bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling survival outcomes of KEYNOTE-564 with standard of care control arm treatment: A simulation study.
Authors: Ghali Fady , Rahman Syed N. , James Spencer
Published: February 2025

517

Background:
The KEYNOTE-564 study, reporting improved overall survival (OS) with use of adjuvant checkpoint inhibitor (CPI), pembrolizumab, following surgery for renal cell carcinoma (RCC) suffers from a common challenge: a large portion of the control arm received non-standard of care (nSOC) subsequent therapy upon progression (in this case dual CPI or CPI + tyrosine kinase inhibitor [TKI]), thus underestimating survival in this group. We sought to model the survival of KEYNOTE-564 control group patients had they received CPI/TKI per current standard of care (SOC) to more accurately assess this intervention.
Methods:
Data were extracted from the Kaplan-Meier plots as published in KEYNOTE-426 and KEYNOTE-564. Patient-level survival data were simulated using an iterative process to adjust the censored and event rates to ensure consistency with published reference survival curves derived from KEYNOTE-426. Thus, these measures estimate a counterfactual survival parameter for the KEYNOTE-564 control group based on results from the KEYNOTE-426 study to approximate the expected increase in survival probability if the percent of control patients which received nSOC therapy had received SOC. The analytical process was conducted using R version 4.3.1, with MASS, splines, survival, dplyr, and survminer packages.
Results:
A total of 52% (N = 109) of patients in the control arm of KEYNOTE-564 that progressed did not receive CPI in the first-line setting. Based on KEYNOTE-426, we estimated a one-year mortality risk of 9.5% for those receiving axitinib-pembrolizumab versus 19.8% in those receiving TKI alone, equating to a 10.3% attributable risk between these arms. When KMA was performed on extracted data where that proportion of patients in the control arm were simulated to have avoided death on an annual basis distributed randomly across five years (n = 51 patients), the re-estimated, unadjusted hazard ratio in this was 1.41 (0.93 to 2.14). As a sensitivity analysis, we conducted this model with a survival parameter of 5% instead of 10% annual mortality risk, resulting in an unadjusted hazard ratio of 0.88 (0.61 to 1.28), and with 2.5% (unadjusted HR 0.72 (0.50 - 1.02).
Conclusions:
We report and validate method for modeling appropriate subsequent therapy for clinical trials where nSOC treatment in the control group limits the interpretation of their conclusions. In a simulation correcting for the under-estimated survival in the control arm of KEYNOTE-564, the reported survival benefit of adjuvant CPI may not be statistically durable.
Association between baseline and changes in hemoglobin levels and treatment response and prognosis in metastatic renal cell carcinoma: A Mexican retrospective study.
Authors: Campos Gomez Saul , Vargas Melendez Sandra , Gonzalez Santana Arturo
Published: February 2025

518

Background:
Clinical markers of response and outcome in metastatic renal cell carcinoma (mRCC) are lacking. Low hemoglobin (Hb) is associated with poor outcomes in the IMDC risk score. Hb levels also appear to be associated with mRCC response to VEGFI monotherapy, although this relationship is nuclear. This study evaluates the role of Hb increases as a predictive biomarker of clinical response and outcomes.
Methods:
Patients with advanced RCC treated with VEGF receptor tyrosine kinase inhibitors (TKIs) as a first-line therapy were identified. Hemoglobin levels were retrieved at baseline and then at monthly intervals for 6 months. Absolute and percentage increases over baseline were evaluated as predictors of objective response rate, progression free survival. Patients were categorized as responders (CR+PR) or nonresponders (SD+PD) using cross-sectional imaging at week 12. The Kaplan-Meier method was used to estimate PFS for patients who had an increase vs. decrease from baseline Hb, and the log-rank test used to assess survival differences between the groups. The Cox proportional hazards model was used for univariate and multivariate regression analysis to determine the significance of individual variables on PFS.
Results:
Among the 47 eligible patients, elevations in hemoglobin were observed in 64%. The median age at start of treatment was 59 years. Changes in hemoglobin at time of response were associated with objective response rate. Landmark analysis at 1 month showed that increases in hemoglobin were associated with longer PFS (mPFS 15 vs. 50 months; P = .004) Responders had a significantly higher Hb level than nonresponders at 1rs month P= 0.004. An increase in Hb was a significant independent predictor of progression-free survival (HR 0.47, P= .039).
Conclusions:
In this retrospective clinical study, we demonstrate that Hb levels are a valuable clinical marker of outcomes in patients receiving first-line therapy for mRCC in our population. These findings are readily applicable to routine clinical practice and may help clinicians deliver more personalized care.
Impact of renal cell cancer histology on outcomes of microscopic positive surgical margins and implications on post-surgical follow-up.
Authors: Meagher Margaret F. , Musso Giacomo , Puri Dhruv , Yuen Kit L. , Saitta Cesare , Wang Luke , Patil Dattatraya H. , Saito Kazutaka , Yasuda Yosuke , Fujii Yasuhisa , Master Viraj A. , Derweesh Ithaar H.
Published: February 2025

