bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time to event following bacillus Calmette-Guerin therapy initiation in Medicare beneficiaries with intermediate- to high-risk non-muscle invasive bladder cancer, 2010-2019.
Authors: Petrilla Allison A. , Silverstein Alison R. , Eccleston Anthony , Thompson Allison , Brinkmann Julia , Bello Temitope , Chang Jane , Cappelleri Joseph C , Chandrasekar Sanjana , Schroeder Amy L 
Published: March 2023

473 Background: For patients with intermediate- to high-risk non-muscle invasive bladder cancer (NMIBC), standard of care includes transurethral resection (TURBT) followed by induction and maintenance intravesical immunotherapy with Bacillus Calmette-Guerin (BCG). This study describes characteristics and clinical outcomes of Medicare beneficiaries newly diagnosed with NMIBC who initiated BCG therapy following TURBT. Methods: Retrospective cohort study using Centers for Medicare and Medicaid-sourced Medicare Fee-for-Service medical/pharmacy claims (100% sample). Patient selection criteria: ≥1 bladder cancer diagnosis 2010-2019, no prior radiotherapy, systemic therapy, cystectomy, or metastasis in 6 months post-diagnosis, continuously enrolled in Medicare ≥12 months pre- and post-index (or death). Index date = date of first BCG instillation. A literature-based definition for adequate maintenance BCG defined adequate (≥7 instillations of BCG within 274 days of BCG initiation) and inadequate (remainder) BCG therapy for patient stratification. Events: time to BCG discontinuation, radical cystectomy, systemic therapy, radiation, and metastasis. Provider access to BCG (due to supply shortage), patient tolerability, and NMIBC risk status are not captured in claims data. Results: Of 46,052 BCG-treated patients eligible for analysis, 19,859 (43.1%) received adequate BCG therapy. The two cohorts had similar baseline characteristics (Table) and median duration of follow up (46 months). Median (interquartile range [IQR]) time from NMIBC diagnosis to BCG initiation was 2.8 (8.2) months for adequate, 3.7 (14.4) months for inadequate BCG. Time from BCG initiation to discontinuation, radical cystectomy, systemic therapy, radiation, and metastasis are reported in the table. Conclusions: Between 2010 and 2019, 57% of Medicare patients initiating BCG following diagnosis of NMIBC and TURBT may not have received adequate BCG therapy. Patients with inadequate BCG therapy had numerically shorter time to radical cystectomy, systemic therapy, radiation, and metastasis than those with adequate BCG therapy. Characteristics & Outcomes by Cohort. [Table: see text]
Neoadjuvant chemotherapy plus radical cystectomy (NAC-RC) versus trimodality therapy (TMT) in early-stage small cell bladder cancer: Comparison of outcomes.
Authors: Jatwani Karan , Roy Arya Mariam , Attwood Kristopher , George Anthony , Perimbeti Stuthi , Jiang Changchuan , Faisal Muhammad Salman , Muthusamy Kumarasamy Vasanthan , Chatta Gurkamal S. , Gopalakrishnan Dharmesh 
Published: March 2023

476 Background: Small cell bladder cancer is a rare and aggressive histological variant with a paucity of data to guide the optimal management strategy in non-metastatic disease. NAC-RC and TMT (maximal transurethral resection of bladder tumor + chemoradiation) have been variably employed based on institutional preferences, and we aim to compare outcomes between these two approaches. Methods: We queried the National Cancer Database for adult patients with small cell bladder cancer diagnosed during the years 2004 to 2018. Patients with small cell histology and early-stage clinically node-negative bladder cancer (cT1-4N0M0) were included and divided into two groups based on the treatment strategy employed – NAC-RC or TMT. Patients who did not receive any definitive local therapy and those who received chemotherapy or radiation in the adjuvant setting were excluded. Fisher’s exact and Mann Whiney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed for multivariate analysis of factors associated with overall survival. Models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 1262 patients were identified – 629 (49.8%) underwent NAC-RC while 633 (50.2%) received TMT. Patients in the NAC-RC group were younger (median 67 vs. 74 years, P <0.001) and more frequently Males (81% vs 76%, p = 0.02). Clinical T stage was comparable between the groups (P = 0.38). Patients with private insurance (P < 0.001) and higher income tiers (P = 0.04) were more likely to receive NAC-RC in lieu of TMT. Overall survival in the NAC-RC group was significantly longer than the TMT group (median of 41.3 vs. 25.4 months, log-rank P < 0.001). On multivariable analysis, only the type of treatment modality employed was independently predictive of overall survival (Hazard Ratio of 1.22 for TMT, with 95% CI 1.05-1.43, P = 0.01). Conclusions: In early-stage clinically node-negative small cell bladder cancer, NAC-RC was associated with significantly longer overall survival compared to TMT.
Comparison of objective response rate and long-term overall survival in patients with treated immune checkpoint inhibitors in metastatic urothelial carcinoma.
Authors: Tural Deniz , Arslan Cagatay , Selcukbiricik Fatih , Olmez Omer Fatih , Akar Emre , Erman Mustafa , Ürün Yüksel , Erdem Dilek , Kilickap Saadettin 
Published: March 2023

