tbuckley/cabot-search huggingface dataset:
Phase 2 study of perioperative sacituzumab govitecan in combination with zimberelimab and domvanalimab for patients with muscle invasive bladder cancer ineligible or who refuse cisplatin-based chemotherapy: The PRISMA-1 study.
Authors: Ignacio Duran, Miguel A. Climent Duran, Iciar García Carbonero, Angela Villares, Ricardo Sánchez-Escribano, Jesus Calleja, Naiara Sagastibelza, Ainara Villafruela, Isabel Galante, Jose Luis Dominguez, Albert Font Pous, Pol Servian, Nuria Lainez, Vicente Grasa, Urbano Anido, Anton Cimadevila, Mario Dominguez, Xavier Garcia del Muro, Oscar Buisan, Javier Puente
Journal: Journal of Clinical Oncology (2025)

TPS884 Background: Neoadjuvant cisplatin-based chemotherapy (NACT) has demonstrated a 5-8% improvement in 5-year overall survival (OS) in patients (pts) with muscle invasive bladder cancer (MIBC). However, its routine implementation is still low due to concerns about toxicity/efficacy. Also, about 50% of pts are considered cisplatin ineligible and therefore unable to receive NACT. Immune-checkpoint inhibitors (ICI) and antibody drug conjugates (ADC) have demonstrated separately clinical activity in the perioperative setting and recently remarkable efficacy of ADC-ICIs combos has been shown in pts with advanced urothelial cancer. Therefore, combining ICIs with ADCs as a neoadjuvant therapy results an interesting approach. PRISMA-1 study will evaluate safety and efficacy of the Trop-2 directed ADC, sacituzumab govitecan (SG) in combination with the anti-PD1 zimberelimab (Z) and the anti-TIGIT domvanalimab (D) in MIBC. This study will also search for predictive biomarkers of response and will evaluate the role of ctDNA in the perioperative setting to better select for patients who need post operative treatment. Methods: PRISMA-1 study (NCT06133517) is a phase II, single arm, multicenter clinical trial that will enroll 70 adult pts with MIBC, [cT2-T4cN0-1cM0], ECOG PS 0-2, non-eligible or who refuse to receive NACT. The primary endpoint is pathological complete response (pCR) rate. Downstaging, relapse free survival and OS along with ctDNA clearance are some of the secondary endpoints. The study has two stages: First 8 pts will receive the combination of neoadjuvant SG+Z to confirm tolerability. Once safety has been confirmed additional 8 pts will receive the triplet SG+Z+D. If no dose limiting toxicities are observed recruitment will continue to enroll a total of 70 patients. Patients will receive three Q3W neoadjuvant cycles of Z (360 mg day 1) + D (1200 mg day 1) plus SG (7.5 mg/m2 days 1 &amp; 8) followed by cystectomy. After surgery, only those pts who do not achieve a pCR or that achieving a pCR still have positive ctDNA will receive 12 additional cycles of adjuvant treatment with only Z + D. The remaining will be followed with serial ctDNA and imaging. Clinical trial information: NCT06133517 .
Correlates of immunotherapy response in metastatic clear cell renal cell carcinoma from circulating cell-free epigenomes.
