tbuckley/cabot-search huggingface dataset:
Impact of upstaging from cT2a–b to pT3a on overall survival (OS) among patients with renal cell carcinoma.
Authors: Taylor Goodstein, Rajvi R. Goradia, Arnav Srivastava, Akshay Sood, Shawn Dason, Viraj A. Master, Eric A. Singer
Journal: Journal of Clinical Oncology (2025)

601 Background: Identifying patients with renal cell carcinoma (RCC) who may benefit from adjuvant systemic therapy has proven difficult. Approximately 40% of patients with cT2a-b tumors will be upstaged to pT3a disease following surgery. These patients, given their large tumor size, may represent a higher risk cohort compared to patients with concordant T3a staging. We assessed OS among cT2a-b patients who were upstaged to pT3a compared to their cT3a counterparts with concordant pathologic staging. Methods: Using the National Cancer Database, we identified N0M0 adult patients with cT2a, cT2b, and cT3a RCC who underwent partial or radical nephrectomy and had pT3a disease on final pathology. We categorized patients into three groups: (1) cT2a to pT3a, (2) cT2b to pT3a, and (3) cT3a to pT3a. We compared OS between the groups using Kaplan Meier estimates and multivariable analysis using Cox proportional hazards models. Subgroup analysis of overall survival was performed for histology (clear cell vs non–clear cell). Results: 11,241 patients met inclusion criteria (3,067 cT2a, 1,893 cT2b, and 6,281 cT3a). Median pathological tumor size was 8.0, 11.2, and 7.5 cm for cT2a, cT2b and cT3a tumors, respectively. Mean 5-year OS was 37% for both cT2a and cT2b disease upstaged to pT3a and 48% for cT3a disease with concordant pathological staging (log rank p &lt; 0.0001). This finding persisted on multivariable analysis (cT3a HR 0.81 [0.77–0.85], p &lt; 0.001). Conclusions: Patients who were pathologically upstaged from cT2 to pT3a disease had worse OS compared to patients with concordant staging, a finding likely related to differences in median tumor size. Our findings imply that it is reasonable to include well-selected cT2 tumors in the next iteration of perioperative trials. However, those designing and conducting clinical trials must power their studies to adjust for heterogeneity in pathologic restaging.
Evaluation of time to metastasis (TTM) from prostatectomy and survival in patients (pts) with metachronous metastatic hormone-sensitive prostate cancer (mHSPC) receiving androgen deprivation therapy (ADT) intensification: A real-world study.
Authors: Nicolas Sayegh, Yeonjung Jo, Zeynep Irem Ozay, Chadi Hage Chehade, Georges Gebrael, Micah Ostrowski, Patrick Campbell, Siqi HU, Nishita Tripathi, Blake Nordblad, Beverly Chigarira, Richard Ji, Gliceida M Galarza Fortuna, Vinay Mathew Thomas, Benjamin L. Maughan, Umang Swami, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2025)

100 Background: Metachronous mHSPC is associated with improved outcomes compared to synchronous (de novo) mHSPC. However, there are limited data on the effect of TTM after radical prostatectomy in patients with metachronous mHSPC treated with systemic therapies. Our objective was to explore the association of TTM after prostatectomy with survival outcomes in a real-world population. Methods: In this IRB-approved retrospective study, eligibility criteria were: pts with metachronous mHSPC who underwent radical prostatectomy and were treated with ADT plus androgen receptor pathway inhibitor (ARPI). Metachronous disease was defined as the absence of metastatic disease within 90 days of initial prostate cancer diagnosis. TTM was defined from the time of prostatectomy to the time of initial metastatic diagnosis and was analyzed as a continuous variable, then categorized. Progression-free survival (PFS) was defined from the start of therapy for mHSPC to disease progression or death from any cause. Overall survival (OS) was defined from treatment initiation for mHSPC to death from any reason or censored at the