519

Background:
Positive surgical margins (PSM) are associated with worsened survival outcomes in Renal Cell Carcinoma (RCC). Current AUA guidelines recommend intensified post-surgical follow-up and clinical vigilance in patients with PSM. We sought to evaluate outcomes of different RCC-histologies with microscopic-PSM.
Methods:
We performed a retrospective analysis of patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for RCC who had microscopic-PSM. The cohort was divided according to RCC-Histology [Chromophobe-RCC (chRCC); Clear Cell-RCC (ccRCC); Papillary-RCC (pRCC) for descriptive and survival analyses. Primary outcome was all-cause mortality (ACM)/overall survival (OS). Secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Cox proportional hazards multivariable analysis (MVA) was used to elucidate predictive factors for ACM and CSM. Kaplan-Meier Analysis (KMA) was performed to analyze 5-year OSS and CSS.
Results:
A total of 8100 patients were analyzed, and we identified 312 patients with microscopic-PSM [26 (8.3%), 236 (75.6%), and 50 (16.0%) of patients had chRCC, ccRCC, and pRCC respectively]. Cox-regression revealed ccRCC to be associated with worsened ACM (versus chRCC [referent] HR=7.8, p=0.042), and worsened CSM (versus chRCC [referent] HR=2.97, p=0.033); pRCC did not demonstrate worsened ACM (p=0.148) and CSM (p=0.201). Comparing chRCC, ccRCC, and pRCC, KMA revealed a 5-year OS of 91%, 87%, and 63%, (p=0.024) and 5-year CSS of 93%, 86%, and 65%. KMA comparing microscopic-PSM versus negative surgical margins (NSM) noted no significant difference in 5-year OS for chRCC (85% vs. 86%, p=0.365) or pRCC (80% vs. 84%, p=0.952), but significantly lower 5-year OS in microscopic-PSM in ccRCC (77% vs. 85%, p<0.001).
Conclusions:
In patients with microscopic-PSM, we noted significant differences according to histology, with ccRCC being associated with significantly worsened survival and mortality outcomes when compared to chRCC and pRCC; microscopic-PSM was also associated with significantly worsened survival compared to NSM in ccRCC, but not chRCC and pRCC. Microscopic-PSM can be considered to represent a higher risk subgroup in ccRCC but not chRCC or pRCC. Intensified post-surgical follow up compared to NSM patient is appropriate in ccRCC, while microscopic-PSM in chRCC and pRCC can be followed similarly to NSM patients with the same histology.
Global and regional burden of kidney cancer: Analysis and future predictions based on GBD data from 1990 to 2021.
Authors: Zhao Haochen , Wei Qiang
Published: February 2025

521

Background:
Kidney cancer, as a common urological malignancy with poor prognosis, shows significant variations in incidence and mortality rates in different countries and regions worldwide. This study aims to investigate the global burden and trends of kidney cancer from 1990 to 2021, and to analyze its associations with various factors.
Methods:
First, data on the number of kidney cancer cases and age-standardized rates (ASR) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021 were collected and analyzed globally. Subgroup analyses based on sex, country, region, and sociodemographic index (SDI) were then performed to examine the current status and time trends from 1990 to 2021 of kidney cancer in the total population and various subgroups. In addition, the age-period-cohort (APC) and Bayesian age-period-cohort analysis (BAPC) models were used to track dynamic changes in disease burden and predict future trends of the above indicators. Finally, risk factors and trend changes related to kidney cancer mortality within SDI subgroups were analyzed.
Results:
Globally, the incidence of kidney cancer increased sharply from 1.6×10
5
in 1990 to 3.9×10
5
in 2021. The ASRs for all measures of kidney cancer burden were higher for men than for women. China has the highest number of cases, deaths and DALYs in 2021, followed by the United States. The country of Cabo Verde and the region of Western Europe have the fastest growing ASRs for both incidence and mortality. 49 countries or regions, mainly in Western Europe and North America, have a decreasing trend in ASR for mortality over the period. Overall, the burden of kidney cancer increased with higher SDIs, with countries with middle and low-middle SDIs having the fastest growing burden of kidney cancer, such as North Africa and the Middle East. The APC and BAPC models predicted a steady decline in the ASRs of incidence, prevalence, mortality and DALYs for kidney cancer over the next 20 years, although the APC model predicted a continued steady increase in the absolute numbers of these indicators. In addition, high BMI and smoking were identified as the major risk factors contributing to kidney cancer deaths. High body mass index was particularly pronounced in countries with low SDIs.
Conclusions:
From 1990 to 2021, the incidence of kidney cancer has declined from historical peaks in developed countries, but remains on an upward trend in developing countries and represents a significant health threat. Revealing some previously unreported findings, the formulation of appropriate policies to reduce population exposure to risk factors associated with kidney cancer could be beneficial in the context of global aging trends.
Cabozantinib in patients (pts) with non-locally pretreated brain metastases (BM) from renal cell carcinoma (RCC): Results of the multicenter CABRAMET phase II trial (NCT03967522).
Authors: Negrier Sylvie , Mourey Loic , Blanc Ellen , Gross-Goupil Marine , Flechon Aude , Flippot Ronan , Barthelemy Philippe , Oudard Stephane , Colomba Emeline , Thibault Constance , Ravaud Alain , Chevreau Christine , Donnat Mathilde , Boyle Helen Jane , Dalban Cécile , Pérol David , Escudier Bernard , Albiges Laurence ,   GETUG investigators
Published: February 2025

