bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an miRNA signature for individual prognostic assessment in seminoma patients.
Authors: Heinzelbecker Julia , Zohari Farzaneh , Eckhart Lea , Ayoubyan Hiresh , Lenhof Hans-Peter , Bohle Rainer Maria , Bremmer Felix , Gayer Fabian Alexander , Che Yue , Albers Peter , Stöckle Michael , Junker Kerstin
Published: February 2025

645

Background:
Due to the risk of long-term toxicities in young non-metastatic seminoma patients, surveillance regimens nowadays are the standard of care. However, up to 20% of patients will relapse and undergo further treatment, requiring even greater efforts in terms of adjuvant therapy. miRNAs are known to be very stable and robust biomarkers. This study aims to establish a prognostic miRNA profile utilizing bioinformatics tools to differentiate between metastatic (met) and non-metastatic (nmet) seminomas.
Methods:
MiRNA was extracted from formalin-fixed paraffin-embedded sections. Using microarray analysis (Agilent Technology), two cohorts of patients with seminoma (24 patients each, 12 nmet and 12 met) were examined. The following criteria were used to preselect relevant miRNAs: absolute median log2 fold change >0.5, distance correlation >0.5, accuracy in single-miRNA classifier trained with leave-one-out cross-validation (met vs. nmet) >0.7. Validation was performed in 88 patients (47 nmet and 41 met) through qPCR using the TaqMan assay, with RNU48, miR-191-5p, and miR-361-5p serving as references. Statistical and bioinformatics analyses were performed using the Mann-Whitney U test and machine learning algorithms.
Results:
The bioinformatics analysis of microarrays identified 16 miRNAs exhibiting an accuracy >70% in differentiating met tumors from nmet ones. The validation of 6 miRNAs by qPCR revealed significant expression differences between met and nmet tumors for miRNAs miR-371a-5p, miR-512-3p, miR−509−3−5p, miR-517a-3p (p<0.05), dependent on the reference used. All 4 miRNAs are higher expressed in met tumors. Synchronous met tumors exhibit stronger differences in the expression of the above-mentioned miRNAs compared to metachronous met tumors, except for miR-509-3-5p. miR-371a-5p was found to be the most robust miRNA to distinguish both synchronous and metachronous met from nmet seminomas. Classifiers trained on the PCR data for different combinations of the 6 investigated miRNAs using leave-one-out cross-validation show a medium performance (average accuracy of 0.59) including one model based on 4 miRNAs with high accuracy of 0.99.
Conclusions:
By using machine-learning algorithms on microarray data, we have established a miRNA signature that can differentiate metastatic from non-metastatic seminomas with high reliability. Validation of 4 miRNAs by qPCR confirms the high prognostic value of miRNAs in seminoma patients. Currently, we examine the suitability of this miRNA panel in liquid biopsy.
Characterization of circulating tumor DNA (ctDNA) burden and its association with real-world overall survival among prostate cancer (PC) patients.
Authors: Du Ping , Liao Jiemin , Watkins Angela , Cristescu Razvan , Barkley Nicole , Markensohn Julia
Published: February 2025

69

Background:
Circulating tumor DNA (ctDNA) from blood-based liquid biopsies is emerging as a promising biomarker with potential prognostic and predictive value for managing patients across tumor types and therapeutic areas. Yet data and understanding of how ctDNA might be used as a prognostic biomarker in prostate cancer (PC) are limited. This study used real-world data (RWD) to evaluate the association between ctDNA burden and clinical characteristics and outcomes in PC.
Methods:
Prostate cancer patients were identified from the Guardant INFORM real-world clinical-genomic database, which connects ctDNA results obtained through the plasma-based next-generation sequencing Guardant360 assay (G360) to de-identified claims data. U.S. PC patients who underwent a G360 test between June 2014 and June 2023 were included. A 6-month baseline period prior to the first G360 test (index) was used to gather clinical information on these patients. ctDNA burden for each patient was defined as the maximum variant allele frequency (MVAF) of all somatic variants. The median MVAF across all samples was used to classify patients into high or low ctDNA burden groups. The association between ctDNA and real-world overall survival (rwOS) was assessed using log rank tests and multivariable Cox proportional hazards models adjusted for age, race/ethnicity, year of test, comorbidity indices, metastasis status, PC clinical state, and presence of androgen receptor ligand binding domain (AR LBD) mutations.
Results:
16,757 PC patients were identified, of which, 13% had undetectable ctDNA burden. Using a median MVAF cut-off of 1.9% (range: 0.01% to 96.4%), 7,216 had low ctDNA burden and 7,330 had high ctDNA burden. Among patients with detectable ctDNA, higher ctDNA burden was observed in patients with metastatic castration resistant prostate cancer (N=5,996, median=2.4%), smokers (N=2,580, median=2.5%), with higher comorbidity burden (N=3,336, median=3.0%), and those AR LBD mutations (N=2,624, median=8.6%). Patients with high ctDNA burden showed significantly shorter rwOS after the index date (16.4 months [95%CI: 15.8-17.0]) than low and undetectable ctDNA burden groups (34.8 [95%CI: 32.8-37.0] and 53.1 months [95%CI: 48.6-65.9], respectively). Multivariable Cox models showed similar results (high ctDNA vs undetectable ctDNA hazard ratio [HR] = 3.16; low ctDNA vs undetectable ctDNA HR = 1.45; high ctDNA vs low ctDNA HR = 2.18).
Conclusions:
In this real-world study with large PC population, ctDNA burden varied by severity of disease and was negatively associated with overall survival after adjustment for other prognostic features. Our study adds to the body of evidence suggesting the utility of ctDNA as a potential prognostic biomarker in PC patients to monitor disease progression and patient outcomes in routine clinical practice.
Assessing practice gaps and challenges for immunotherapy integration in treatment of metastatic urothelial carcinoma.
Authors: McGregor Bradley Alexander , Patel Taral H , Chavula Thandiwe , Dewald Ilona , Carter Jeffrey D. , Heggen Cherilyn , McKinnon Kelly
Published: February 2025