last follow-up. Multivariable analyses for PFS and OS were performed using a Cox proportional hazards model, adjusting for disease volume (per CHAARTED criteria), Gleason score, log-transformed PSA, and age. Results: Overall, 186 pts with metachronous mHSPC who previously underwent prostatectomy were eligible and included. Pts with a Gleason score of ≥ 8 comprised 44% of the cohort and those with age ≥ 65 comprised 68% of the cohort. A high volume of disease was present in 34% of the pts. Overall, median TTM was 46 months. On univariate analysis, a longer TTM was not associated with improved PFS (HR 1.0, 95% CI 1.0-1.1, P=0.3) or OS (HR 1.0, 95% CI 1.0-1.1, P=0.8), and results were consistent on multivariate analysis. No PFS or OS benefit was observed in pts achieving a TTM ≥1, 2, 3, and 4 years respectively, versus those who do not (Table). Conclusions: A prolonged TTM is not associated with survival outcomes after onset of metachronous mHSPC in pts treated with ADT + ARPI. OS and PFS in the mHSPC setting appear to be independent of timing of metastatic disease post prostatectomy in this pt population. Univariate Multivariate HR (P-value) PFS OS PFS OS TTM Continuous 1.0 (0.3) 1.0 (0.8) 1.0 (0.5) 1.0 (0.4) TTM &lt;1 vs ≥1 0.9 (0.7) 0.8 (0.6) 0.7 (0.5) 0.7(0.5) TTM &lt;2 vs ≥2 0.9 (0.8) 0.9(0.7) 0.6 (0.3) 0.6 (0.3) TTM &lt;3 vs ≥3 0.9 (0.5) 0.8 (0.6) 0.6 (0.2) 0.6 (0.2) TTM &lt;4 vs ≥4 0.9 (0.7) 1.1 (0.7) 0.9 (0.7) 0.9 (0.7)
A phase 2/3 multicenter trial evaluating safety and efficacy of a new mucoadhesive gemcitabine suspension for ablation of upper tract urothelial carcinoma.
Authors: Marie-Pier St-Laurent, Veronika Schmitt, Martin Gleave, Peter Colin Black
Journal: Journal of Clinical Oncology (2025)

TPS889 Background: Patients with large, multifocal, or frequently recurrent low-grade (LG) upper tract urothelial carcinoma (UTUC) often require nephroureterectomy to effectively manage their disease, despite the low oncologic risk of progression. There is a need for safer, more effective nephron-sparing treatments. Intraluminal therapies are underdeveloped and limited by the short dwell time of drugs in the collecting system. Intravesical gemcitabine has shown efficacy and minimal toxicity in treating bladder urothelial carcinoma, suggesting a similar potential for UTUC. The investigational drug (ST-02) is a novel mucoadhesive gemcitabine suspension designed for pyelocaliceal instillation. It changes from a liquid to a mucoadhesive gel in the collecting system once in contact with water, thereby facilitating prolonged exposure to gemcitabine. This trial aims to demonstrate that intraluminal administration of ST-02 can effectively and safely ablate LG UTUC. Methods: This is a prospective, multicenter, single-arm, open-label phase II/III clinical trial (NCT06124976) designed to enroll 70 patients with biopsy-confirmed LG UTUC. The study employs a two-stage design with early stopping rules, where the trial will be halted if there are 8 or fewer complete responses (CR) among the first 30 participants (phase II). Eligible patients must have tumors measuring 5-15 mm at treatment initiation. ST-02 will be instilled via retrograde or antegrade catheterization weekly for 6 weeks. The primary endpoint is the CR rate, assessed by ureteroscopic evaluation 6 weeks after the last instillation. Maintenance therapy with ST-02 will be offered to participants with ongoing CR at 3, 6, 9, 12, and 15 months. Secondary objectives include evaluating the durability of CR at 12 months, objective response rates based on tumor size, event-free survival, and safety. The trial includes a safety lead-in phase with pharmacokinetic evaluation in the first 10 patients. An independent Data Monitoring Committee will oversee safety and efficacy assessments. Clinical trial information: NCT06124976 .
Chimeric RNA landscape in the Chinese population and the role of <i>SFT2D2-TBX19</i> in prostate cancer progression.