533

Background:
Despite dramatic progress in metastatic RCC treatments, pts with BM remain with poor outcome and were mostly excluded from clinical trials. Local treatments on BM are standard today.
Methods:
Adult pts with histologically proven RCC and BM ≥ 5 mm (or > 8 mm if solitary) including at least one non-locally pretreated, < 3 prior systemic treatments excluding cabozantinib, ECOG PS 0 or 1 and steroids < 40 mg/day were included. Primary endpoint was BM progression free survival rate at 6 months (6m-BM-PFS) according to modified RANO-BM criteria by central review. Secondary endpoints were BM response and response duration, extracranial response, PFS, overall survival and safety. 25 evaluable pts were required to evaluate the main endpoint.
Results:
26 pts were included, 25 were evaluable for the primary endpoint and median follow up time was 39.8 months [5.9-49.7]. The 6m-BM-PFS was 56.0% [unilateral 95%CI 37.9-] (14/25 pts). BM response was partial response (PR) for 61.5% (16/26) pts and median duration of response was not reached, 66.7% pts being event-free 24 months after BM response. Extracranial response was PR for 38.5% (10/26). Median PFS was 8.1 months [95%CI 4-11.9], and median BM PFS 8.4 months [95%CI 5.4-NR]. Median overall survival was 15.8 months [95%CI 9.7-35.0]. No new safety signals were observed.
Conclusions:
This is the first prospective trial assessing cabozantinib in RCC pts with non-locally pretreated BM. These results confirm the efficacy of cabozantinib on BM previously reported in retrospective series. Clinical trial information:
NCT03967522
.

Pts characteristics.

Pts number
N = 26

Median age (years) [range]
67 [44-86]

Gender: F / M, n
5 / 21

ECOG PS: 0 / 1,n
10 / 16

RCC: non-clear cell / clear cell, n
2 / 24

Prior nephrectomy : n
16

Number of BM: 1 / 2 / >3, n
9 / 7 / 10

Prior BM treatments: Overall/ Surgery/ Radiation, n
10 / 3 / 10

Prior systemic treatment: 0 / 1 / >2, n
7 / 15 / 4

IMDC: Favorable / Intermediate / Poor, n
7 / 10 / 9
Understanding incidence and outcomes of testicular and ovarian germ cell tumors from 2000–2017 using population-based cancer registries.
Authors: Escobar Domenique , Chen Irene , Liu Lihua , Siegmund Kimberly , Daneshmand Siamak , D'souza Anishka , Cortessis Victoria K
Published: February 2025

649

Background:
Both testicular (TGCT) and ovarian germ cell tumors (OGCT) originate from a common primordial germ cell lineage prior to differentiation into sperm or eggs and share several features. While TGCT are extensively studied, less is known about OGCT but given the relative rarity of both TGCT and OGCT, we aimed to comprehensively assess the current landscape of these diseases using population-based cancer registries that surveil the entire civilian population of the US. Importantly, this analysis includes all data from 2000 to 2017 and is therefore not subject to the impacts on cancer data reporting during the COVID-19 pandemic in the US.
Methods:
We accessed population-based data available from the year 2000 forward from Surveillance, Epidemiology, and End Results (SEER) and National Program of Cancer Registries (NPCR) registry networks to obtain information about incidence and outcomes of TGCT and OGCT. NPCR+SEER was utilized to characterize nation-wide patterns of incidence according to demographic features and histologic type, SEER21 to describe age-specific patterns, SEER18 to describe outcomes and SEER9 to describe long-term patterns of age-specific incidence according to year of diagnosis and year of birth. Detailed descriptive analysis were performed. Age-adjusted incidence rates (AAIRs) and temporal trends were calculated overall and stratified by race/ethnicity and histology. Observed and relative survival were also assessed overall and according to race/ethnicity and histology.
Results:
TGCTs were far more common than OGCTs and the majority of all GCTs occurred in adolescents and young adults. The AAIRs of TGCT were greatest in NH white men and for OGCT, greatest in Hispanic White women. Seminoma was the most common histology in TGCT, and dysgerminoma was most common in OGCT. For TGCT, the most drastic increases in incidence were noted in Hispanic and American Indian/Alaska Native men, whereas incidence was relatively stable in non-Hispanic white men. For OGCT, incidence was relatively similar amongst racial/ethnic groups. We also found that observed survival in Black men with TGCT is worse than all other racial/ethnic groups, but relative survival is comparable. A similar and more pronounced finding was seen in OGCT, but Black women experienced both worse observed and relative survival compared to the other groups. Regarding histology, those with seminoma or dysgerminoma had better survival than those with NSGCT/non-dysgerminoma.
Conclusions:
We present a contemporary and comprehensive assessment of incidence and outcomes of TGCT and OGCT for the entire US civilian population from 2000-2017, that is not subject to impacts of cancer reporting during the COVID-19 pandemic. We identified various racial/ethnic differences in incidence and survival both within and between TGCT and OGCT, which highlights opportunities to intervene.
Racial disparities in secondary metastasis in patients with bladder cancer: A 5-year National Inpatient Sample study.
Authors: Saowapa Sakditad , Polpichai Natchaya , Tanariyakul Manasawee , Wannaphut Chalothorn , Kanitthamniyom Chanakarn , Garcia Pleitez Hector J , Olavarria Bernal Diego Alonso , Pangkanon Watsachon , Tran Vivie , Siladech Pharit , Tijani Lukman Aderoju
Published: February 2025