694

Background:
The approval of pembrolizumab with enfortumab vedotin in the first-line setting has shifted the treatment paradigm for patients with metastatic urothelial carcinoma (mUC). However, integrating these novel therapies into clinical practice can be challenging for health care providers (HCPs). To better understand real-world challenges and barriers for integrating immunotherapy in routine practice, we surveyed providers across community-based oncology settings.
Methods:
Between 02/2024 and 04/2024, multidisciplinary (MDT) oncology team members (N = 60) across the US were surveyed to assess providers' current practices and challenges regarding biomarker testing, immunotherapy use, and multidisciplinary coordination in mUC care. Teams then participated in a network-wide workshop to develop action plans for improving mUC care.
Results:
HCPs reported ongoing challenges in integrating novel therapies in clinical practice, including individualizing treatment plans and sequencing (28%), keeping up with clinical evidence (24%), and differentiating available immunotherapy and combination regimens (14%). Additionally, HCPs reported challenges in providing patient-centered supportive care (12%) and engaging patients in shared decision-making (10%). Most HCPs routinely tested for PD-L1 (82%), HER2 expression (63%) and alteration (55%), and
FGFR (62%)
, and <50% tested
PIK3CA
and
CDKN2A
alterations. While HCPs felt confident in applying the latest guidelines to treatment selection (62%), only 45% of cisplatin-ineligible patients were reported to have received approved first-line immunotherapy combination in the metastatic setting. Most HCPs felt confident recognizing and managing immune-related adverse events (64%) and reported that only 15% of patients required treatment discontinuation due to adverse events. Only 21% of HCPs were
fully satisfied
with MDT coordination/communication and believed that improving MDT collaboration (33%) and provider education on integrating immunotherapy and combination approaches (31%) would most improve mUC care. After participating in a network-wide workshop, teams developed action plans including improving MDT coordination, standardizing and streamlining biomarker testing, and increasing education on treatment sequencing guidelines. Following integration of these action plans, 100% of HCPs reported improved/increased alignment with evidence-based guidelines. Additionally, HCPs reported increasing provider education on integrating immunotherapy and combination therapies into practice (71%) and improving MDT collaboration (71%).
Conclusions:
These data and actionable insights can inform future targeted initiatives to improve integration of evidence-based immunotherapy and combination targeted agents into practice for patients with mUC.
Evaluating cost-effectiveness in the evolving treatment landscape for metastatic urothelial carcinoma.
Authors: Rieger Constantin , Pfister David A. , Schluechtermann Joerg , Heidenreich Axel , Weiten Richard , Storz Enno
Published: February 2025

695

Background:
Metastatic urothelial carcinoma (mUCa) is the most expensive cancer to treat on a per-patient basis, largely due to the need for frequent interventions and costly follow-up care. In examining first-line therapies, combinations such as enfortumab-vedotin plus pembrolizumab (EV + P) and gemcitabine/cisplatin plus nivolumab show substantial overall survival advantages over the standard treatment (SoC) of gemcitabine/cisplatin. This study presents a cost-effectiveness analysis for mUCa.
Methods:
We developed a Markov model from a payer's perspective, utilizing clinical data derived from the Phase III Checkmate-901 and EV302/Keynote-A39 trials. To identify the optimal treatment from a socioeconomic standpoint, we employed Monte Carlo simulation, focusing on Germany and the United States (US). Subsequently, we compared the incremental cost-effectiveness ratio (ICER) for each treatment modality across various willingness-to-pay (WTP) thresholds.
Results:
At a lifetime horizon, SoC, gemcitabine/cisplatin plus nivolumab and EV + P were associated with average costs of €163,424 (US: $458,006), €206,853 (US: $597,802), and €401,170 (US: $1,228,455), respectively, while achieving QALYs of 1.21, 1.71, and 2.31, respectively. The ICERs for the newer treatment strategies were €87,340 (US: $281,142) for gemcitabine/cisplatin plus nivolumab and €216,140 (US: $700,448) for EV + P. At a commonly accepted WTP threshold of €/$100,000, gemcitabine/cisplatin plus nivolumab emerged as the optimal strategy in Germany, while EV + P would necessitate a price reduction of 46% (US: 82%) to achieve cost-effectiveness.
Conclusions:
QALYs nearly double with the combination of EV + P compared to the current SoC; however, the associated costs may not be justifiable from a strict socioeconomic perspective. Despite offering lower oncological benefits, gemcitabine/cisplatin plus nivolumab should be considered for first-line therapy due to its favorable cost-effectiveness, particularly in Europe. Furthermore, identifying individual risk factors is crucial for optimizing therapeutic responses and managing treatment costs in the future.
Cardiovascular mortality risk in primary penile cancer patients: A retrospective cohort study from 2000 to 2021.
Authors: Cheema Asfand Yar , Munir Mishaal , Mandala Aashray , Ogedegbe Oboseh John , Unlu Serhan , Thiagarajan Praveena Shree
Published: February 2025

