bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing Indiana regimen salvage high-dose chemotherapy in relapsed germ cell tumors in Slovakia.
Authors: Chovanec Michal , Rusinakova Zuzana , Ladicka Miriam , Obertova Jana , Palacka Patrik , Rejlekova Katarina , Sycova-Mila Zuzana , Orszaghova Zuzana , Lesko Peter , Mardiak Jozef , Vranovsky Andrej , Mego Michal , Drgona Lubos
Published: February 2025

642

Background:
Salvage chemotherapy for relapsed testicular germ cell tumors (GCT) remains controversial, however, large retrospective series show higher cure rates with high-dose chemotherapy (HDCT) and peripheral blood stem cell transplant (PBSCT) compared to conventional dose chemotherapy (CDCT). Successful implementation of HDCT salvage treatment in high-volume centers is an important step towards achieving optimal cure rates in relapsed GCTs.
Methods:
22 relapsed GCT patients were treated at National Cancer Institute in Slovakia with first (41%), second (54%) and third line (5%) salvage HDCT between 2014 and 2024. Median age at 1
st
HDCT cycle was 33 years (range 21-55). Of the 22 patients, 3 (14%) had pure seminoma, 3 (14%) had primary mediastinal non-seminoma (PMNSGCT), 10 (45%) patients had cisplatin resistant disease, 7 (32%) and 15 (68%) of patients received 1 and 2 cycles of HDCT, respectively, 5 (23%) received maintenance oral etoposide and 6 (27%) had post-HDCT surgery. Indiana regimen consisted of 750mg/m2 etoposide and 700mg/m2 of carboplatin given on days -5,-4,-3 followed by PBSCT on day 0. Of 22 patients, 3 have received single dose CarboPEC (carboplatin, etoposide, cyclophosphamide) regimen in 2014 and 2015.
Results:
Median time between two cycles was 43 days (range 26-89) showing decreasing trend over the last years. 2-year PFS and OS were 40% (95% CI 0.19-0.61) and 34% (95% CI 0.13-0.55) and 5-year PFS and OS were 32% (95% CI 0.1-0.54) and 27% (0.06-0.48). Kaplan-Meier analysis produced inaccurate outcomes due to small sample size, currently 32% of patients is alive and disease-free. Predictors of unfavorable outcome were non-seminoma, NPMGCT, 1 cycle of HDCT, CarboPEC regimen and platinum resistant disease. Patients who underwent post-HDCT surgical resection had longer OS compared to patients unable to undergo surgery HR 4,85 (95% CI 1,69-13,9), p = 0.01 Patients receiving pre-HDCT bridging CDCT regimens had significantly worse OS compared to patients going directly to HDCT, HR 0 (95% CI 0-0), 5 year OS 19% vs 100%, p = 0.05. 10% of patients with cisplatin resistant disease is surviving beyond 5 years. There was one (4.5%) treatment-related death due to septic shock.
Conclusions:
HDCT is an effective salvage option in heavily pretreated relapsed GCTs. Our study suffers from weakness associated with small number of patients and selection biases. However, increasing expertise and timely delivery of HDCT results in cures in relapsed GCTs including cisplatin resistant subgroup.
Evaluation of MIR-371A-3P for clinical implementation in a CLIA-certified laboratory.
Authors: Gür Melis , Pandit Kshitij , Lafin John T. , Scarpini Cinzia , Amini Armon , Konneh Bendu , Howard Jeffrey , Gerald Thomas , Nuno Michelle , Piao Jin , Coleman Nicholas , Frazier Lindsay , Murray Matthew , Murray Sarah , Bagrodia Aditya
Published: February 2025

648

Background:
MicroRNAs (mi-RNAs) have emerged as promising biomarkers for the detection of viable germ cell tumors (GCT). Our previous work in a research lab demonstrated optimal performance with positive results that had Cq values less than 28, an indeterminate range between 28-35 and negative results greater than 35. In this study, we assessed performance characteristics of miR-371a-3p in a CLIA certified lab at UCSD.
Methods:
Due to workflows, equipment and scaling, several modifications were required from our original research protocol. Ultimately, serum samples from 53 cases and 139 controls were analyzed using qPCR for miR-371a-3p in the CLIA lab. Initial runs and re-runs were conducted for the indeterminate samples. Metrics used for calculation of performance were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC) and Youden’s index.
Results:
We used two analytic pipelines for classifying positive and negative Cq values: 1) a binary cutoff of 26.9 and, 2) an indeterminate range of 25.6 to 31.5. Using the binary cutoff, a sensitivity of 86%, specificity of 98%, PPV of 94%, NPV of 95%, AUC of 0.94 and Youden index of 0.85 was observed. In contrast, initial runs on the indeterminate ranges yielded a sensitivity of 95%, specificity of 99%, PPV of 97%, NPV of 98%, AUC of 0.97 and Youden index of 0.94. However, 36% (51 of 139) controls fell into the indeterminate range. Re-runs on these samples demonstrated similar findings.
Conclusions:
Our data demonstrated that there are likely lab specific, protocol specific and disease-state specific analytics and thresholding for circulating miR-371a-3p testing. These factors will need to be carefully considered while moving towards clinical implementation.
Efficacy and safety of CAR-T cell therapy in penile and urethral carcinomas: A meta-analysis of preliminary clinical trials and case studies.
Authors: Hashim Hashim Talib , Alhatemi Ahmed Qasim Mohammed , Sarwar Atif Hussain , Saddique Muhammad Nabeel , Shamoon Sheena
Published: February 2025