Authors: Razane El Hajj Chehade, Karl Semaan, Ze Zhang, Noa Phillips, Lexi Grisham, Rebecca Prather, Katy Beckermann, Ulka N. Vaishampayan, Naomi Balzer Haas, Hans J. Hammers, David F. McDermott, Lauren Michelle Wood, Travis Solley, Brian I. Rini, Eric Jonasch, Toni K. Choueiri, Matthew Freedman, Scott Mattox Haake, Sylvan C. Baca, Jacob E Berchuck
Journal: Journal of Clinical Oncology (2025)

593 Background: Immune checkpoint inhibitors (ICIs) are a mainstay of treatment for metastatic clear cell renal cell carcinoma (mccRCC). With a growing number of treatment options for mccRCC, biomarkers are needed to guide treatment selection by predicting benefit from ICIs. Cell-free DNA (cfDNA)-based assays that measure tumor DNA in plasma are promising biomarkers for treatment response in several cancers, but their role in RCC remains unclear. Here, we tested whether epigenomic profiling of cell-free DNA can identify or predict radiographic responses to immunotherapy in mccRCC. Methods: Plasma samples were obtained from 180 patients (400 total samples collected, up to 4 samples per patient) with mccRCC enrolled in the DOD-funded Kidney Cancer Research Consortium ctDNA study (NCT04883827). Patients received an immune checkpoint inhibitor and were categorized as non-responders or responders based on CT scan results obtained at 3- or 6-months following treatment initiation. Cell-free chromatin immunoprecipitation sequencing (cfChIP-seq) was performed on patient plasma to profile H3K4me3, a histone modification associated with active gene promoters. DNA methylation was profiled with cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq). H3K4me3 signal at the promoters of ccRCC-associated genes variation between pre-treatment and on-treatment timepoints was assessed for non-responders and responders. We calculated changes in H3K4me3 signal for on- and pre-treatment plasma draws. We then compared these changes between non-responders and responders using the Wilcoxon sum-rank test. The immune cell types contributing to cfDNA were inferred from cfMeDIP-seq data. Results: Comparing pre- and on-treatment timepoints drawn between 1-5 months after starting therapy, cfDNA promoter H3K4me3 at RCC-associated genes was concordant with radiographic response in 10 of 11 patients (91%), with signal increasing from pre- to on-treatment samples in 6 of 7 non-responders (86%) and decreasing in 4 of 4 responders (100%). The median change in H3K4me3 differed significantly for non-responders and responders (p = 0.02). Analysis of cfDNA methylation profiles identified a higher proportion of memory CD8 T cell-derived cfDNA in non-responders compared to responders in pre-treatment samples (p = 0.003) Conclusions: This pilot study suggests that epigenomic profiling of cfDNA may identify pre-treatment and on-treatment biomarkers of ICI response. Profiling of larger cohorts is underway to test the generalizability of these findings.
Presurgical treatment for inferior vena cava tumor thrombus in patients with renal cell carcinoma: A scoping review.
Authors: Bohdan Baralo, Natasha Dziarnowski, Cody McIntire, Peter Daniels, Morgan Puglisi, Hyun Lee, John W. Melson, Asit KR Paul
Journal: Journal of Clinical Oncology (2025)

602 Background: To date, there is no evidence-based standard of care for the management of patients with tumor-related thrombus (TT) in the inferior vena cava (IVC) associated with renal cell carcinoma (RCC).The aim of our study is to analyze published papers on presurgical treatment and their effect on reducing the TT length, level and deintensification of surgical approach. Methods: MEDLINE, Embase, and Cochrane Central were systematically searched using PRISM-Scr checklist for studies evaluating presurgical therapies intended to decrease the TT length, and level in RCC patients as well as surgical outcome. Patient were reviewed to have the following outcomes: clinically significant (&gt;20%) reduction in TT length, reduction in TT level by Mayo classification and deintensification of planned surgical intervention. Results: After comprehensive review of 1175 studies by PRISMA-Scr protocol, 21 studies fulfilled prespecified criteria that included 1 phase II clinical trial, 3 case series and 16 retrospective cohort studies. Among 216 patients reviewed, 178 (82.4%) had clear cell RCC, 106 (49.07%) had stage T3b and 53 (24.53%) had nodal involvement. Presurgical regimes included Thyrosine Kinase Inhibitors (TKI) (81%), TKI-Immune check point inhibitor (ICI) combination (6%), ICI monotherapy (3%), Stereotactic radiation (4%) and others (6%). Significant decrease in length in TT was reported in 40.29%, 42.86% and 84.62% of patients treated with TKI, ICI and TKI-ICI combination, respectively. Levels of TT were decreased in 30.32%, 46.15% and 14.29% patients treated with TKI, ICI and TKI-ICI combination, respectively. Among the patients reported to have less invasive surgical approach following presurgical treatment (n=34), 29.41% avoided cardiac bypass. Conclusions: Published studies have reported benefits of presurgical treatment in reducing length and level of TT as well as improving surgical outcome. However, significant heterogeneity exists and prospective studies are required to draw a meaningful conclusion.
Protein analysis of urachal carcinoma tissue based on different antibody-drug conjugate therapeutic targets.