7

Background:
Primary penile cancer is a rare malignancy, representing less than 1% of all cancers in men in developed countries. The disease predominantly affects older males and is frequently associated with risk factors such as human papillomavirus (HPV) infection, chronic inflammation, smoking, and poor hygiene. Given the age and comorbidities of patients diagnosed with penile cancer, cardiovascular disease (CVD) is a significant concern. Penile cancer patients often present with multiple risk factors for CVD, including advanced age, smoking, obesity, and pre-existing hypertension. Despite improvements in cancer-specific survival, non-cancer causes of death, particularly cardiovascular mortality (CVM), may disproportionately affect these patients. Understanding the cardiovascular mortality in penile cancer patients is crucial for holistic care and survivorship.
Methods:
We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with primary penile cancer who experienced cardiovascular mortality (CVM) between 2000 and 2021. CVM was defined as mortality resulting from heart disease, hypertension (without concomitant heart disease), cerebrovascular disease, atherosclerosis, aortic aneurysm and dissection, and other diseases of the arteries, arterioles, and capillaries. Standardized mortality rates (SMR) were calculated to assess the relative risk of CVM among penile cancer patients compared to the general population. Absolute excess risk (AER) was also estimated to quantify the additional number of CVM-related deaths attributed to this patient population.
Results:
Out of a total cohort of 6,889 patients diagnosed with primary penile cancer, 689 experienced cardiovascular mortality. Patients with Non-cardiovascular death and patients with unknown ag, race and cancer stage were excluded. We compared the CVM of each group to the general US population. In our cohort based on race we didn't note statistically significant increase in CVD SMRs. Regarding race American Indians/Alaska Natives has (SMR 0.99, CI 0.24-3.98), Asians or Pacific Islanders (SMR 0.99 CI 0.68-1.46), Blacks (SMR 0.99 CI 0.75-1.33), Whites (SMR 1.00 CI 0.91-1.08). In terms of age, patients aged 30-50 years (n=27) had SMR of 0.99 (CI 0.68-1.44), 50-79 year (n=359) had SMR of 0.99 (CI 0.90-1.10), while 80 years and above (n=222) had SMR of 1.00 (CI 0.87-1.14).
Conclusions:
Our analysis evaluates the burden of CVD-related mortality in patients with primary penile carcinoma. In this cohort, no statistically significant increase in cardiovascular mortality was observed when compared to the general U.S. population, stratified by race and age. Further research is required to better understand potential associations or disparities and to identify any underlying factors that may influence cardiovascular outcomes in this population.
Sociodemographic disparities in treatment (tx) patterns and clinical outcomes among real-world patients (pts) with locally advanced/metastatic urothelial carcinoma (la/mUC) in the US.
Authors: Tawagi Karine , Pierzynski Jeanne , Freeman Emily , Schmidt Kerstin , Sierecki Mitchell Robert , Brockman Jane Michelle , Parikh Mamta
Published: February 2025

707

Background:
Sociodemographic disparities in la/mUC pt population include worse survival outcomes observed among certain pt subgroups. This study evaluates disparities among la/mUC pts receiving systemic therapies overall and those initiating an antibody drug conjugate in the real world.
Methods:
This descriptive, retrospective cohort study used US Flatiron Health electronic health record–derived de-identified database. Pts aged ≥ 18 yrs were grouped into cohorts C1 (all pts with la/mUC) and C2 (2L+ sacituzumab govitecan [SG] or 1L+ enfortumab vedotin [EV]) with tx initiation on/after Jan 2017 and Dec 2019, respectively; data cutoff for both cohorts was July 2024. Pt demographics and clinical outcomes (overall survival [OS] and time to tx discontinuation [TTD]) were calculated overall and by race. Socioeconomic status (SES) index was calculated using Yost index score (1 = lowest category; 5 = highest). Predictors of survival were assessed using Cox proportional hazards model.
Results:
C1 comprised 5102 pts. Most were White (68%) followed by Other race (11%), Black (5%), and Asian (1%); 15% were missing race. The racial distribution among C2 (N = 767) was similar to C1. Median age across C1 and C2 was similar (74 and 73 yrs, respectively), with Black pts being the youngest in both cohorts (median ages in C1 and C2: 70 and 65 yrs, respectively). Across both cohorts, Black and Asian pts, respectively, had the greatest proportion of pts in the lowest SES index group (C1: 36.7% and 13.3%; C2: 43.6% and 22.2%). In C1, median TTD (95% CI) was 3.0 (2.8-3.0) mos and was similar across all races. In C2, median TTD was higher for Asian (6.8 [4.2-NR] mos) and Black pts (6.5 [2.3-8.1] mos) and lowest for Other race (3.1 [1.9-4.3] mos). Median OS (95% CI) was 13.3 (12.6-13.9) mos in C1 and 11.9 (10.4-12.9) mos in C2. In both C1 and C2, Asian pts had the longest survival (median OS: 25.2 [11.9-41.9] and 14.0 [9.3-NR] mos, respectively) and Black pts had the shortest survival (median OS: 11.2 [9.2-15.9] and 11.4 (6.9-20.5] mos, respectively). Exploratory Univariate Cox modeling (limited by small sample size) suggested older age, history of smoking, treatment in community setting, de novo metastatic diagnosis, and ECOG score ≥ 2 are factors associated with low survival in C1 and only history of smoking and ECOG score ≥ 2 in C2.
Conclusions:
In this real-world study of treated pts with la/mUC, sample sizes, especially in C2, further research is needed to understand disparities and pt-centric factors that may impact tx decisions, TTD patterns, and reasons for discontinuation to define and address the unmet medical needs of these pts.
Real-world analysis of the efficacy and safety of enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma: A multicenter retrospective study.
Authors: Hatakeyama Shingo , Ozaki Kai , Yamamoto Hayato , Sekine Yuya , Mori Kanami , Kobayashi Mizuki , Numakura Kazuyuki , Yoneyama Takahiro , Sato Satoshi , Habuchi Tomonori , Ohyama Chikara
Published: February 2025

