bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncological benefit of avelumab maintenance therapy for advanced or metastatic urothelial carcinoma in comparison with patients with conventional chemotherapy alone era.
Authors: Hatakeyama Shingo , Sekine Yuya , Shinohara Masanao , Numakura Kazuyuki , Yoneyama Takahiro , Kawashima Yohei , Sato Satoshi , Habuchi Tomonori , Ohyama Chikara
Published: February 2025

711

Background:
The benefit of avelumab maintenance therapy for advanced or metastatic urothelial carcinoma in real world practice remains unknown. We evaluated the oncological outcomes of avelumab maintenance therapy in comparison with conventional platinum-based 1
st
line chemotherapy in real-world practice.
Methods:
We retrospectively evaluated 302 and 85 patients treated with and conventional platinum-based first-line chemotherapy without avelumab (chemo group) and avelumab maintenance therapy (avelumab group) between March 2004 to Sep 2024. We compared overall survival (OS) between the patients with the chemo and avelumab groups stratified by the number of cycles of first-line chemotherapy. Primary outcome was the comparison of OS in patients without progression disease (non-PD) at cycle 4 between the chemo and avelumab groups. Secondary outcomes were the impact of the administration of pembrolizumab on OS in patients with non-PD at cycle 4 in the chemo group and the comparison of OS in patients with non-PD at cycle 2-3 between the chemo and avelumab groups. Exploratory outcomes were disease-free survival (DFS) and OS based on response rate of first-line chemotherapy, first-line treatment regimen, and number of first-line chemotherapy cycles in the avelumab group.
Results:
We identified 124 and 49 patients with non-PD at cycle 4 in the chemo and avelumab groups, respectively. The OS from the initiation of first-line chemotherapy in the avelumab group was significantly longer than that in the chemo group (70 vs. 23 months, P = 0.009). We identified 104 and 33 patients with non-PD at cycle 2-3 in the chemo and avelumab groups, respectively. The OS from the initiation of first-line chemotherapy in the avelumab group was significantly longer than that in the chemo group (33 vs. 13 months, P = 0.002). A multivariable Cox regression analysis showed administration of avelumab was significantly associated with reduced risk of OS (hazard ratio, 0.41; P < 0.001). Of 85 patients with avelumab, the median DFS was 17 months from first-line therapy and 8.1 months from the avelumab maintenance therapy, respectively. No significant differences were observed in DFS and OS between first-line treatment regimens, and between the object response rate for first-line chemotherapy. However, the DFS and OS tended to improve in patients with first-line chemotherapy 4 cycles or more.
Conclusions:
We found a potential benefit of avelumab maintenance therapy on oncological outcome in real-world practice regardless of number of first-line chemotherapy. No progression within first 4 cycles of platinum-based chemotherapy might be one of the key factors for improved outcome. Further long-term follow-up is necessary.
First-line therapies analysis in advanced/metastatic urothelial carcinoma: Prognostic insights with propensity score analysis and RNA-seq.
Authors: Wang Jingjing , Jiang Yupeng , Zou Wen , He Wei , Chen Minfeng , Xu Chao
Published: February 2025

713

Background:
The combination of antibody-drug conjugates (ADCs) and immunotherapy has great prospects for first-line treatment of advanced urothelial carcinoma (UC). This study aimed to explore the efficacy, safety, and prognostic biomarkers of disitamab vedotin (DV) combined with a PD-1 inhibitor and compared them with other first-line regimens without DV.
Methods:
Patients with advanced UC received first-line treatment and were enrolled retrospectively from July 2021 to December 2023 in two cancer centers. Propensity score (PS) matching analysis was used to compare the DV group and the non-DV group. In the DV group, RNA-seq was used to analyze differential expressed genes.
Results:
A total of 97 patients were included. The 1-year overall survival (OS) and progression-free survival (PFS) rates were 74.4% and 49.7%, respectively. PS score and first-line treatment regimen were independent prognostic factors for both OS and PFS. Survival analysis showed that DV combined with PD-1 inhibitor significantly improved PFS compared with other 3 regimens, including chemotherapy alone (P≤0.01), PD-1 inhibitor plus chemotherapy (P≤0.01), and PD-1 inhibitor alone (P≤0.01). DV combined with PD-1 inhibitor also led to better OS compared to chemotherapy (P≤0.01) or PD-1 inhibitor alone(P≤0.01), with a trend toward improved OS versus PD-1 inhibitor plus chemotherapy (P＝0.129). After PS matching, there were 40 patients, each in the DV group and Non-DV group. There were significant differences between the DV group and Non-DV group in terms of objective response rate (77.5% vs.37.5%, p=0.001), 1-year PFS rate (72% vs.22.2%, p=0.000), and 1-year OS rate (84% vs. 62%, p=0.003). Additionally, differentially expressed genes were identified between patients using DV with PFS >1 year and PFS <1 year and RNA-Seq analysis highlighted enriched pathways such as cytosolic and metabolic pathways, offering potential insights into DV resistance mechanisms.
Conclusions:
The first-line regimen of DV plus immunotherapy for patients with advanced UC was more effective and safer than the regimen without DV.
Enfortumab vedotin plus pembrolizumab in metastatic urothelial carcinoma: First results on outcomes and safety in a German multicenter real-world patient cohort (GUARDIANS).
Authors: Zschaebitz Stefanie , Casuscelli Jozefina , Büttner Thomas , Darr Christopher , Volk Anna-Lisa , Hennig Martin , Holzwarth Nina , Zengerling Friedemann , Dib Muammar , Schlack Katrin , Paffenholz Pia , Heinzelbecker Julia , Mandal Subhajit , Wessels Frederik , Seidl Daniel , Erne Eva , Foller Susan , Höllein Alexander , Grünwald Viktor , Schnabel Marco Julius ,   GUARDIANS
Published: February 2025