671

Background:
Bladder cancer is one of the most common cancers globally, with significant variations in disease outcomes observed across racial groups. Secondary metastasis plays a critical role in determining disease prognosis and overall survival in bladder cancer patients. However, racial disparities in the metastatic progression of bladder cancer remain underexplored. This study aims to investigate how race influences the patterns of metastasis in bladder cancer patients using a large national database.
Methods:
A retrospective analysis of the National Inpatient Sample (NIS) from 2016 to 2020 was performed to identify adults diagnosed with bladder cancer using ICD-10 codes. Patients were categorized based on the presence of metastasis. Multivariable logistic regression models were used to assess the impact of race on secondary metastasis to key organ systems, including the lung, liver, bone, and brain, while adjusting for potential confounders. Caucasians were used as the reference group, and statistical significance was defined as p-values ≤ 0.05.
Results:
The study cohort included 411,360 patients with bladder cancer, of whom 66,805 (16.2%) had secondary metastasis. The mean age of patients with metastasis was significantly lower (71.00 years, 95% CI: 70.78–71.22) compared to those without metastasis (74.02 years, 95% CI: 73.90–74.14) (p < 0.001). Racial disparities were observed, with African American patients having higher odds of lung metastasis (OR 1.23, 95% CI: 1.11–1.38, p < 0.001) and liver metastasis (OR 1.18, 95% CI: 1.05–1.33, p = 0.005). Asian patients were more likely to develop bone metastasis (OR 1.29, 95% CI: 1.13–1.47, p < 0.001) and brain metastasis (OR 1.46, 95% CI: 1.03–2.09, p = 0.036). Other factors associated with higher metastasis risk included radiation therapy (OR 3.71, 95% CI: 2.16–6.38, p < 0.001), while comorbidities like diabetes (OR 0.64, p < 0.001) and hypertension (OR 0.86, p < 0.001) were associated with lower odds of metastasis.
Conclusions:
This study highlights significant racial disparities in the metastatic progression of bladder cancer, with African American and Asian patients showing higher odds of metastasis to key organ systems compared to Caucasians. These findings underscore the need to consider racial differences in the clinical management and treatment strategies for bladder cancer patients. Further research is required to explore the underlying causes of these disparities and their impact on long-term survival.
Postoperative adjuvant treatment of HER2 overexpression in upper urinary tract urothelial carcinoma with the combination of disitamab vedotin and toripalimab: A real-world retrospective study.
Authors: Zhang Shun , Zhang Shiwei , Deng Yongming , Guo Hongqian , Wu Hao
Published: February 2025

673

Background:
Radical nephroureterectomy (RNU) bears a high recurrence risk. Thus, postoperative treatment is necessary for upper urinary tract urothelial carcinoma (UTUC) patients. The CheckMate-274 study proved the feasibility of immunotherapy after surgery for urothelial carcinoma (UC), but showing no significant efficacy difference compared to placebo in UTUC. Disitamab vedotin is an antibody-drug conjugate (ADC) composed of an anti-HER2 antibody disitamab and MMAE payload. Clinical studies have showed that combining Disitamab vedotin with Toripalimab is an efficacious regimen for advanced urothelial carcinoma. Thus, we are investigating whether this combination therapy following RNU can offer improved survival outcomes.
Methods:
A retrospective analysis was conducted on data from patients who underwent RNU at Nanjing Drum Tower Hospital between April 2022 and April 2024. The study included patients pathologically diagnosed with cT
2-4a
N
0
M
0
UTUC and HER2 positive status (HER2 IHC2+ or HER2 IHC3+). Patients received 26 cycles of Toripalimab (240mg, IV, Day 1, q2w) combined with 8 cycles of Disitamab vedotin (2mg/kg, IV, Day 1,q2w). CT scans of the chest and abdomen were performed every three months. The primary endpoint was the 12-month disease-free survival (DFS) rate.
Results:
The study included 36 cases of UTUC patients after RNU. Among them, 12 cases received treatment with Disitamab vedotin combined with Toripalimab, while 24 cases did not receive postoperative adjuvant therapy. In the treatment group, the 12-month DFS rate was 91.7% (1/12), compared to 62.5% (9/24) in the non-adjuvant therapy group. The most common treatment-related adverse events (TRAEs) in the treatment group were abnormal liver function (41.6%), decreased appetite (50%), and peripheral sensory neuropathy (33.3%), with no Grade 3 or higher adverse events observed.
Conclusions:
Disitamab vedotin combined with Toripalimab demonstrated efficacy as adjuvant therapy following radical nephroureterectomy for UTUC. Based on the one-year DFS outcomes, this combination could be considered as an adjuvant therapy option post-surgery.
Trends in inpatient outcomes of bladder cancer: 2008-2021.
Authors: Olafimihan Ayobami Gbenga , Jackson Inimfon Nsikak , Ntukidem Olanipekun Lanny , Ogedegbe Oboseh John , Shaka Hafeez
Published: February 2025

