bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary results of bladder sparing by short-course radiotherapy combined with toripalimab in high-risk/extremely high-risk non-muscle invasive bladder cancer (HOPE-04).
Authors: Wen Feng , Tan Ping , Lin Tianhai , Zeng Hao , Wei Qiang , Zhang Peng , Shen Yali 
Published: June 2024

e16557 Background: To evaluate the treatment safety and efficacy of short-course radiotherapy combined with PD-1 antibody (Toripalimab) as a potential bladder-preserving therapy for high-risk / extremely high risk non-muscle invasive bladder cancer (NMIBC). Methods: HOPE-04 is a single-arm open-label, phase II trial, which designs to evaluate the safety and efficacy of short-course radiotherapy (5 × 5 Gy) and Toripalimab as a novel bladder sparing treatment in patients with high-risk / extremely high risk NMIBC. Fifty-five pathological and imaging diagnosed NMIBC patients with or without BCG treatment will be recruited. Radiotherapy of 5× 5 Gy/fractions will be given to the whole bladder followed by a focal tumour bed boost and concomitant administration of Toripalimab of 240 mg intravenous infusion every 21 days for 12 cycles (about one year). The primary endpoints are disease free survival (DFS) and safety. The secondary endpoint is overall survival. Additional indicators include implementation rate of salvage surgery and quality of life. Results: Until now, 11 patients were included successfully, with 2 female patients and 9 male patients. And the median age was 62.36 years old. Of them, 5 patients were low grade differentiation, and 6 patients were high grade. The median follow-up time was 12.56 months. Two patients with history of multiple recurrence sites repeatedly suffered from local recurrence after radiotherapy and received radical cystectomy. The pathologic stagings were pT1N0 for both patients after surgery. Therefore, the one year- bladder intact DFS rate was 62.5% and the median RFS was not achieved. No patient died so far. For safety analysis, 4 patients suffered from immune-related adverse event, namely, grade 2 arthritis, grade 1 rash and grade 1 hyperthyroidism which led to treatment interruption of Toripalimab. And 2 patients experienced radiotherapy related toxicities, including grade 1 frequent urination and urgency, grade 1 erythra and grade 1 anal sagging sensation. No treatment related dose reduction happened. Conclusions: HOPE-04 is the first encouragement of short-course radiotherapy and Toripalimab combination in the treatment of high-risk / extremely high risk NMIBC, which extends the therapeutic options of bladder preservation treatment for this population. Our preliminary results show a promising effect both in prevention of local recurrence as well as distant metastasis, and toxicities were manageable, which would be verified by the final analysis. Clinical trial information: ChiCTR2200059970 .
Gemcitabine/paclitaxel/adriamycin (GTA) as a nephron-sparing regimen in urothelial carcinoma: The MD Anderson Cancer Center (MDACC) experience.
Authors: Moussa Mohammad Jad , Subramanian Naveen G. , Haro-Silerio Jaime , Chen Lily , Shah Amishi Yogesh , Gao Jianjun , Corn Paul Gettys , Goswami Sangeeta , Msaouel Pavlos , Wang Jianbo , Kamat Ashish M. , Guo Charles C. , Tannir Nizar M. , Siefker-Radtke Arlene O. , Alhalabi Omar , Campbell Matthew T 
Published: June 2024

e16576 Background: GTA (Gemcitabine 900 mg/m2 IV; Paclitaxel 135 mg/m2 IV and Adriamycin 30 mg/m2 IV, with pegfilgrastim 6mg SQ on a 14-day cycle) was initially reported from a prospective phase II study of 39 patients (pts) by Siefker-Radtke et al. Urology (2016). We report real-world efficacy and survival outcomes with this nephron-sparing regimen in locally advanced or metastatic urothelial carcinoma (LA/mUC). Methods: We retrospectively reviewed records of n=76 pts with frontline (1L) GTA for LA/mUC between March 2016 and April 2023 at MDACC. Imaging-based best overall responses (BOR) using RECIST v1.1 were noted as partial (PR), stable (SD), progressive (PD) or non-evaluable (NE). We use Kaplan-Meier (KM) method to estimate overall survival (OS) and progression-free survival (PFS) from GTA start, and reverse KM for follow-up (FU). Results: Baseline characteristics (n=76) are shown in Table. Median age at diagnosis was 70.6 [IQR: 65.3 – 76.3]. The decision to start GTA was justified by tumor-related (55, 72.4%) or non-tumor-related (14, 18.4%) renal insufficiency, and general comorbidities (7, 9.2%).n=48 (63.2%) had percutaneous nephrostomy or ureteral stenting before GTA initiation. Pts