712

Background:
We investigated the efficacy and safety enfortumab vedotin (EV) in patients with locally advanced or metastatic urothelial carcinoma in real-world practice.
Methods:
This multicenter retrospective study included 419 patients treated for locally advanced or metastatic urothelial carcinoma between April 2004 to April 2024. The patients were categorized into the following three groups: 87 patients who underwent first-line chemotherapy and sequential chemotherapy alone (chemo-alone group), 217 patients who underwent maintenance immunotherapy or second-line immunotherapy after first-line chemotherapy (chemo-ICI group) and 115 patients who were treated with EV after first-line chemotherapy and immunotherapy (chemo-ICI-EV group). The primary outcome was the comparison of progression-free survival (PFS) of first-line therapy and overall survival (OS) from first-line therapy between the three treatment groups. Secondary outcomes included the efficacy and safety in the chemo-ICI-EV group focusing on skin adverse events (AEs).
Results:
The OS from first-line therapy was significantly longer in the chemo-ICI-EV group than that in the other groups. There was no significant difference in the first-line PFS of first-line therapy between the three groups. A multivariable Cox regression analysis showed the administration of EV was significantly associated with prolonged OS. Skin AEs were observed in 69 (60%) as a major adverse event. The PFS and OS in the patients with skin AEs was significantly longer than in the patients without skin AEs despite the reduced dose of EV. A multivariable Cox regression analysis showed that skin AEs were significantly associated with prolonged RFS and OS.
Conclusions:
The administration of EV significantly improved oncological outcomes in the real-world practice. Dose adjustment of EV may be key for long-term use and oncological outcomes.
AVENANCE real-world study of avelumab first-line (1L) maintenance treatment for advanced urothelial carcinoma (UC): Analyses in low tumor burden subgroups.
Authors: Barthelemy Philippe , Loriot Yohann , Thibault Constance , Flechon Aude , Voog Eric , Eymard Jean Christophe , Simon Camille , Pouessel Damien , Chasseray Matthieu , Lorgis Veronique , Josse Constant , Lambert Prisca , Paret Laurent , Gross-Goupil Marine
Published: February 2025

718

Background:
The effectiveness and safety of avelumab 1L maintenance was confirmed in the large real-world AVENANCE study in France. In patients with advanced UC, low tumor burden is associated with a better prognosis, which may inform treatment decisions. Here, we report post hoc analyses from AVENANCE in subgroups with disease characteristics associated with low tumor burden.
Methods:
AVENANCE (NCT04822350) is a noninterventional ambispective study that enrolled patients with locally advanced or metastatic UC who were progression free after 1L platinum-based chemotherapy (PBC) and who had previous, ongoing, or planned avelumab 1L maintenance treatment. The primary endpoint is overall survival (OS) from the start of avelumab treatment. In post hoc analyses, OS and progression-free survival (PFS) were analyzed in subgroups who had locally advanced disease, nonvisceral metastases (excluding bone), or lymph node (LN)–only disease at the start of PBC.
Results:
Of patients with available data in the overall effectiveness population (N=595), 49 (8.3%) had locally advanced disease, 80 (14.7%) had nonvisceral metastases, and 61 (10.3%) had LN-only disease. At data cutoff (July 15, 2024) in the overall effectiveness population, median follow-up from start of avelumab was 33.2 months (95% CI, 31.7-34.2), median OS was 21.2 months (95% CI, 17.3-23.3), and median PFS was 5.7 months (95% CI, 5.2-6.6). In subgroups with locally advanced disease, nonvisceral metastases, or LN-only disease, median OS (95% CI) was not reached (17.4 months-not estimable [NE]), 27.2 months (16.8-NE), and not reached (19.9 months-NE), and median PFS (95% CI) was 19.8 months (9.6-NE), 9.0 months (5.8-16.1), and 13.4 months (6.9-26.5), respectively. Subsequent treatment was received by 17 patients (34.7%) with locally advanced disease (enfortumab vedotin [EV] in 3 [6.1%]), 45 patients (56.3%) with nonvisceral metastases (EV in 12 [15.0%]), and 33 patients (54.1%) with LN-only disease (EV in 8 [13.1%]).
Conclusions:
Subgroup analyses from AVENANCE show pronounced clinical benefits with avelumab 1L maintenance in subgroups with low tumor burden characteristics. Results are consistent with previous analyses from JAVELIN Bladder 100 and other real-world studies (eg, READY, an Italian compassionate use program) and further support the use of avelumab 1L maintenance as a standard of care in patients with advanced UC without progression after 1L PBC, including those with low tumor burden. Clinical trial information:
NCT04822350
.
Real world effectiveness of systemic treatment in patients (pts) with advanced upper tract urothelial carcinoma (UTUC) with histological variants.
Authors: Moinard-Butot Fabien , Amrane Karim , Campedel Luca , Pouessel Damien , Bennamoun Mostefa , Flechon Aude , Roulleaux Dugage Matthieu , Pierre-Etienne Jr.  , Thibault Constance , Abbar Baptiste , Barbe-Richaud Jean-Baptiste , Dumont Clement , Barthelemy Philippe
Published: February 2025