715

Background:
The prospective phase 3 study EV-302 demonstrated superiority regarding efficacy of Enfortumab vedotin plus Pembrolizumab (EVP) compared to platinum-based chemotherapy in patients (pts) that received first-line (1L) therapy for metastatic urothelial carcinoma (mUC). Since presentation of the data in September 2023 EVP was considered a new standard of care (SOC) however only approved in Europe in August 2024. We analyzed efficacy and safety outcomes of pts treated with EVP outside of clinical trials.
Methods:
Retrospective data were collected from 19 German academic and community hospitals for pts with metastatic UC who received EVP as off-label therapy when reimbursed by their insurance company before European Medicines Agency (EMA) approval, or as SOC treatment after EMA approval. Imaging and therapy management were in accordance with local standards. Adverse events (AEs) were reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Median progression-free survival (mPFS) and overall survival (mOS) were estimated using the Kaplan-Meier method by local investigators.
Results:
We identified 215 pts for the safety cohort (all pts who received EVP at least once) and 164 pts for the efficacy cohort (all pts who received at least one staging or died prior to first planned imaging).The median age for the eligible patients was 71 yr (range 25-89). The Eastern Cooperative Oncology Group performance status (ECOG PS) was 0/1/2/3-4/unknown for 46.0/31.6/17.2/4.7/0.5% of patients. The overall response rate was 60.7% (partial response 51.0%, complete response 9.7%). mOS was not reached and mPFS was 13 mo (95% confidence interval 4.5-21.5). Any-grade AEs were observed in 73.0% and CTCAE grade ≥3 AEs in 30.2%. Any-grade immune-related AEs were observed in 37.7% and CTCAE grade ≥3 AEs in 16.7%. The most common AEs were peripheral sensory neuropathy (all grade: 30.2%) and skin toxicity (all grade:24.2%). No treatment-related fatal event occurred. Limitations include the retrospective design and short follow-up.
Conclusions:
Administration of EVP in a real-world patient population showed promising effectiveness and an acceptable toxicity profile. No new safety signals were reported. Our results support the use of EVP in 1L in pts with mUC. Updated data with longer follow-up will be presented at the meeting.
Feasibility and efficacy of cisplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer in older patients: A retrospective French GETUG study.
Authors: Combe Benjamin , Dumont Clement , Roubaud Guilhem , Pouessel Damien , Lafitte Elsa , De Vries Manon , Laguerre Brigitte , Boyle Helen Jane , Guilbert Aymeric , Narciso Bérengère , Mahammedi Hakim , Borchiellini Delphine , Abbar Baptiste , Gross-Goupil Marine , Laramas Mathieu , Bruyere Franck , Biogeau Julie , Cancel Mathilde
Published: February 2025

735

Background:
Cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy is the gold standard in localized muscle-invasive bladder cancer (MIBC), for fit patients. However, NAC is less prescribed in older patients, mainly due to safety concerns. This study aimed to evaluate the feasibility and efficacy of NAC for patients aged ≥ 75.
Methods:
We retrospectively included older patients, from 14 French GETUG centers. All patients had received at least one cycle of cisplatin-based NAC for localized MIBC, between 2010 and 2022. Primary outcome was NAC feasibility evaluated as the rate of patients that underwent optimal treatment, defined as at least 4 cycles of chemotherapy followed with local treatment (surgery or chemoradiotherapy). Secondary outcomes were NAC safety and efficacy.
Results:
156 pts were included. Median age was 77 (from 75 to 96), with 20% aged ≥ 80. Patients were in good general condition: 54% were PS 0, with a median serum albumin level of 39 g/L, and 86% had a creatinine clearance ≥ 60 ml/min. 108 (69%) had a cT2N0 MIBC. 75 (48%) received dose dense MVAC (ddMVAC), 80 (51%) received gemcitabine-cisplatin (GC) and one patient received MVAC. 96 (62%) received an optimal treatment. 50 patients (32%) prematurely stopped NAC, due to death (3 pts, 2 from unknown causes), progressive disease (4), infection (3), toxicity (34 patients) mainly renal and hematological ones. Among them, 38 (76%) underwent local treatment. Among the 112 patients that underwent cystectomy, pathological complete response (pCR) was significantly more frequent when they received ≥ 4 cycles (36/78 = 46% versus 5/34 = 15%, p = 0.002). Median follow up from diagnosis was 28 months, with 97 patients (62%) that were still alive at the end of follow-up. Median disease-free survival was 3 years and 3 months. 2-years overall survival (OS) was 72%; 5-years OS was 56%.
Conclusions:
These data suggest that NAC for MIBC is feasible in selected older patients, even if toxicity was the main reason for cisplatin-based regimen discontinuation. Older patients who received optimal treatment were more often in pCR. OS in the this cohort of older patients was very similar to the results published in younger patients.
Radical cystectomy in female patients: Does the urinary diversion type affect postoperative complications?
Authors: Zahir Mazyar , Moghaddam Farshad Sheybaee , Ladi Seyedian Seyedeh Sanam , Miranda Gus , Cai Jie , Aron Monish , Desai Mihir , Gill Inderbir , Schuckman Anne K. , Daneshmand Siamak , Djaladat Hooman
Published: February 2025

752

Background:
Data is limited on the possible impact of urinary diversion (UD) type on post cystectomy complications, particularly in women. This study aims to investigate this issue and identify predictors of post-cystectomy complications in female population.
Methods:
We utilized our prospectively maintained IRB-approved radical cystectomy (RC) database (#HS-01B014) to identify all female patients who underwent RC between 2003 and 2021. Patients were categorized into three groups based on their UD type: ileal conduit (IC), neobladder (NB) and continence cutaneous diversion (CCD). Demographics, baseline characteristics and postoperative complications were compared across the three groups. A multivariate logistic regression analysis was used to assess the predictors of complications at 90 days postoperatively.
Results:
A total of 531 female patients were included: 263 (49.5%) with IC, 206 (38.8%) with NB, and 62 (11.7%) with CCD. The table outlines the patients' demographics and perioperative characteristics. The overall 30-day complication rates were comparable across groups: 54.9% for NB, 51.6% for CCD, and 61.6% for IC (p = .195). Similarly, 90-day complication rates were also comparable (NB = 65.5%, CCD = 64.5%, IC = 70.3%; p = .456). 90-day complication subgroups including cardiac, pulmonary, gastrointestinal, hematologic, infectious, and neurologic were comparable between different UDs. However, genitourinary complications were significantly higher in CCD (32.3%) compared to IC (13.3%) and NB (14.6%) (p < .001). Multivariate analysis showed that patients with CCD had increased odds of 90-day genitourinary complications compared to NB (OR = 2.83 [95%CI: 1.38, 5.72], p= .001), while preoperative eGFR was protective (OR = 0.987 [95%CI; 0.977, 0.997], p = .010).
Conclusions:
Our results suggested that UD type has minimal influence on cumulative 30- and 90- day post-cystectomy complications. However, CCD was associated with an increased odds of 90-day genitourinary complications.