had a median number of 3 cycles (IQR: 2-5). At GTA start, most pts (38, 50%) had one Barjorin risk factor (either bone/liver/lung mets or ECOG PS ≥2), 28 (36.8%) had none and 10 (13.2%) had both factors. Median OS was 11.3 mo (95% CI: 9.1 – 15.1 mo) with a median FU of 64.8 mo (95% CI: 26.2 – 83.6). Median PFS was 3.4 mo (95% CI: 3.03 – 4.5 mo). Overall response ratewas 26.3%, and BOR to 1L GTA included: PR 20/76 (26.3%), SD 25/76 (32.9%), PD 17/76 (22.4%) and NE 14/76 (18.4%). NE responses were due to transition to cisplatin-based regimens or other therapies in 8/14, toxicity in 3/14, pt death in 2/14 and pt preference in 1/14. GTA dose reduction was required in 15 (19.7%), and serious adverse events leading to hospitalization occurred in 18 (23.7%). Finally, among 69 pts with tumor or non-tumor related renal insufficiency, 16/69 (23.2%) were able to receive cisplatin post-GTA. In a paired t-test analysis of 76 GFR pairs, an improvement in GFR post-GTA was observed compared to pre-GTA GFR, with a significant difference of 11.2 mL/min [95% CI: 7.4 – 14.9, p < 0.0001]. Conclusions: GTA shows modest efficacy as a 1L regimen in LA/mUC. The facilitation of cisplatin-based regimens after GTA in a subset of pts might be explained by restoring patency in partially obstructed collecting systems. This ‘GTA bridging’ strategy may be beneficial for pts for whom nephrostomy or ureteral stenting proves impractical or insufficient to address renal insufficiency. [Table: see text]
Comparison of clinical outcomes of bladder preservation and surgery in a real-world study of patients with muscle invasive urothelial carcinoma using urine and plasma based MRD (minimal residual disease) assays.
Authors: Au Cherry , Tan Alan 
Published: June 2024

e16580 Background: Recently, non-invasive urine/plasma-based minimal residual disease (MRD) assays have demonstrated the ability to reliably detect deep molecular alterations in bladder cancer patients. Similar to circulating tumor DNA, urinary tumor DNA (utDNA) is a noninvasive method of measuring MRD by evaluating the molecular landscape of tumor DNA shed in urine with next generation sequencing techniques. UtDNA can reflect the tumor landscape in real-time in patients with urothelial carcinoma via direct shed into the urine and can be utilized in monitoring for disease progression and also treatment response. This study investigates tissue-informed blood MRD and urine-informed urine MRD tests in the real world setting. Methods: A cohort of 40 real-world bladder and UTUC patients were included in this study. Treatment modalities such as neoadjuvant chemotherapy, trimodality therapy (TMT) for bladder preservation, and systemic chemotherapy/immunotherapy were utilized. Matching time point blood samples and urine samples were collected at variable intervals depending on the treatment regimens the patients received. Urine samples were tested using the PredicineBEACON urine MRD assay, which used the urine PredicineWES+ whole exome sequencing results from baseline urine samples for the design of a personalized MRD panel. Patients were followed up with MRD tests until otherwise censored. Results: There were a total of 94 urine and 253 plasma-based MRD tests with a success rates of over 90%, indicating the maturation of liquid biopsy lab technologies. Patients were followed for a median of 6.5 months between the first MRD assay and most recent follow up. MRD status and tumor fraction (TF) were monitored. The TF and kinetics from the urine MRD assay were in high concordance with the blood MRD assay results at matching time points. The mutation allele frequency time course changes matched with patient treatment responses and progression events in most cases. Clear increase in mutations and TF were observed in patients with progressive disease. Patients receiving definitive therapy had good disease-free survival time (longest >2 years), and there is no significant difference between bladder preservation or surgery-based intervention. Conclusions: In this study, we observed no significant difference in clinical outcomes between bladder cancer patients receiving bladder preservation or surgery-based intervention. Urine and blood-based MRD tests closely correlated with clinical outcomes. Our study emphasizes the value of serial monitoring of urine/plasma-based MRD assays in informing MRD status or treatment response for patients who undergo bladder preservation or cystectomy. The number of cases was limited in this study and further follow up will be needed to confirm the findings in this study.