655

Background:
Penile and urethral carcinomas are rare and aggressive cancers with limited treatment options, often leading to poor prognoses. Chimeric Antigen Receptor T-cell (CAR-T) therapy has shown promise in various malignancies, but its efficacy and safety in penile and urethral carcinomas remain under-explored. This meta-analysis aims to evaluate the preliminary clinical trials and case studies on CAR-T cell therapy in treating these rare carcinomas.
Methods:
The PubMed, Embase, Scopus and Cochrane databases were systematically searched from inception until June 2024 using relevant keywords. We performed proportional meta-analysis of untransformed proportions using Random Effects model in OpenMeta (version 5.3). The I
2
and X
2
statistics were used to evaluate inter-study heterogeneity. An I
2
value of >50% was considered significant heterogeneity. Subgroup analyses were performed to identify factors influencing treatment outcomes.
Results:
A total of 15 studies, including 10 clinical trials and 5 case reports, comprising 230 patients were included in the meta-analysis. The pooled overall response rate (ORR) was 42% (95% CI: 30%-55%), with a complete response rate (CRR) of 15% (95% CI: 8%-25%). Common adverse effects included cytokine release syndrome (CRS) (35%) and neurotoxicity (20%). Pre-existing comorbidities and prior treatments were significant factors affecting outcomes. No treatment-related mortality (TRM) was reported.
Conclusions:
CAR-T cell therapy demonstrates encouraging efficacy in penile and urethral carcinomas, with manageable safety profiles. While preliminary results are promising, larger and more comprehensive studies are needed to validate these findings and optimize treatment protocols.
Nectin-4 targeted ADC, SHR-A2102, in patients with advanced or metastatic urothelial carcinoma: A phase 1 study.
Authors: Tang Bixia , Sheng Xinan , Guo Jun , Niu Haitao , Shen Yali , Jiang Shusuan , Fu Bin , Guo Jianming , Wahafu Wasilijiang , Yao Kai , Liu Nan , Gu Jiang , Chen Yu , Li Zhenhua , Lin Tianxin , Ma Liping , Lin Jiaqin , Zhang Chi , Wang Wenliang
Published: February 2025

657

Background:
SHR-A2102 is a novel ADC that consists of a fully humanized IgG1 monoclonal antibody targeting nectin-4, a cleavable linker, and a topoisomerase I inhibitor payload with high membrane permeability and potent cell-killing efficacy. We have initiated a first-in-human phase 1 study to assess the safety, tolerability, and efficacy of SHR-A2102 in advanced solid tumors. Here, we present preliminary findings, focusing on urothelial carcinoma.
Methods:
Patients (pts) with locally advanced unresectable or metastatic urothelial carcinoma, who had failed or were intolerant to standard therapies, were eligible. SHR-A2102 was given intravenously at 1, 2, 4, 6, 8 mg/kg on D1 Q3W and 4 mg/kg on D1 and D8 Q3W during dose escalation. 6 and 8 mg/kg were selected for dose and efficacy expansions.
Results:
As of Aug 2, 2024, 73 UC pts were enrolled (median age: 65 yrs; ≥2 lines of prior systemic therapies: 57.5%; prior ADC: 42.5%). Efficacy outcomes were summarized in Table. Confirmed ORR was 38.4% (28/73; 95% CI, 27.2–50.5) in all pts, and was 32.3% (10/31; 95% CI, 16.7–51.4) in the 6 mg/kg dose group and 50.0% (16/32; 95% CI, 31.9–68.1) in the 8 mg/kg dose group. 6-mo DoR rate was 59.3% (95% CI, 23.1–83.0) in all pts, and was 66.7% (95% CI, 5.4–94.5) and 54.0% (95% CI, 12.7–83.2) in the 6 and 8 mg/kg groups, respectively. Of note, 31 pts had received ADC prior to study treatment; among them, 12 (38.7%; 95% CI, 21.9–57.8) pts achieved confirmed PR. Overall, TRAEs of grade 3 or worse occurred in 32 (43.8%) pts, with the most common (≥10%) being anemia (23.3%), decreased WBC count (19.2%), and decreased neutrophil count (17.8%).
Conclusions:
SHR-A2102 showed promising anti-tumor activity in pts with advanced or metastatic urothelial carcinoma, even after ADC therapy, along with manageable safety profile. Clinical trial information:
NCT05735275
.

Efficacy summary.

All UC pts(N=73)
6 mg/kg(N=31)
8 mg/kg (N=32)
ADC pretreated pts (N=31)

Best overall response, n (%)

Confirmed PR
28 (38.4)
10 (32.3)
16 (50.0)
12 (38.7)

SD
30 (41.1)
18 (58.1)
10 (31.3)
11 (35.5)

PD
12 (16.4)
3 (9.7)
3 (9.4)
7 (22.6)

NE
3 (4.1)
0
3 (9.4)
1 (3.2)

Confirmed ORR, % (95% CI)
38.4 (27.2–50.5)
32.3 (16.7–51.4)
50.0 (31.9–68.1)
38.7 (21.9–57.8)

DCR, % (95% CI)
79.5 (68.4–88.0)
90.3 (74.3–98.0)
81.3 (63.6–92.8)
74.2 (55.4–88.1)

6-mo DoR rate, % (95% CI)
59.3 (23.1–83.0)
66.7 (5.4–94.5)
54.0 (12.7–83.2)
60.0 (12. 6–88.2)

6-mo PFS rate, % (95% CI)
41.4 (23.6–58.4)
54.7 (24.0–77.4)
38.0 (13.4–62.7)
39.1 (16.6–61.3)
Safety and efficacy of neoadjuvant immunotherapy with durvalumab (MEDI 4736) in combination with neoadjuvant chemotherapy (gemcitabine/cisplatin or carboplatin) in patients with operable high-risk upper tract urothelial carcinoma.
Authors: Houede Nadine , Chevallier Thierry , Loic Jaffrelot , Thibault Constance , Yann Neuzillet , Abraham Jaillon Christine , Masson-Lecomte Alexandra , Gravis Gwenaelle , Tartas Sophie , Pouessel Damien , Laguerre Brigitte , Audenet Francois , Xylinas Evanguelos , Guillaume Luquiens , Roupret Morgan
Published: February 2025

