tbuckley/cabot-search huggingface dataset:
Extracellular DNA in patients with urothelial carcinoma of the bladder.
Authors: Patrik Palacka, Hana Kováčová, Iveta Mikolášková, Magda Suchánková, Mária Paulovičová, Boris Kollárik, Peter Celec, Ľuba Hunákova
Journal: Journal of Clinical Oncology (2025)

834 Background: Higher concentration of extracellular DNA (ecDNA) in plasma of subjects with various cancers is associated with worse prognosis. The association of ecDNA and its subcellular origin – nuclear DNA (ncDNA) and mitochondrial DNA (mtDNA) with urothelial carcinoma of the bladder (BC) is unexplored. Deoxyribonuclease (DNase) can cleave ecDNA and modulate the observed association. The objective of this study was to identify the potential differences in ecDNA, ncDNA, mtDNA and DNase between patients with non-muscle-infiltrating BC (NMIBC) and muscle-infiltrating BC (MIBC) compared to controls. Methods: We analyzed a population of 62 individuals with BC (44 males, median age 67.5 years), 20 had Ta stage, 26 T1 stage (NMIBC) and 16 T2–T3 stage (MIBC). The control group consisted of 15 males and 6 females without history of cancer, median age 67.3 years. EcDNA was quantified fluorometrically after isolation from double centrifuged plasma. The subcellular origin of ecDNA was analyzed using quantitative real time PCR targeting specific nuclear and mitochondrial sequences. DNase activity was assessed using the single radial enzyme diffusion method. For statistical analysis, basic nonparametric tests were used. Results: In patients with BC compared to controls, we identified significantly higher ecDNA (median 15.0 v 11.7 ng/ml, P=.021) and ncDNA (median 4707 v 2136 GE/ml, P=.0046), but not mtDNA and DNase. Moreover, we determined a higher activity of DNase (median 2.3 vs 1.9 ng/ml, P=.0084) in subjects with NMIBC (Ta+T1) v MIBC. By mutual comparisons of all subgroups, following significant differences were recognized: ecDNA and ncDNA in MIBC v controls (P=.0065 and P=.0127, respectively) and DNase for Ta v MIBC (P=.0177). In addition, we detected a significant correlation on a stage of BC and rising ecDNA concentrations (P=.0076). Conclusions: In this study, we showed higher plasma ecDNA and ncDNA in patients with MIBC than controls and lower DNase activity in MIBC compared to NMIBC. The ecDNA concentrations increased with rising tumor stage. These results suggest a possible diagnostic and a likely prognostic value of ecDNA and DNase in BC. Further studies will focus on a potential association between plasma ecDNA and urinary ecDNA, which are assessed non-invasively and more frequently. This study was supported by the Ministry of Education, Science, Research and Sport of the Slovak Republic (grant number : VEGA 1/0090/22), the Slovak Research and Development Agency (grant number: APVV-22-0231) and OncoReSearch. Key Words: Bladder Cancer. Extracellular DNA. Nuclear DNA. Mitochondrial DNA. Nuclease.
Progressive T cell exhaustion and predominance of aging tissue associated macrophages with advancing disease stage in penile squamous cell carcinoma.
Authors: Hiroko Miyagi, Xiaoqing Yu, Taylor Peak, Jasreman Dhillon, Casey Le, Xuefeng Wang, Sean J. Yoder, Douglas C. Marchion, Xin Lu, Curtis Alvin Pettaway, Carlos Moran Segura, Gabriel Roman Souza, Alice Yu, Chaomei Zhang, Logan Zemp, Philippe E. Spiess, Jad Chahoud
Journal: Journal of Clinical Oncology (2025)

11 Background: Penile squamous cell carcinoma (PSCC) is a rare malignancy with limited understanding of the tumor immune microenvironment (TIME). The interplay between PSCC and the immune system across disease progression and HPV infection status remains poorly characterized. This study aims to assess the TIME changes from localized to advanced disease and between HPV-positive versus negative tumors, we hope to identify potential immune evasion mechanisms for advanced PSCC. Methods: scRNA-seq was performed on ten PSCC tissue samples from penile, lymph node and distant metastatic sites with four matched penile and lymph node samples to understand the cellular heterogeneity within PSCC tumors. Analysis of immune cell populations and transcriptional hallmarks were performed stratified by localized (pT1-3, N0) versus advanced (N1-3, M0 or any N, M1) disease states and HPV infection status. Results: Patients with advanced stage disease were found to have a TIME enriched with terminally exhausted C8+ T cells. The myeloid compartment showed an increase in aging and immunosuppressive M2-like macrophages. Additionally, hypoxia-induced response patterns were more pronounced in advanced stages. HPV-negative tumors exhibited a quiescent TIME characterized by low immune cell infiltration. Conclusions: We observed significant differences in immune cell infiltration between localized and advanced PSCC disease states. Advanced disease states demonstrated an exhausted immune phenotype, characterized by terminally exhausted CD8 + T cells, M2-like macrophages and hypoxic signature. HPV-negative tumors displayed low immune cell infiltration. These findings offer valuable insights into the evolving PSCC immune landscape, paving the way for the development of potential novel macrophage directed therapies for PSCC.
