tbuckley/cabot-search huggingface dataset:
An open-label phase 1, window-of-opportunity study of ultrasound-guided long acting periprostatic neuraxial block with ethanol in patients with high-risk prostate cancer.
Authors: Ali Zahalka, George Haines III, Vitaly Margulis, Ashutosh K. Tewari
Journal: Journal of Clinical Oncology (2025)

391 Background: Patients (pts) with high-risk prostate cancer (PCa) have an elevated risk of disease recurrence/progression after definitive therapy. These pts also exhibit increased levels of adrenergic nerve density on PCa histology. Pre-clinical evidence from murine models of PCa suggest that PCaNeurolysis of periprostatic adrenergic nerves inhibits cancer progression and metastasis by inhibiting angiogenesis, altering cancer metabolism, and inhibiting cell migration (PMC5783182). Pure Ethanol (&gt;99%) injection for neurolysis is FDA-approved in chronic cancer pain and may have a survival benefit in late-stage cancers (PMC1242819). Ultrasound-guided (US) short-acting periprostatic neuraxial block with lidocaine is commonplace in urologic practice. Thus, PCaNeurolysis with ethanol may have both a protective effect in high risk PCa and be feasibly implemented. Methods: Pts with NCCN high risk PCa who were interested and eligible for surgery, and who did not have any prior PCa treatments received in-office US guided PCaNeurolysis with either 3mL or 5mL of pure ethanol 4 to 6 weeks prior to radical prostatectomy (surgery was not delayed for trial participation). Dose escalation was determined by keyboard design with 6 pts per group (dose limiting toxicity [DLT] period = 6 weeks; DLT ³ Grade 3 events). Results: Dose escalation: 12 pts, median age 68, were treated at 2 dose levels: 3/5mL (n=6/6) with no DLTs in either group, suggesting 5mL was maximal tolerated dose to use in future studies. Additionally, no off-target effects including no decrease in erectile function (Sexual Health Inventory for Men score), no increase in urinary symptoms (International Prostate Symptom Score), and no added difficulty (eg. Destruction of tissue planes) during prostatectomy were observed in any pts. 7 pts underwent prostatectomy (43% cT3a) and were included in secondary analysis: median decrease in adrenergic density on final pathology (35%), ≥pT3a (0%), 18month biochemical recurrence (14%). Conclusions: PCaNeurolysis with ethanol was well tolerated, and 5mL was the maximum tolerated dose to use in future studies. Histologically significant decrease in adrenergic nerve density was observed suggesting the intervention acts upon its intended target, and the intervention may have antitumor activity (43% pre-injection cT3a, but 0% ≥pT3a on final pathology after injection). These Phase 1 results encourage continued investigation of PCaNeurolysis in high risk PCa pts.
Mental health monitoring in clinical trials for FDA-approved genitourinary cancer treatments: A decade review.