661

Background:
Most patients following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) face a poor prognosis. Combination of chemotherapy and immunotherapy in neoadjuvant setting have demonstrated survival improvement in several tumors. Additional systemic therapy in a neoadjuvant setting may prolong survival for UTUC patients, especially those after RNU who are ineligible to receive nephrotoxic chemotherapy.
Methods:
Phase 2 clinical trial (NCT04617756) was conducted in 10 French centers. Eligible patients had non metastatic, high-grade disease on ureteroscopic tumor biopsy or on urine cytology and infiltrative aspect of renal pelvis/ureteral wall on CT imaging. Subjects received a combination of: Durvalumab/Gemcitabine/Cisplatin (cohort 1) or Carboplatin (cohort 2) every 3 weeks for a total of 4 cycles based on glomerular filtration rate, prior to RNU. The primary objective was to assess the pathological complete response (ypT0) rate (pCR) of each combination.
Results:
A total of 50 patients were enrolledbetween 2021 and 2023 (31 in cohort 1 and 19 in cohort 2). Median age was 66 years old (range 38-79), 58% were males. 90% of patients (44) received 4 cycles of treatment, 3 patients 3 cycles and 2 patients received 2 cycles. Five patients switched for carboplatin during chemotherapy. We observed in cohort 1 : 20/31 (65%) patients with non infiltrative residual tumor; In cohort 2 : 9/19 (42%) patients (table). Secondary endpoint was safety, no immunotherapy-mediated AE was observed, 2 patients had Grade 3 neutropenia, 1 grade 4, 1 patient had grade 3 thrombopenia and 1 grade 3 anemia.
Conclusions:
Combination of durvalumab with platin-based chemotherapy, especially cisplatin, showed promising activity in UTUC, with the occurrence of complete responses and a high rate of non-infiltrative residual tumor. Safety profile was secure without increasing surgical risk. A randomized Phase 3 controlled study comparing neoadjuvant chemotherapy with chemotherapy combined with immunotherapy in patients with high-risk localized UTUC (iNDUCT-3) will open soon to validate these encouraging results. Clinical trial information:
NCT04617756
.

Pathological response rate.

ypT0
ypTIS /ypTa
ypT1
ypT2
ypT3
ypT4
Missing data
Withdrawal surgery
Total

Cis-Gem Durva
4 (13%)
5 (16%)
11 (36%)
1 (3%)
6 (19%)
1 (3%)
1
2
31

Carbo-Gem Durva
1 (5%)
6 (32%)
1 (5%)
3 (16%)
5 (26%)
1 (5%)
1
1
19
Neoadjuvant treatment with disitamab vedotin plus perioperative toripalimab in patients with muscle-invasive bladder cancer (MIBC) with HER2 expression: Updated efficacy and safety results from the phase II RC48-C017 trial.
Authors: Sheng Xinan , Zhang Cuijian , Ji Yongpeng , Zhou Li , Zou Benkui , Huang Hang , Wang Yonghua , Yang Kaiwei , Bai Xue , Feng Dan , Yang Yong , Bian Jiasheng , Yu Zhixian , Niu Haitao , Du Peng , Fang Jianmin , He Zhisong , Guo Jun
Published: February 2025

665

Background:
This single-arm phase II trial was conducted to evaluate the efficacy and safety of neoadjuvent disitamab vedotin (DV, a HER2-targetted monoclonal antibody conjugated with monomethyl auristatin E) plus perioperative toripalimab (an anti-PD-1 inhibitor) in MIBC patients (pts) with HER2 expression. The preliminary results showed promising efficacy and acceptable safety with neoadjuvant treatment with DV plus toripalimab in pts with HER2-expressing MIBC (Sheng, et al. ASCO Annual meeting 2024).
Methods:
Key eligibility criteria included previously untreated MIBC (cT2-4aN0-1M0) with HER2 expression (immunohistochemistry [IHC] ≥1+ by local test), and eligible for curative-intent radical cystectomy and pelvic lymph node dissection (RC+PLND). Pts received DV (2 mg/kg) plus toripalimab (3 mg/kg) every 2 weeks for 6 cycles at neoadjuvant phase. After RC+PLND, pts received adjuvant toripalimab (3 mg/kg every 2 weeks) for up to 20 cycles. The primary endpoint was pathological complete response (pCR, ypT0N0) rate assessed by the investigators; secondary endpoints included pathological response rate (≤ypT1N0M0), overall survival, safety, etc. Here we present the updated efficacy and safety results and post-hoc event-free survival (EFS) analysis with data cutoff date (DCO) of September, 2024.
Results:
As of DCO, patient enrollment was completed with 47 pts enrolled and treated (including 10.6% pts with HER2 IHC 1+, 57.4% IHC 2+, and 31.9% IHC 3+; 83.0% pts at baseline T2-4N0M0 and 17.0% at cT2-4aN1M0 stage). RC+PLND was performed in 33 (70.2%) pts. The pCR rate was 63.6% (95% CI: 45.1%-79.6%) and the pathological response rate was 75.8% (95% CI: 57.7%-88.9%). A higher pCR rate of 84.6% was observed in patients with HER2 IHC 3+. The pCR rate was 77.8% and 62.5% in PD-L1-positive and PD-L1-negative subgroups, respectively. The one-year EFS rate was 89.5% (95% CI: 69.8%-96.7%). The safety profile was consistent with the previous ASCO presentation without new toxicity signals observed. No adverse events delayed the surgery. Survival data were immature.
Conclusions:
The updated data supported perioperative treatment with DV plus toripalimab had promising efficacy and acceptable safety in pts with HER2-expressing MIBC. It warrants further investigation in this patient population. Clinical trial information:
NCT05297552
.
Survival disparities by race in advanced urothelial carcinoma (aUC): A real-world analysis.
Authors: Barsouk Adam , Elghawy Omar , Sussman Jonathan Henry , Xu Jessica , Mamtani Ronac , Mei Lin
Published: February 2025