722

Background:
Upper tract urothelial carcinoma is a rare and heterogeneous disease that accounts for up to 5% of all urothelial neoplasms. Variant histology is an important prognostic factor in patients affected by bladder cancer and its presence is associated with adverse pathological features and worse survival outcomes. However, few data exists regarding the impact of histological variants in patients affected by UTUC treated with systemic therapy.
Methods:
PEMBROBLAD is a retrospective multicenter RW study conducted in 24 French GETUG centers. Eligible patients had advanced UC with mixed variants (UC-V) or pure non-UC (NUC). All patients received ICI as a second line treatment. We identified all patients with UTUC within the whole study cohort. The primary endpoint was overall response rate (ORR) in first-line setting; secondary endpoints included disease control rate (DCR) in first-line setting, overall response rate (ORR) in second-line setting, DCR in second-line setting and overall survival (OS).
Results:
Out of 139 patients (pts) in the PEMBROBLAD cohort, 32 had UTUC. Median age was 72 years (range 49-88), 69.6 % were male with ECOG PS 0/1 in 64.5% of cases. Mixed UC represented 75% (n=24) of UTUC with histological variants. The most common were squamous cell carcinoma (n=9, 37.5%), micropapillary (n=7, 29.2%), sarcomatoïd (n=3, 12.5%), neuroendocrine (n=1, 4.2%), nested (n=4, 16.7%) and adenocarcinoma (n=3, 37.5%). Non UC concerned 25% (n=8) of UTUC with histological variants, including 4 patients with squamous cell carcinoma (n=4, 50%). Fifteen pts (46.9%) was treated with Carboplatin based combination in first-line and 14 pts (43.75%) with Cisplatin based treatment. The ORR was 33.3% and DCR was 50.0%. All patients received immunotherapy in second-line setting. The ORR was 18.7% and DCR was 28.1%. Median overall survival from first-line treatment is 8.9 months (CI95%, 3.6-18.5). Serious TRAE occurred in 5 pts (16.1%). Discontinuation due to TRAEs occurred in 9.6% of pts. Thirteen pts (41.9%) had a third-line of treatment.
Conclusions:
Our results suggest efficacy of chemotherapy in first-line setting and ICI in pretreated advanced UC-V and NUC. No new safety concerns were identified. Survival data will be updated for the meeting.
Treatment sequence (TS) and overall survival (OS) in patients with metastatic urothelial cancer (mUC): An observational, multicenter, real-life STATES-Bladder study.
Authors: Moinard-Butot Fabien , Barbe-Richaud Jean-Baptiste , Baudry Edwige , Amrane Karim , Maillet Denis , Barthelemy Philippe
Published: February 2025

724

Background:
mUC remains of poor prognosis despite standard first-line platinum-based chemotherapy (PBC), maintenance avelumab for ptd non progressing PBC. Enfortumab vedotin (EV) and erdafitinib offers a promising option in later lines of therapy. However all patients will not receive the whole sequence and the attrition rate remains crucial. As the therapeutic landscape evolved over the last 5 years no recent data are available on an whole mUC population including responder and non responder to PBC. This study aims to evaluate OS and treatment outcomes in real-world practice across multiple centers in France.
Methods:
This retrospective study included 180 patients with mUC treated with first-line PBC between January 2020 and December 2023. The primary objective was to assess OS in the overall population. Secondary objectives included OS by treatment sequence, performance status (PS), and attrition rates across treatment lines. We analyzed OS in patients receiving maintenance avelumab, those progressing to second-line therapies, and attrition at each treatment line. Additionally, OS was compared between patients with WHO PS 0-1 and WHO PS 2-3.
Results:
The median age was 72 years (41-91), with 81% male. Synchronous metastases were observed in 52% of patients, while 48% had metachronous metastases. The most common metastatic sites were lymph nodes (68%), lung (33%), bone (32%) and liver (21%). 44% of patients received cisplatin-based chemotherapy, while 56% were treated with carboplatin. Among patients with WHO PS 2-3 (20%), median age was 73 years (41-91), with a greater proportion having liver (25%) and bone (42%) metastases. For the entire population, median OS was 22.4 months [CI95%,17.2-26.7]. Patients receiving avelumab maintenance had a median OS of 29.0 months [CI95%,22.5-NA], while those progressing to second-line therapy showed a median OS of 15.6 months [CI95%,12.4-24.4]. Median OS for patients treated with EV at any treatment line was 26.1 months [CI95%,22.5-NA]. 58% of patients received avelumab maintenance. Attrition rates were 57% after first-line, 37% after second-line, and 9% after third-line therapy. Patients with WHO PS 0-1 had a significantly better median OS of 26.4 months [CI95%,22.5-NA], compared to 7.2 months [CI95%,6.1-13.1] for those with WHO PS 2-3 (p<0.001).
Conclusions:
These real-world survival outcomes are consistent with large phase 3 trials. The particularly poor prognosis of patients with WHO PS 2-3 underscores the need for innovative treatment strategies, such as EV plus pembrolizumab, as highlighted by the EV-302 study, to potentially improve outcomes in this challenging subgroup.
Bacillus Calmette-Guérin (BCG) treatment patterns and real-world outcomes in high-risk (HR) non-muscle-invasive bladder cancer (NMIBC): A systematic literature review (SLR).
Authors: Eccleston Anthony , Koshy Abin , Musat Mihaela Georgiana , Tzonev Cristiana , Brinkmann Julia , Chang Jane
Published: February 2025