Demographics and perioperative characteristics of patients stratified by urinary diversion type.

Patient characteristics
Neobladder(N = 206)
Continent Cutaneous Diversion (N =62)
Ileal conduit(N = 263)
p

Age (yrs.)
64.4 ± 9.8
64.2 ± 10.5
73.5 ± 10.4
<.001

Charleson Comorbidity Index
0
80 (38.8%)
25 (40.3%)
41 (15.6%)
<.001

1
63 (30.6%)
11 (17.8%)
60 (22.8%)

>=2
63 (30.6%)
26 (41.9%)
162 (61.6%)

Preoperative eGFR (mL/min)
73.2 ± 24.7
72.3 ± 32.0
63.8 ± 29.0
<.001

Surgical Approach
Open
196 (95.1%)
60 (96.8%)
177 (67.3%)
<.001

Robotic assisted
10 (4.9%)
2 (3.2%)
86 (32.7%)

Pathological Staging
OC (< (y)pT2; pN0)
166 (80.6%)
44 (71.0%)
168 (63.9%)
.002

EV (> (y)pT2; pN0)
26 (12.6%)
9 (14.5%)
62 (23.6%)

LN+ (pN+)
14 (6.8%)
9 (14.5%)
33 (12.5%)
Body composition and immunotherapy outcomes in patients with advanced urothelial carcinoma.
Authors: Kim Sojin , Yoon Shinkyo , Park Inkeun , Lee Jae Lyun , Jeong Hyehyun , Ko Yousun , Kim Kyung Won , Kim Sun Young
Published: February 2025

762

Background:
Abnormalities in body composition, including sarcopenia and myosteatosis, have been identified as prognostic factors in patients (pts) receiving cytotoxic chemotherapy. However, data regarding the impact of these factors in patients undergoing immune checkpoint inhibitors (ICI) therapy, particularly in those with advanced urothelial carcinoma (aUC), remain limited. This study aimed to evaluate the prognostic significance of body compositions obtained from abdomen-pelvis computed tomography (APCT) in pts with aUC.
Methods:
This retrospective study included pts with aUC who received ICI (atezolizumab or pembrolizumab) between Jan 2019 and Dec 2022 at Asan Medical Center, Seoul, Korea. Body composition was evaluated using selected axial images at the L3 lumbar vertebrae level from APCT, through an artificial intelligence-driven imaging analysis platform. T-score ≤-2 (-2 SD from the mean reference value in Korean population) was used as cutoff points for sarcopenia and myosteatosis. Visceral obesity (VO) was defined as visceral fat area ≥ 100cm
2
and subcutaneous obesity (SFO) as subcutaneous fat area / height
2
≥ 50cm
2
/m
2
in males and 42cm
2
/m
2
in females. The associations between body composition parameters with overall survival (OS) and progression-free survival (PFS) were analyzed.
Results:
A total of 212 pts were included. Median age was 68 (range, 31-86) and 53 pts (25%) were females. ICIs were primarily administered as second-line treatment following failure to platinum-based treatment (N=207, 98%), with 5 pts (2%) receiving ICI as first-line treatment in a metastatic setting. Atezolizumab was given to 174 pts (82%) and pembrolizumab to 38 pts (18%). The prevalence of sarcopenia prior to treatment was 22% (45/212), while myosteatosis was observed in 52% of pts (110/212). VO and SFO were present in 62% and 43% of pts, respectively, with 37% classified as overweight (body mass index (BMI) ≥25kg/m
2
). Myosteatosis at baseline was associated with an increased risk of mortality (HR 1.58, 95% CI: 1.11–2.23), while sarcopenia, VO, SFO, and BMI did not show significant associations with OS. PFS was not affected by any body composition parameters. Multivariate Cox regression analysis demonstrated that liver metastasis (HR 2.78, 95% CI: 1.94–4.00), hemoglobin (HR 0.52, 95% CI 0.35-0.77), and myosteatosis (HR 1.57, 95% CI 1.12-2.19) were independently associated with OS after adjusting for age and sex.
Conclusions:
In pts with aUC treated with ICI, myosteatosis showed poorer OS, while sarcopenia, VO, SFO, and BMI did not demonstrate a significant impact. Myosteatosis was significantly associated with OS after adjusting for other clinical factors, which suggests a possibility of a novel prognostic marker in pts with aUC receiving ICI.
Association between radiation therapy to the recurrence sites and oncological outcomes in patients who experienced local recurrence and/or pelvic lymph node metastases after radical cystectomy: A multicenter retrospective study.
Authors: Fujita Naoki , Hosogoe Shogo , Tanaka Toshikazu , Ishii Noritaka , Momota Masaki , Ito Hiroyuki , Yoneyama Takahiro , Ohyama Chikara , Hatakeyama Shingo
Published: February 2025

