tbuckley/cabot-search huggingface dataset:
A clinical trial evaluating the efficacy and safety of disitamab vedotin plus tislelizumab combined with re-TURBT in the treatment of HER-2-high expression (2+-3+) non-muscle invasive bladder cancer at high-risk and very high-risk.
Authors: Jianhui Chen, Yiming Su, Rong Liu, Ru Chen, Shaoxing Zhu, Qianyi Qiu
Journal: Journal of Clinical Oncology (2025)

TPS895 Background: Current studies indicate that the combination of Disitamab Vedotin and PD-1 inhibitors can enhance the efficacy of systemic therapy in patients with HER2-positive urothelial carcinoma, with an acceptable safety profile. However, the evidence supporting its use in high-risk and very high-risk NMIBC remains limited. And several clinical guidelines recommend a re-TURBT for high-risk NMIBC patients, as it has been shown to significantly reduce the 5-year recurrence and progression rates.Therefore, this study aims to evaluate the efficacy and safety of the triplet regimen of Disitamab Vedotin, Tislelizumab (a PD-1 inhibitor), and re-TURBT in patients with HER2 IHC 2+ or 3+ high-risk and very high-risk NMIBC. Methods: Patients diagnosed with high-risk and very high-risk NMIBC, based on medical history, clinical presentation, imaging examinations (such as MRI with plain and enhanced scanning), and transurethral resection for tissue pathological biopsy, are included in the "case screening process".After excluding surgical contraindications, TURBT is performed; postoperative tissue pathological examination confirms NMIBC, and patients with immunohistochemical results of HER2 as 3+ or 2+ enter further screening. Referring to the AUA guidelines, high-risk and very high-risk NMIBC are included in subsequent analysis, where those who meet the inclusion criteria of this study, excluding the exclusion criteria, and who have recovered well after the initial TURBt and are assessed to be able to complete a second TURBT within six weeks are considered as the final candidates for enrollment.Eligible patients for single-arm enrollment (N=40) will receive Tislelizumab (200mg) + Disitamab Vedotin (120mg for weight ≤60Kg or 2.0mg/Kg for weight ≥60Kg) the day after the initial TURBT, to be repeated every 3 weeks (Q3W). Patients are also scheduled to undergo a second TURBT within 6 weeks, and after the surgery, they will continue with three more courses of Tislelizumab + Disitamab Vedotin (Q3W) until the end of the 3-year follow-up period. The primary endpoint for evaluation in this study phase is the 1-year event-free survival rate (EFS),which is defined as the possibility of patients have not experienced any events for at least 12 months after receiving treatment, including death, disease progression, switch to chemotherapy, addition of other treatments, fatal or intolerable side effects, etc. Clinical trial information: NCT06630871 .
Safety and efficacy of intravesical bacillus Calmette-Guerin instillation for superficial recurrence following bladder-sparing therapy of muscle invasive bladder cancer.
Authors: Gan Du, Rui-Yang Xie, Honglei Cui, Xingang Bi, Hongzhe Shi, Aiping Zhou, Youyan Guan, Jianzhong Shou
Journal: Journal of Clinical Oncology (2025)

787 Background: Patients treated with bladder-preserving therapy for muscle-invasive bladder cancer are at risk of developing recurrent non-muscle-invasive bladder cancer. This study aims to evaluate the efficacy and adverse events of postoperative Bacillus Calmette-Guerin (BCG) instillation in patients with superficial recurrence following bladder-preserving therapy for muscle-invasive bladder cancer. Methods: We retrospectively analyzed 120 patients diagnosed with non-muscle-invasive bladder cancer who underwent transurethral resection followed by BCG instillation. The 19 patients with prior muscle-invasive bladder cancer were categorized as the NMIBC-M group, while the remaining 101 patients formed the NMIBC group. All patients completed a six-cycle BCG course. Results: Both groups showed no significant differences in baseline characteristics, except for the number of BCG instillations (15.5 vs. 9, p = 0.010). Overall survival, recurrence-free survival, metastasis, bladder preservation, and adverse event profiles were comparable between groups. However, patients in the group with prior muscle-invasive bladder cancer reported lower rates of urinary retention (28.7% vs. 0.0%, p = 0.017) and fever (30.7% vs. 5.3%, p = 0.044). Conclusions: Postoperative BCG instillation in patients with superficial recurrence following bladder-preserving therapy for muscle-invasive bladder cancer showed comparable efficacy and side effects to those without muscle-invasive bladder cancer history.