481 Background: In this study, we evaluated RECIST criteria-based objective response rate (ORR) as potential surrogate endpoints for overall survival (OS) in patients who were treated with immune checkpoint inhibitors therapy (ICT) and with long-term follow-up in metastatic urothelial carcinoma. Methods: The primary endpoint was overall ORR and OS, duration of treatment (DOR) with ICT. ORR was analyzed using Fisher’s exact test. Median follow-up and OS were estimated by using the Kaplan-Meier method. Results: The median follow-up time was 58 (1.15–71) months (mo). Progression developed in 94 (47%) patients during the first three months of treatment with ICT. The rate of complete response (CR) to ICT, partial response (PR) rate, and stable disease were 10% (n=20), 23% (n=46), and 20% (n=41), respectively. There was an imbalance in baseline characteristics between patients who had ORR and non-responder groups (Table). The 5–year OS rates for CR and PR were 73% and 23%, respectively. The median DOR for CR, PR, and SD were 51.8 mo% (44.5–59.1), 20.7mo (16.7–24.6), and 8.8 mo (5.5–12.1), respectively. Of the sixteen (80%) patients who had CR and 14 (30%) patients who had PR had an ongoing response at the time of the analysis. In univariate analysis, neutrophil-to-lymphocyte ratio (NLR) >3, liver metastases, ECOG PS ≥1, and hemoglobin levels below 10 mg/dl, PR, and CR were all significantly associated with OS. In multivariate analysis, liver metastases [HR=2.3; 95% CI 1.3-4.2; p < (0.004)] were independent related variable with short OS. Other hand, PR [HR=0.3; 95% CI 0.15-0.5; p < (0.001)] and CR [HR=0.06; 95% CI 0.014-0.27; p < (0.001)] were associated with improved OS. Conclusions: This five-year analysis of real-world data indicated a significant correlation between ORR, especially CR and OS in patients who received immune checkpoint inhibitors in metastatic urothelial cancer. Therefore, the identification of a potential surrogate marker for survival in patients treated with ICT would represent an important advance in the early identification of patients’ response or resistance to ICT.
Occurrence and prognostic significance of different histology relative to urinary tract tumors: A SEER population-based study.
Authors: Liu Haoyang , Chen Junru , Liu Zhenhua , Shen Pengfei , Zeng Hao 
Published: March 2023