788

Background:
Local recurrence and/or pelvic lymph node metastases after radical cystectomy (RC) are often observed in patients with muscle-invasive bladder cancer (MIBC). Although chemotherapy and immune checkpoint inhibitors are the main treatment strategies in such patients, radiation therapy (RT) to the recurrence sites might be one of the treatment options. However, its effects on oncological outcomes remain unclear.
Methods:
This multi-institutional retrospective study included 106 patients who experienced local recurrence and/or pelvic lymph node metastases without distant metastases after RC. Patients were divided into two groups: patients who were treated with RT to the recurrence sites (RT group) and without (non-RT group). Multivariable Cox-proportional hazards regression analyses were performed to evaluate the effects of RT on cancer-specific survival (CSS) and overall survival (OS) after recurrence.
Results:
The median age at recurrence was 72 years, and the median follow-up period after recurrence was 13 months. Of the 106 patients, 65 (61%) received neoadjuvant chemotherapy (NAC) and 30 (28%) were treated with RT after recurrence. CSS and OS were not significantly different between the two groups (
P
= 0.569 and
P
= 0.456, respectively). In univariable analyses, NAC, pure urothelial carcinoma, tumor grade, and lymphovascular invasion were significantly associated with CSS. Similarly, NAC, pure urothelial carcinoma, tumor grade, lymphovascular invasion, and pathological lymph node involvement were significantly associated with OS. After adjustment for these confounding variables, RT to recurrence sites was not significantly associated with prolonged CSS and OS (Table).
Conclusions:
RT to recurrence sites might have no effects on oncological outcomes in patients who experienced local recurrence and/or pelvic lymph node metastases after RC.

Multivariable analyses for CSS and OS.

CSS
Factor

P
value

HR
95% CI

NAC
Received
0.080
0.649
0.400–1.053

Pure urothelial carcinoma
Positive
0.059
0.577
0.326–1.022

Tumor grade
Grade 3
0.644
1.167
0.606–2.247

LVI
Positive
0.003
2.407
1.353–4.283

Radiation therapy
Positive

0.244

0.735

0.438–1.234

OS
Factor

P
value

HR
95% CI

NAC
Received
0.030
0.552
0.323–0.944

Pure urothelial carcinoma
Positive
0.113
0.574
0.289–1.141

Tumor grade
Grade 3
0.694
0.868
0.428–1.759

LVI
Positive
0.005
2.438
1.305–4.556

Pathological N stage
≥ pN1
0.328
1.372
0.728–2.584

Radiation therapy
Positive

0.161

0.652

0.359–1.186
Final overall survival of ARIES trial evaluating first line avelumab monotherapy for patients with advanced urothelial cancer (aUC) unfit for cisplatin and outcome analysis based on baseline characteristics.
Authors: Occhipinti Denis , Ciccarese Chiara , Santoni Matteo , Puglisi Silvia , Buttigliero Consuelo , Mosillo Claudia , Buti Sebastiano , Stumbo Luciano , Naglieri Emanuele , Galli Luca , Verri Elena , Fantinel Emanuela , Di Girolamo Stefania , De Vivo Rocco , Milesi Laura , Biscaldi Elisa , Ligato Chiara , Brunelli Matteo , Tortora Giampaolo , Iacovelli Roberto
Published: February 2025

797

Background:
ARIES trial evaluated avelumab monotherapy in PD-L1+ve aUC patients (pts) not eligible to cisplatin-based chemotherapy, reaching its primary endpoint (Iacovelli R et al. ASCO-GU 2022). Treatment landscape for aUC has changed since enfortumab-vedotin and pembrolizumab (EV+P) has become the new standard for platinum-eligible pts reporting also a mPFS of 10.6 mos and 1-y OS rate of about 80% in cisplatin ineligible (carboplatin-eligible) pts. Unfortunately, up to 20% of pts are not eligible to platinum-based chemotherapy (PBC) and guidelines continue to recommend immunotherapy alone.
Methods:
Pts with PDL1+ve aUC and not eligible for cisplatin-based chemotherapy were enrolled and treated with avelumab until progression of disease. Here we reported the final OS, and we evaluated the baseline differences between pts with longer PFS compared to those who immediately progressed. Baseline characteristic included in this analysis were sites of metastases, performance status, body mass index (BMI), haematological values and the Neutrophils-to-Lymphocytes Ratio (NLR).
Results:
71 pts were enrolled, the median age was 75 years (range 38 – 88); bladder cancer was the primary tumour in 73.2% of cases, 25.3% had liver metastases, 31% had ECOG=2 and 31% had renal function <50ml/min. After a median FU of 52 mos, the median OS was 10.3 mos (95%CI 5.3 – 15.3) and the median PFS was 2.1 mos (95%CI 1.8 – 2.4). 26 pts (37%) received subsequent therapies, with gem+carbo as most frequently used (15 pts, 21%). A total of 18 pts (25%) had a PFS ≥9 mos while 44 (62%) had a PFS ≤3 mos. Significant differences between these two groups were the presence of liver mets (11% vs. 36%; p=0.047), the presence of node only disease (39% vs 5%; p<0.001) and the rate of pts with NLR>4 (22% vs. 61%; p=0.005). At multivariable analysis only NLR>4 and liver mets were confirmed to be independent prognostic factors. The 27 pts (38%) without liver mets and with NLR>4 had significantly (p=0.001) prolonged mPFS (7.7 vs. 1.9 mos), mOS (20.4 vs. 5.7 mos), and 1y OS rate (67% vs. 32%).
Conclusions:
ARIES trial confirmed the activity of avelumab in cisplatin-ineligible aUC pts including those not eligible to PBC. This analysis also identified the absence of liver mets and low values of NRL as potential markers of significant benefit from immunotherapy alone. This evidence can be used for a personalized approach in the evolving treatment landscape of aUC. Clinical trial information:
NCT03891238
.
Preliminary results from LEGEND: A phase 2 study of detalimogene voraplasmid (EG-70), a novel, non-viral intravesical gene therapy for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS).
Authors: Taylor John Arthur , Joshi Shreyas , Satkunasivam Raj , Dickstein Rian J. , Salmasi Amirali , Lotan Yair , Johnson Scott , Pruthi Raj , Tosone Christine , Schuckman Anne K. , Liu Jen-Jane
Published: February 2025