Authors: Parnian Jabbari, Farzad Teymouri, Omid Yazdanpanah, Aditya Mahadevan, Arash Rezazadeh, David Joseph Benjamin
Journal: Journal of Clinical Oncology (2025)

696 Background: The treatment landscape for genitourinary (GU) malignancies, including bladder, kidney, and prostate cancers, has evolved with several novel therapies approved in the past decade. The importance of mental health in patients with cancer is being more and more recognized in the past years. This study evaluates the monitoring of mental health and psychiatric symptoms in trials leading to FDA approvals for GU cancers. Methods: We comprehensively reviewed trial protocols and publications for FDA-approved GU cancer therapies from 2015-2024. For each approved therapy, we examined whether psychiatric side effects were monitored, the tools used, and the timing of assessments. Results: Of 42 trials for 31 approved treatments, 85% (36/42) monitored some psychiatric monitored psychiatric or mental health-related outcomes. EORTC QLQ-C30, EQ-5D-5L, and BPI-SF were the most common tools used for monitoring. However, 15% of trials did not assess mental health, and long-term follow-ups were inconsistent as described in the table. Depression and anxiety were the most evaluated symptoms. Nonetheless, the majority of the other psychiatric manifestations were not consistently assessed throughout trials. Conclusions: Psychiatric monitoring is present in many GU trials but remains inconsistent. Mental health assessments are typically part of broader quality-of-life evaluations rather than focused psychiatric tools. Future trials should adopt standardized psychiatric assessments to better manage patient well-being during treatment. Psychiatric symptoms monitoring in FDA-approved GU cancer trials - 2015 to 2024. Symptom Assessed (%) Baseline Long-Term Publications Prostate Kidney Bladder Depression 80% Yes Yes No Yes Yes Yes Anxiety 80% Yes Yes No Yes Yes Yes Insomnia 61% Yes Yes Yes Yes Yes Yes Cognitive Impairment 38% Yes Yes No Yes Yes Yes Irritability 38% Yes Yes No Yes Yes Yes Emotional Lability 9% Yes Yes No Yes No Yes Delirium 2% No No No No Yes No Psychosis 2% No No No No Yes No
Genomic characteristics of patients with metastatic hormone-sensitive prostate cancer treated with ARPI-based therapy: A single-center analysis.
Authors: Brigida Anna Maiorano, Antonio Cigliola, Chiara Mercinelli, Valentina Tateo, Giovanni Luigi Pastorino, Maurizio Colecchia, Dean Pavlick, Jeffrey S. Ross, Andrea Necchi
Journal: Journal of Clinical Oncology (2025)

244 Background: The addition of androgen receptor pathway inhibitors (ARPI) to androgen deprivation therapy (ADT) has improved survival in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC), both as doublets and as triplets with docetaxel. The prognostic role of genomic alterations (GA) is of growing interest in this setting. We evaluated the GA profiling of a population treated with ARPI-based therapy in a single-center institution. Methods: Our retrospective analysis included patients with mHSPC treated at IRCCS San Raffaele Hospital between 2020 (when ARPI were authorized for mHSPC in Italy) and 2023 (when triplets of ARPI + ADT + docetaxel were authorized). Included patients had a diagnosis of mHSPC, tissue biopsy available for genomic profiling, and were treated with ARPI plus ADT (plus or minus docetaxel) within 120 days of initial diagnosis. Comprehensive genomic profiling (CGP) using a commercial hybrid capture-based system (Foundation Medicine) was performed on all pts to evaluate all classes of GA, homologous recombination score (HRDsig), genomic ancestry, and signature. The log-rank test and Cox proportional hazards models compared GA between responders (Rs: defined as non-progressive pts) and not-responders (NRs: pts developing a progressive disease). Kaplan Meier analysis was used to estimate progression-free survival (PFS) and overall survival (OS). Results: 28 patients were included in our analysis. Among them, 25 pts received ARPI + ADT, 3 ARPI + ADT + docetaxel. The median age was 71.8 years (range 53.1-83.9). After a median follow-up of 55.1 months, there were no differences in median PFS (mPFS) between patients treated with triplets and doublets (55.42 vs. 78.0 mos - HR = 1.12; 95%CI, 0.13-9.87; p = 0.92). The median OS (mOS) was not reached in both subgroups, without significant differences in survival rates (HR = 0.32; 95%CI, 0.01-7.33; p = 0.48). The overall response rate was 71.4%, and the disease-control rate was 85.7%. Comparing the CGP profiling between responders and progressive-pts, SPOP mutations were more frequent among Rs than NRs to ARPI (25% vs 0%; p = 0.183). TMPRSS2 - ERG fusions, which tend to be less frequent in SPOP mutated cases, were less frequent in Rs (12.5%) than NRs (20.0% - p = 0.648). There was a similar incidence of other GAs between the two groups of pts, such as PTEN , BRCA1/2 , ATM , and CDK12 (all 12.5% vs. 10.0%; all p &gt; 0.05). Conclusions: In a real-world setting, response to ARPI-based therapy may be associated with characteristic genomic features, such as SPOP mutations, or TMPRSS2 / ERG fusions, both in doublets and in triplet regimens. These findings underscore the importance of larger cohorts to further validate this hypothesis and inspire future research in the treatment selection for mHSPC pts.