First-line therapies analysis in advanced/metastatic urothelial carcinoma: Prognostic insights with propensity score analysis and RNA-seq.
Authors: Jingjing Wang, Yupeng Jiang, Wen Zou, Wei He, Minfeng Chen, Chao Xu
Journal: Journal of Clinical Oncology (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 &gt;1 year and PFS &lt;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.
The Man Van phase 2 results: Mobile targeted case finding for prostate cancer.
Authors: Masood Moghul, Fionnuala Croft, Fiona Mutch, Elisabeth Westaway, Kathyrn Bradshaw, Patrick Kierkegaard, Netty Kinsella, Declan Cahill, Nicholas David James
Journal: Journal of Clinical Oncology (2025)

317 Background: Early intervention is potentially lifesaving in prostate cancer and is a major limitation of cancer outcomes with ethnicity and deprivation being determinants of inequalities that impact outcomes. The Man Van is designed to address health inequalities and barriers to accessing healthcare that affect prostate cancer with novel community-based targeting of high-risk groups using a mobile clinical unit. These inequalities are particularly relevant for men from ethnic minorities and lower socio-economic groups. Methods: A bespoke nurse-led mobile clinical unit was moved to community-based locations in areas of high deprivation indices in London (UK) with targeted invitations to high-risk men. Men were offered prostate-specific antigen (PSA) tests and a general health check including: blood pressure, body mass index and an HbA1c test for diabetes. Results: Between January 2023 and January 2024, 3379 men attended a Man Van clinic (non-attendance rate 15.1%). The median age of attendees was 59 years (range 39-97). 36.4% of attendees were non-White including 16.7% of men who were Black. The median IMD rank was within the 6 th lowest decile. 310 men were referred for prostate cancer investigations, 262 had prostate MRI scans. 139 (53.1%) of MRIs were PIRADS 1/2, 35 (13.4%) PIRADS 3, 85 (32.4%) were PIRADS 4/5. 3 (1.1%) scans could not be scored. 127 patients underwent a prostate biopsy (48.5% of men having an MRI scan), with 94 prostate cancers diagnosed (74.0% of biopsies). 81 (86.2%) of these were cancers with clinically significant disease, being grade group 2 (i.e. Gleason 7) or higher (all with &gt;5% pattern 4 Gleason scores). The overall diagnostic rate of clinically significant disease was 2.8%. No prostate cancers were metastatic at presentation, with only one being T4. Of the men diagnosed with prostate cancer (N=94), 25 (26.6%) were managed with active surveillance, 2 (2.1%) were managed with cryotherapy, 2 (2.1%) were managed with low dose-rate brachytherapy, 39 (41.5%) underwent robotic prostatectomy and 26 (27.7%) underwent radiotherapy. 59 patients were referred on two week wait pathways for haematuria (visible or persistent non-visible). One bladder cancer (TCC) was diagnosed (G3pT1bN0M1). 43 patients (2%) were diagnosed with diabetes, 207 patients (11%) with pre-diabetes. Conclusions: The Man Van initiative is a novel method of linking primary and secondary care for a range of health checks, including PSA. With a streamlined and more efficient service we have maintained high uptakes for health checks a willingness to engage with health improvement measures from deprived and ethnic minority groups. As well as comparatively high levels of prostate cancers diagnosed at early stages, high levels of other health conditions were found; improving the economic value of the service. Clinical trial information: NCT06357416 .
Biomarker analysis in localized urothelial cancer DUART patients post-treatment.