674

Background:
Bladder cancer is a common malignancy of the urinary tract that is associated with about 16,840 estimated deaths in 2024. With the recent advances in bladder cancer treatment, it is unknown whether the trends in hospitalization outcomes have changed over time. We evaluated the trends in hospitalization outcomes among patients with a diagnosis of bladder cancer.
Methods:
This is a retrospective longitudinal trends study using the Nationwide Inpatient Sample (NIS) database (2008-2021). We identified hospitalizations with bladder cancer using ICD-9 and ICD-10 codes. Multivariate logistic and linear regression models were used to examine the trends in mortality outcomes stratified by demographic subgroups (age, gender and race).
Results:
There were over a million (1,123,567) hospitalizations with bladder cancer between 2008 and 2019. 73.5% were males; The mean age of the patients was 73.5 years. There was an overall increase in mortality amidst admissions with bladder cancer, from 4.5% in 2008 to 4.9% in 2021 (adjusted odds ratio [aOR]: 1.01; P-trend = 0.010). In the age subgroup, elderly patients (≥65 years) had an increase in mortality (aOR: 1.007; P-trend = 0.028). The young adults (18 - 44 years) and middle-aged adults (45 - 64 years) had no significant change in mortality rate (P-trend = 0.31 and P-trend = 0.131 respectively). For gender subgroup analysis, worse mortality outcomes were seen for males (aOR:1.01; P-trend=0.001); females had similar mortality over the period (P-trend=0.53). Racial subgroup analysis showed increased mortality outcomes for non-Hispanic White patients (aOR:1.01; P-trend=0.03). Black (P-trend=0.77) and Hispanic (P-trend=0.46) patients had no significant change in mortality outcomes.
Conclusions:
There was an overall increase in hospital mortality outcomes for bladder cancer patients from 2008-2021. While treatment advances continue to show improvement in survival outcomes, efforts are needed to ensure that hospitalized patients with bladder cancer have improved mortality outcomes.

Inpatient mortality trends of bladder cancer stratified by demographic subgroups.

Adjusted Odds Ratio
P-Trend
95% Confidence Interval

Overall Mortality
1.01
0.010
1.002-1.014

Young adults (18 - 44 years)
1.03
0.31
0.971-1.099

Middle-aged adults (45 - 64 years)
1.01
0.131
0.997-1.024

Elderly patients (≥65 years)
1.01
0.028
1.001-1.014

Male
1.01
0.001
1.005-1.019

Female
1.0
0.53
0.986-1.007

Non-Hispanic White
1.01
0.03
1.001-1.015

Black
1.00
0.77
0.979-1.016

Hispanic
0.99
0.46
0.968-1.015
Second primary malignancy in bladder cancer: A retrospective population-based analysis.
Authors: Ogedegbe Oboseh John , Bai Sakshi , Ntukidem Olanipekun Lanny , Egwom Peter , Malik Duresha , Olafimihan Ayobami Gbenga , Atencah Stanley Ntow
Published: February 2025

676

Background:
Bladder cancer is responsible for about 4% of cancers in the United States. It is the fourth most common cancer in men. A second primary malignancy is a significant complication in cancer survivors, with dire effects on morbidity and mortality. The data on second primary malignancies (SPM) in bladder cancer is limited. Therefore, we aim to evaluate and discuss this risk.
Methods:
We analyzed the Surveillance, Epidemiology, and End Results (SEER) database, comparing secondary cancer rates among bladder cancer cases diagnosed from 2000 to 2021. A second primary malignancy was defined as a malignancy developing six or more months after an index bladder cancer diagnosis. We used the SEER MP-SIR session to obtain the p-value, observed/Expected (O/E) ratio, and absolute excess risk (AER) per 10,000.
Results:
238,358 bladder cancer cases from 2000-2021 met our inclusion criteria and were included in our study. Of these cases, 46,859 (19.7%) developed second primary malignancies. The mean age of SPM was 75.03 years. The risk of developing SPM was significantly higher than the general population, with an O/E ratio of 1.48 (CI 1.46-1.49, AER 99.85, p < 0.05). Most common SPMs included Hypopharynx (O/E ratio 1.3 CI 1.0-1.67, p < 0.05), Esophagus (O/E ratio 1.15 CI 1.05-1.26, p < 0.05), Liver (O/E ratio 1.14 CI 1.05-1.23, p < 0.05), Lung (O/E ratio 1.89 CI 1.85-1.93, p < 0.05), Vagina (O/E ratio 2.58 CI 1.71-3.73, p < 0.05, Prostate (O/E ratio 1.39 CI 1.36-1.42, p < 0.05, Acute Myeloid Leukemia (AML) (O/E ratio 1.58 CI 1.01-2.34, p < 0.05).
Conclusions:
Compared to the general population, there is a statistically significant increased risk of secondary primary malignancies in bladder cancer patients. Bladder cancer survivors would benefit from proactive screening modalities and follow-up for the development of SPM.
Ethnic disparities in clinical trials for FDA-approved drugs in urothelial cancer: An analysis in the post-COVID-19 era (2020-2024).
Authors: Bastos Bruno R. , Schwartz Michael A. , Gligich Oleg , Bhandari Akshay , Kuritzky Nicolas , Borregales Leonardo , Barrientos Jacqueline Claudia , Nieder Alan , Linzer Debra , Ramirez-Ridelli Antonio , Cusnir Mike
Published: February 2025