802

Background:
Detalimogene voraplasmid is a novel, investigational, non-integrating, non-viral gene therapy specifically engineered for intravesical administration to elicit local activation of anti-tumor immune responses in the bladder and drive durable efficacy in patients with high-risk NMIBC, including BCG-unresponsive disease, while mitigating the risk of systemic toxicities from immune stimulation. Preclinically, detalimogene voraplasmid remodels the tumor microenvironment, activating both innate and adaptive anti-tumor immune responses. Results from the Phase 1 portion of LEGEND (NCT04752722) demonstrated a promising safety/tolerability profile and an overall CR of 73% in patients with NMIBC with CIS. The pivotal Phase 2 portion is ongoing, and the preliminary outcomes will be reported herein.
Methods:
Patient eligibility criteria: age ≥18 years; ECOG PS 0−2; BCG-unresponsive NMIBC with CIS ± Ta/T1 disease, ineligible for, or elected not to undergo, cystectomy; satisfactory bladder function with ability to retain study drug for ≥60 minutes. Based on the Phase 1 portion of the study, a dose concentration of 0.8 mg/mL was administered at a four-dose 50 mL instillation schedule at study weeks 1, 2, 5 and 6 of a 12-week cycle. After completing the initial 12-week cycle, patients without progressive disease remained on detalimogene voraplasmid for up to three additional 12-week cycles. Primary endpoint: Week 48 CR rate; secondary endpoint: safety and tolerability. Efficacy data on BCG-unresponsive patients with CIS (n=26; Cohort 1) and safety data on all patients dosed (N=42) are reported.
Results:
Twenty-six patients (20 males/6 females; median age 74 (range 47–92) years have been enrolled in Cohort 1. Treatment-related adverse events (TRAEs; any grade) were reported in 20 (47.6%) patients and were all Grade 1/2 in severity. The most common TRAEs were dysuria in 9 (21.4%) patients, bladder spasm in 8 (19.0%); pollakiuria in 5 (11.9%), and fatigue in 5 (11.9%) patients. In the efficacy-evaluable population for Cohort 1, the overall CR rate was 71% (15/21), with a CR rate of 67% (14/21) at 3 months, and 47% (8/17) at 6 months. The Kaplan-Meier estimate of the 6-month CR is 51%.
Conclusions:
Preliminary data from the pivotal Phase 2 portion of the LEGEND study suggest a promising safety/tolerability profile, with TRAEs that were largely consistent with instrumentation/intravesical administration. Overall, 71% of patients dosed with detalimogene voraplasmid achieved a CR, with 67% achieving a CR at 3 months and 47% achieving a CR at 6 months. Cohort 1 (BCG-refractory patients with CIS) continues to enroll, with a target accrual of 100 patients. Clinical trial information:
NCT04752722
.
Efficacy and toxicity profile of antibody-drug conjugate (ADC) based combination therapy in patients with advanced urothelial carcinoma (aUC): A systematic review of clinical trials.
Authors: Jaime-Casas Salvador , Zugman Miguel , Barragan-Carrillo Regina , Zang Peter D. , Ebrahimi Hedyeh , Mercier Benjamin , Castro Daniela V. , Yip Wesley , Li Xiaochen , Dizman Nazli , Salgia Nicholas , Hsu Joann , Nguyen Charles B , Chehrazi-Raffle Alex , Zengin Zeynep Busra , Meza Luis A , Pal Sumanta Kumar , Tripathi Abhishek
Published: February 2025

813

Background:
ADCs have revolutionized the treatment landscape of aUC and are being evaluated as part of combination regimens with checkpoint inhibitors (CPI) or other ADCs. We sought to evaluate the efficacy and safety/tolerability profile of ADC-based combination therapy in aUC.
Methods:
We systematically searched the PubMed and Embase databases for published prospective clinical trials through July 2024. Peer-reviewed clinical trials evaluating ADCs as part of a combination regimen in aUC were included. We extracted safety and efficacy outcomes, including objective-response rate (ORR), any-grade adverse events (AEs), and grade ≥3 AEs. We excluded reviews, editorials, retrospective studies, and case reports. Two independent reviewers screened titles and abstracts for relevance, followed by a full-text review to confirm eligibility.
Results:
627 evaluable patients from 5 prospective trials investigating enfortumab vedotin or sacituzumab govitecan were identified. Overall, we recorded an ORR of 66.2%. 366 patients across all studies experienced ≥ grade 3 AEs, for a risk rate (RR) of 58.4%. By using a random-effects model, the pooled RR for AEs (Grade≥3) was 61% (95% CI, 52%–69%; P=0.18; Table). The most common grade ≥3 AEs were neutropenia (RR 0.14 [95% CI 0.04- 0.40]), anemia (RR 0.10 [95% CI 0.03-0.30]), and maculopapular rash (RR 0.10 [95% CI 0.04-0.23]). Distribution of specific AEs varied significantly based on regimen, with a higher incidence of ≥grade 3 anemia, neutropenia, and diarrhea in SG-based combinations (SG+ EV and SG+ CPI).
Conclusions:
While ADC-based combination regimens show promising responses, they also have high rates of AEs in patients with aUC. Further clinical trials evaluating these combination regimens are crucial to further optimize the role of ADCs in this disease setting.

Safety/tolerability profile for any grade and grade ≥3 AEs.

Toxicity
Any Grade
Grade≥3

Risk rate, 95% CI
Risk rate, 95% CI

Anemia
0.31 [0.09; 0.66]
0.10 [0.03; 0.30]

Neutropenia
0.24 [0.05; 0.65]
0.14 [0.04; 0.40]

Diarrhea
0.51 [0.19; 0.82]
0.07 [0.02; 0.17]

Peripheral sensory neuropathy
0.50 [0.47; 0.54]
0.03 [0.02; 0.05]

Fatigue
0.45 [0.26; 0.65]
0.06 [0.03; 0.13]

Maculopapular rash
0.36 [0.26; 0.47]
0.10 [0.04; 0.23]
NECTIN4
RNA expression and clinical outcomes with first-line (1L) platinum-based chemotherapy (PBC) and avelumab 1L maintenance in locally advanced or metastatic urothelial carcinoma (la/mUC): Exploratory analyses from JAVELIN Bladder 100.
Authors: Klümper Niklas , Eckstein Markus , Grivas Petros , Grande Enrique , Brägelmann Johannes , Hoffman Jason , Shah Parantu K. , Bogatyrova Olga , Grünwald Viktor
Published: February 2025