Authors: Tian Han, Honglei Cui, Xingang Bi, Hongzhe Shi, Youyan Guan, Jianzhong Shou, Aiping Zhou
Journal: Journal of Clinical Oncology (2025)

852 Background: Urachal carcinoma (UrC) is an extremely rare cancer, and there is still a lack of standard drug treatment models for advanced UrC. Antibody-drug conjugate (ADC) therapy represents a promising cancer treatment method. However, the efficacy of ADC on UrC remains unclear due to the scarcity of knowledge about the immunohistochemical features of relevant targets. This study focused on the immunohistochemical features of UrC based on ADC therapeutic targets and its relationship with overall survival (OS), providing a basis for UrC treatment. Methods: A total of 45 postoperative pathological specimens confirmed to be UrC were collected. Using immunohistochemistry, protein expression levels of ADC targets HER2, Nectin-4, Claudin18.2, Trop2, Mesothelin, and the immunotherapy target PD-L1 were assessed, with the proportion of high expression (2+ or 3+) of target proteins evaluated. 38 cases with complete clinical information were screened to evaluate the relationship between the expression of target proteins and OS. Results: Among the ADC therapeutic targets, Trop2 had the highest high expression rate (55.6%) in UrC tissues, followed by Mesothelin (46.7%), Claudin18.2 (31.1%), Nectin-4 (22.2%), and HER2 (15.6%). The high expression rate of PD-L1 was 15.6%. The median age of UrC patients was 53.5 years. Sheldon stage I, III and IV patients accounted for 2.6%, 89.5% and 7.9%, respectively. Survival analysis revealed that the five-year survival rate was 85.7% in the low Trop2 expression group and 49.2% in the high expression group. High expression of Trop2 was associated with poor OS (P=0.031). Conclusions: The target proteins of ADC are expressed in UrC tissue. Trop2 exhibits a significant high expression rate, and UrC patients with high Trop2 expression have a worse prognosis. Trop2 could be a pivotal target for future ADC treatment of UrC.
Cancer-control outcomes of metastatic castration resistant prostate cancer patients with <i>BRCA</i> -gene or tumor suppressor mutations undergoing 177-lutetium PSMA radioligand therapy.
Authors: Mike Wenzel, Florestan Koll, Benedikt Hoeh, Clara Humke, Henning Reis, Peter Wild, Thomas Steuber, Markus Graefen, Derya Tilki, Amir Sabet, Daniel Groener, Felix Chun, Philipp Mandel
Journal: Journal of Clinical Oncology (2025)

71 Background: Several tumor gene mutations are known for metastatic castration-resistant prostate cancer (mCRPC) are known. The individual response to 177-Lutetium Prostate-specific membrane antigen (Lu-PSMA) therapy is under current investigation regarding the genomic profile of mCRPC patients. Methods: We relied on the FRAMCAP database and compared progression-free (PFS) and overall survival (OS) rates of mCRPC patients with Breast Cancer related antigen ( BRCA ) or tumor suppressor gene mutations ( TP53, PTEN, RB1 [TSG]). Especially, subgroup analyses were performed for Lu-PSMA-treated mCRPC patients. Results: Of 194 mCRPC patients, 22% were BRCA1/2 vs. 14% TSG vs. 63% without one of these mutations. Patients with no mutation harbored significantly lower Gleason score 8-10, relative to BRCA and TSG patients. In PFS analyses of first line mCRPC, no difference between all three groups was observed, while median OS differed significantly with 46.3 vs. 48.7 vs. 95.4 months for BRCA vs. TSG vs. no mutated patients (p&lt;0.05). In univariable Cox regression models, BRCA mutated patients were at higher risk for death (hazard ratio [HR]: 2.57, p&lt;0.01), while TSG patients were not (p=0.4). Of 87 Lu-PSMA treated mCRPC patients, significant differences in PFS and OS were made (both p≤0.02). In univariable and multivariable Cox regression models, BRCA mutated Lu-PSMA patients were at higher risk for death, while TSG patients had similar outcomes as no mutated patients. Conclusions: In real-world setting, substantially lower OS in mCRPC is observed for BRCA and TSG mutated patients, while no difference in first line PFS could be computed. In Lu-PSMA-treated patients, worst outcomes were observed for BRCA patients. Age at mCRPC, years 149 68 (61, 75) 66 (61, 71) 69 (65, 80) 69 (63, 76) 0.3 PSA at CRPC, ng/ml 105 12 (3, 50) 12 (1, 72) 5 (3, 36) 13 (4, 46) 0.8 Treatment lines mCRPC 194 3.00 (1.00, 4.00) 3.00 (1.00, 4.50) 3.00 (1.00, 4.00) 3.00 (1.00, 4.00) 0.6 ECOG status at mCRPC 79 0.017 0 47 (59%) 7 (44%) 12 (92%) 28 (56%) 1 32 (41%) 9 (56%) 1 (7.7%) 22 (44%) ≥2 0 (0%) 0 (0%) 0 (0%) 0 (0%) Cardiovascular disease 168 52 (31%) 9 (23%) 6 (21%) 37 (37%) 0.15 Gleason Score 179 0.032 8-10 130 (73%) 34 (83%) 22 (81%) 74 (67%) De Novo mHSPC 186 123 (66%) 32 (76%) 18 (64%) 73 (63%) 0.3 High volume mHSPC 126 73 (58%) 24 (71%) 12 (63%) 37 (51%) 0.13 Metastatic sites at mCRPC 92 0.2 M1a 6 (6.5%) 1 (4.5%) 2 (10%) 3 (6.0%) M1b 75 (82%) 15 (68%) 17 (85%) 43 (86%) M1c 11 (12%) 6 (27%) 1 (5.0%) 4 (8.0%) PARPi Treatment 194 25 (13%) 15 (35%) 1 (3.6%) 9 (7.3%) &lt;0.01 1 Median (IQR); n (%). 2 Kruskal-Wallis rank sum test; Fisher’s exact test; Pearson’s Chi-square test.