The Oncopig bladder cancer model, an innovative large animal platform for evaluating treatment effects.
Authors: Viranda Jayalath, Andreas Autlitzky, Natalia Kudinova, Jonathan Coleman, Lawrence B Schook, Kyle Schachtschneider
Journal: Journal of Clinical Oncology (2025)

857 Background: Bladder cancer carries a high recurrence rate despite availability of several treatment options including surgery, chemotherapy, radiation, and immunotherapy, resulting in the highest cost of lifelong treatment per patient and highlighting the need for development of novel diagnostic and therapeutic strategies. Unfortunately, results from current bladder cancer models do not effectively translate to clinical practice (mouse models) or are rare and not inducible (canine models). This, in addition to the use of endoscope-based approaches for bladder cancer treatment highlights the critical need for large animal bladder cancer models to improve patient outcomes. Pigs represent an ideal platform that provide both regulatory acceptable and clinically relevant large animal cancer models due to their similar physiology, size, genetics, immunity, and metabolism in relation to humans. The Oncopig bladder cancer model is an ideal tool for testing endoscopic and other oncolytic-based treatments. Methods: The Oncopig cancer model develops tumors following induced expression of KRAS G12D and TP53 R167H driver mutations utilizing an adenoviral vector encoding Cre recombinase (AdCre). Two procedures for cystoscope-based AdCre delivery were evaluated. In procedure I (Proc-I) a combination of AdCre and N-Dodedcyl-beta-maltoside, a sugar-like surfactant utilized to dissolve the glycoaminoglycans layer, was instilled into the bladder (1h; n=3). In procedure-II (Proc-II) the bladder urothelium was superficial denuded at 3 sites and subsequent AdCre was instilled into the bladder (1h; n=4). Oncopigs underwent CT scans and follow-up cystoscopy, and were euthanized at 3 timepoints (day 14, 21, and 28) to assess temporal bladder tumor growth. Tumor samples were collected at necropsy for histopathological evaluation (H&amp;E, TP53, Ck34be12, vimentin, and CD3) and to evaluate tumor stage. Results: In total 6/7 Oncopigs developed endoluminal tumors. Tumor-induction efficacy was 100% for Proc-I (n=3/3) and 75% for Proc-II (n=3/4). Two tumor types were observed: urothelial cell carcinomas of sarcomatoid variant (Proc-I: n=3/3; Proc-II: n=2/4) and inflammatory tumors (Proc-II: n=1/4). After 14 days, pT1 tumors were observed for Proc-I, while pT2 tumors were observed for Proc-II. After 21 days, both pT1 and pT2 tumors were observed for Proc-I, while Proc-II tumors remained pT2. Conclusions: The Oncopig bladder cancer model can develop both superficial and muscle invasive urothelial cell carcinomas with sarcomatoid variant. Tumors develop rapidly (within 2 weeks), with tumor invasiveness correlated with time post tumor induction and procedure used, making this an ideal model for evaluation of novel therapeutic approaches. Further exploration and development of additional tumor models including further translational characterization will be important for broader utility.
The evaluation of therapeutic outcomes of percutaneous US/CT-guided bipolar radiofrequency ablation for small renal masses under local anesthesia.