Neoadjuvant cisplatin-based chemotherapy followed by selective bladder preservation chemoradiotherapy in muscle-invasive urothelial carcinoma of the bladder: Post hoc analysis of two prospective studies.
Authors: Kim Min Jung , Cho Sung Wook , Lim Sung Hee , Park Se Hoon 
Published: June 2024

e16583 Background: Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies (Sung HH, Investig Clin Urol 2022; Kim H, Cancer Res Treat 2023) 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 NAC 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 survival was defined as the date of commencing CRT. Results: Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine/cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n = 20), metastatic only (n = 16), and both (n = 7). In 27 patients with intravesical recurrence, transurethral resection and BCG treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% CI, 25.1-67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (HR, 0.465; 95% CI, 0.222-0.976). Conclusions: The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.
Bacillus Calmette-Guerin (BCG) utilization and treatment (Tx) patterns in Chinese patients (pts) with non-muscle invasive bladder cancer (NMIBC): Results from a national urologist survey.
Authors: He Wang , Zhuang Suili , Liu Zhenhua , Jia Lifang , Mao Huirong , Huang Jian 
Published: June 2024

e16587 Background: China has the highest annual incidence (>85,694 new cases) and mortality (>39,393 deaths) from bladder cancer of any country; NMIBC is the most common subtype and is associated with a high risk of recurrence and progression. While intravesical BCG following transurethral resection (TURBT) is effective for NMIBC, there are limited real-world data on patient characteristics, BCG use and factors informing Tx decisions in China. Methods: We performed a cross-sectional, questionnaire-based survey of 300 urologists with experience of administering BCG for NMIBC from 13 cities and 10 provinces across China. Here, we summarized patient characteristics, urologists’ approach to risk assessment, BCG use and Tx patterns. Net Importance Score (NIS) was defined as the percentage of urologists who stated a factor was important (6–7 on a scale from 0–7) minus those who did not (1–4/7). Results: Pts with NMIBC had a median age of 59.6 years, 73% were male, 33% had a low annual household income (≤100,000 CNY [~13,700 USD]), 19% had a family history of cancer and the most common TNM stage was T1 (48%). The most common risk assessments (following the NCCN guidelines) were low- or intermediate-risk (both 35% of pts), followed by high risk (26%) and highest risk (4%). Urologists rated tumor stage and grade as the two most important factors for evaluating pt risk level. For pre-treated pts, the most common prior therapy was TURBT (87.1%). Among newly diagnosed pts and pts with recurrent NMIBC, 24% and 32% received BCG, respectively (overall 27%). BCG was most commonly monotherapy and at a dose of 120mg in both newly diagnosed (98% monotherapy/72% 120mg) and recurrent (96% monotherapy/74% 120mg) settings. Most urologists gave a schedule of induction (85%; BCG weekly, duration 6–8 weeks) followed by intensive Tx (65–69%; BCG Q2W, 6–8 weeks), and then maintenance (54%-68%;monthly; ≤1 year), depending on risk level. Compared with chemotherapy, 88% of responders agreed that BCG was more effective in preventing recurrence. The most important factors for choosing BCG were recurrence frequency and risk level and TNM stage (Table); 89% and 88% of urologists responded that limited BCG supply and pricing were important factors in continuing BCG. Post BCG, the most popular subsequent Tx was radical/partial cystectomy (35%) and intravesical chemotherapy (22%) although 15% of responders indicated they would extend BCG. Conclusions: These descriptive survey data provide important insights into real-world BCG utilization and factors influencing BCG use in NMIBC in China. [Table: see text]
Chemoradiation versus cystectomy for locally advanced bladder cancer: A global, propensity-matched retrospective cohort study.