Real world outcomes of <sup>177</sup> Lu-PSMA-617 PSMA in a racially diverse cohort of patients with metastatic castration resistant prostate cancer (mCRPC).
Authors: Margo Gerke, Angelo Marra, Yuan Liu, Saima Muzahir, Jacqueline T Brown, Bassel Nazha, Jacob E Berchuck, Ravi Bharat Parikh, Jordan Alana Ciuro, Caitlin Hartman, Greta Russler McClintock, Sarah Caulfield, Omer Kucuk, Bradley Curtis Carthon, David M. Schuster, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2025)

97 Background: 177 Lu-PSMA-617 is approved for treatment of mCRPC based on the VISION trial cohort with limited racial diversity. We analyzed real-world outcomes of 177 Lu-PSMA-617 in a diverse cohort. We aim to determine patient characteristics predictive of a clinical response to 177 Lu-PSMA-617. Methods: A retrospective analysis was conducted on patients with mCRPC treated with 177 Lu-PSMA-617 at Emory Winship Cancer Institute between 2022-2024. Primary endpoints were PFS, OS, and PSA reduction ≥ 50% (PSA50). Univariate association by survival analysis and logistic regression was carried out. Results: We analyzed 84 patients with PSMA PET+ mCRPC treated with 177 Lu-PSMA-617; 47.6% identified as Caucasian and 42.9% identified as Black. The median cohort age was 71.5 (IQR: 64-77.5). 35.6% had grade group 5 disease. Median number of prior lines of therapy was 5 (range: 4-7). 98.8% of patients had prior treatment with novel hormonal agents; 84.5% received prior taxane treatment. 84.5% were characterized as high-volume diseases using the CHAARTED trial criterion. Median baseline PSA was 105.5 (IQR: 20.4-454.8), and ALP was 103.5 (IQR: 72-177.5). The cohort completed a median number of 4 cycles of 177 Lu-PSMA-617; 35.7% completed six cycles. The overall cohort had a 12-month survival of 84.4%. 12-month survival rate was 88.3% in the white cohort compared to 81.4% in the non-white cohort. mPFS for the overall cohort was 6 months with a 12-month PFS rate of 41.9%. 12-month mPFS for the non-white cohort was 42.7% compared to 41.5% in the white cohort. 50.0% of the overall cohort had a PSA50 response. 56.1% of the non-white cohort had a PSA50 compared to 43.9% of the white cohort (p=0.377). Net BMI decline during treatment was associated with a 56% increased risk of mortality (OS HR 1.56, CI 1.18-2.06, p&lt;0.002). Conclusions: With similar PFS, OS, and PSA50 in this racially diverse cohort of patients with mCRPC, our results demonstrate 177 Lu-PSMA-617 effectiveness in a real-world patient population. Prospective studies are needed for further validation.
Cadonilimab combined with lenvatinib for neoadjuvant therapy in early-stage renal cell carcinoma with indications for partial nephrectomy but high surgical risk: A prospective single-arm phase II clinical trial.