827

Background:
Nectin-4 is widely expressed in UC tumors, although protein expression levels vary between patients. Prior analyses have suggested that low overall Nectin-4 expression based on immunohistochemistry may be associated with worse outcomes in patients with advanced UC irrespective of treatment. We report exploratory biomarker analyses from the JAVELIN Bladder 100 phase 3 trial evaluating response to 1L PBC and survival outcomes with avelumab administered as 1L switch-maintenance treatment in subgroups defined by tumor
NECTIN4
RNA expression.
Methods:
In JAVELIN Bladder 100 (NCT02603432), patients with unresectable la/mUC without progression after 4-6 cycles of 1L PBC were randomized to receive avelumab 1L maintenance + best supportive care (BSC) or BSC alone. Whole-transcriptome profiles in tumor samples (primary tumors in ≈75%) were generated using RNA sequencing, and transcript levels were quantified using Personalis ACE technology.
NECTIN4
RNA expression was assessed as a continuous variable for subgroups defined by response to 1L PBC, and as a dichotomous variable (median split) for survival analyses.
Results:
In biomarker-assessable patients enrolled in JAVELIN Bladder 100, no significant differences were observed in tumor
NECTIN4
RNA expression in patients who had complete response (n=149), partial response (n=261), or stable disease (n=150) to 1L PBC (Kruskal-Wallis p=0.192). In subgroups with high or low
NECTIN4
RNA expression, overall survival (OS) and progression-free survival (PFS) improvements with avelumab + BSC vs BSC alone were consistent with improvements observed in the overall study population (Table). No significant differences in OS and PFS were observed between subgroups with high or low
NECTIN4
RNA expression within the avelumab + BSC (p=0.26 and 0.89) and BSC alone (p=0.34 and 0.94) arms. Limitations include ad hoc exploratory analysis and potential selection bias.
Conclusions:
Exploratory analyses from JAVELIN Bladder 100 suggest that
NECTIN4
RNA expression was not prognostic or predictive of level of response to 1L PBC or survival with avelumab 1L maintenance treatment in patients with la/mUC without progression after 1L PBC. Clinical trial information:
NCT02603432
.

Avelumab + BSC
BSC alone

High
NECTIN4
RNA expression

n=139
n=140

Median OS (95% CI), months
22.0 (18.2-30.9)
14.8 (12.9-19.4)

Median PFS (95% CI), months
5.65 (4.60-9.00)
3.29 (1.97-3.75)

Low
NECTIN4
RNA expression

n=145
n=136

Median OS (95% CI), months
30.0 (21.4-35.2)
18.7 (13.7-25.5)

Median PFS (95% CI), months
5.65 (3.81-9.95)
2.20 (1.91-3.71)
Prospective observational study in Japanese patients with metastatic castration-sensitive prostate cancer (mCSPC) with or without intraductal carcinoma of the prostate (IDC-P).
Authors: Kato Masashi , Tsuzuki Toyonori
Published: February 2025

87

Background:
Intraductal carcinoma of the prostate (IDC-P) is a high-grade, high-volume, invasive form of prostate cancer (PCa) associated with poor clinical outcomes. The International Society of Urological Pathologists (ISUP) recommends incorporating IDC-P into the Gleason scoring system. However, existing data on survival outcomes for prostate cancer patients with IDC-P are primarily based on retrospective analyses. This study aims to prospectively evaluate the survival outcomes of Japanese patients with metastatic castration-sensitive prostate cancer (mCSPC), with and without IDC-P, using real-world data from a multi-institutional observational study.
Methods:
Between 2018 and 2021, we prospectively enrolled 102 de novo mCSPC patients from affiliated healthcare institutions. Eligible patients were those diagnosed with mCSPC via prostate needle biopsy and classified as high-risk according to the LATITUDE criteria. All participants underwent a standard extended biopsy (≥10 cores) to diagnose IDC-P, ensuring minimal sampling error. A single genitourinary pathologist reviewed all biopsy slides based on the 2019 ISUP grading system. Patients received treatment with androgen receptor signaling inhibitors (ARSI) with or without docetaxel.
Results:
The median age of the patients was 72 years (range 57–92), and the median serum PSA level was 441 ng/mL (range 3.9–9807 ng/mL). The median follow-up period was 38.3 months (range 8.2–67.4 months). All patients had a Gleason grade ≥ 3, with 66 (64.7%) exhibiting a Gleason pattern 5. Lymph node metastasis was present in 67 patients (65.7%), visceral metastasis in 23, and bone metastasis in all patients. IDC-P was identified in 86 patients (84%). Multivariate analysis revealed that elevated lactate dehydrogenase (LDH) levels and the presence of IDC-P were independent predictors of poor castration-resistant prostate cancer (CRPC)-free survival (HR 4.387, p<0.001; HR 2.009, p=0.01) and progression-free survival (PFS2) (HR 6.801, p<0.001; HR 1.796, p=0.016).
Conclusions:
This prospective observational study demonstrated that higher LDH levels and the presence of IDC-P in biopsy samples were significantly associated with poorer survival outcomes in Japanese patients with mCSPC. These findings underscore the prognostic importance of IDC-P in mCSPC management.
Clinicopathological variations between early and late recurrence in bladder cancer post-radical cystectomy.
Authors: Ku Josh , Doshi Chirag , Dadabhoy Anosh , Xia Leilei , Daneshmand Siamak
Published: February 2025