668

Background:
Retrospective population data suggest poorer survival for non-White aUC patients. However, data on survival disparities in the era of immuno- and targeted therapies is limited.
Methods:
This cohort study used Flatiron Health’s nationwide de-identified electronic health record (EHR)-derived database. 7,244 patients (pts) were identified. Pts who started systemic therapy for aUC from 1/1/2017 to 5/1/2024 and had a recorded race were included. Baseline demographics, including social determinants of health (SDOH) score, performance status (PS), disease characteristics, treatment history, and clinical outcomes were abstracted. Progression free survival (PFS) and overall survival (OS) were compared between Black, White and Asian patients via Kaplan-Meier log-rank analysis and Cox proportional hazards models. Independent sample t-tests and chi-square analyses were used for univariate comparisons. P-values < 0.05 were considered statistically significant.
Results:
A total of 2,388 pts with aUC were identified, with 1.4% Asian, 5.2% Black, 14.4% “other,” and 78.9% White. In 1L, 17.9% received immunotherapy (IO) monotherapy, 4.2% received enfortumab vedotin + pembrolizumab (EVP), 37.5% received carboplatin-based regimens (carbo), 27.8% cisplatin-based regimens (cis), and 12.5% other chemotherapy (p=0.317). ECOG PS>1 at diagnosis was associated with non-White race (p=0.022). Black patients received treatment at an academic center (41.0%) more often than White patients (25.6%; p<0.001). Black pts had lower SDOH score compared White (p<0.001). Asian (HR0.73, p=0.3) and Black (HR1.07, p=0.3) pts had similar PFS to White pts, as well as similar OS with HR0.85(p=0.4) and HR1.05(p=0.4), respectively. On Cox univariate analysis, there was no significant 1L PFS difference between White, Asian, and Black pts on cis (n=665, p=0.3), carbo (n=895, p=0.7), EVP (n= 25, p=0.8), or IO (n=428, p=0.3). OS was not significantly different by race for any 1L therapy.
Conclusions:
In a large real-world database, race did not affect overall aUC survival.

Baseline characteristics and survival by race.

Black (n=124)
White (n=1884)
Asian (n=33)
Other (n=344)
Sig (p)

Baseline Characteristics

ECOG PS

0-1 (%)
55.5
64.6
58.2
62.1

0.027

2-4 (%)
18.5
15.5
19.4
15.2

Academic treatment center (%)
36.6
25.9
13.4
13.2

<0.001

Mean SDOH score (0-5)
2.27
3.26
3.38
2.97

<0.001

1L Treatment

IO (%)
23.8
16.4
20.0
17.5
0.317

EVP (%)
5.7
3.9
4.4
4.0

Carbo (%)
32.9
36.5
37.4
38.0

Cis (%)
27.4
29.2
27.8
29.8

Other (%)
10.2
14.0
10.4
10.7

Survival

1L mPFS (m)
5.2
4.6
5.1
4.2
0.300

mOS (m)
5.3
6.9
8.7
5.2
0.400

Sig values (p<0.05) in bold.
Optyx study: Clinical characteristics and preferences for initiating relugolix in a cohort of US patients in real-world care settings.
Authors: Spratt Daniel Eidelberg , McKay Rana R. , Ross Ashley , Lowentritt Benjamin H , Flanders Scott C , Zhong Yi , Hong Agnes , Ryan Michael , Dorff Tanya B.
Published: February 2025

67

Background:
Relugolix is the only oral androgen deprivation therapy indicated for advanced prostate cancer (PC). The OPTYX study is the first prospective study to collect evidence on the long-term safety, effectiveness, treatment patterns, disease course, and patient outcomes with relugolix in real-world care. Enrollment is completed and this analysis assessed key baseline variables, reasons for starting relugolix, and treatment patterns.
Methods:
The multi-center observational OPTYX study enrolled men with PC starting relugolix across various disease stages and treatment regimens (e.g., mono or combination therapy). Enrollment occurred in diverse clinical settings including urology, oncology, and radiation oncology. Eligibility required intent to treat with relugolix for more than 4 months. Data collected included baseline demographics, clinical characteristics, reasons for initiating treatment, treatment patterns, and quality of life (FACT-P) questionnaires from Oct 2022 to Sept 2024.
Results:
By September 2024, 999 men were enrolled and received relugolix with a median treatment duration of 242 days. The median age was 71 years; 77.4% self-identified as White, 16.4% as Black. Over 80% submitted FACT-P questionnaires at baseline. Disease states included localized (42.0%), locally advanced (16.7%), biochemical recurrence (11.2%), metastatic castration sensitive PC (18.7%), non-metastatic (1.5%), metastatic castration resistant PC (4.8%), and unknown (5.0%). Of these, 476 men (47.7%) received relugolix in combination with other PC therapies including radiation and systemic therapies. Prior ADT was reported in 21.0% of patients. Mean (SD) baseline testosterone and PSA were 293.1 (227.8) ng/dL and 61.3 (342.4) ng/mL, respectively. The top reasons physicians prescribed relugolix were preference for oral over injection administration (41.5%), rapid testosterone suppression (34.6%), and safety (29.0%), while patients reported physician recommendation (72.3%), oral over injection (36.4%), and rapid testosterone recovery (10.2%).
Conclusions:
The OPTYX study enrolled 999 patients to assess real-world experience with relugolix. Nearly half started relugolix with other therapies. Many patients and physicians preferred the oral formulation, and other top reasons for initiation included safety and rapid testosterone suppression and recovery. Clinical trial information:
NCT05467176
.

Relugolix Initiation Preference n (%)
By Physician
By Patient

Oral Instead of Injection
415 (41.5)
364 (36.4)

Rapid Testosterone Suppression
346 (34.6)
98 (9.8)

Safety Profile
290 (29.0)
95 (9.5)

Efficacy Data
255 (25.5)
66 (6.6)

Rapid Testosterone Recovery
209 (20.9)
102 (10.2)

Tolerability
119 (11.9)
55 (5.5)

Co-morbid Disease
76 (7.6)
17 (1.7)

Physician Recommended
60 (6.0)
722 (72.3)

Other/Unknown
45 (4.5)
22 (2.2)
Patient profiles as drivers of physician choice for first-line (1L) treatment (tx) in locally advanced or metastatic urothelial cancer (la/mUC): Perspectives from a US study.
Authors: Milloy Neil , Walley Maria , Simpson Amber , Forshaw Cameron , Morris Valerie A. , Kearney Mairead
Published: February 2025