Authors: Qiong Wang
Journal: Journal of Clinical Oncology (2025)

406 Background: Specific gene fusions and their fusion products (chimeric transcripts and proteins) have served as ideal diagnostic markers and therapeutic targets for cancer. However, few systematic studies for chimeric transcriptome have been conducted in prostate cancer (PCa), and none in the Chinese populations. Methods: We analyzed raw RNA-seq data from PCa patients in the Chinese Prostate Cancer Genome Epigenome Atlas (CPGEA) to predict chimeric RNAs using the Eriscript. Fluorescence-activated cell sorting (FACS) was employed to isolate tumor cells, cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and T cells from fresh clinical specimens. Cellular functional assays, western blotting, FISH, electron microscopy, RNA pull-down, and immunofluorescence were employed to elucidate the underlying mechanisms by which the chimeric SFT2D2-TBX19 regulates prostate cancer progression. Results: Over 100,000 chimeric RNAs have been predicted in CPGEA. After several rounds of screening, we identified 301 of them with differential expression between cancerous and adjacent normal tissues, and 101 out of them were validated in clinical samples. About 20% showed prognosis correlation, indicating their potential biomarker values. Further experiments found differential expression of those chimeras among cancer epithelial cells, CAFs, TAMs, and T cells. We further examined the effect of these chimeric RNAs, and found examples of chimeric RNAs directly regulates the growth and motility of tumor cells, and regulate communications between tumor cells and their microenvironment, which jointly facilitate tumor progression. An important chimeric RNA, SFT2D2-TBX19 , was identified as encoding the TBX19-202 protein. Both TBX19-202 and its parental TBX19, which share homologous amino acid sequences, enhance prostate cancer cell proliferation, migration and invasion. Additionally, SFT2D2-TBX19 also can work as a lncRNA which could interact with the ATP synthase F1 subunit ATP5F1A, increasing ATP5F1A phosphorylation, which stabilizes the interaction between ATP5F1A and ATP5F1B. The region spanning 1801-2400bp of SFT2D2-TBX19 and the intermediate structural domain of ATP5F1A are crucial functional areas. This stabilization of ATP5F1A and ATP5F1B enhances mitochondrial ATP synthase activity and ATP production, thus maintaining prostate cancer cell proliferation. Conclusions: These findings established the atlas of chimeric transcriptome in PCa from the Chinese populations, and provided a large list of validated chimeric RNAs that have the potentials of becoming novel biomarkers and/or treatment targets. Our research provides comprehensive evidence that the SFT2D2-TBX19 promotes prostate cancer progression by encoding the TBX19-202 protein and stabilizing mitochondrial ATP synthase through ATP5F1A phosphorylation.
Clinical protocols to monitor efficacy of [ <sup>177</sup> Lu]Lu-PSMA radiopharmaceutical therapy in metastatic castration-resistant prostate cancer.
Authors: Lena Unterrainer, NIcolas De Leiris, Marcus Unterrainer, Harun Ilhan, Astrid Delker, Linus Hempel, Zachary Ells, Joseph Zahner, Adrien Holzgreve, Mathias J. Zacherl, Jozefina Casuscelli, Kevin Kiraz, Julien Leenhardt, Emmanuelle Jacquet, Jerome Long, Mathieu Laramas, Channing Judith Paller, Lilja B Solnes, Andrei Gafita, Loic Djaileb
Journal: Journal of Clinical Oncology (2025)

39 Background: To assess the prognostic value of post-therapy [ 177 Lu]Lu-PSMA (LuPSMA)-SPECT/CT by visual RECIP 1.0 during LuPSMA radioligand therapy and to develop an evidence-based clinical protocol to monitor efficacy to LuPSMA. Methods: Patients who received LuPSMA between April 2019 and November 2023 and who underwent at least two LuPSMA-SPECT/CT (SPECT) were included. Three independent readers interpreted pairs of baseline and interim LuPSMA-SPECT/CT after 2 cycles of therapy for visual Response Evaluation Criteria In PSMA-imaging (RECIP) 1.0. The primary outcome was the prognostic value of post-therapeutic SPECT by RECIP 1.0 for overall survival after LuPSMA. The secondary outcome was the agreement between SPECT and PSMA-PET/CT (PET) performed after 2 cycles of LuPSMA. Results: 105 patients were included. In SPECT PD was associated with shorter OS compared to SD (HR=2.51;95%;CI:1.19-5.28;p=0.015) and to PR (HR=6.48;95%;CI:2.67-15.70;p&lt;0.001). 73/105 (69.5%) had a PET after 2 cycles. 7/73 (10%), 30/73 41%), 22/73 (30%), and 30/73 (41%) patients had a tumor progression by SPECT, PET, SPECT+PSA, and PET+PSA, respectively. All 7/73 (10%) patients with PD by SPECT had PD by PET. The C-index for SPECT was inferior to the one of SPECT+PSA (0.54 vs 0.62; p=0.03) and PET (0.54 vs 0.66; p&lt;0.001) while SPECT+PSA did not differ significantly from PET (0.62 vs 0.66; p=0.07). Conclusions: Post-therapeutic SPECT/CT by RECIP 1.0 after 2 cycles of LuPSMA therapy is prognostic for overall survival and can be used for treatment response evaluation purposes. PSMA-PET/CT identified significantly higher number of patients with progressive disease compared to LuPSMA-SPECT/CT. A composite classification system of LuPSMA-SPECT/CT+PSA was not significantly different from interim PSMA-PET/CT for response evaluation to LuPSMA.