677

Background:
Ethnic and racial disparities in oncology clinical trial participation continue to pose significant challenges. Despite initiatives by the NCI and FDA to address these disparities through policies established in 2017, notable gaps in both cancer treatment and clinical trial involvement persist. There is a lack of comprehensive data regarding minority participation in clinical trials for FDA-approved urothelial cancer therapies in the post-COVID-19 context.
Methods:
From 2020 to 2024, we examined data from 2,755 patients recruited in eight industry-sponsored clinical trials (BCL2001, CheckMate 274, CheckMate 901, EV-302, KEYNOTE 057, CS-003, QUILT-3.032, TROPHY) that led to the FDA approval of new agents or indications for urothelial cancer. We assessed and tabulated the reporting of racial demographics within these trials, employing chi-square statistics and machine learning algorithms to compare participation among White, Black, Asia and Hispanic patients against SEER data on urothelial cancer incidence.
Results:
Race data was reported in 7 (BCL2001, CheckMate 274, CheckMate 901, EV-302, CS-003, QUILT-3.032, TROPHY) out of 8 trials (87.5%), but only 5 (CheckMate 274, CheckMate 901, EV-302, CS-003, TROPHY) of these trials (71%) included data on Black and Asian populations alongside White participants. Notably, none of the trials reported date on Hispanic participants. Our analysis revealed that in the 7 trials providing race data, 79% of participants were White, indicating overrepresentation (p=0.013). among the 5 trials with comprehensive race reporting, Blacks were unrepresented at 2.3% (p=0.001), while Asians constituted 10%, showing no statistical significance (p=0.90) in difference in representation. No data was available for Hispanics.
Conclusions:
The continued underrepresentation of minorities in FDA-approved clinical trials for urothelial cancer is a pressing concern still in the post-COVID-19-era. To rectify these issues, it is essential to implement policies that improve data collection and standardize ethnic nomenclature. Furthermore, international collaborative trials should prioritize separate data reporting for U.S. participants, utilizing NCI SEER nomenclature to endure accurate representation and analysis.
The impact of social vulnerability on perceived health in individuals with bladder cancer.
Authors: Jatwani Karan , Miran Seyedeh Azadeh , Ma Philip , Whalen Michael Joseph , Jain Maneesh Rajiv , Khosla Atulya Aman
Published: February 2025

678

Background:
Bladder cancer is the sixth most common malignancy in the United States. Social determinants of health (SDOH) have been increasingly recognized as drivers of disparities in cancer care. Improved understanding of the role of social vulnerabilities could better inform the cancer care delivery interventions towards equitable cancer care for bladder cancer patients. We aimed to study the impact of key SDOH measures (everyday discrimination, supportive relationships, neighborhood characteristics, and food and housing security) on the perception of overall health in bladder cancer patients using a publicly available database.
Methods:
A cross-sectional study was conducted using overall health and SDOH survey data collected by the National Institutes of Health All of Us Research Program from June 2017 to June 2022. Ordinal logistic regression was utilized to assess associations between overall perception of health and each specific SDOH survey domain. All statistical tests were two-sided, and a p-value less than 0.05 was statistically significant; multiplicity adjustments were not made. The Statistical package (0.13.5) of Python (Version 3.1) was used for all statistical analyses.
Results:
1,796 participants with bladder cancer met the inclusion criteria. 640 (38.58%) had completed the SDOH surveys and were considered for analysis. Of the total population, there was a significant male preponderance (66.1% vs 31%). 559 (87.3%) were White, 3.4% Black or African American, and 3.6% with Hispanic ethnicity. In the ordinal logistic regression models. for every unit increase in the score of the supportive relationships SDOH domain (more supportive relationships), participants were 4% (OR = 1.04, 95% CI = [1.018, 1.053], p<0.0001) more likely to have a higher perception of general health. Similarly for every unit increase in the food and housing security domain (more secure food and housing status), participants are 19% ((OR =1.19, 95%CI= [1.06,1.34], p 0.004) more likely to have a higher perception of general well-being. Controlling for all other variables, Black race, Hispanic ethnicity, smokers, and age less than 65 years were independently significant for poor perception of overall health (p < 0.05).
Conclusions:
This is one of the first studies evaluating the role of each component of SDOH on the perception of overall health in bladder cancer patients. Our study demonstrates a clear predictive link between social determinants of health and the perceived overall health of bladder cancer patients. Specifically, stronger social support networks and secure access to food and housing were significantly associated with a more positive perception of health. These findings suggest that future directions in bladder cancer care should prioritize the development and implementation of comprehensive care models that address these social needs.
Inclusion of patients with reduced performance status (ECOG 2 or higher) in FDA registrational trials for urothelial cancer.
Authors: Parab Panah , Juthani Ronit , Seetharaman Kala
Published: February 2025

680

Background:
The Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) is a tool used to describe a cancer patient’s functional status and recruit participants into clinical trials. Clinical trials recruit patients with a good performance status (ECOG 0 or 1) which is not concordant with the real-world population. ASCO-Friends of Cancer Research in a joint statement has recommended the inclusion of patients with reduced PS in clinical trials. We evaluated the inclusion of patients with ECOG 2 or greater in urothelial cancer clinical trials leading to FDA approvals between 2014 and 2024.
Methods:
The US Food and Drug Administration (FDA) website was searched for all the drugs or drug combinations approved for the treatment of urothelial cancer in the last 10 years. We used identifiers like the drug name, trial name, and registration number to retrieve data on participant ECOG scores from public databases. The data was then tabulated and trends were analyzed.
Results:
The US FDA approved 16 drugs and combinations for the treatment of urothelial cancer from 2014-2024. The trials for these drugs enrolled a total of 5621 participants, of which only 107 (1.9%) belonged to ECOG PS 2 or more. ECOG data was not available for OLYMPUS trial. Only one of the trials included 3 participants with ECOG 3. Five trials did not have any participants belonging to ECOG 2 or higher. Most of the trials had percentage enrollment of ECOG 2 <10% except EV-201.
Conclusions:
Participants with ECOG 2 and greater have minimal enrolment in registrational clinical trials of urothelial cancer. This limits the options available for treatment of urothelial cancer in patients with reduced PS. Greater inclusion of poor PS patients is needed in future trials for greater health equity.

