (EQ-5D-5L) questionnaires. PRO-Common Terminology Criteria for Adverse Events (PRO-CTCAE) and CTCAE were assessed for 20 selected symptoms by both patients and clinicians in a blinded manner. Agreement in severity between clinicians and patients for all grade ≥3 symptoms was calculated with Cohen's kappa coefficient. Results: 39 patients were analyzed. Baseline completion rates were 69%, 62%, 59% and 12.8% for EORTC QLQ-C30, EQ-5D-5L, PRO-CTCAE and CTCAE respectively. Baseline median EORTC QLQ-C30 global health and summary scores were respectively 66.7 [interquartile range; 54.2, 79.2] and 83.6 [73.9, 94]. Improvement in EORTC QLQ-C30 global health median score to cycle 2 was observed in 33.3% patients, while the remaining patients experienced worsening score. Baseline mean EQ-5D-5L Visual Analog Scale score was 65.3 (Standard deviation (SD), 21.6), and 63.5 (SD, 16.1) at cycle 2. EQ-5D-5L domains scored level 1 decreased between baseline and cycle 2 for mobility (16 vs 14 patients) (p=0.0143), self-care (16 vs 14 patients) (p=0.0048), and usual activities (15 vs 14 patients) (p=0.015). Of 17 severity assessed symptoms, the Cohen's kappa coefficient was fair ĸ=0.35 (95% confidence interval (CI) [-0.08; 0.78]) for general pain, and bad ĸ=-0.063 (95%CI [-0.17; -0, 04]) for abdominal pain. In terms of symptom frequency, patients reported 19 symptoms at each visit. However, clinicians reported 13 and 14 symptoms respectively at baseline and cycle 2. Conclusions: HRQoL for la/mUC patients after first pembrolizumab infusion showed contradictory results with previous reports with a trend for HRQoL degradation after one treatment cycle. Comparative symptom severity assessment showed poor agreement between patients and clinicians. Clinicians graded symptoms less severely than patients. The final analysis will provide more complete data with longitudinal analysis to strengthen our preliminary conclusions. Clinical trial information: NCT03584659 .
Early efficacy results from atezolizumab (ATZ) with split doses of cisplatin plus gemcitabine in patients with locally advanced or metastatic urothelial carcinoma (SOGUG-AUREA).
Authors: de Velasco Guillermo , García-Carbonero Iciar , Esteban-Gonzalez Emilio , Pinto Alvaro , Lorente David , Gomez De Liano Lista Alfonso , Martínez Ortega Esther , Jimenez Colomo Laura , Puente Javier , Gonzalez Iria , Fernandez-Calvo Ovidio , Anguera Georgia 
Published: March 2023

502 Background: Urothelial carcinoma (UC) commonly affects patients (pts) who are ineligible for full doses of cisplatin-based chemotherapy (CT) due to bad performance status, advanced age, or renal impairment. The combination of split-dose cisplatin with ATZ might be a feasible treatment for pts with UC who are unfit for full doses of cisplatin. Methods: The phase II SOGUG-AUREA clinical trial recruited treatment-naive pts in advanced or metastatic settings considered unfit for full dose of platinum-based CT. Pts received a split dose of cisplatin (35 mg/m2) and gemcitabine (1000 mg/m2) days 1 and 8 (up to 6 cycles) in combination with 3-weekly ATZ 1200 mg in D1 intravenously until progression, unacceptable toxicity, or absence of clinical benefit. Here we present the early results from the confirmed objective response rate (ORR) according to RECIST 1.1, the primary endpoint for efficacy, progression-free survival (PFS), overall survival (OS) and safety. Results: Between Jan 2021 and Mar 2022, 82 pts were screened, 66 pts were enrolled and received at least one dose of study treatment. Baseline characteristics are outlined in the table. The median duration of ATZ treatment was 4.4 months (m) (95%CI: 4.1-4.6). The confirmed ORR was 40.9%, with 5 (7.6%) pts having CR and 22 (33.3%) PR. The median duration of the response was 7 m (95%CI: 4.9-10.4). The clinical benefit rate (CBR) was 53%, and SD (maintained > 6m) was reported in 8 (12.1%) pts. Eight (12.1%) pts were not evaluable for response due to exitus previous to disease evaluation (9.1%), non measurable target lesions (1.5%) or withdrawal (1.5%). With a median follow-up of 9.3 m (range: 0.6-18.1), the median PFS was 6.9 m (95%CI: 6.4-9.2), with a 6-m PFS rate of 67.1% (95% CI: 56.5-79.7). The reasons for platinum ineligibility did not correlate with PFS. The 6-m OS rate was 78.2% (95%CI: 68.6-89). Most frequent grade 3-4 toxicities were neutrophil count decreased (24.2%), anemia (21.5%) and platelet count decreased (13.6%). Conclusions: ATZ with split doses of CT was safely administered in a population of frail pts with mUC who were unfit for CT showing promising preliminary survival outcomes in terms of response. Final survival results are awaited. Clinical trial information: NCT04602078 . [Table: see text]
Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Long-term follow-up from the JAVELIN Bladder 100 trial in subgroups defined by 1L chemotherapy regimen and analysis of overall survival (OS) from start of 1L chemotherapy.
Authors: Sridhar Srikala S. , Powles Thomas , Gupta Shilpa , Climent Miguel Ángel , Aragon-Ching Jeanny B. , Sternberg Cora N. , Cislo Paul , Costa Nuno , Di Pietro Alessandra , Bellmunt Joaquim , Grivas Petros 
Published: March 2023

508 Background: For platinum-eligible patients (pts) with advanced UC, 1L cisplatin- or carboplatin-based chemotherapy regimens followed by avelumab maintenance in pts without progression has become the standard of care. This is based on the results of the phase 3 JAVELIN Bladder 100 trial (NCT02603432), which showed significantly longer OS and progression-free survival (PFS) from start of maintenance (randomization) with avelumab maintenance + best supportive care (BSC) vs BSC alone (median OS, 23.8 vs 15.0 months; HR, 0.76 [95% CI, 0.63-0.91]; p=0.0036). We report post hoc analyses of long-term outcomes by 1L chemotherapy regimen and OS from start of 1L chemotherapy. Methods: Pts with unresectable locally advanced or metastatic UC that did not progress with 4-6 cycles of 1L cisplatin + gemcitabine or carboplatin + gemcitabine were randomized 1:1 to receive avelumab + BSC (n=350) or BSC alone (n=350). The primary endpoint was OS measured from randomization. Secondary endpoints included PFS and safety. Results: At data cutoff (June 4, 2021), median follow-up from randomization was ≥38 months in both arms. In subgroups treated with 1L cisplatin + gemcitabine or carboplatin + gemcitabine, OS and PFS (measured from start of maintenance [randomization]) were longer in the avelumab + BSC arm than in the BSC alone arm (Table). Safety findings were similar in both subgroups. In the overall population, median OS measured from the start of 1L chemotherapy was 29.7 months (95% CI, 25.2-34.0) in the avelumab + BSC arm and 20.5 months (95% CI, 19.0-23.5) in the BSC alone arm (HR, 0.77 [95% CI, 0.635-0.921]). Conclusions: Long-term follow-up from the JAVELIN Bladder 100 trial confirms that avelumab 1L maintenance provides similar OS and PFS benefits in pts with advanced UC who are progression free following standard-of-care 1L cisplatin- or carboplatin-based chemotherapy, with an acceptable safety profile. The median OS measured from start of chemotherapy further supports the use of avelumab 1L maintenance as standard of care in this setting and provides a benchmark for future clinical trials. Clinical trial information: NCT02603432 . [Table: see text]