874

Background:
Over 50% of patients diagnosed with muscle-invasive bladder cancer are estimated to experience urothelial cell carcinoma (UCC) recurrence following radical cystectomy (RC). Current studies have found clinicopathological factors associated with overall UCC recurrence; however, there is a lack of data on variations between patients with early versus late recurrence. This study examines the clinicopathological differences of these cohorts.
Methods:
Within our single institutional IRB-approved cystectomy database, we reviewed 1,050 patients from 1971 - 2023 who underwent RC with intent to cure for primary UCC and experienced recurrence at the University of Southern California. Patients included had documented recurrence via biopsy or imaging. Patients with distant metastasis at RC were excluded. Clinicopathological factors were chosen based on significance in prior studies. Early recurrence (ER) was defined as within two years of cystectomy, the most common time frame for UCC, and late recurrence was beyond two years. Cox regression and chi-squared tests were utilized to compare the groups.
Results:
Among 1,050 patients, the median age was 68. Of the 928 open cystectomies, 73.2% had ER, compared to 87.7% of the 122 robotic cystectomies. ER rates were 71.9% for the 588 orthotopic diversions, 69.9% for the 143 continent diversions, and 82.5% for the 319 incontinent diversions. Factors predictive of ER included older age (OR = 1.582, p = 0.0017), higher Charlson Comorbidity scores (OR = 1.460, p = 0.0112), higher ASA scores (OR = 1.900, p = 0.001), hydronephrosis prior to RC (OR = 1.944, p = <0.0001), lymphovascular invasion (OR = 1.472, p = 0.0383), lymph node involvement at RC (OR = 2.770, p = <0.0001), neoadjuvant chemotherapy (OR = 3.457, p = <0.0001), incontinent urinary diversions (OR = 1.832, p = 0.0008), greater than pT3 pathological staging (p = <0.0001), and variant histology (OR = 1.782, p = 0.0006).
Conclusions:
This study identifies clinicopathological risk factors significantly associated with ER. By describing these factors, this study aims to improve predictions of UCC recurrence patterns and inform personalized treatment. Further research is needed to validate our findings and optimize surveillance protocols for at risk patients.

Multivariate analysis of variables predictive of early recurrence.

Variable
Hazard ratio
p-value

Age > 70
1.464 (1.054 - 2.042)

0.0238

Pre-operative Albumin
0.990 (0.981 - 0.999)

0.0227

Neoadjuvant Chemotherapy
3.527 (2.187 - 5.930)

<0.0001

Pathological Staging Organ - Confined Extravesical Lymph Node Positive
Ref4.511 (2.955 - 7.024)7.553 (5.000 - 11.636)

<0.0001

Urinary Diversion Orthotopic Diversion Continent Diversion Incontinent Diversion
Ref0.807 (0.513 - 1.281)1.459 (1.003 - 2.139)
0.0531

Adjuvant Chemotherapy
0.568 (0.372 - 0.863)

0.0083
Impact of perioperative acute kidney injury on future renal outcomes in patients who undergo radical cystectomy: A multi-institutional retrospective cohort study.
Authors: Fujita Naoki , Hosogoe Shogo , Tanaka Toshikazu , Ishii Noritaka , Momota Masaki , Ito Hiroyuki , Yoneyama Takahiro , Ohyama Chikara , Hatakeyama Shingo
Published: February 2025

879

Background:
Acute kidney injury (AKI) is one of the frequent complications in patients who undergo radical cystectomy (RC). Although AKI has been reported to have a negative impact on renal outcomes in several diseases, the impact of perioperative AKI on major adverse kidney events (MAKE) in patients who undergo RC remains unclear.
Methods:
This multi-institutional retrospective cohort study included 702 patients with muscle invasive bladder cancer who underwent RC. AKI was defined according to the KDIGO criteria. Patients were divided into two groups: patients who developed AKI after RC (AKI group) and patients who did not (non-AKI group). MAKE was a composite of sustained ≥50% decline in eGFR, doubling of serum creatinine from the baseline, and sustained decrease in eGFR to <15 ml/min/1.73m
2
. The laterality and grade of hydronephrosis at the time of MAKE onset or last follow-up were evaluated. Multivariable Cox-proportional hazards regression analysis was performed to evaluate the impact of perioperative AKI on MAKE-free survival.
Results:
The median age and follow-up period were 70 years and 48 months, respectively. Of the 702 patients, 368 (52%) developed AKI after RC, with 26% having severe AKI (stage 2-3). Significant declines in eGFR at one-, three, and five-year after RC were observed in the AKI group compared with those in the non-AKI group (
P
<0.001,
P
<0.001, and
P
<0.001, respectively). MAKE-free survival in the AKI group was significantly shorter than that in the non-AKI group (
P
<0.001). After adjustment for confounding variables, including age, comorbidity, preoperative renal function, and hydronephrosis, AKI was independently and significantly associated with shorter MAKE-free survival (Table).
Conclusions:
Perioperative AKI had a negative impact on future renal outcomes in patients who underwent RC.

Multivariable analysis for MAKE-free survival.

Factor

P
value

Hazard ratio
95% CI

Age
Continuous
0.730
1.005
0.978–1.033

Body mass index
Continuous
0.051
1.068
1.000–1.142

Hypertension
Presence
0.454
1.182
0.762–1.834

Dyslipidemia
Presence
0.187
1.397
0.850–2.296

Diabetes mellitus
Presence
0.370
1.257
0.762–2.072

Preoperative eGFR
Continuous
0.146
0.990
0.977–1.003

Grade of hydronephrosis
Continuous

<0.001

1.509
1.206–1.888

Laterality of hydronephrosis
Bilateral
0.301
0.734
0.409–1.318

AKI
Positive

0.003

1.932

1.254–2.977
Prostate Cancer Real World Evidence Registry (PROCARE): Recurrent and metastatic prostate cancer.
Authors: Hadaschik Boris A. , Von Amsberg Gunhild , Herrmann Ken , Merseburger Axel Stuart , Goebell Peter J. , Belleville Erik , Fasching Peter A. , Haeberle Lothar , Roessler Andrea , Grimm Marc-Oliver
Published: February 2025