Authors: Yifan Sun, Wang Wei, Guo Hongqian
Journal: Journal of Clinical Oncology (2025)

556 Background: This study is to evaluate the safety and feasibility of local anesthesia (LA) for percutaneous ultrasound/computed tomography (US/CT)-guided bipolar radiofrequency ablation (RFA) for small renal masses (SRMs) by comparing the LA with general anesthesia. Methods: A retrospective review was carried out between 2018 to 2023, 212 patients with SRMs were treated with US/CT-guided bipolar RFA. General anesthesia (GA) was performed in 91 and LA was performed in 121 patients. Demographics, tumor characteristics, peri-procedural data, pathologic and follow-up outcomes were analyzed. The factors associated with pain were also identified. Results: There was no significant difference in demographics and tumor characteristics between the LA and GA group. Several statistically significant decrease were observed in terms of procedural time ( P &lt;0.001), hospital stays ( P &lt;0.001) and hospital costs ( P &lt;0.001). The maximum perceived pain in LA group comprised 57.9% (70 of 121) mild, 42.1% (51 of 121) moderate. The anxiety in LA group comprised 62.0% (75 of 121) mild, 36.3% (44 of 121) moderate, 1.7% (2 of 121) severe. On multivariate analysis, tumor diameter was a significant predictor for pain in RFA procedure (OR 1.470, P &lt;0.001). All patients were followed up for a median (range) of 36 (12-48) months. Local recurrence occurred in 15.7% (19 of 121) of the LA group and in 13.2% (12 of 91) in GA group ( P =1.000). Moreover, there was no significant difference in the difference between postoperative eGFR and preoperative eGFR when comparing the two groups. Conclusions: Percutaneous bipolar RFA of SRMs using CT and ultrasound guidance under LA can be an effective and tolerable method for patients who are unfit for surgery and provide satisfactory oncologic control.
Impact of PSMA-PET and conventional imaging on contemporary management in patients with biochemical recurrence after radical prostatectomy.
Authors: Arielle Ilano, Lufan Wang, Janet E Cowan, Samuel L Washington, Hao Nguyen, Matthew R. Cooperberg, Thomas A. Hope, Peter Carroll, Carissa E Chu
Journal: Journal of Clinical Oncology (2025)

43 Background: Prostate-specific membrane antigen (PSMA) PET imaging is recommended for patients with biochemical recurrence (BCR) after radical prostatectomy (RP). This study describes the early clinical impact of PSMA-PET compared to conventional imaging (CT, MRI, or bone scintigraphy) in a contemporaneous period. Methods: This retrospective study includes patients with BCR after RP (defined as PSA≥0.2 after undetectable PSA post-operatively) who underwent PSMA-PET or conventional imaging (CI) between 2010-2023. The primary outcome was positive detection rate. The secondary outcomes were rates of salvage treatment (XRT±ADT) and second BCR. Cox proportional hazards modeling was used to predict risk of salvage treatment and second BCR. Results: 217 post-RP patients were included. Of the 146 patients who underwent PSMA-PET and the 71 who underwent CI, 77 (52.7%) and 7 (9.9%) patients had positive imaging findings at a median PSA value of 0.23 (IQR 0.21-0.33) and 0.25 (IQR 0.25-0.44), respectively (p=0.36). 48 patients received both imaging modalities; 4 had positive results in both PSMA-PET and CI, while 26 were positive for PSMA-PET only, and 2 were positive on CI only. Patients underwent salvage therapy at lower median PSA values in the PSMA-PET group (0.40 vs 0.51, p&lt;0.01). On unadjusted survival analysis, there were no differences in salvage therapy rates or second BCR rates between PSMA-PET or CI groups. On multivariable Cox proportional hazards modeling, year of PSA recurrence (HR 0.89, 95% CI 0.84-0.95), BMI (HR 1.45, 95% CI 1.02-2.07), ≥GG3 (HR 1.77 95% CI 1.3-2.4), and undetectable PSA≥6 months after RP (HR 0.50 95% CI 0.34-0.72) were associated with salvage treatment, but imaging modality was not. High genomic risk scores (Decipher&gt;0.60) may be associated with second BCR (HR 2.03 95% CI 0.99-4.18, p=0.05) while other variables were not. Conclusions: PSMA-PET usage increased over the period of this study with higher sensitivity at lower median PSA at BCR. Imaging modality did not predict rates of salvage therapy or second BCR, while other clinical risk factors such as adverse pathology and high genomic risk score did. Analysis with a historical cohort is pending.
Darolutamide plus androgen-deprivation therapy (ADT) in patients with high-risk biochemical recurrence (BCR) of prostate cancer: A phase 3, randomized, double-blind, placebo-controlled study (ARASTEP).