Ethnic disparities in clinical trials for FDA-approved drugs in renal cell carcinoma: An analysis in the post-COVID-19-era (2020-2024).
Authors: Bruno R. Bastos, Michael A. Schwartz, Oleg Gligich, Jacqueline Claudia Barrientos, Antonio Ramirez-Ridelli, Leonardo Borregales, Akshay Bhandari, Alan Nieder, Nicolas Kuritzky, Debra Linzer, Mike Cusnir
Journal: Journal of Clinical Oncology (2025)

452 Background: Ethnic and racial disparities in oncology clinical trial participation remain a pressing challenge. Despite initiatives by the NCI and FDA since 2017 aimed at addressing these disparities, significant gaps persist in cancer treatment access and clinical trial involvement for minority populations. Notably, data on minority participation in clinical trials for FDA-approved renal cell carcinoma treatments during the post-COVID-19 era is limited. Methods: From 2020 to 2024, we analyzed data from 2,940 patients enrolled in five clinical trials (CheckMate 9ER, CLEAR, KEYNOTE 564, LITESPARK 005, TIVO-3) that resulted in FDA approval of new agents or indications for renal cell carcinoma. All trials were industry-sponsored. We assessed and tabulated the reporting of racial demographics within these trials, employing chi-square statistics and machine learning algorithms to compared participation rates among White, Black, Asian and Hispanic patients against SEER data on renal cell carcinoma incidence. Results: Among the five trials, three (KEYNOTE 564, LITESPARK-005, and TIVO-3) reported racial data, but only two (KEYNOTE 564 and LITESPARK-005) provided information beyond White participants, including Black and Asian populations. No data on Hispanic participation was reported. Our analysis revealed that in the three trails providing racial data, 88% of participants were White indicating statically significant overrepresentation (p&lt;0.0001). In the two trials with broader racial data, Black participation was only 1.2% signifying substantial underrepresentation (p&lt;0.0001), while Asian representation was 11.6% with no significant disparity observed (p=0.05). Conclusions: The underrepresentation of minority groups (particularly Blacks and Hispanics) in FDA-approved clinical trials for renal cell carcinoma remains a significant concern in the post-COVID-19 landscape. Addressing these disparities necessitated the implementation of policies that enhance data collection and standardize ethnic classification. Additionally, international collaborative trials should prioritize distinct data reporting for U.S. participants, utilizing NCI SEER nomenclature for consistency.
Phenotypic and genetically predicted leukocyte telomere length and prostate cancer risk: Results from a large-scale longitudinal cohort study.
Authors: Xiaoyang Liu, Shengzhuo Liu, Xin Yan, Jing Zhou, Yunfei Yu, Qiang Dong
Journal: Journal of Clinical Oncology (2025)

404 Background: Previous studies on the correlation between leukocyte telomere length (LTL) and prostate cancer (PCa) have shown contradictory results. Our study aims to further explore the potential relationship between LTL and PCa. Methods: In this study, a total of 229,022 male individuals were enrolled from the UK Biobank to investigate this association . Both unadjusted and covariates-adjusted Cox proportional hazards regression models were employed. The primary outcome was defined as the diagnosis of incident prostate cancer using in-patient data and the death registry of the UKB cohort. To validate the reliability of the primary findings, secondary analyses, including Mendelian randomization (MR) were conducted. Results: The primary analysis demonstrated that longer LTL was substantially associated with higher risk of prostate cancer, with associations remaining robust after adjusting for potential covariates (HR: 1.444, 95% CI: 1.247-1.673, P &lt; 0.001). Similar results were observed when LTL was analyzed as both a continuous and categorical variable, and the association were shown to be inversely U-shaped. At the genetic level, the association was further validated using MR across different prostate cancer databases, with results consistent with our primary analysis. Conclusions: Our findings offer compelling evidence that leukocyte telomere length is an important risk factor for prostate cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between leukocyte telomere length (analyzed both as a continuous variable and by quartile categories) and prostate cancer risk in the UK Biobank study. Model I Model II Model III Cases N Median HR 95%CI HR 95%CI HR 95%CI 10693 198830 0.810 1.505 1.301-1.741 1.454 1.256-1.683 1.444 1.247- 1.673 &lt;0.001 &lt;0.001 &lt;0.001 2761 49708 0.683 ref ref ref 2782 49707 0.773 1.088 1.032 -1.147 1.087 1.031 - 1.145 1.084 1.029-1.143 2607 49707 0.849 1.090 1.033-1.151 1.086 1.029-1.146 1.084 1.028-1.144 2543 49708 0.960 1.187 1.124-1.253 1.174 1.112- 1.240 1.170 1.108-1.236 &lt;0.001 &lt;0.001 &lt;0.001 Model I adjust for age; Model II adjust for demographic variables (age; ethnic background) and socioeconomic variables (socioeconomic status; education); Model III adjust for demographic variables (age class; ethnic background) socioeconomic variables (socioeconomic status; education) and lifestyle variables (alcohol intake frequency; smoking history; body mass index; duration of walks; sleep duration; blood pressure).