TPS274

Background:
Prostate cancer remains the most common malignancy among men and the fifth leading cause of cancer-related mortality globally. Over the past 15 years, advances in imaging techniques and therapeutic options have significantly transformed the management of recurrent, advanced, and metastatic prostate cancer. However, treatment efficacy and toxicity are highly influenced by prior therapy sequences, highlighting the need for a deeper understanding of the optimal treatment sequence. The prospective real-world evidence registry, PROCARE, addresses this gap by documenting treatment patterns, imaging exams, oncologic outcomes, and safety profiles in routine clinical practice.
Methods:
This study focuses on four distinct patient cohorts: biochemical recurrence after local treatment with curative intent (e.g. radical prostatectomy, radiotherapy of the prostate or combination thereof), non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic hormone-sensitive prostate cancer (mHSPC), and metastatic castration-resistant prostate cancer (mCRPC). PROCARE is a comprehensive long-term follow-up registry designed to document treatment patterns and outcomes in patients receiving systemic treatment. The study aims to enroll 5,000 patients across 50 sites in Germany. Recruitment is being conducted independently for each cohort, beginning with the mHSPC and mCRPC cohorts. First patient in was in January 2024. Patients will remain in the registry from the time of enrollment until death, withdrawal of consent, or study cohort closure. Throughout the study, additional blood samples will be collected at baseline and with each treatment change, respectively, and at first routine follow-up visit thereafter for exploratory research purposes, such as assessing circulating tumor DNA and RNA, as well as genome-wide single nucleotide polymorphisms (SNPs). This approach will enable a deeper understanding of treatment distribution, sequencing, efficacy, and safety in the real-world setting, contributing valuable insights into the evolving therapeutic landscape. Furthermore, analyses from liquid biopsies might provide important insights potentially guiding future therapeutic strategies for recurrent and metastatic prostate cancer. Clinical trial information:
DRKS00033411
.
Efficacy and safety of organoid-based drug sensitivity screening to guide the treatment of mCRPC patients progressed after first-line treatment.
Authors: Zhao Diwei , Zhao Junliang , Li Yuanwei , Cai Xinyang , Yang Zhenyu , Chen Meiting , He Liru , Liu Yang , Zhou Fangjian , Li Yonghong , Wang Jun
Published: February 2025

TPS278

Background:
Treatment for metastatic castration-resistant prostate cancer (mCRPC) patients progress after first-line therapy remains challenging due to limited options and heterogeneous response. Organoid-based drug sensitivity screening offers an innovative approach by simulating the tumor microenvironment in vitro, potentially allowing for personalized treatment strategies based on individual tumor responses to various drugs. This study aims to assess the efficacy and safety of using organoid-based drug sensitivity screening to guide treatment decisions in mCRPC patients.
Methods:
This is a prospective, open-label, single-arm observational study designed to recruit 30 mCRPC patients with bone metastases who have progressed after first-line therapy. Residual tissue from biopsies of bone metastatic lesions will be used to culture organoids for drug sensitivity screening. Screening regimens include at least Olaparib, Docetaxel or platinum-based chemotherapy, and Abiraterone plus Niraparib, as recommended by current guidelines. Additionally, 141 other drugs from a previously established library are available for screening, based on investigator and patient preferences. The treatment regimen will be selected based on the agent that demonstrates the highest sensitivity in the screening process. The primary endpoint is PSA response rate, defined as a 50% decrease in PSA levels from baseline. Secondary endpoints include radiologic progression-free survival (rPFS), objective response rate (ORR), duration of response (DOR), and overall survival (OS). Patient recruitment is ongoing at Sun Yat-sen University Cancer Center, with 5 patients (5/30, 16.7%) enrolled as of September 3, 2024. Data analysis is expected to begin in 2025, following the completion of recruitment. Clinical trial information:
NCT06529549
.
Mevrometostat (PF-06821497) in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate: The phase 3, randomized MEVPRO-1 study.
Authors: Agarwal Neeraj , Schweizer Michael Thomas , Castro Elena , Azad Arun , George Daniel J. , Chakrabarti Jayeta , Narayanan Sujata , Tang Yiyun , Fizazi Karim
Published: February 2025

TPS288

Background:
Resistance to androgen receptor (AR) pathway inhibitors (ARPI; e.g., abiraterone, enzalutamide) in metastatic castration-resistant prostate cancer (mCRPC) may be driven by preservation of AR signaling through various mechanisms. Enhancer of zeste homolog 2 (EZH2) is implicated in the pathogenesis of prostate cancer and ARPI resistance. Combining ARPI with therapies that modulate alternative signaling pathways, including epigenetic modifiers such as EZH2, could be a promising treatment approach to overcome resistance. Mevrometostat (PF-06821497) is a potent and selective small molecule EZH2 inhibitor. Results from the dose-escalation period of a phase 1 study (NCT03460977) showed promising activity for mevrometostat combined with enzalutamide, with a manageable adverse-event profile in abiraterone-exposed patients with mCRPC (Schweizer MT, et al.
J Clin Oncol
. 2024;42(16_suppl):5061). The current trial aims to evaluate radiographic progression-free survival (rPFS), overall survival (OS), and safety of mevrometostat plus enzalutamide compared with standard of care in patients with mCRPC previously treated with abiraterone.
Methods:
MEVPRO-1 (NCT06551324) is a global, open-label, phase 3 trial in patients with mCRPC aged ≥18 years with progression on/after ≥12 weeks abiraterone, castration testosterone levels ≤50 ng/dL, ECOG performance status 0–2, and life expectancy ≥6 months. Approximately 600 patients will be randomized 1:1 to receive mevrometostat (875mg BD with food) with enzalutamide (160mg QD), or physician’s choice of enzalutamide (160mg QD) or docetaxel (75mg/m
2
intravenously every 21d). Randomization will be stratified by previous docetaxel in metastatic castration-sensitive setting, physician’s choice of comparator (enzalutamide/docetaxel), and presence of hepatic metastases. The primary endpoint is BICR-assessed rPFS per RECIST 1.1 (soft tissue) and PCWG3 (bone) assessed by blinded central radiology review. Key secondary endpoint is OS. Secondary endpoints include anti-tumor activity, safety, pharmacokinetics, ctDNA, and patient-reported outcomes. Stratified log-rank
P
-values, HRs, and 95% CIs will be estimated using a stratified Cox proportional hazard model, and Kaplan–Meier analysis will summarize time-to-event endpoints. Clinical trial information:
NCT06551324
.