Authors: Yulu Peng, Pei Dong, Hui Han, Fangjian Zhou, Zhiling Zhang
Journal: Journal of Clinical Oncology (2025)

530 Background: Partial nephrectomy is the standard treatment for early-stage renal cell carcinoma; however, in some patients, although the tumor is early-stage, the surgical difficulty may preclude its implementation. This study aims to evaluate the efficacy and safety of Cadonilimab combined with Lenvatinib in neoadjuvant therapy for renal cell carcinoma with indications for partial nephrectomy but high surgical risk. Methods: This is a single-center, single-arm Phase II clinical trial. Eligible patients included those with biopsy-confirmed clear cell renal carcinoma who had indications for partial nephrectomy but were at high surgical risk (criteria: 1. tumors measuring 4-7 cm located at the renal hilum or endophytic ≥75%; 2. tumors larger than 7 cm). Patients received Lenvatinib at a dosage of 8 mg or 12 mg QD combined with Cadonilimab at 6 mg/kg every two weeks for 3-6 cycles, for a total treatment duration of 6-12 weeks. Cadonilimab is a first-in-class bispecific antibody targeting both PD-1 and CTLA-4. All patients are scheduled to undergo partial nephrectomy after neoadjuvant therapy. The primary endpoint was the objective response rate (ORR) based on RECIST 1.1 criteria. Secondary endpoints included the renal preservation success rate, safety, and incidence of perioperative complications. Results: A total of 27 patients were enrolled in the study. Sixteen patients completed 6 cycles of Cadonilimab treatment, 6 patients completed 3 cycles, and 5 patients did not complete the pre-set treatment cycles. One patient underwent surgery after experiencing a grade 4 adverse event (diabetic ketoacidosis) following the second cycle of Cadonilimab; four patients discontinued treatment for subjective reasons and proceeded to surgery after the second cycle. All 27 patients underwent surgical procedures. The primary endpoint ORR was 55.6% (15/27), with a tumor control rate of 100%. All patients demonstrated tumor reduction prior to nephrectomy, with an average maximum tumor diameter reduction rate of 26.5%. Furthermore, 100% of patients completed partial nephrectomy. Two patients achieved pathological complete response, and all patients exhibited tumor necrosis, with an average tumor necrosis rate of 45%. Adverse events (AEs) of grade ≥3 occurred in 10.5% of patients, including hyperglycemia and elevated ALT/AST. One patient experienced a grade 4 AE, and no grade 3 postoperative complications were reported. The main limitation of this study is that it is a single-center, small-sample study. Conclusions: Cadonilimab combined with Lenvatinib for neoadjuvant treatment in early clear cell renal carcinoma with indications for partial nephrectomy but high surgical risk demonstrates clear efficacy and safety, warranting further clinical validation. Clinical trial information: NCT06138496 .
Safety profile of lutetium-177 in patients with impaired renal function: A retrospective analysis of adverse events in mCRPC treatment.
Authors: Allen Seylani, Peter D. Zang, Erasmus Poku, Phil Kuo, Dave Yamauchi, Tanya B. Dorff
Journal: Journal of Clinical Oncology (2025)

123 Background: Lutetium-177 vipivotide tetraxetan (Lu177) is the first FDA-approved radioligand therapy for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). Not much is known regarding the safety of dosing of Lu177 in patients with creatinine clearance outside the range included in VISION trial (Sartor et al.) which was ≥50 mL/min. Using an institutional database of patients treated with Lu177, we sought to analyze whether there were increased incidences of adverse events (AEs) in patients with impaired renal function who received Lu177. Methods: We retrospectively identified 58 patients with mCRPC who received Lu177 from 2022 - 2024 at a single center (City of Hope). Impaired renal function was defined as an eGFR ≤ 60 mL/min prior to initiation of Lu177 and not confounded by acute renal injury. Statistical analysis was performed using R (v.4.4.1). A Fisher’s Exact test was used to determine whether impaired renal function was associated with increased frequency of AEs. Results: Among the 58 patients, 28 (48.28%) were Caucasian/White, 19 (32.76%) were Latino/Hispanic, 6 (10.34%) were African American/Black, and 5 (8.62%) were Asian/Pacific Islander. Median age was 68.5 years old (40-86 years old). There were 6 patients with low GFR (37 to 60 ml/min) and 36 patients with normal GFR &gt;60 mL/min. Both groups received standard pluvicto doses. In terms of AEs, the most common AEs were anemia (41.54%), thrombocytopenia (12.31%), xerostomia (10.77%), and fatigue (10.77%). For G3/G4 AEs, the most common were anemia (56.25%) and thrombocytopenia (18.75%). Only one patient with prior impaired renal function (GFR &lt;60 mL/min) experienced deterioration of renal function. There was no significant difference noted in incidence of AEs, incidence of anemia, and incidence of G3/G4 anemia between those with impaired renal function and those with normal function (p = 1, p = 0.7119, p = 0.6649 respectively). Conclusions: Patients with GFR &lt; 60 mL/min did not identify an increased incidence of AEs, including anemia, when treated with Lu177. Patients with impaired GFR experienced a similar AE profile (anemia, thrombocytopenia, and xerostomia) as described in prior data sets. Our findings suggest that Lu177 may be safely dosed in patients with impaired renal function as low as eGFR 37 mL/min, without significantly increasing the risk of AEs.