Authors: Mackey James David , Atieh Khaled 
Published: June 2024

e16603 Background: Prior studies have attempted to determine whether chemoradiation is comparable to cystectomy for treatment of locally advanced bladder cancer. Some studies have shown no significant difference, while others indicate a small benefit in favor of cystectomy. The purpose of this study was to use the large, multi-institutional TriNetX database to evaluate for differences in overall survival and development of metastatic disease between the two treatments at five years. Methods: The TriNetX research database was used for this study. Two patient cohorts were created by utilizing International Classification of Disease-10 (ICD-10) codes and Current Procedural Terminology (CPT) codes. Both cohorts of patients were required to have a diagnosis of bladder cancer (C67) and were prohibited from having any known sites of metastatic disease (C78 or C79). The cystectomy cohort was constructed by using CPT codes 51590, 51595, or 51596. Chemoradiation treatment was identified by encounters for chemotherapy and radiation occurring on the same day (Z51.11 and Z51.0). The chemoradiation cohort was prohibited from having any cystectomy surgery, and the cystectomy cohort was prohibited from having had any radiation treatment. The cohorts were then balanced by propensity score matching and the greedy nearest neighbor algorithm for age, race, gender, and ethnicity. This resulted in 232 patients in each arm. The cohorts were then compared for the outcome of death at 5 years, as well as the development of metastases to lymph nodes, lung, bone, liver, and peritoneum (C79.51, C78.0, C77, C78.7, C79.89). Results: Patients who underwent chemoradiation had significantly higher mortality at five years than those that underwent cystectomy (38.4% vs 20.3%, RR 1.89, 95% CI (1.40,2.56), P value < 0.0001). Patients treated with chemoradiation were also six times more likely to develop metastatic disease to lymph nodes, lung, bone, liver, or peritoneum (31.0% vs 5.2%, RR 6, 95% CI (3.3,10.8), P value < 0.0001). Conclusions: Patients with stage II or III bladder cancer can be treated with either cystectomy or chemoradiotherapy. Both options are Category 1 recommendations of the National Comprehensive Cancer Network, with patient preference often a deciding factor. This study found that the development of metastatic disease and mortality may be more substantial than previously believed, suggesting that bladder cancer is a relatively chemoradiation resistant malignancy.
Burden of non-muscle–invasive bladder cancer (NMIBC) leveraging a novel American Urological Association Quality Registry Qdata module: A real-world data analysis based on manual data abstraction.