485 Background: To evaluate the prevalence and prognostic value of variant histology in urinary tract tumors according to primary location and metastatic status. Methods: Using the Surveillance, Epidemiology, and End Results registry (SEER, 2004-2015) databases, patients with urinary tract tumors were identified. Propensity Score Matching was used to balance the clinicopathologic features between different histologies. Kaplan-Meier plots were used to compare the cancer specific survival (CSS) and overall survival (OS) of different histologies. The cox regression analysis were also applied. Results: Of all 93,200 eligible patients with urinary tract tumors, 87,323 (93.7%) harbored bladder cancer (3,685 in M1 stage). Among them, urothelial tumors (UC) accounted for 96.67%, followed by squamous neoplasm (SCC), urachal carcinoma (Urachal), adenocarcinoma (Adeno), neuroendocrine tumors (NE) and tumor of Müllerian type (Müllerian). A total of 5877 (6.35%) harbored upper urinary tract tumors (950 in M1 stage). Among them, UC accounted for 96.39%, followed by SCC, Urachal, Müllerian, NE, Adeno. In patients with localized diseases, those with non-urothelial tumors had significantly worse prognosis in overall urinary tract tumors based on OS and CSS (P<0.001). In terms of specific histology in bladder cancer (BC), patients with UC had most favorable prognosis, followed by Adeno, Urachal and Müllerian, while those with SCC and NE were associated with the worst survival outcomes. In patients with upper urinary tract tumors (UUTT), those with Müllerian had the best survival outcomes, followed by UC, while those with NE, Adeno, SCC, and Urachal had relatively worse prognosis. In M1 stage, although there was a statistical difference in OS and CSS between all patients with urothelial and non-urothelial tumors (P<0.001), the 5-year survival rate (3.74%, 2.50%) and 5-year CSM (4.93%, 3.28%) were similar. In metastatic BC, there was no difference in OS among all histology. However, in terms of CSS, significant differences were still observed in patients with different histologies. In metastatic UUTT, no difference in survival was found among different histologies. After PSM, the similar results were observed in BC, while there is no statistical difference of survival among different histologies in UUTT, no matter the M stage. Cox analyses revealed that primary location, histology type, surgery, chemotherapy and M stage were the common and strong independent prognostic factors in both BC and UUTT. Conclusions: In urinary tract tumors, the incidence of different histology types between BC and UUTT is roughly similar. Overall, patient with variant histology have a worse prognosis than those with urothelial carcinoma. However, differences in survival among the histology types vary by primary location and metastatic status, especially the metastatic status.
Radical nephroureterectomy followed by adjuvant chemotherapy (RNU-AC) versus observation (RNU-O) in early-stage upper urinary tract cancers with variant histology (UUTC-VH).
Authors: Jatwani Karan , Muthusamy Kumarasamy Vasanthan , Roy Arya Mariam , Attwood Kristopher , George Anthony , Faisal Muhammad Salman , Perimbeti Stuthi , Chatta Gurkamal S. , Gopalakrishnan Dharmesh 
Published: March 2023

487 Background: Upper urinary tract cancers (UUTC) are less frequent and associated with poorer stage-for-stage prognosis compared to bladder cancer, with variant histology being an independent predictor of inferior outcomes. The POUT trial included only patients with predominantly urothelial tumors. We aimed to compare outcomes among patients with UUTC-VH who were treated with RNU-AC vs. RNU-O. Methods: We queried the National Cancer Database for adult patients with UUTC-VH diagnosed between 2004 and 2018. Only patients who underwent RNU with node-negative disease on pathological staging (pT2-4N0M0) were included and divided into two groups based on the postoperative treatment strategy - RNU-AC and RNU-O. Patients who received neoadjuvant chemotherapy were excluded from analyses. Fisher’s exact and Mann Whiney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed for multivariate analysis of factors associated with overall survival. Models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 522 patients were identified – 133 (25.5%) received RNU-AC while 389 (74.5%) underwent RNU-O. Patients in the RNU-AC group were younger (median 69 vs. 76 years, P <0.001). Patients with small cell (15.8% vs 4.9%), micropapillary (9.8% vs 5.9%) and adenocarcinoma (9% vs 6.7%) histologies were more likely while those with squamous histology was less likely to receive AC (38.3% vs 50.6%) (p < 0.001 for all comparisons). A significant majority of patients in each T stage were treated with AC – 87.1% of pT1, 73.2% of pT2, and 68.4% of pT3 (P = 0.009). Overall survival in the RNU-AC and RNU-O groups were comparable (median of 27 vs 24.1 months, log rank-P = 0.63). On multivariable analysis, neither AC nor histological subtype were not independently predictive of OS (HR for AC = 0.96, 95% CI 0.74-1.24, P = 0.75). Conclusions: This is the largest study to date evaluating outcomes with AC after RNU in UUTC-VH since these patients were largely excluded from AC clinical trials. We observed that AC was not associated with improved overall survival after RNU in this population.
Neoadjuvant cisplatin-based chemotherapy followed by selective bladder preservation chemoradiotherapy (CRT) in muscle-invasive urothelial carcinoma of bladder (MIBC): A combined retrospective analysis of two prospective studies.
Authors: Hong Joohyun , Choi Daeho , Sung Hyun Hwan , Jeong Byong Chang , Park Se Hoon 
Published: March 2023