Clinical trial
Year
Reduced PS% (ECOG 2 or higher)

QUILT-3.0320
2024
3.5%

BLC3001
2024
9.4%

EV-302/KN-A39
2023
2.9%

nadofaragene firadenovec-vncg
2022
2.5%

CHECKMATE-274
2021
2.3%

EV-201
2019
12.4%

JNJ-42756493
2019
7.1%

KEYNOTE-045
2017
1.1%

CHECKMATE-901, EV-301, TROPHY, JAVELIN Bladder 100, KEYNOTE-057, durvalumab, atezolizumab
2016-2024
<1%
Understanding metastatic squamous cell carcinoma patients receiving pelvic exenteration vs radical cystectomy: A nationwide context.
Authors: Bine Christopher Reese , Czaplicki Alec , Silberstein Peter T.
Published: February 2025

681

Background:
Squamous Cell Carcinoma (SCC) is a rare subtype of bladder cancers, consisting of 2-5% of all bladder cancers. SCC is associated with chronic bladder inflammation often due to catheters, kidney stones, and bladder outlet obstruction. While gold standard treatment for SCC is radical cystectomy (RC), many patients receive more extensive surgery such as pelvic exenteration (PE). PE involves removing all organs from a person’s pelvic cavity whereas RC involves removing the bladder and nearby tissue. This study will examine the characteristics of metastatic SCC patients receiving PE vs RC to better understand why some patients may not receive RC.
Methods:
The National Cancer Database (NCDB) was used to identify patients diagnosed with bladder squamous cell carcinoma from 2004 to 2020 using the histology codes 8050, 8070-8076, 8084 and NCDB analytic stage code IV as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05.
Results:
Of the 561 patients in the sample, 211 (37.6%) received PE and 350 (62.4%) received RC. Patients receiving PE survived 32.8 months and patients receiving RC survived 35.8 months (p>0.05). Patients receiving PE were more likely to receive adjuvant radiation or chemoradiation, have no residual tumor or microscopic residual tumor after surgery, receive care from an academic facility, and to have lymph vascular invasion (p<0.05). These patients were also more likely to present at a younger age (62.86 vs 65.37 years) yet interestingly were more likely to have fewer regional lymph nodes positive (9.27 vs 14.90) (p<0.05). There were no significant differences between income level, race, the number of comorbid conditions (Charlson-Deyo Score), insurance status, tumor size, or time to surgery (p>0.05) between the two groups.
Conclusions:
37.6% of patients in this sample received PE over RC, the gold standard. PE patients had disease that more greatly invaded the lymphatics and had better surgical margins, yet PE offered no significant survival benefit. More research is needed to better understand why some patients receive more extensive surgical intervention.
Role of circulating tumor DNA (ctDNA) in locally advanced (LA) and metastatic urothelial cancer (mUC).
Authors: Aslanova Minira , Lawrence Arianna , Wang Hongkun , Aragon-Ching Jeanny B.
Published: February 2025

685

Background:
The role of ctDNA is emerging as an adjunctive prognostic tool for survival in the laUC setting, but its role is evolving in mUC. We aimed to analyze ctDNA in the real-world setting and correlate its trend with available clinical, radiographic, and next generation sequencing (NGS) data.
Methods:
Patients with a diagnosis of laUC and mUC were included in the analysis of an IRB-approved protocol. Clinical/pathologic stage, systemic therapy received, NGS (TEMPUS) results, and tumor-informed detection and quantification (Signatera, Natera, Inc) was analyzed with baseline ctDNA data (positive + vs. negative -). Mean tumor molecules (MTM) levels were obtained and time to radiographic progression (TTrP), radiographic progression-free survival (rPFS) and overall survival (OS) evaluated. If baseline ctDNA was negative (ctDNA-), time to initial ctDNA+ was recorded. Analyses of time in days (d) from ctDNA- to ctDNA+ with regard to radiographic progression and OS was analyzed using Kaplan-Meier method and between group comparison by Log-rank test. Descriptive statistics were used to evaluate ctDNA trends in patients receiving various systemic therapies.
Results:
47 patients (n=24 laUC; n=23 mUC) were included in analyses; 34 Male, 14 Female. The median rPFS in patients with baseline ctDNA+ was 189d. Higher baseline levels did not significantly affect rPFS (p=0.0518, HR=1.007) or TTrP (p=0.2718, HR=1.004). The median rPFS in baseline ctDNA- level was 553d. The overall TTrP was worse in mUC baseline ctDNA+ vs baseline ctDNA- (log-rank p=0.037). Median OS in baseline ctDNA+ was 266d and ctDNA- was not evaluable. Patients who received immunotherapy-based treatment or antibody-drug-conjugate based therapy had a decline in baseline ctDNA at 1 month follow up. Lack of response or clearance of ctDNA served as predictor of mortality. Of the mUC patients who had baseline ctDNA +, mortality was as high as 70% at the time of follow up. No correlation with specific NGS findings were seen.
Conclusions:
The use of ctDNA allowed for identification of earlier disease relapse than radiographic imaging alone which allows for earlier switch in therapeutic management. Obtaining a baseline positive ctDNA result without conversion to a negative value portends a poor prognosis in mUC.
Detection of early-stage urothelial cancers using methylation patterns in urine cell-free DNA.
Authors: Stewart Tyler F. , Shenoy Archana , Safavi Rojin , Stuart Sarah , McClintock Kelly , Alchaar Amani , Bagrodia Aditya , Kader Karim , McKay Rana R. , Recio Neil , Wagner Heidi , Fleshner Neil Eric , Larson Matthew H. , Salmasi Amirali
Published: February 2025