Authors: Adriana Sophia Ramos Medero, Junjia Zhu, Monika Joshi, Todd D. Schell
Journal: Journal of Clinical Oncology (2025)

859 Background: Patients with localized unresectable or cisplatin-ineligible urothelial cancer (UC) have limited treatment options. Biomarker identification can guide targeted therapies. In the DUART study, pre-treatment immune cell subsets were significantly linked to disease control. Our planned correlative aim was to evaluate the same biomarkers using post-adjuvant treatment (post-Rx) peripheral blood mononuclear cells (PBMCs). Methods: This was a prospective, multi-institutional study BTCRC-GU15-023. Our N=16 all had valid Post-Rx values and disease control status. Eligibility criteria: &gt;18yrs, advanced/unresectable UC, and available tumor specimen. All received concurrent durvalumab and radiation therapy followed by adjuvant durvalumab in a Phase II study. Blood samples were taken at pretreatment, 12 weeks, and post-Rx. Biomarkers were detected using multicolor flow cytometry-based analysis of PBMCs to detect T lymphocyte subsets and by dimensionality reduction using FlowJo. Correlative objective: Evaluate post-Rx time points for biomarkers that contribute to disease progression or response. Two-sample T-tests were used to study the association. All tests were two-sided and the statistical significance level used was 0.05. Results: Standard flow cytometry analysis revealed a statistically significant increase in ICOS+ CD4 and CD8 T cells in post-Rx samples among patients with progression-free survival at one year. In addition, responder patients (CR/PR/SD, n=12) showed a significant decrease in CD8 central memory T cells compared to progressors (PD, n=4) in post-Rx samples. Although not statistically significant, additional trends were noted, including decreased PD-1+ CD4 T cells in responder patients, decreased CD4 T effector memory RA+ (TEMRA), and increased CD4 naïve T cells in responder patients. There was a slight increase in interferon gamma-producing CD8 T cell subsets in responder patients and a significant decrease in central memory CD8 T cells. tSNE analysis revealed similar trends in the data, including increased naïve CD4 T cells in responder patients and slight increases in some cytokine-producing CD8 T cell subsets. Conclusions: Our small cohort demonstrates some significant differences in post-Rx T cell populations linked to therapy response, and further evaluation in a larger cohort of patients is needed. The identification of predictive biomarkers could help a more personalized therapeutic approach.
Functional and oncological outcome of primary nerve sparing retroperitoneal lymph node dissection in marker negative testicular germ cell tumors in clinical stage IIA/B.
Authors: Julian Heidenreich, Axel Heidenreich
Journal: Journal of Clinical Oncology (2025)

641 Background: Guideline recommended treatment of choice for clinical stage IIA/B testicular nonseminomatous germ cell tumors (NSGCT) is the delivery of chemotherapy with 3 cycles PEB, 4 cycles PE. Despite its high curative efficacy, chemotherapy is associated with significant long-term toxicities. We evaluated the functional and oncological outcome of primary nerve sparing retroperitoneal lymph node dissection in marker negative NSGCT as a therapeutic option. Methods: Between 2018-2024 49 patients underwent primary RPLND for marker negative clinical stage IIA/B testicular germ cell tumors. All patients underwent nerve-sparing RPLND with a unilateral or bilateral template dissection. None of the patients received adjuvant chemotherapy. Follow-up was performed according to the EAU guidelines. The surgeries were performed by a single surgeon using an open transperitoneal approach. Results: The median age and median follow-up were 30.1 (17-35) years and 29.4 (11-47) months, respectively. The mean operative time, blood loss, and hospitalization duration were 131 (105-195) minutes, &lt; 150ml, and 4.5 (3-9) days, respectively. 10 patients (9.18%) experienced a Clavien-Dindo grade 3a complication. Antegrade ejaculation was preserved in 90.8% of cases. On average, 21 (7-42) lymph nodes were dissected. 5 patients exhibited teratomatous elements in the primary orchiectomy specimens and 4 patients demonstrated teratomatous elements in the resected lymph nodes. The mean number of positive lymph nodes was 2 (1-3), with an average size of 1.3 (0.3-3.0) cm. Ten patients (20.4%) showed a pN0 stage. Six patients (12.2%) developed a recurrence and were cured by salvage chemotherapy. Conclusions: Primary RPLND for marker negative clinical stage II/ABnonseminomatous germ cell tumors results in a high cure rate without additional chemotherapy and it is associated with a low rate of complications if performed in experienced hands. Additionally, nsRPLND can safe unnecessary cytotoxic systemic therapy in 20% of patients. Furthermore, 8.1% of patients with teratoma containing lymph nodes would not have been cured by chemotherapy. Primary nsRPLND should be included in the management of marker negative CS IIA/B NSGCT.