730

Background:
Transurethral resection followed by induction and maintenance intravesical BCG is currently standard of care for patients with HR NMIBC. HR is generally defined as stage T1, high grade (HG), carcinoma in situ, tumors >3 cm, variant histology, BCG failure in HG tumor, or lymphovascular invasion. Considering the variability in HR definitions and BCG maintenance schedules, we analyzed the evidence on maintenance utilization and outcomes in patients with HR NMIBC.
Methods:
We conducted an SLR of English-language real-world evidence (RWE) studies published 01/01/2011–06/12/2024 reporting efficacy or safety outcomes with BCG in patients with HR NMIBC using MEDLINE, Embase, and Cochrane supplemented by manual searches of relevant conference proceedings 2021–2024. Studies reporting treatment patterns or progression-/recurrence-related outcomes were analyzed.
Results:
Among 244 RWE studies identified, 86 reported data on HR populations, which was defined by commonly accepted definitions such as T1 high grade (HG) or any HG, with 37.2% using AUA/EAU guidelines. Across studies reporting BCG maintenance patterns in the HR population, 40.7% of patients (6,795/16,712; 16 studies) received some form of maintenance. Details on maintenance duration were reported in 11 studies; among them, 27.9% of patients (1,154/4,142) completed ≥1 year of maintenance. Details on adequate BCG treatment were reported in 8 studies, defined as receipt of ≥5/6 induction instillations and ≥2/3 maintenance instillations. Across these eight studies, 59.5% of patients (10,122/17,007) did not receive adequate BCG treatment. While comparisons across studies should be interpreted with caution due to heterogeneity in study populations. Median 2-year recurrence-free survival (RFS), 5-year RFS, and 2-year progression-free survival (PFS) across studies was numerically longer with maintenance versus induction alone (table). However, median 5-year PFS across studies appeared similar with or without maintenance.
Conclusions:
Less than 50% of HR patients who started BCG treatment received some form of maintenance; however, studies were highly heterogenous in reporting patterns of BCG treatment and definitions of HR NMIBC. Although maintenance duration was underreported, ~30% of patients completed ≥1 year of maintenance. In patients with HR NMIBC, RWE suggests improved outcomes with maintenance versus induction alone. More studies are needed to confirm the benefit of different maintenance schedules and durations.

Real-world efficacy outcomes: HR NMIBC population.

Induction, median (range) [n studies], %
Induction + maintenance, median (range) [n studies], %

2-year PFS
85.7 (81–95) [3]
92.0 (89–98) [8]

2-year RFS
66.7 (53–81) [2]
77.1 (62–85) [7]

5-year PFS
82.6 (72–89) [4]
84.0 (53–98) [13]

5-year RFS
53.0 (31–75) [6]
64.7 (27–78) [10]
Real-world treatment patterns in patients diagnosed with metastatic castration-resistant prostate cancer in the US, 2018-2023.
Authors: Efstathiou Eleni , Li Weiyan , Roose James , Kerr Brendan T , Orji Chinelo , Yeh Nina , Corson Stephen , Mukherjee Kumar
Published: February 2025

74

Background:
The treatment landscape in patients with metastatic castration-resistant prostate cancer (mCRPC) has evolved in recent years. This real-world study evaluates treatment patterns among a large contemporary cohort of patients with mCRPC in the US.
Methods:
This retrospective cohort study included patients with a confirmed mCRPC diagnosis from 1/1/2018 to 12/31/2023 in the US nationwide Flatiron Health electronic health record-derived deidentified database. Treatment patterns were evaluated by disease setting (metastatic hormone-sensitive prostate cancer [mHSPC], nonmetastatic castration-resistant prostate cancer [nmCRPC], mCRPC) and by use of androgen receptor pathway inhibitors (ARPI; abiraterone, enzalutamide, apalutamide, darolutamide) before mCRPC diagnosis. Patients were considered ARPI-experienced if they received at least 1 line of therapy (LOT) containing an ARPI before progressing to mCRPC. Patients were considered ARPI-naive otherwise.
Results:
Of 6301 patients with mCRPC (mean age, 75 years), 4915 (78%) received ≥1 LOT in the mCRPC setting. Among those with ≥1 LOT, 48% received second-line (2L) therapy. The most common first-line (1L) and 2L therapies in mCRPC were ARPI (1L, 75%; 2L, 55%) and chemotherapy (1L,16%; 2L, 33%). Most patients (4491, 71%) were ARPI-naive before mCRPC diagnosis. Among the 1810 (29%) patients who were ARPI-experienced before their mCRPC diagnosis, the median treatment duration with ARPI was 23 months. Use of ARPI in the mHSPC setting increased from 11% to 39% in patients diagnosed with mCRPC in 2018 and 2022, respectively. Similarly, in the nmCRPC setting, this figure rose from 20% to 39%. Consecutive use of ARPI in the mCRPC setting, with variations based on the year of mCRPC diagnosis, was observed in 54% to 65% of ARPI-naive patients and 31% to 48% of ARPI-experienced patients who received 1L ARPI and any 2L therapy. Use of chemotherapy increased from 13% to 19% in 1L and 29% to 40% in 2L in the mCRPC setting but decreased from 11% to 7% in mHSPC setting.
Conclusions:
In this community practice-based study, ARPI was the most common 1L and 2L therapy, followed by chemotherapy, in patients diagnosed with mCRPC from 2018 to 2023. Although ARPI use before mCRPC diagnosis has increased, more than two-thirds of patients overall remain ARPI-naive at mCRPC diagnosis. Despite not being recommended by guidelines, consecutive use of ARPI in the mCRPC setting was common in patients regardless of ARPI use before mCRPC diagnosis.
Complications after transurethral resection of bladder tumor: Findings from the 2022 ACS NSQIP database.
Authors: Doshi Chirag , Zahir Mazyar , Escobar Domenique , Xia Leilei , Daneshmand Siamak
Published: February 2025