Phase III randomized trial of stereotactic ablative radiotherapy (SAbR) for oligometastatic advanced renal carcinoma (EA8211-SOAR).
Authors: Suzanne Cole, Se Eun Kim, Andrew Wentland, Mu-Han Lin, Payal Kapur, Elizabeth Marie Wulff-Burchfield, Daniel Shevrin, Tami Gurley, John C Lin, Lynne I. Wagner, Rana R. McKay, James Brugarolas, Qian Qin, Tyler Gunter, Christos Kyriakopoulos, Seema Harichand-Herdt, Glenn Sykes, Naomi Balzer Haas, Michael A Carducci, Raquibul Hannan
Journal: Journal of Clinical Oncology (2025)

TPS615 Background: The optimal frontline management strategy for oligometastatic renal cell carcinoma (omRCC) is uncertain. Systemic therapy (ST) is the standard, but Stereotactic Ablative Radiation (SAbR) offers an alternative, and may potentially reduce ST-associated toxicity. However, concerns remain about occult micro-metastases progression with SAbR. Retrospective studies suggest focal therapies may improve outcomes in select patients, but prospective data is limited. This ECOG-ACRIN phase 3 randomized trial compares SAbR with ST in omRCC, assessing whether SAbR followed by delayed ST can offer non-inferior OS with lower toxicity compared to upfront ST. The co-primary endpoints are OS and grade ≥3 toxicity. Hypothesis: For omRCC patients with 2-5 measurable metastases, SAbR followed by delayed ST will result in non-inferior OS compared to immediate while reducing grade ≥3 toxicity. Methods: This phase 3 trial will enroll patients with oligometastatic RCC with 2-5 extracranial metastases amenable to SAbR and an ECOG performance status of 0-2, categorized as favorable or intermediate risk according to modified IMDC criteria. Patients must have their primary tumor treated by surgery or radiation before enrollment. Exclusions include brain metastases, sarcomatoid histology, prior systemic therapy for metastatic disease (adjuvant therapy is allowed), and poor-risk IMDC classification. Participants will be stratified by number of metastases, histology, IMDC risk, prior adjuvant therapy, and time since primary site treatment. Patients will be randomized to either upfront ST or SAbR with delayed ST. Statistical Design: The trial has 85% power to establish non-inferiority of SAbR with respect to OS, assuming a null hazard ratio of 1.24 and an alternative of 0.85. If non-inferior OS is shown, the study will test whether SAbR reduces grade ≥3 toxicity. Secondary endpoints include progression-free survival (PFS) and quality of life, measured by NFKSI-19 and EQ-5D-5L scales. Exploratory endpoints will assess cost-effectiveness and circulating tumor DNA (ctDNA) as a biomarker. The study opened in September 2023. Research sponsor: U.S. National Institutes of Health. Clinical trial information: NCT05863351 .
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: Nadine Houede, Thierry Chevallier, Jaffrelot Loic, Constance Thibault, Neuzillet Yann, Christine Abraham Jaillon, Alexandra Masson-Lecomte, Gwenaelle Gravis, Sophie Tartas, Damien Pouessel, Brigitte Laguerre, Francois Audenet, Evanguelos Xylinas, Luquiens Guillaume, Morgan Roupret
Journal: Journal of Clinical Oncology (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