687

Background:
Urine cell-free DNA (ucfDNA) has the potential to improve detection and monitoring of early-stage urothelial carcinoma (UC). We previously demonstrated the utility of ucfDNA methylation patterns to detect non-muscle invasive bladder cancer (NMIBC) in patients with suspicious bladder lesions (by cystoscopy or imaging). Based on those results, we trained a biopsy-free urine classifier for cancer detection. Here, we evaluate the performance of the urine classifier in an independent test set of patients with early-stage NMIBC or upper tract UC (UTUC).
Methods:
The urine classifier was trained using GRAIL’s biobank of plasma and cancer tissue, as well as prospectively collected urine from cancer and non-cancer participants (urine samples, n = 468). The locked classifier was evaluated at 95% and 98% target specificities on an independent test set of biobanked urine from patients with a new diagnosis of NMIBC (n = 49, 24 low grade and 25 high grade) and UTUC (n = 19, 9 low grade and 10 high grade), as well as age- and gender-matched non-cancer controls (n = 66).
Results:
The observed specificities in the test set at target specificities of 95% and 98% were 93.9% (62/66, 95% CI 85.2-98.3%) and 97.0% (64/66, 95% CI 89.5-99.6%), respectively. Observed sensitivity was the same at both target specificities. Of the 68 patients with a new diagnosis of either NMIBC or UTUC, 57 were classified as cancer, while 11 were classified as non-cancer. The urine classifier had a sensitivity of 100% for high grade NMIBC (25/25; 95% CI 86.3-100%) and 58.3% for low grade NMIBC (14/24; 95% CI 36.6-77.9%). For patients with UTUC, the urine classifier had a sensitivity of 100% for high grade UTUC (10/10; 95% CI 69.2-100%) and 88.9% for low grade UTUC (8/9; 95% CI 51.8-99.7%).
Conclusions:
A biopsy-free urine classifier based on ucfDNA methylation patterns is able to identify early-stage NMIBC and UTUC with high sensitivity at high specificity, particularly for patients with high grade disease. The classifier performance was validated in urine with an independent test set and did not require matched blood or tissue, highlighting the potential for a non-invasive and cost-effective method for UC screening. Current efforts are focused on evaluating urine classifier performance in prospective cohorts of UC patients undergoing both screening and recurrence monitoring.
Targeting more than tumors: The impact of enfortumab vedotin and pembrolizumab (EV/P) on skeletal muscle loss and sarcopenia in metastatic urothelial carcinoma (mUC).
Authors: Aydogdu Can , Hahn Simon Erwin , Brinkmann Isabel , Götz Melanie , Enzinger Benazir , Semmler Marie , Berg Elena , Kolligs Frederik , Tamalunas Alexander , Stief Christian G. , Casuscelli Jozefina
Published: February 2025

689

Background:
Sarcopenia and skeletal muscle loss are associated with poor prognosis and limited survival in metastatic cancer patients. This study aims to assess the impact of systemic treatment with enfortumab vedotin and pembrolizumab (EV/P) on skeletal muscle index (L3SMI) in patients with metastatic urothelial carcinoma (mUC).
Methods:
We conducted a retrospective analysis of mUC patients treated with EV/P at a single German tertiary care center. L3SMI was measured at baseline (before treatment) and at the first radiographic staging, approximately three months post-treatment on routinely obtained CT (computed tomography) or PET CT (positron emission tomography) imaging. L3 muscle area was measured using OsiriX software and normalized by height squared to calculate L3SMI. Sarcopenia was defined using L3SMI cutoffs based on body mass index (BMI): for men with BMI <25 kg/m², L3SMI <43 cm²/m²; for men with BMI ≥25 kg/m², L3SMI <53 cm²/m²; and for women, regardless of BMI, L3SMI <41 cm²/m².
Results:
Between November 2023 and October 2024, 24 patients with metastatic urothelial carcinoma (mUC) who had available imaging were included in the analysis. The median time between baseline and first follow-up imaging was 84 days. At baseline, 46% of patients met the criteria for sarcopenia, and by the first follow-up, 33% had experienced significant L3SMI loss (>4%), leading to 50% of patients being classified as sarcopenic. Despite this, significant L3SMI loss was not associated with poorer radiographic staging outcomes. Of the patients, 62.5% achieved a partial response (PR), 25% had stable disease (SD), and 12.5% showed progressive disease (PD). Conversely, 16% of patients showed a significant gain in L3SMI during the same period. A moderate, non-significant correlation was found between sarcopenia at first follow-up and treatment-related adverse events (r=0.339,
p=0.11
). In contrast, a significant correlation was observed between the onset of therapy-induced peripheral neuropathy and sarcopenia (r=0.418,
p=0.042
).
Conclusions:
This study emphasizes the high prevalence of sarcopenia in real-world mUC patients undergoing EV/P therapy, along with notable muscle loss within the first few months of treatment. Interestingly, this early decline in L3SMI did not correlate with poorer radiographic outcomes. Given that EV/P is a continuous therapy with the inevitable development of cumulative toxicities, monitoring muscle loss may help to implement strategies to avoid them. Our findings suggest a potential causal relationship between EV/P therapy and L3SMI loss, warranting further investigation. Larger studies with extended follow-up are needed to gain deeper insight into the long-term impact of sarcopenia in patients receiving EV/P treatment.