496 Background: Bladder preservation CRT in patients with a clinical complete response (cCR) following neoadjuvant cisplatin-based chemotherapy is one of the promising treatment strategies for MIBC. A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT. Methods: The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving neoadjuvant chemotherapy followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survivals was defined as the date of commencing CRT. Results: Sixty-four patients received gemcitabine/cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. After completion of planned neoadjuvant chemotherapy, 66 patients with a cCR and 10 who did not have a cCR but refused surgery were treated with CRT. With a median follow-up of 45 (95% CI, 41-48) months, a total of 39 recurrences was observed (51%): metastatic (n=28) and within the urinary tract (n=11). Median DFS or MFS was not reached. The 12- and 24-month DFS rates were 81% and 66%, respectively. MFS rates at 12- and 24-month were 87% and 75%, respectively. Both DFS (P=0.055) and MFS (P=0.014; HR 0.38; 95% CI, 0.17-0.85) appeared to be affected by the achievement of a cCR. Conclusions: The strategy of neoadjuvant chemotherapy followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC.
Sequential intravesical gemcitabine and docetaxel versus bacillus Calmette-Guérin for the treatment of high-risk, treatment-naïve, non-muscle invasive bladder cancer.
Authors: McElree Ian M. , Steinberg Ryan L. , Mott Sarah L. , O'Donnell Michael A. , Packiam Vignesh T. 
Published: March 2023

497 Background: Due to ongoing bacillus Calmette-Guerin (BCG) shortages, sequential intravesical gemcitabine and docetaxel (Gem/Doce) has been increasingly utilized as first-line adjuvant treatment for patients with high-risk non-muscle invasive bladder cancer. Herein, we compared oncologic outcomes and tolerance of Gem/Doce versus BCG. Methods: We retrospectively identified 312 patients with high-risk, treatment-naïve, NMIBC treated at our institution between January 2011 and December 2021; 174 treated with BCG and 138 treated with Gem/Doce. After complete TURBT, patients received a 6 weekly intravesical induction regimen of Gem/Doce or BCG, followed by maintenance if disease free at first follow-up. The primary outcome was high-grade (HG) recurrence-free survival (RFS). Cox multivariable regression analyses were performed. Adverse events were reported using CTCAE v5. Results: Median follow-up for patients receiving Gem/Doce and BCG was 23 and 49 months, respectively. Baseline clinicopathologic characteristics were similar between groups, including presence of CIS (41% vs 44%, p=0.6) and T1 (37% vs 41%, p=0.5) disease for patients receiving Gem/Doce and BCG, respectively. HG-RFS estimates at 6, 12, and 24-months were 92%, 85%, and 81% for Gem/Doce and 76%, 71%, and 69% for BCG, respectively. On multivariable Cox regression analyses controlling for age, gender, treatment year, and presence of CIS, Gem/Doce treatment was associated with superior HG-RFS (HR 0.57, p=0.04) and RFS (HR 0.56, p=0.02) versus BCG (Table). Progression-free, cystectomy-free, cancer-specific, and overall survival were similar between groups. Induction BCG was associated with greater treatment discontinuation (9.2% vs 2.9%, p=0.02), dysuria (p=0.03), and arthralgias (p=0.02), but less bladder spasms (p<0.01) than Gem/Doce, respectively. Conclusions: In the setting of ongoing BCG production shortages, we found Gem/Doce to be an efficacious and well-tolerated alternative first-line therapy for high-risk NMIBC. Prospective randomized evaluation is being planned.
Safety and efficacy of immune checkpoint inhibitors (ICI) in advanced penile squamous cell carcinoma (PeCa): An international study from the Global Society of Rare Genitourinary Tumors (GSRGT).
Authors: El Zarif Talal , Nassar Amin , Jiang Lijuan , Pond Gregory Russell , Zhuang Tony , Velev Maud , Hahn Andrew Warren , Buti Sebastiano , Álvarez Pablo , McKay Rana R. , Vincenzi Bruno , El-Am Edward , Hui Gavin , Lee Jae-Lyun , Mouhieddine Tarek H. , Milowsky Matthew I. , Matthews Harrison , Barata Pedro C. , Apolo Andrea B. , Sonpavde Guru P. 
Published: March 2023