NEO-BLAST: Neoadjuvant therapy for bladder cancer followed by active surveillance vs treatment.
Authors: Marie-Pier St-Laurent, Bernhard J. Eigl, Ren Yuan, Silvia Chang, Peter Colin Black
Journal: Journal of Clinical Oncology (2025)

TPS890 Background: Neoadjuvant therapy (NAT) followed by radical cystectomy (RC) is the standard of care for muscle-invasive bladder cancer (MIBC). Approximately 35-40% of patients have no residual cancer at the time of surgery, suggesting that these patients could potentially avoid definitive bladder treatments (DBT), including RC or trimodal therapy (TMT). However, the current clinical tools used to detect residual disease prior to cystectomy are inadequate. The question remains whether patients with complete response (CR) require DBT or if active surveillance (AS) could be a safe alternative. The NEO-BLAST trial investigates whether a combination of bladder MRI, circulating tumor DNA (ctDNA), urinary tumor DNA (utDNA) and transurethral bladder tumor resection (TURBT) can accurately identify MIBC patients with a clinical CR (cCR) following NAT, and whether AS is non-inferior to standard of care (SOC) in those who achieved cCR. Methods: This is a multicenter, phase II/III, non-inferiority open-label clinical trial that will randomize patients with MIBC who achieve cCR after NAT to AS versus SOC DBT, including either RC or trimodal therapy (TMT) (NCT06537154). The primary endpoint is feasibility of randomization for the phase II pilot-RCT, and metastasis-free survival (MFS) at two years for the phase III. Eligible patients will be adults with non-metastatic MIBC (≥T2, N0M0) who are candidates to SOC NAT followed by DBT as per the current practice. After enrolment, ctDNA and utDNA will be collected. Only participants who complete SOC NAT will then undergo a comprehensive clinical restaging process, including repeat ctDNA and utDNA, bladder mpMRI, urine cytology, and TURBT with template biopsies. Participants meeting criteria for cCR, defined as negative ctDNA, utDNA, MRI, and TURBT, will be randomized to either AS-arm or DBT-arm, while those without cCR will receive SOC. Participants will be monitored with cystoscopy and urine cytology (if bladder in situ) every three months for 2 years, along with ctDNA and imaging at 3, 6, 12, 18, and 24 months. The pilot-RCT will plan to enrol 72 patients, and if 25% is found to have cCR and accept to be randomized, the trial will be considered feasible. Assuming a 5% event rate at 2 years (MFS) in both groups and a type I error of 5% (1-sided), 78 per group will provide 80% power to reject the hypothesis of inferiority. We anticipate enrolling 688 patients for the phase 3 to have a total of 172 patients with cCR randomized, assuming 10% lost to follow-up. An independent Data Monitoring Committee will oversee safety and efficacy throughout the trial. Clinical trial information: NCT06537154 .
Racial disparities in incidence-based mortality and survival outcomes in testicular cancer in adolescent and young adults.