Authors: Alicia K. Morgans, Tamim Niazi, Neal D. Shore, Jürgen E. Gschwend, Ashley Ross, Thomas A. Hope, Alex Chehrazi-Raffle, Stephane Supiot, Philippe Barthelemy, Andreas Røder, Andrea Juliana Gomes, Bernardo Herrera Imbroda, Matthieu Gratton, Carmen Belen Congregado Ruiz, Heikki Joensuu, Miryana Dimova-Dobreva, Marie-Aude Le Berre, Iris Kuss, Karim Fizazi
Journal: Journal of Clinical Oncology (2025)

TPS432 Background: Patients with prostate cancer treated with radiotherapy (RT) or radical prostatectomy (RP) as primary therapy may develop BCR, defined by a prostate-specific antigen (PSA) increase with no evidence of metastases on conventional imaging. Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) may detect lesions in patients with BCR. Patients with BCR are at high risk of disease progression, and lesions identified by PSMA PET/CT need effective treatment to delay progression. Darolutamide, a structurally distinct and highly potent androgen receptor inhibitor, significantly improved metastasis-free survival (MFS) and overall survival (OS) in patients with nonmetastatic castration-resistant prostate cancer (CRPC). ARASTEP (NCT05794906) will evaluate whether darolutamide when added to ADT improves radiologic progression-free survival (rPFS) by PSMA PET/CT vs placebo plus ADT in patients with BCR following primary therapy and PSMA PET/CT-positive lesions. Methods: Eligible patients were treated by primary RT or RP +/- adjuvant RT (ART) or salvage RT (SRT), present with high-risk BCR (PSA doubling time [PSADT] &lt;12 months and PSA ≥0.2 ng/mL after primary RP [± ART/SRT] or PSA ≥2 ng/mL above nadir after primary RT only), and must have ≥1 PSMA PET/CT-positive lesion of prostate cancer without visible lesions on conventional imaging, and serum testosterone ≥150 ng/dL. Approximately 750 patients from 221 global sites will be randomized 1:1 to oral darolutamide 600 mg twice daily or placebo, both with ADT, for 24 months or until disease progression, unacceptable toxicity, or withdrawal of consent. Patients with detectable PSA values (≥0.2 ng/mL) after 24 months will continue study treatment until PSMA PET/CT progression by blinded independent central review (BICR). Stratification factors are PSADT &lt;6 vs ≥6–&lt;12 months, intent to treat baseline PSMA PET/CT lesions with image-guided RT/surgery (Yes vs No) and distant ± locoregional vs locoregional-only lesions. The primary endpoint is rPFS by PSMA PET/CT assessed by BICR. Secondary endpoints include MFS on conventional imaging by BICR, time to CRPC, OS, quality of life, and safety. As of October 2024, 248 patients have been randomized. Clinical trial information: NCT05794906 .
Using AI to identify optimal clinical, genomic, and radiographic prognostic features and novel risk classifiers compared to routinely available risk classifiers.
Authors: Benjamin Victor Tward, Skyler B Johnson, Jonathan David Tward
Journal: Journal of Clinical Oncology (2025)

396 Background: This study investigated the use of artificial intelligence (AI) and traditional statistical techniques to identify and validate clinical (Clin), MRI-report-derived (MRIr), and genomic classifier (GC) features important for prognostic biomarker development and staging systems for prostate cancer metastasis. AI models were compared with conventional risk classifiers for prognostic accuracy. Methods: Data from 576 patients in a prospectively collected research registry, including 35 Clin, 1 GC, and 7 MRIr features, were used. Random forest (RF) classification and artificial neural networks (ANNs) using Leave-One-Out Cross-Validation evaluated the key features predictive of metastasis. Models with 35, 9, 6, or 0 Clin features were compared to those ± MRIr or GC features. ANN prognosticators from each model were fed into competing-risk regressions and compared to other established risk classifiers (CAPRA, STARCAP, 22-gene genomic assay (Decipher), Cell-Cycle Progression (CCP, Prolaris) score, and Combined Clinical Cell-Cycle Risk (CCR, Prolaris)) by the 5-year AUC (AUC5) for prognostic accuracy. Results: AI-derived models combining Clin ±GC +MRIr features (AUC5 range 0.72-0.76) outperform models excluding MRIr features (AUC5 0.66-0.71). AI models perform similarly to contemporary risk classifiers like Prolaris, CAPRA, STARCAP (AUC5 of 0.79. 