Clinicopathological characteristics and prognosis of metastatic non-clear cell renal cell carcinoma.
Authors: Jie Wu, Hong-Lei Cui, Hongzhe Shi, Youyan Guan, Xin-Gang Bi, Aiping Zhou, Jianzhong Shou
Journal: Journal of Clinical Oncology (2025)

504 Background: Non-clear cell renal cell carcinoma (nccRCC) is a clinicopathological heterogeneous disease that comprises a complex mixture of different pathology subtypes, accounting for approximately 20% of all RCC cases. Due to its heterogeneity and rarity, standard treatment strategy for metastatic nccRCC remain poorly defined. Methods: We conducted retrospective analysis of 105 metastatic nccRCC patients at our center from June 2010 to April 2022. Demographic, clinicopathological, and systemic therapy data were collected. The data of 872 metastatic ccRCC patients were also collected for comparison.The end points included progression-free survival (PFS) and overall survival (OS). Results: Among 105 metastatic nccRCC patients, the most prevalent histology was papillary RCC (pRCC, 39.0%). The second most common histological type was translocation RCC (tRCC, 29.5%), followed by unclassified RCC (24.8%). The median age of metastatic nccRCC patients was 50 years old. 68.6% patients had advanced primary tumor stage of T3/4, and 48.6% patients had regional lymph node metastasis. The most common distant metastasis site was lung metastasis (52.4%), followed by bone metastasis (33.3%), and 21.0% patients had liver metastasis. The proportion of the favorable, intermediate, and poor IMDC risk group were 19.0%, 54.3%, and 26.7%, respectively. Among metastatic nccRCC patients, 26 received first-line IO-TKI therapy, 79 received first-line TKI monotherapy therapy. During the median follow-up of 22.2 months, there was no statistical significance between the prognosis of IO-TKI and TKI monotherapy group (PFS: 10.9 months vs. 8.6 months, P = 0.23; OS: 23.3 months vs. 24.0 months, P = 0.39). The PFS of tRCC was significantly longer than pRCC and unclassified RCC (P＜0.001). According to the Cox regression model, unclassified RCC pathology (HR=2.027，P=0.023) and poor IMDC risk group (HR=2.285，P=0.011) were identified as the independent risk factors for PFS. Poor IMDC risk group was also identified as the independent risk factors for OS (HR=2.638，P=0.007). Compared to metastatic ccRCC, the metastatic nccRCC patients were younger, with more advanced T and N stage, having a higher proportion for liver metastasis. The outcome of metastatic nccRCC was also poorer than metastatic ccRCC patients (P＜0.001), with a median OS of 24.0 months and 38.0 months, respectively. Conclusions: Compared to metastatic ccRCC, the prognosis of the patients with metastatic nccRCC was poorer, and the metastatic nccRCC patients were younger, with more advanced T and N stage, having a higher proportion for liver metastasis. Unclassified RCC pathology and poor IMDC risk group were the independent risk factors for poor prognosis. For metastatic nccRCC, the efficacy of IO-TKI was not superior than TKI monotherapy.Therefore, it is of great significance to investigate novel therapeutic targets for metastatic nccRCC.
Survival outcomes of testicular cancer (TC) in Hispanic men based on analyses from the National Cancer Database (NCDB).