719

Background:
As the number of tx options for patients with la/mUC increases, physicians aiming to optimize tx choice and sequencing must make complex decisions. Although recommended options provide clinical benefits, each has a distinct toxicity profile that limits its use in routine clinical care. This study assessed physician perspectives for 1L la/mUC tx selection based on hypothetical patient and disease characteristics.
Methods:
Data were drawn from the Adelphi Real World mUC Disease Specific Programme, a cross-sectional survey that captured data from medical oncologists and urologists responsible for treating people with la/mUC in the US, from Jan-July 2024. Physicians self-reported which 1L tx option they would be most likely to prescribe based on patient and disease characteristics provided. Tx options presented were: platinum-based chemotherapy followed by avelumab maintenance (PBC & Ave), enfortumab vedotin plus pembrolizumab (EV & P), cisplatin/gemcitabine plus nivolumab (cis/gem & nivo), and other. Descriptive statistics were used for all analyses.
Results:
Of the 49 physicians who participated, 23 (47%) primarily worked in academic practices, 19 (39%) in community-based practices, and 7 (14%) in other care settings. At data collection, physicians were making tx decisions for a median of 24 patients with la/mUC (IQR, 10-44). Physicians most frequently reported that they would choose PBC & Ave for patients with liver disease (53%) and EV & P for patients with only lymph node involvement (55%). A breakdown of physician-reported 1L tx choices by patient/disease profile is presented in the Table.
Conclusions:
Despite the limited sample size, this real-world study provides contemporary insights into la/mUC tx choice among practicing US physicians in an evolving therapeutic landscape. We found heterogeneity in clinician-reported choices for 1L tx based on patient profiles, and inconsistency vs guideline recommendations. Multidisciplinary discussion and consensus are needed to support physicians in identifying patient profiles that may derive the greatest benefit from different 1L tx options while minimizing potential risks. Criteria that guide clinicians and inform policy decisions should evolve and gain broader acceptance as novel therapeutics are incorporated into routine care.

Physician-reported 1L tx choice (N=49)

Characteristic, n (%)

PBC & Ave

EV & P

Cis/Gem & Nivo

Other

Liver disease
26 (53)
16 (33)
7 (14)
-

Visceral disease
18 (37)
25 (51)
6 (12)
-

Liver metastases
17 (35)
22 (45)
10 (20)
-

Frail/elderly patients
9 (18)
24 (49)
8 (16)
8 (16)

Pre-existing peripheral neuropathy
15 (31)
25 (51)
3 (6)
6 (12)

Diabetes
24 (49)
19 (39)
5 (10)
1 (2)

Only lymph node involvement
19 (39)
27 (55)
3 (6)
-

Low tumor burden
15 (31)
21 (43)
12 (24)
1 (2)

High tumor burden
20 (41)
19 (39)
10 (20)
-
Modified transurethral resection of bladder tumors: A comparison study of chemotherapy-enhanced endoscopic submucosal en bloc dissection versus conventional resection.
Authors: Liu Xi , Wang Yiding , Wang Zhe , Shao Bo , Liu Qiang , Li Changqi , Lv Chengcheng , Bi Huan , Shan Guangyi , Chen Ang , Zeng Yu
Published: February 2025

721

Background:
High recurrence rates plague patients with nonmuscle invasive bladder cancer (NMIBC) following transurethral resection of bladder tumors (TURBT). In response, we have developed a modified TURBT procedure that integrates
en bloc
resection, endoscopic submucosal dissection, and the injection of chemotherapeutic drugs into the submucosa (cESD-TURBT).This study aims to determine if cESD-TURBT yields better outcomes than conventional TURBT (cTURBT).
Methods:
This retrospective observational study was conducted on patients diagnosed with cTa–T1 bladder cancer who received TURBT between December 2020 and July 2023 in Liaoning Cancer Hospital. Participants were grouped based on the type of treatment they received: cESD-TURBT (n=118) or conventional TURBT (cTURBT, n=105). Hydroxycamptothecin was the chemotherapeutic agent used for submucosal injections. The primary outcome was recurrence-free survival (RFS) of the treated bladder cancer. Secondary outcomes included disease recurrence within one year, operation duration, length of postoperative hospitalization, and complication rates. Statistical analyses were performed using appropriate tests, with a threshold of P < 0.05 defined as statistically significant.
Results:
Among the 223 patients, cESD-TURBT cohort demonstrated enhanced RFS compared to cTURBT cohort, with a median follow-up of 775 days (IQR 414-1040). The recurrence rate in the cESD-TURBT cohort was 18.64% (22/118), against 39.05% (41/105) in the cTURBT cohort, with a log-rank hazard ratio of 0.49 (95% CI 0.29-0.82; p=0.0053). Furthermore, cESD-TURBT registered fewer postoperative complications than cTURBT, markedly reducing occurrences such as the obturator reflex (2% vs. 9%). The difference in operation times was not statistically significant, with cESD-TURBT averaging 49.0 ± 21.0 minutes and cTURBT 44.3 ± 23.8 minutes, the difference being statistically negligible (p=0.127).
Conclusions:
For patients with NMIBC, cESD-TURBT significantly lowers recurrence rates compared to cTURBT and is associated with fewer postoperative complications. Our study reveals that the chemotherapy-enhanced ESD-TURBT technique significantly improves recurrence-free survival and reduces complications, making it a superior method over conventional TURBT for bladder tumor removal.
Avelumab first-line (1L) maintenance therapy in advanced urothelial carcinoma: Final analysis from a real-world study in the UK.
Authors: Jones Robert Jones , Shah Yatri , Birtle Alison Jane , Challapalli Amarnath , Chan Joachim , Enting Deborah , Hudson Andrew , Linch Mark David , Otter Sophie , Protheroe Andrew , Sharma Anand , Turner Rufus , Chengat Prakashbabu Bhagyalakshmi , Rice Wendy , Jedy-Agba Elima Enaji
Published: February 2025