0.77, 0.76, respectively (Table)). Models with 6 Clin, 4 MRIr, and a GC (Clin: Age, BMI, PSA, cT, alcohol use, and primary Gleason score; MRIr: prostate volume, max tumor diameter, extracapsular spread, and lymphadenopathy suspicion; GC: CCP score) performed as well as conventional classifiers. The classifier with the best ability to prognosticate early metastasis was Prolaris (AUC5 0.79). Conclusions: The findings indicate that AI biomarker discovery pipelines, integrating Clin, MRIr, and GC features, can successfully identify new and previously identified prognostic factors. AI-derived models have similar accuracy in predicting metastasis compared to contemporary risk classifiers. Adding MRIr and GC features improves risk prediction of early metastasis in AI-trained models. Lifestyle factors may have an important role in metastasis. Total # Features Genomic Features Radiographic Features Clinical Features Time-Dependent Competing Risk Regression 3-Year AUC 5-Year AUC 35 Clinical Feature AI Models (n=576) 43 1 7 35 0.70 0.72 42 7 35 0.69 0.72 36 1 35 0.64 0.66 35 35 0.62 0.65 11 Clinical Feature AI Models (n=576) 16 1 6 9 0.72 0.76 15 6 9 0.71 0.75 10 1 9 0.67 0.71 9 9 0.67 0.70 6 Clinical Feature AI Models (n=576) 11 1 4 6 0.73 0.75 10 4 6 0.73 0.75 7 1 6 0.61 0.64 6 6 0.62 0.65 0 clinical feature AI Models 7 1 6 0 0.66 0.68 6 6 0 0.65 0.67 Prolaris (n=570) 6 1 5 0.75 0.79 STARCAP (n=566) 5 5 0.72 0.77 CAPRA (n=570) 6 6 0.72 0.76 CCP score (n=576) 1 1 0.73 0.74 Decipher (n=25) 1 1 0.40 0.29
Low-dose abiraterone in metastatic castration-resistant prostate cancer.
Authors: Julia Belone Lopes, Ana Elisa Sanches, Beatriz De Menezes Dobbert, Fabio Leite Couto Fernandez, João Daniel Cardoso Guedes, João Pedro Homse Netto, Luiza Ferreira, Lorena Forner, Daniel Vilarim Araujo
Journal: Journal of Clinical Oncology (2025)

164 Background: Abiraterone acetate (AA) is a selective and irreversible inhibitor of CYP17 approved for locally advanced and metastatic prostate cancer. The standard dose is 1000 mg orally while fasting. However, AA has a significant food effect, with serum levels increasing 5-7 times with a low-fat meal. Data suggest that a lower dose (250 mg with food, AALD) provides similar oncological outcomes to the standard dose, with a 75% cost reduction. In Brazil, 80% of patients are treated through the national public healthcare system, which does not afford AA in its label dose. Hospital de Base incorporated AALD since March 2021.Herein we present the data of patients with metastatic castration resistant prostate cancer treated with AALD. Methods: We retrospectively reviewed patients with mCRPC who received AALD at any treatment line, regardless of prior chemotherapy, from March 2021 to May 2023. The primary endpoint was PSA response rate (defined as a decrease of ≥ 50% in PSA concentration after 12 weeks of treatment). Secondary endpoints included time to treatment failure (TTF), overall survival (OS), and PSA response rate ≥ 50% at nadir. Data were summarized in medians, means and proportions. Chi-square was used for associations. Survival was calculated through Kaplan-Meier method. Cox-proportional hazards was used to compare groups. A p &lt; 0.05 was considered statistically significant. Results: Ninety-six patients were included. The median age was 75 years (IQR 12.5), and most had an ECOG scoreof 1 (52.1%). Sixty-three patients (65.6%) received AALD in first-line, 26 (27.1%) in second-line, and 7 (7.3%) in third-line or beyond. The median PSA level before AALD was 20.9 (IQR 98.7). Twenty-seven patients (28.1%) had received docetaxel in mCRPC. After a median follow-up of 24.4 months, 53 patients (60.2%) had a ≥ 50% PSA response at 12 weeks, and 65 (69.9%) achieved a reduction of ≥ 50% at nadir. Patients treated with AALD pre-docetaxel had a higher PSA response at 12 weeks (68.3% vs. 40%, p = 0.015) and at nadir (76.1% vs. 53.8%, p = 0.036). First-line AALD was associated with better PSA responses. The median TTF was 7.9 months (5.5 – 10.3), and the median OS was 20.6 months (14.1 – 26). Achieving a ≥ 50% PSA response at 12 weeks was associated with improved TTF (13.6 vs. 4.6 months, HR = 0.37, p &lt; 0.001) and OS (28.9 vs. 12.2 months, HR = 0.44, p = 0.004). Conclusions: AALD showed meaningful efficacy and survival outcomes. We advocate for AALD, particularly in settings where the standard dose is not affordable.