Sociodemographic disparities in treatment (tx) patterns and clinical outcomes among real-world patients (pts) with locally advanced/metastatic urothelial carcinoma (la/mUC) in the US.
Authors: Karine Tawagi, Jeanne Pierzynski, Emily Freeman, Kerstin Schmidt, Mitchell Robert Sierecki, Jane Michelle Brockman, Mamta Parikh
Journal: Journal of Clinical Oncology (2025)

707 Background: Sociodemographic disparities in la/mUC pt population include worse survival outcomes observed among certain pt subgroups. This study evaluates disparities among la/mUC pts receiving systemic therapies overall and those initiating an antibody drug conjugate in the real world. Methods: This descriptive, retrospective cohort study used US Flatiron Health electronic health record–derived de-identified database. Pts aged ≥ 18 yrs were grouped into cohorts C1 (all pts with la/mUC) and C2 (2L+ sacituzumab govitecan [SG] or 1L+ enfortumab vedotin [EV]) with tx initiation on/after Jan 2017 and Dec 2019, respectively; data cutoff for both cohorts was July 2024. Pt demographics and clinical outcomes (overall survival [OS] and time to tx discontinuation [TTD]) were calculated overall and by race. Socioeconomic status (SES) index was calculated using Yost index score (1 = lowest category; 5 = highest). Predictors of survival were assessed using Cox proportional hazards model. Results: C1 comprised 5102 pts. Most were White (68%) followed by Other race (11%), Black (5%), and Asian (1%); 15% were missing race. The racial distribution among C2 (N = 767) was similar to C1. Median age across C1 and C2 was similar (74 and 73 yrs, respectively), with Black pts being the youngest in both cohorts (median ages in C1 and C2: 70 and 65 yrs, respectively). Across both cohorts, Black and Asian pts, respectively, had the greatest proportion of pts in the lowest SES index group (C1: 36.7% and 13.3%; C2: 43.6% and 22.2%). In C1, median TTD (95% CI) was 3.0 (2.8-3.0) mos and was similar across all races. In C2, median TTD was higher for Asian (6.8 [4.2-NR] mos) and Black pts (6.5 [2.3-8.1] mos) and lowest for Other race (3.1 [1.9-4.3] mos). Median OS (95% CI) was 13.3 (12.6-13.9) mos in C1 and 11.9 (10.4-12.9) mos in C2. In both C1 and C2, Asian pts had the longest survival (median OS: 25.2 [11.9-41.9] and 14.0 [9.3-NR] mos, respectively) and Black pts had the shortest survival (median OS: 11.2 [9.2-15.9] and 11.4 (6.9-20.5] mos, respectively). Exploratory Univariate Cox modeling (limited by small sample size) suggested older age, history of smoking, treatment in community setting, de novo metastatic diagnosis, and ECOG score ≥ 2 are factors associated with low survival in C1 and only history of smoking and ECOG score ≥ 2 in C2. Conclusions: In this real-world study of treated pts with la/mUC, sample sizes, especially in C2, further research is needed to understand disparities and pt-centric factors that may impact tx decisions, TTD patterns, and reasons for discontinuation to define and address the unmet medical needs of these pts.