723

Background:
In the JAVELIN Bladder 100 phase 3 trial, avelumab 1L maintenance therapy plus best supportive care (BSC) significantly improved overall survival (OS) and progression-free survival (PFS) vs BSC alone in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) that had not progressed with 1L platinum-based chemotherapy (PBC). In the UK, initial access to avelumab was provided via the Early Access to Medicines Scheme (EAMS) from September 2020. This study reports 24-month real-world outcomes in patients treated with avelumab 1L maintenance via the EAMS in the UK.
Methods:
Patients aged ≥18 years who had been diagnosed with la/mUC, demonstrated at least stable disease following 1L PBC, and initiated avelumab since October 2020 were recruited consecutively from 10 UK hospitals. Primary outcomes included real-world OS, real-world PFS, and treatment patterns by 24 months. Recruitment was completed in June 2022, and all patients had completed 24 months of follow-up from avelumab initiation by June 2024.
Results:
Of 106 patients recruited, 78 (73.6%) were male. Median age at diagnosis of la/mUC was 72 years. Primary tumor site was bladder in 40 (78%), and the most common metastatic sites were lymph node in 64 (60.4%), lung in 31 (33%), and bone in 20 (21.3%). ECOG performance status was 0 in 35 (33.0%),1 in 36 (34%), 2-4 in 5 (4.7%), and not recorded in 30 (28.3%). 1L PBC was carboplatin/gemcitabine in 55 (51.9%) and cisplatin/gemcitabine in 49 (46.2%). Response to 1L PBC was partial or complete response in 63 (60.0%). From avelumab initiation, median OS was 16.8 months (95% CI, 11.6-23.4) and median PFS was 8.7 months (95% CI, 7.1-14.2). Median OS from the start of 1L PBC in this population without disease progression after 1L PBC was 21.8 months (95% CI, 17.0-28.9). In subgroup analyses of patients who had received 1L carboplatin/gemcitabine or cisplatin/gemcitabine, median OS from avelumab initiation was 14.4 months (95% CI, 10.1-not estimable [NE]) and 21.4 months (95% CI, 15.4-NE), and median OS from start of 1L PBC was 19.5 months (95% CI, 14.8-NE) and 26.7 months (95% CI, 20.5-NE), respectively.
Conclusions:
These results provide evidence of the clinical effectiveness of avelumab 1L maintenance therapy in patients who were progression free following 1L PBC in a UK real-world setting. Median OS was shorter than previously observed in the JAVELIN Bladder 100 trial, which may be due to the worse ECOG performance status and higher proportion of patients who had received 1L carboplatin-based chemotherapy in this real-world population.
Efficacy and safety of disitamab vedotin combined with toripalimab as neoadjuvant treatment for patients with locally advanced muscle-invasive bladder cancer: A mono-institutional retrospective study.
Authors: Zhang Geng , Fu Qiang , Zhang Fuxun , Yang Fan , Hou Haozhong
Published: February 2025

726

Background:
Currently, the efficacy of cisplatin-based neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer (MIBC) is unsatisfied. Disitamab vedotin (RC48) as an antibody-drug conjugate is composed by a monoclonal antibody against human epidermal growth factor receptor 2 (HER2) and a cytotoxic agent monomethyl auristatin E. Although this drug was approved in 2021 for HER2-overexpressing gastric cancer, disitamab vedotin as mono- or combination regimen is in clinical development for treating other solid tumors now. This study aims to assess the safety and efficacy of disitamab vedotin combined with toripalimab as neoadjuvant treatment for patients with HER2 positive locally advanced MIBC.
Methods:
The data of patients with HER2 positive locally advanced MIBC who received combination therapy [disitamab vedotin (2.0mg/kg, iv, D
1
, Q3W) combined with toripalimab (240mg, iv, D
1
, Q3W) were collected retrospectively and analyzed. The primary endpoint was pathological complete response (pCR), and the secondary endpoints included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs). All outcomes were assessed by a blinded independent review committee.
Results:
The data of 20 included patients who received combination regimen from 2023 Jun to 2023 Sept were analyzed. Among them, the median age was 65 (47-86) years. The overall pCR was 79%, while the ORR was100%. The median PFS was 4.5 (2.45-9.6) months, and overall survival (OS) was not reached. The most common TRAEs were nausea (7,35.0%), alopecia (8,40.0%), and rash (3,15%). Only 1 patients reported Grade 3 TRAE (feeble), and no grade 4 TRAEs were observed.
Conclusions:
The safety and efficacy of neoadjuvant disitamab vedotin combined with toripalimab in patients with HER2 positive locally advanced MIBC were promising. This study will be verified in future.
Survival impact of concomitant squamous differentiation in upper tract urothelial carcinoma patients receiving adjuvant chemotherapy.
Authors: Ye Jianjun , Liao Xinyang , Zhang Shiyu , Wei Qiang , Bao Yige
Published: February 2025

729

Background:
Adjuvant platinum-based chemotherapy after radical nephroureterectomy (RNU) was a strong recommendation for patients with pT2–4 and/or pN+ upper tract urothelial carcinoma (UTUC). However, the efficacy of adjuvant chemotherapy (AC) on UTUC with squamous differentiation (UTUCSD) remains unclear. This study was conducted to investigate survival impact of SD on UTUC patients receiving AC, and further assessed the efficacy of AC on UTUCSD.
Methods:
Data of 868 UTUC patients who underwent RNU at West China Hospital of Sichuan University from May 2003 to June 2021 were retrospectively included, and only patients with the history of postoperative adjuvant chemotherapy were further analyzed. The end points included overall survival (OS), cancer-specific survival (CSS) and metastasis-free survival (MFS). Propensity score matching (PSM), Kaplan‒Meier curves and Cox proportional hazard model were utilized.
Results:
Overall, the prevalence rate of UTUCSD is 10.7% (93/868), and UTUCSD significantly tended to be locally advanced (pT>2), high grade and lymph node metastasis (LNM) disease. After PSM for tumor stage, grade, and LNM, 32 paired cohorts at a ratio of 1 to 3 among patients received chemotherapy (according to the presence/absence of SD) were derived. Compared with pure UTUC patients receiving AC, UTUCSD patients showed significantly inferior OS (HR 1.99, 95% CI 1.06-3.71) and CSS (HR 1.95, 95% CI 1.09-3.47) but comparable MFS (HR 1.33, 95% CI 1.0.71-2.50). Furthermore, AC could not bring significant survival benefit to patients with UTUCSD in terms of OS (HR 0.73, 95% CI 0.40-1.31) and CSS (HR 0.88, 95% CI 0.46-1.69).
Conclusions:
Concomitant SD acted as an inferior survival predictor among UTUC patients receiving AC. UTUCSD is less sensitive to chemotherapy and effective treatments need to be further studied.
A retrospective real-world study of disitamab vedotin combined with tislelizumab versus chemotherapy in patients with previously untreated metastatic urothelial carcinoma.
Authors: Se Han , Gui Xiaomeng , Wang Lin , Jing Jing , Si Riguleng , Li Haojing , Lv Dongchen , Li Jia , Chi Ning , Li Sanxiang , Yang Hong
Published: February 2025