742

Background:
Transurethral resection of bladder tumor (TURBT) is a widely utilized procedure for the diagnosis and treatment of bladder cancer (BC). Despite its well-established role, TURBT is associated with a relatively high rate of postprocedural complications. This study aimed to provide an update on the most prevalent complications following TURBT, using data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) 2022 database.
Methods:
The ACS NSQIP 2022 database was queried for all patients who underwent TURBT. Current Procedure Terminology (CPT) codes 52234, 52235, and 52240 were used to identify size-specific TURBTs. Standard statistical analysis using R version 4.4.1 was performed to determine complications.
Results:
A total of 9,448 TURBTs were included in our analysis. Median age was 73 years old (IQR: 58-88), 2,315 females and 7132 males that received a TURBT within the cohort. Patients with concurrent procedures were removed from the final analyses, but those who received intravesical chemotherapy or underwent concurrent ureteroscopy were retained. The overall complication rate of TURBT was 8.04% in 2022. Postprocedural urinary tract infection (UTI) - within 30 days after TURBT - was the most common complication, accounting for 4.5% of total complications. 160 patients or 1.7% were found with more than one complication. There were no significant differences in complications by age or sex (p = 0.129 and p = 0.124); however larger tumors were related to higher likelihood of post-operative complications.
Conclusions:
Serious adverse complications after TURBT are rare and TURBTs are generally a safe procedure. However, the ACS NSQIP database suggests that postprocedural UTI are the most common but the rate may be marginally higher than previously reported in TURBT patients. The key limitation of this study was the inability to report the most serious complications of TURBT – i.e. bladder perforation and TUR syndrome – due to NSQIP database’s inability to capture detailed case-specific data. More detailed studies assessing patient-reported outcomes may provide a better method to evaluate the types of complications following TURBT.

30-day complications after TURBT in 2022.

30-day Complications
Frequency
Percentage

Acute Renal Failure
4
0.043%

Cardiac Arrest Requiring CPR
10
0.108%

Still in Hospital after 30 days
15
0.161%

Stroke/CVA
22
0.237%

Pneumonia
31
0.333%

DVT/PE/Thrombophlebitis
48
0.508%

Transfusions Required
122
1.312%

Progressive Renal Insufficiency
135
1.452%

Related Reoperations within 30 days
148
1.592%

Urinary Tract infections
430
4.603%

Total
760
8.044%
The impact of micropapillary histology and clinical staging on overall survival in bladder cancer: A retrospective analysis.
Authors: Alkazemi Muhammad Hassan , Alam Syed Muneeb , Zhang Ao , Pietzak Eugene J. , Donat S. Machele , Herr Harry W. , Bochner Bernard H. , Chen Jie-Fu , Al-Ahmadie Hikmat
Published: February 2025

744

Background:
Micropapillary variant bladder cancer (MPC) is a rare subtype of urothelial carcinoma, representing 0.01–2.2% of cases, with a higher stage at diagnosis and increased metastatic potential. The prognostic role of MPC remains uncertain, and previous studies have been limited by small cohort sizes, with only a few larges studies. This study analyzed the prognostic impact of MPC on clinical stage and survival outcomes in the largest single-institution cohort of patients with MPC who underwent radical cystectomy (RC).
Methods:
This retrospective study included 130 patients who underwent RC at Memorial Sloan Kettering Cancer Center for MPC between June 21, 1995, and April 14, 2023. Data included demographic, histologic, and clinical variables, as well as overall survival (OS) outcomes. Cystectomy specimens were reviewed by genitourinary pathologists to determine the proportion of the MPC component (MPC%) in each tumor. For OS comparison, a separate cohort of 430 patients with urothelial carcinoma not otherwise specified (UC NOS) who also underwent RC was used. Patients with MPC were further stratified by stage at diagnostic transurethral resection of bladder tumor (TURBT) as either non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC). Additional stratifications included MPC% ( < 50% vs. ≥50%, < 20% vs. > 80%) and receipt of neoadjuvant chemotherapy (NAC).
Results:
MPC was associated with a significantly shorter OS compared to UC NOS patients (p = 0.011). The MPC cohort had a mean OS of 83.8 months (95% CI: 62.2–105.4) and a median OS of 36.8 months (95% CI: 22.3–51.3), whereas the UC NOS cohort had a mean OS of 72.1 months (95% CI: 66.6–77.6) and a median OS of 84.4 months (95% CI: 64.5–104.2). Within the MPC cohort, patients with MIBC at initial TURBT had significantly worse OS compared to those with NMIBC (p = 0.0005). MPC% did not impact OS, with no differences between patients with < 50% versus ≥50% MPC (p = 0.59) or < 20% versus > 80% MPC (p = 0.57). Additionally, NAC did not affect OS within the MPC cohort (p = 0.055). N stage at cystectomy (N0 vs. N1+) was also not predictive of OS (p = 0.16).
Conclusions:
The presence of MPC, regardless of its proportion or the use of NAC, predicts poor outcomes. Clinical stage—particularly the presence of muscle invasion—remains the key predictor of survival. These findings emphasize the importance of clinical staging in guiding treatment decisions and prognostic assessments in the management of this disease.
Clinical efficacy of enfortumab vedotin-pembrolizumab (EV-P) in locally advanced (LA) or metastatic urothelial carcinoma (mUC): A real-world retrospective study.
Authors: Jain Prateek , Naqvi Syed Arsalan Ahmed , Anjum Muhammad Umair , Khan Muhammad Ali , Afzal Muhammad Umar , Yum Ji-Eun , Warraich Kainat , Jajja Salman Ayub , Swati Fnu , Tripathi Nikita , Childs Daniel S , Orme Jacob , Zakharia Yousef , Tyson Mark , Yu Nathan Y , Riaz Irbaz Bin , Singh Parminder
Published: February 2025