Changes in circulating tumor cells (CTCs) and HER2 expression in evaluating the efficacy of neoadjuvant disitamab vedotin plus toripalimab treatment in patients with muscle-invasive bladder cancer (MIBC).
Authors: Yudong Cao, Ruojing Li, Shuo Wang, Jinchao Ma, Yongpeng Ji, Chen Lin, Peng Du
Journal: Journal of Clinical Oncology (2025)

837 Background: Disitamab vedotin (DV) combined with toripalimab has shown promising efficacy as neoadjuvant therapy for MIBC, with a pathological CR (pCR) rate of 62.1% in the previous report (2024 ASCO). In real-world practice, many patients who achieved clinical complete response (cCR) after neoadjuvant therapy, confirmed by re-TURBT, imaging, and urine cytology, opted for bladder-preserving treatment (BPT). However, biomarkers to confirm the absence of residual tumors in cCR pts are lacking. This study aims to evaluate the correlation between changes in CTCs and HER2+ CTCs during neoadjuvant therapy with clinical efficacy outcomes in MIBC. Methods: 18 pts were retrospectively included from July 2023 to July 2024. The primary endpoint was to assess the correlation between changes in CTCs and HER2+ CTCs before and after neoadjuvant therapy, and clinical efficacy (cCR or non-cCR). Eligible pts had previously untreated MIBC (cT2-T3N0-1M0) with HER2 expression of IHC ≥ 2+. Pts received DV (2 mg/kg) plus toripalimab (3 mg/kg) every two weeks for six cycles, followed by radical surgery or BPT for cCR pts (choice made after communication between the physician and the pts). cCR criteria included no residual tumor confirmed by re-TURBT, no evidence of tumor on imaging, and negative urine cytology. Peripheral blood samples were collected to measure CTC counts and HER2 phenotype by HER2-iFISH. Results: Among 18 pts, 15 (83.3%) achieved cCR, while 3 pts (16.7%) were in the non-cCR group, including 2 pts with cPR confirmed as pT2N0 postoperatively, and 1 pt with clinical progression (cPD). All 15 cCR pts underwent BPT. There were no significant differences in the total CTCs and HER2+ CTCs between the cCR and non-cCR groups before treatment (P = 0.426, P = 0.654, respectively). After neoadjuvant therapy, CTC and HER2+ CTC counts were significant lower in the cCR group compared to the non-cCR group (P = 0.039, P = 0.005, respectively). Only 1 (6.7%) cCR pt had detectable HER2+ CTCs post-treatment, while all 3 non-cCR pts had measurable HER2+ CTCs. Conclusions: Changes in CTCs and HER2+ CTCs correlated with clinical efficacy outcomes of DV plus toripalimab neoadjuvant therapy, particularly in HER2+ CTCs. CTCs and CTC HER2 expression may serve as potential biomarkers for evaluating clinical efficacy and guiding treatment strategies in MIBC. The clinicopathological characteristics of the 18 MIBC patients. Characteristic All patients (n=18) cCR (n=15) non-cCR (n=3) P value Clinical T stage, n (%) 1.00 cT2 10 (55.6) 8 (53.3) 2 (67) cT3 8 (44.4) 7 (46.7) 1 (33) Clinical N stage, n (%) 1.00 cN0 15 (83.3) 12 (80.0) 3 (100) cN1 3 (16.7) 3 (20.0) 0 (0) HER-2 expression, n (%) 0.44 2+ 15 (83.3) 13 (86.7) 2 (66.7) 3+ 3 (16.7) 2 (13.3) 1 (33.3)