733

Background:
Eligible patients with metastatic urothelial carcinoma (mUC) typically receive platinum-based chemotherapy as first-line therapy. Recently, antibody-drug conjugates (ADCs) combined with PD-1 antibody have shown good efficacy and safety in metastatic urothelial carcinoma (mUC). And HER2-positive thought to be an unfavorable prognostic factor and associated with poor outcomes but can benefit from anti-HER2 ADCs such as Disitamab Vedotin (RC48-ADC). The aim of this retrospective study is to evaluate the efficacy and safety of RC48-based therapy in real-world untreated mUC, especially in comparison to standard chemotherapy.
Methods:
We retrospectively collected data from 70 consecutive patients with mUC who received routine care between July 2022 and December 2023 including 30 received RC48-ADC plus Tislelizumab (DT-group) and 40 received the conventional regimen of Gemcitabine plus Cisplatin (GC-group). Last follow-up on 30 March 2024. The primary endpoints were objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs).
Results:
The median age of the DT-group and GC-group patients were 67-y and 64-y, with 66.7% (n=20) and 82.5% (n=33) HER-2 negative (identified as IHC 0 or 1+). Baseline characteristics of the two groups, including age, gender, pathological grading, ECOG score, tumour location, metastasis and HER-2 expression showed no statistically difference (P > 0.05). The ORR in DT-group was 1.5 times higher than in GC-group, reaching 73.3% (22/30) versus 47.5% (19/40) with a higher CR rate (20% vs 0%). Even in HER-2 negative subgroup from DT-group, the RC48-ADC plus Tislelizumab therapy achieved impressive outcomes (ORR 55% (11/20)) comparable to chemotherapy. For survival analyses, PFS was longer in the DT-group than in GC-group (median, 10.98 months vs. 7.67 months; P<0.005), as was OS (median, not reached vs. 11.34 months). Two groups showed a similar safety profile (p > 0.05). The most reported TRAEs were bone marrow suppression, gastrointestinal and hepatobiliary disorders, malaise, alopecia and rash, and no ≥ grade 3 TRAEs or treatment-related deaths were reported.
Conclusions:
This retrospective study of patients with treatment-naïve mUC demonstrated administration of RC48 for real-world patients is both effective and safe. Several global clinical trials (DV-001, RC48-G001) evaluating efficacy and safety of RC48-ADC in combination with immunotherapy are ongoing. These data further solidify the benefit of anti-HER2 ADC combined with checkpoint inhibitors for frontline treatment of patients with mUC.
Optimizing treatment approaches in nested bladder tumors: A multicenter retrospective study.
Authors: Giannatempo Patrizia , Ambrosini Paolo , Maruzzo Marco , Mistretta Francesco , Da Pozzo Luigi , Soria Francesco , Barella Marco , Rametta Alessandro , Quistini Alberto , La Croce Giovanni , D'Andrea David , Di Marco Andrea , Hurle Rodolfo , Contieri Roberto , Gontero Paolo , Musi Gennaro , Procopio Giuseppe , Miceli Rosalba , Polymeropoulos Alessio , Nicolai Nicola
Published: February 2025

743

Background:
Identifying optimal treatment strategies in nested bladder tumors is critical. This multicenter study aims at evaluating progression-free survival (PFS) end overall survival (OS) according to disease extent, presentation and treatment including Bacillus Calmette-Guérin (BCG), radical cystectomy (RC) and chemotherapy (CT).
Methods:
Data were collected from 61 patients with nested bladder tumors across 5 centers over a 10-year period (2013–2023). Patients were stratified according to 1) time of diagnosis of nested variant (disease onset Vs recurrence) 2) disease extent (NMIBC
vs
MIB,
vs
cN+ Vs M+) 3) treatment groups based on their initial treatment: ( BCG ± RC
vs
RC only Vs RC + CT). Kaplan-Meier analysis was used to assess median PFS (mPFS) and median OS (mOS), while p-values <0.05 was used to determine statistical significance across groups.
Results:
The median follow-up was 30.6 months (95% CI: 16.4–40.6). At diagnosis 15 (24.6%) were NMIBC, 26 (42.6%) MIBC, 15 (24.6%) N+ and 5 (8.2%) metastatic (M). Of the 15 NMIBC 80% received initial BCG. Pts with nested bladder tumors at onset had worse PFS and OS (mPFS of 99.6 months (95% CI: 55.2-NR) and mOS of 107.3 months (95% CI: 71.6-NR) than those with nested bladder tumor at recurrence mPFS of NR (95% CI: 42.1-NR) and mOS 138.4 (95% CI: 51.7-NR). None of these differences were statistically significant. Patients with M and N+ stages showed a trend towards a worse prognosis than those with NMIBC and MIBC, with no statistically difference in mPFS and mOS between MIBC and NMIBC stages. According to treatment, the best mPFS and mOS were recorded among patients receiving RC and CT [mPFS 99.6 months (95% CI: 55.2-NR) and mOS of 107.3 months (95% CI: 107.3-NR)]. Those receiving BCG followed by RC group had a mPFS of 84.2 months (95% CI: 68.1-NR) and mOS of 85.9 months (95% CI: 71.6-NR) while those undergoing RC alone apparently had the worse mPFS of 42.1 months (95% CI: 42.1-NR) and mOS of 51.7 months (95% CI: 14.7.1-NR). None of these differences were statistically significant.
Conclusions:
This study represents the largest case series of nested bladder tumors. It suggests limited benefit from BCG treatment. Most patients had advance disease, most of NMIBC finally need CT. Diagnosis at recurrence and combination of RC and CT tend to better survivals. Analyses that are more detailed are ongoing to evaluate clinical benefits according to the different clinical features.
Assess the journey: Characterizing muscle-invasive bladder cancer patients who receive neoadjuvant therapy and do not proceed with cystectomy.
Authors: Ogunkeye Jay , Belay Ruth E , Skinner Eila C.
Published: February 2025