Authors: Oboseh John Ogedegbe, Olanipekun Lanny Ntukidem, Sakshi Bai, Ayobami Gbenga Olafimihan, Asfand Yar Cheema
Journal: Journal of Clinical Oncology (2025)

650 Background: Testicular cancer is the most common malignancy in males aged 15-35, with increasing incidence worldwide. Despite overall high survival rates, significant outcome disparities persist across race, socioeconomic status, and geographic location. Addressing these disparities is crucial to ensure equitable access to early diagnosis, treatment, and supportive care for all patients. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) 17 Research database program was utilized to obtain the annual percentage change (APC) in incidence of testicular cancer from 2000 - 2021 for patients aged 15 - 39 years (AYA group). Patient characteristics were expressed in proportions (%). The Kaplan Meier method was used to determine overall survival (OS) and cancer-specific survival (CSS). Cox regression was performed to determine predictors of survival. A p-value ≤0.05 was considered statistically significant. Results: A total of 19680 met our specified criteria and were included in our studies. We excluded cases with unknown race, and non testicular cancer cases. Our reference race was Hispanics. Compared to Hispanics. Non hispanic American Indian/Alaska Native had HR 1.696, (CI 1.290-2.229, p &lt; 0.001, Non hispanic Asian/Pacific Islander had HR 0.880 (CI 0.712-1.087, p = 0.234), Non Hispanic Blacks had HR 1.608 (CI 1.267-2.039, p &lt; 0.001), Non Hispanic Whites had HR 0.770 (CI 0.682-0.870, p &lt; 0.001). Conclusions: Our study reveals significant racial disparities in testicular cancer survival outcomes with Non hispanic American Indian/Alaska Native and Non Hispanic Blacks having higher mortality risk. These findings highlight the need for targeted interventions to address survival disparities in testicular cancer across different racial and ethnic groups within the AYA demographic.
Impact of loss of PRLHR on aneuploidy and initiation of bladder cancer.
Authors: Xi Zheng, Bingjie Yang, Wenya Wang, Anca Azoitei, Felix Wezel, Christian Bolenz, Hongqian Guo, Cagatay Günes
Journal: Journal of Clinical Oncology (2025)

854 Background: The question still remains for the presence of yet unknown genetic modifiers in the initiation and/or progression of bladder cancer (BC). It remains challenging to identify the key factors, the mechanism and potential target behind. A genome-wide CRISPR library colony formation assay was performed using UROtsa cells, an immortalized ureter epithelium cell line, in order to identify novel genes that promote the transformation of normal urothelial cells. As one of the top candidate genes, the Prolactin Releasing Hormone Receptor (PRLHR) was identified. To date, only a few studies addressed the impact and the correlation of PRLHR in cancer and reports in the context of BC are missing altogether. Methods: We assessed the gene and protein expressions via public database, qPCR and Western blot analyses in a set of nontumour cell strains (Y235T, UROtsa) and a set of BC cell lines (RT4, T24). Following the shRNA knockdown in the PRLHR-proficient cells(Y235T) and the ectopic PRLHR expression in the cell lines with low/absent PRLHR expression(T24), we performed functional experiments, such as soft agar colony formation assay, MTT, invadopodia and gelatine degradation assays. We determined the invasion and migration abilities of these genetically modified cells by using the and wound-healing, Boyden chamber and porcine bladder ex vivo organ culture invasion assay. Metaphase spread assay and Immunofluorescence was performed in modified Y235T cells for chromosome counting and microscopy observation (centrsomes, chromosomal misalignments and lagging chromosomes). Results: The available in silico expression data and expression analyses in BC cell lines and matched normal/tumour patient samples revealed the repression of PRLHR early in BC tumorigenesis. Soft agar experiments confirmed that ectopic PRLHR impairs colony formation of T24 cells, providing indirect evidence that the CRISPR-Cas9 mediated deficiency of PRLHR promoted UROtsa cells transformation in the screening assay. Functional experiments using the MTT and the wound healing assays showed that ectopic PRLHR improved the viability and migration abilities of BC cells. The Boyden chamber assay and the porcine bladder organ culture model revealed that PRLHR impairs BC cell invasion, likely by the inhibition of the AKT/PKB pathway. Moreover, we observed an abnormal number of centrosomes, an increasing number of lagging chromosomes in the anaphase and telophase of the PRLHR-knockdown cells during mitosis. Conclusions: The screening procedure identified PRHLR as a new candidate tumour suppressor factor, and that loss/down-regulation of this protein contributes to the progression of bladder cancer. Downregulation of PRLHR leads to aneuploidy and genome instability in urothelial cells. PRLHR might serve as a novel biomarker or potential target for BC.