Authors: Gallagher Shannon , Abdul Sultan Alyshah , Sands Kathryn , Chin Iris , Cote Sarah , Spigelman Samuel , Baculea Simona , Bepple Jennifer 
Published: June 2024

e16607 Background: Bladder cancer ranks among the most common cancers globally. At diagnosis, 75% of patients have non-muscle-invasive bladder cancer (NMIBC). However, there is limited evidence on the real-world burden of NMIBC by risk categories specified by the International Bladder Cancer Group (IBCG). Large routinely collected data lack reliable granular information on tumor size, multiplicity, grade, and recurrence history and can lead to misclassification. Methods: Electronic health record data from the American Urological Association (AUA) Quality (AQUA) Registry, which is a national Qualified Clinical Data Registry was leveraged within the de-identified NMIBC Qdata module to identify and risk stratify patients based on the updated IBCG guidance. This EHR-derived module was linked to Komodo Health claims to increase capture of procedures. A random sample (n=2,500) from approximately 54,000 study-eligible NMIBC patients within the overall database was identified between 2015 and 2022 with a valid T-stage reading anytime in their medical record. Information on relevant parameters (e.g., tumor size, multifocality, stage, grade) were manually abstracted based on a standard protocol and summarized. Abstraction quality was ensured through a comprehensive disease and study training and test cases in which the clinical abstractor met ³85% agreement with the gold standard. Audits were also performed on ³10% of cases. Results: Of the 501 records initially abstracted, 96% of patients had information on relevant parameters to classify them by risk based on the IBCG guidelines. At first presentation during the study period, the majority of patients were Ta (65%), whereas 8% and 27% presented as Tis and T1, respectively. During the observation period, 291 (65%) patients were classified as high-risk whereas 114 (24%) and 135 (28%) were ever classified as low and intermediate risk, respectively. For patients with intermediate risk NMIBC, the proportion of newly diagnosed versus recurrence was similar (50%). Conclusions: This study leveraged one of the largest US-created NMIBC databases to provide contemporary, real-world distribution of NMIBC risk founded on the updated IBCG guidance. The study demonstrates that a high proportion of NMIBC patients that have explicit tumor characteristics documented are classified as high risk followed by intermediate risk, warranting the need for innovative therapies in these patient groups.
Stratified absolute benefit with adjuvant immunotherapy (aIO) in muscle-invasive bladder cancer (MIBC): A meta-analysis.
Authors: Naqvi Syed Arsalan Ahmed , Saxena Akshat , Faisal Kunwer Sufyan , Bibi Arifa , Khan Muhammad Ali , Cobran Ewan Kemar , Hussain Syed A. , Riaz Irbaz Bin , Bryce Alan Haruo , Singh Parminder 
Published: June 2024

e16619 Background: Should patients (pts) with MIBC receive aIO given the DFS benefit seen in AMBASSADOR and CheckMate 274 trials is an important clinical question. Thus, we aimed to quantify the magnitude of absolute benefit across different subgroups to aid clinicians in shared decision-making with their patients. Methods: Phase III trials evaluating aIO as compared to observation or placebo (obs/plac) in pts with MIBC were considered eligible. Outcomes of interest included DFS and OS. Pre-specified subgroups included disease location, PDL1 status, neoadjuvant chemotherapy (NAC) receipt, and tumor and nodal (TN) staging. Pairwise comparisons were made using a DerSimonian-Lairds (DL) random-effects meta-analysis. Stratified baseline risks (obtained from clinical trials) and relative effect estimates were used to estimate corresponding intervention risks (CIRs). The difference in CIRs and baseline risk was calculated to present absolute risk differences (ARDs) in each subgroup category. Results: Analysis included three trials with 2220 pts (pembrolizumab, nivolumab, and atezolizumab assessed in each). No significant difference was observed in OS with aIO compared to obs/plac (hazard ratio: 0.91; 0.76-1.09). However, aIO significantly improved DFS compared to obs/plac (0.76; 0.64-0.91) in the overall population. In pts with bladder/lower tract disease, aIO improved DFS compared to obs/plac (0.72; 0.56-0.92); however, no significant difference was observed in DFS in pts with upper tract disease. There was a statistically significant effect modification by disease location (p: 0.01). Adjuvant IO significantly improved DFS in PDL1- (0.78; 0.64-0.94) but not in PDL1+ pts (0.75; 0.52-1.08). Likewise, aIO significantly improved DFS in pts who received NAC (0.69; 0.53-0.90) but not in pts who did not receive NAC (0.89; 0.75-1.05). In terms of TN staging, aIO improved DFS in T2-3N0 (0.73; 0.57-0.94), T4N0 (0.76; 0.61-0.95), and in T2-4N1 patients (0.75; 0.59-0.95). No statistically significant modifications were observed among these subgroups. Stratified ARDs for DFS by each subgroup are outlined (Table). Conclusions: When delayed disease progression is a vital consideration, a risk-adapted strategy for the optimal patient selection to receive aIO should be considered. Disease location (lower tract/bladder), node positivity, and receipt of NAC emerged as groups likely to derive greater benefit with aIO. [Table: see text]