745

Background:
The combination of EV-P therapy has recently been approved as first-line (1L) therapy for patients with LA/mUC based on the results of the EV-302 trial. Herein, we report the updated results from a cohort of patients with LA/mUC who received EV-P in real world clinical setting.
Methods:
This retrospective study included patients with LA/mUC (07/2022-08/2024) at the Mayo Clinic who completed at least one cycle of EV-P. The best overall response (BOR) was evaluated using radiographic imaging and was adjudicated as complete response (CR), partial response (PR), stable disease (SD), mixed response (MR), or progressive disease (PD). The median progression-free survival (PFS), defined as the time from treatment initiation to disease progression or death, was estimated using the Kaplan-Meier method. Patients who had not experienced disease progression by their last follow-up were censored for the PFS analysis.
Results:
A total of 120 patients were included; 79 (65.8%) were males, 41 (34.1%) females, 109 (91%) White, and 119 (99%) were non-Hispanic/Latino. The median age was 72 years (IQR: 65-77). Of these, only 22 (18.3%) had locally advanced disease while the remaining had mUC; 62 (51.6%) had lower tract urothelial carcinoma (LUTC), 36 (30%) had upper tract urothelial carcinoma (UTUC). The median follow-up time was 7.1 months (IQR: 4.93-9.26). In terms of BOR, 56 patients (46.6%) experienced PR, 34 (28.3%) CR, 12 (10%) PD, 7 (5.8%) MR, and 8 (6.6%) experienced SD. 3 (2.5%) patients were not evaluable. The BOR across subgroups, LA and mUC, including LUTC and UTUC, is summarized in the table. Among the responders, the median number of treatment cycles to first response was 3 (IQR: 2.25–4). Within the follow-up, 28 patients (23.3%) experienced eventual radiographic disease progression; death was observed in 25 patients (20.8%). The median PFS was 12.7 months (95% CI: 9.8-NE), and OS was 25.1 months (16.3-NE).
Conclusions:
In real world setting, the combination of EV-P in LA/mUC demonstrated clinical efficacy compatible with the findings from the EV-302 trial. Our results showed comparable efficacy with EV-P in both UTUC and LUTC, highlighting it's broad therapeutic potential. However, clinical data at longer follow-up is required to fully evaluate overall survival and the durability of response.

mUC
LA

Overall

LUTC

UTUC

Total patients
98
62
36
22

BOR

CR
23 (23.4%)
13 (20.9%)
10 (28.5%)
11 (50%)

PR
49 (52.6%)
31 (50%)
18 (50%)
7 (31.8%)

SD
6 (6.4%)
2 (3.2%)
4 (11.4%)
2 (9.0%)

PD
10 (10.7%)
9 (15.5%)
1 (2.8%)
2 (9.0%)

MR
7 (7.5%)
5 (8.6%)
2 (5.7%)
0 (0%)
Trends and demographic disparities in the preferred place of death for bladder cancer patients in the United States (2000–2020): An analysis from the CDC database.
Authors: Pustake Manas Vaibhav , Ganiyani Mohammad Arfat , Khosla Atulya Aman , Harisingani Avi Ravi , Eysha Mostafa
Published: February 2025

747

Background:
Understanding trends in end-of-life care for bladder cancer patients, particularly their preferred place of death (PPOD), is essential for improving palliative care planning. Despite being a leading cause of mortality in the U.S., there is limited insight into how preferences for end-of-life settings have evolved over time, or how they vary across demographic groups. Identifying these trends can help enhance care quality and address disparities in access to hospice and home-based care. This study aims to provide a comprehensive analysis of PPOD trends for bladder cancer patients from 2000 to 2020.
Methods:
Data from the CDC WONDER database were used to analyze bladder cancer mortality trends between 2000 and 2020. Deaths were categorized by place of death (home, hospice, medical facility, nursing home), age, race, census region, and year. Descriptive statistics summarized mortality trends, and chi-square tests assessed associations between demographic characteristics and place of death. Logistic regression identified factors associated with hospice utilization, adjusting for age, race, and region. The analysis also examined the impact of the COVID-19 pandemic on end-of-life care in 2020.
Results:
Between 2000 and 2020, there were 293,906 bladder cancer deaths in the U.S., with the South accounting for the highest proportion (35.6%). Home was the most common place of death (41.6%), followed by medical facilities (24.4%), nursing homes (19.5%), and hospice facilities (9.0%). Significant associations were found between place of death and age, race, and region (p < 0.001). Logistic regression showed younger individuals (under 85) had higher odds of dying in hospice, while Black individuals were less likely to use hospice than White individuals (OR = 0.699, p < 0.001). Hospice utilization increased over time (OR = 1.134 per year, p < 0.001). In 2020, home and hospice deaths increased, with a decline in medical facility deaths, likely due to the COVID-19 pandemic.
Conclusions:
Hospice care and home-based end-of-life care have become more prominent, though disparities in access persist, particularly among racial and regional groups. These findings highlight the need for more inclusive palliative care strategies to ensure equitable access to compassionate end-of-life care for all patients.

Logistic regression results for factors influencing hospice utilization.

Variable
B
S.E.
p-value
Odds Ratio

35-44 years
-18.100
1742.864
0.992
0.000

45-54 years
0.309
0.041
<0.001
1.362

55-64 years
0.291
0.023
<0.001
1.338

65-74 years
0.207
0.018
<0.001
1.230

75-84 years
0.121
0.017
<0.001
1.128

Asian or Pacific Islander
-19.165
946.130
0.984
0.000

Black or African American
-0.358
0.031
<0.001
0.699

Year (2000-2020)
0.126
0.001
<0.001
1.134