Authors: Eun-mi Yu, Hongkun Wang, Jeanny B. Aragon-Ching
Journal: Journal of Clinical Oncology (2025)

622 Background: The incidence of TC among Hispanic men has been rising, as reported in our analysis of patients in the United States (Yu et al., JCO 2024 42 (4):503). We sought to determine the survival outcomes in Hispanic men based on data obtained from the National Cancer Database (NCDB). Methods: We extracted patient-level data from the NCDB and identified the incidence, demographics, treatment patterns, and outcomes in Hispanic men with TC diagnoses (non-seminoma, NS; seminoma, S) from 2004 to 2020. Results: There were a total of 89550 patients (pts) in the database. Median age at diagnosis was 37 years and 29 years for S and NS pts, respectively. There were 11005 (12.3%) TC pts designated as Hispanic (H), of whom 5396 and 5609 had S and NS TCs, respectively. In contrast, there were a total number of 74350 non-Hispanic (NH) patients with TC; n = 43629 with S, n = 30721 with NS. The majority of H pts had a Charlson-Deyo score of 0 (94.2%). Less than half of H pts had private insurance (48.8%) compared to three-quarters of NH patients (75.1%). 19.6% of H pts were diagnosed with stage II &amp; III TC (compared to 15.8% in NH pts). Pts were treated at academic/research centers in 6.6% of H pts versus 10.8% in NH pts. For S pts, radiation was utilized in 19.4% of H pts vs 25.8% in NH pts, chemotherapy utilized in 28.3% H pts vs 24.4% in NH pts, whereas chemotherapy for NS pts was utilized in 60.1% in H pts vs 53.4% in NH pts. Overall Survival (OS) was not significantly different in S pts for H pts vs NH pts (Log-rank p = 0.066), but among NS pts, H patients did worse compared to NH pts (Log-rank p &lt; 0.001) although OS differences were seen in pooled analyses of S and NS pts (log-rank p &lt; 0.001). Conclusions: Our analysis reports on the treatment patterns and survival of Hispanic men with TC. Survival appears to be worse for Hispanic patients with non-seminoma compared to non-Hispanic patients, but outcomes for seminoma are similar. We also noted slight differences in patterns of treatment receipt for seminoma versus non-seminoma in Hispanic men which may have to do with stage at diagnosis and access to care.
The prognostic significance of prostate-specific antigen dynamics during abiraterone therapy in patients with high-risk metastatic hormone-sensitive prostate cancer.
Authors: Qian Wang, Hong Zeng, Jindong Dai, Qiyu Zhu, Jinge Zhao, Xingming Zhang, Hao Zeng, Pengfei Shen
Journal: Journal of Clinical Oncology (2025)

78 Background: The depth reduction in prostate-specific antigen (PSA) levels serves as a prognostic indicator for patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC) undergoing treatment with abiraterone. However, the potential impact of the duration of PSA level depth reduction on prognosis remains uncertain. Methods: We conducted a comprehensive review of data from 153 high-risk mHSPC patients undergoing first-line abiraterone therapy. The group analysis was conducted based on the alterations in PSA levels during abiraterone therapy. Kaplan-Meier survival curves and Cox proportional hazards regression analysis were used to evaluate the association between the trend and duration of PSA decline and treatment outcomes, which include PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS). Results: Among the 153 patients treated, 85 exhibited a minimum PSA level of less than 0.2 ng/ml, 48 had a minimum PSA level ranging from 0.2 to 0.4 ng/ml, and 20 presented with a minimum PSA level exceeding 4 ng/ml.During abiraterone treatment, the lowest PSA level of &lt;0.2 ng/ml was significantly associated with improved mPSA-PFS (51.0 vs. 18.5 vs. 6.9 months, P &lt; 0.0001), mrPFS (52.0 vs. 24.3 vs. 10.3 months, P &lt; 0.0001), and mOS (NR vs. 48.5 vs. 28.1 months, P &lt; 0.0001). A reduction in PSA levels exceeding 90% was correlated with enhanced patient survival outcomes; additionally, a baseline PSA level of &lt;80 ng/ml at the initiation of abiraterone therapy significantly improved patients' mPSA-PFS (43 .1 vs .26 .0 months, P=0 .01), mrPFS (46 .8 vs .27 .5 months, P=0 .01), and mOS (NR vs .43 .8 months, P=0.03).In the cohort with the lowest PSA levels (PSA &lt; 0.2 ng/ml), achieving a PSA level of less than 0.2 ng/ml within six months and maintaining this level for over ten months significantly enhanced clinical outcomes, as evidenced by mPSA-PFS (NR vs. 26.9 months, P &lt; 0.0001), mrPFS (NR vs. 27.5 months, P &lt; 0.0001), and mOS (NR vs. 44.4 months, P &lt; 0.0001). Cox regression analysis indicated that achieving a PSA level of less than 0.2 ng/ml within six months, sustaining this level for more than ten months, along with age and initial PSA at diagnosis were independent prognostic factors. Conclusions: In mHSPC patients undergoing first-line abiraterone treatment, a sustained improvement in PSA levels serves as an indicator of therapeutic response, while the rate and depth of PSA decline, along with its duration, are critical prognostic determinants.