5 Background: Management options for patients (pts) with advanced (locally advanced or metastatic) PeCa are limited. The GSRGT assembled an international cohort of pts with advanced PeCa treated with ICI to evaluate toxicity and clinical outcomes. Methods: We retrospectively collected data on pts with advanced PeCa receiving ≥1 cycle of ICI between 2015-2022 at 18 medical centers in the US, Europe, and Asia. Immune-related adverse events (irAE) were graded per the Common Terminology Criteria for Adverse Events v5.0. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Objective response rate (ORR) was determined by the clinical investigator per RECIST 1.1 criteria, whenever feasible. Results: Among 72 pts with advanced PeCa treated with ICI, 24 (33%) were Hispanic and 7 (10%) were Black. 60 (83%) pts had metastases while the remainder had locally advanced disease. The median age was 64 (inter-quartile range (IQR): 54,70) years and 48 (67%) had ECOG performance status ≥1. Most pts (n=60, 83%) were treated in the ≥2nd line setting and received pembrolizumab (n=23), nivolumab (n=15), cemiplimab (n=15), nivolumab and ipilimumab (n=7), or other anti-PD1/L1-based therapies (n=12). Among 37 pts with available data on HPV status, 24 (65%) were HPV+. 3 (4%) pts were HIV+. irAE of any grade occurred in 18 (25%) pts, 7 (10%) were grade ≥3, 7 (10%) required steroids, 6 (9%) required hospitalization, and 8 (11%) led to treatment discontinuation. The median OS and 24-month OS and median PFS and 24-month PFS were 9.4 (95%CI: 6.8, 12.8) months and 19.3% (95%CI: 9.2, 32.1) and 2.8 (95%CI: 2.1, 3.9) months and 11.2 % (95%CI: 4.9, 20.2), respectively. Among 66 pts evaluable for response, ORR was 7/66 (11%) (2 with complete response, 5 with partial response), and 16 (24%) pts had stable disease for a disease control rate of 35%. The median duration of response was 7.9 (IQR: 3, not reached) months. Conclusions: In the largest retrospective cohort of ICI-treated advanced PeCa, ICI showed no new safety signals, however, overall anti-tumor activity was limited. Future translational studies are needed to identify pts that are more likely to derive clinical benefit from ICI.
Comparison of costs incurred by patients treated with adjuvant nivolumab versus placebo for high-risk muscle-invasive urothelial carcinoma.
Authors: Yin Xin , Mitra Shreya , Patel Miraj Y , Ranjan Sandip , Bhandari Hitesh , Potluri Ravi , Rosenblatt Lisa 
Published: March 2023

500 Background: The global, phase 3 CheckMate 274 trial showed significant and clinically meaningful benefit of adjuvant nivolumab (NIVO) treatment versus placebo (PBO) in reducing risk of disease recurrence or death in patients with muscle-invasive urothelial carcinoma (MIUC) at a high risk of recurrence after radical cystectomy. The implications of these benefits on costs associated with the treatment are unknown. Here, we estimate and compare per-patient medical and subsequent therapy costs in the United States for patients with high-risk MIUC initiating treatment with adjuvant NIVO or PBO. Methods: This analysis used individual data from all randomized patients for healthcare resources utilized (HCRU) from the CheckMate 274 trial. Medical (inpatient, lab, office visits, procedures, concomitant drugs) and subsequent treatment (surgery, radiotherapy, systemic therapy) resources were included, while the costs of NIVO were not included. US-based unit costs were applied to these resources and were obtained from Healthcare Cost and Utilization Project, Micromedex RED BOOK, and CMS databases, supplemented by inputs from published literature. HCRU was only captured on 2 follow-up visits after discontinuation of study therapy: follow-up 1 occurred approximately 35 days after the last dose or coinciding with the date of discontinuation, and follow-up 2 occurred approximately 80 days after follow-up 1. To align with data captured at follow-up visits, HCRU and related costs were analyzed from randomization to 12 months and 16 months. Costs were adjusted for censoring using the Kaplan–Meier sampling average estimator. Results: Total per-patient costs incurred by the NIVO-treated cohort (n = 353) were 6% lower than the PBO cohort (n = 356) over the 12-month period from randomization ($36K vs $38K) and 13% lower over the 16-month period from randomization ($41K vs $47K) (Table). The NIVO cohort, compared with placebo, had lower subsequent treatment costs ($2K vs $11K over 12 months, and $3K vs $18K over 16 months) despite higher medical costs ($34K vs $27K over 12 months, and $37K vs $29K over 16 months). Conclusions: Patients treated with adjuvant NIVO incurred lower total costs versus PBO, with the differential increasing over time. The slightly higher medical costs incurred by the NIVO cohort were offset by the substantially lower subsequent therapy costs. [Table: see text]