746

Background:
The standard treatment of muscle invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC), offering a 5-10% survival benefit and reducing recurrence by 35%. However, little is known about the patients who start NAC but do not proceed to RC. In the SWOG-8710 trial, 18% of patients did not undergo surgery after NAC. Platinum-based regimens, while generally well tolerated, sometimes cause severe side effects. With increasing NAC use and evolving treatment options, some patients start NAC without completing definitive treatment. This study aims characterize patients who do not proceed with RC, focusing on their NAC experience and alternative treatments.
Methods:
A retrospective analysis was performed on MIBC patients recommended for neoadjuvant therapy followed by RC between 2020-2023 by a single provider at Stanford Health Care. Eligible patients had clinically localized bladder cancer (cT2-T4N0) who initiated neoadjuvant therapy and were deemed surgical candidates. Patients who were not platinum-eligible received alternative therapies on clinical trials
.
Data were collected on patient demographics, comorbidities, functional status, renal and hematologic function, and NAC administration. Patients who underwent cystectomy were excluded.
Results:
A total of 90 patients with MIBC who had a treatment plan involving neoadjuvant therapy followed by RC between 2020-2023 were identified. 22% (20/90) of these patients did not undergo cystectomy. The median age was 76, 75% male, 75% white. 50% of patients had variant or non-urothelial carcinoma histology. 60% were cT2 at time of initial consult. The majority of patients (80%) received platinum-based NAC, with only 4 receiving alternative therapies. One patient died of a stroke before completing NAC. The reasons for not undergoing RC were declining additional treatment (30%) and inability to tolerate surgery due to toxicity from therapy (30%), followed by patient preference of radiation therapy (20%), and disease progression (10%). Two additional patients were taken to the operating room; however, surgery was aborted due to unresectable disease and anesthetic complications. Among those who did not undergo RC, 42% opted for surveillance, 37% received trimodal therapy (TMT), and 21% received additional immunotherapy.
Conclusions:
In this study, we were able to gain a better understanding of our patient cohort who started neoadjuvant therapy but did not proceed to cystectomy. Reasons for this decision included toxicity related to neoadjuvant therapy, personal desire to forgo surgery, or prioritization of bladder preservation. These findings highlight the need for future efforts aimed at trying to predict this patient population and further comparative analysis of outcomes between this cohort and those who underwent cystectomy.
Impact of adding immunotherapy to chemotherapy for metastatic neuroendocrine bladder cancer in the National Cancer Database.
Authors: Meng Lingbin , Wang Peng , Wang Shihua , Yang Yuanquan , Hong Feng , Collier Katharine A. , Hasanov Elshad , Wang Shang-Jui , Sundi Debasish , Sood Akshay , Zimmerman Danielle Elise , Bicer Fuat Bicer , Gauntner Timothy D. , Folefac Edmund , Monk Paul , Mortazavi Amir , Clinton Steven K.
Published: February 2025

748

Background:
Metastatic neuroendocrine bladder cancer is a rare and aggressive malignancy characterized by poor prognosis and limited effective treatment options. Standard chemotherapy has shown limited success, necessitating novel therapies. We hypothesized that adding immunotherapy to chemotherapy would improve overall survival (OS) in these patients.
Methods:
We conducted a retrospective cohort study of 1,410 patients diagnosed with metastatic neuroendocrine bladder cancer between 2004 and 2020 using the National Cancer Database (NCDB). Treatment groups included no treatment, chemotherapy alone, and combined immunochemotherapy. Survival outcomes were analyzed using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards regression models, adjusting for age, tumor size, Charlson-Deyo comorbidity score, and residential area.
Results:
Median OS was 1.8 months (95% CI: 1.6-2.0) for patients receiving no treatment (n=460), 9.6 months (95% CI: 8.9-10.1) for chemotherapy alone (n=860), and 11.7 months (95% CI: 9.6-14.8) for combined immunochemotherapy (n=90) (P < 0.001 for immunochemotherapy vs. both other groups). Further analysis revealed that first-line immunotherapy initiated within 30 days of chemotherapy (n=21) significantly improved OS (median 11.6 months; 95% CI: 6.8–16.1; P=0.0374) compared to chemotherapy alone. Notably, immunotherapy initiated after 30 days (n=69, median OS 12.4 months; 95% CI: 9.0–14.8; P=0.0264), whether as first-line or second-line therapy, also showed superior efficacy to chemotherapy alone. These findings suggest that if first-line immunotherapy is not administered, subsequent immunotherapy should still be considered. Multivariable Cox regression analysis showed that immunochemotherapy compared to chemotherapy alone was associated with a lower hazard for death (HR = 0.80; 95% CI: 0.66-0.97; P = 0.0242), while patients receiving no treatment had an increased risk of death (HR = 3.50; 95% CI: 3.00-3.90; P < 0.0001). Additional factors associated with increased mortality included older age, larger tumor size, and higher Charlson-Deyo score.
Conclusions:
Adding immunotherapy to chemotherapy significantly improved OS in metastatic neuroendocrine bladder cancer. First-line immunochemotherapy showed substantial benefits, but late initiation also improved outcomes. These findings support incorporating immunotherapy into first-line protocols and consider it for subsequent lines. Prospective clinical trials are needed to optimize immunotherapeutic strategies for this aggressive malignancy.