tbuckley/cabot-search huggingface dataset:
Barriers to and facilitators of first-line treatment intensification (TI) in metastatic castration-sensitive prostate cancer (mCSPC) by practice setting and intensification frequency: A sub-analysis of IMPLEMENT.
Authors: Neeraj Agarwal, Stacy Loeb, Nader N. El-Chaar, Laura de Ruiter, Janet Kim, Jessica Mack, Betty Thompson, Sarah Rich-Zendel, Jay Sheldon, Jin Su Joo, Judith Dyson
Journal: Journal of Clinical Oncology (2025)

48 Background: First-line TI (i.e., androgen-deprivation therapy + chemotherapy, androgen receptor pathway inhibitors, or both) is recommended for mCSPC but is underutilized. Phase 1 of IMPLEMENT identified barriers to and facilitators of TI. Phase 2 prioritized these factors and identified resources to increase TI. This sub-analysis describes the results in academic and nonacademic settings, and among high and low intensifiers (physicians who use first-line TI in &gt;50% vs ≤50% of patients, respectively). Methods: Phase 1: Semi-structured virtual interviews with 18 oncologists and 18 urologists, using an implementation science approach based on the Theoretical Domains Framework to analyze themes by setting and intensification frequency. Phase 2: Discrete choice experiment with 302 physicians who reviewed descriptions of potential resources across 12 scenarios and selected the most helpful for increasing TI. We used a mixed-effects logistic regression model to calculate a coefficient of helpfulness for each resource to identify those with the strongest impact on TI decisions. Results: Phase 1:Low intensifiers and nonacademic physicians more frequently reported barriers to TI. Low intensifiers had gaps in clinical trial knowledge, tended to reserve TI for later, and had low-intensifier peers; nonacademic physicians had concerns about side effects, cost, and impact on quality of life. High intensifiers and academic physicians more frequently reported facilitators such as good clinical support and anticipated regret about missing the best chance at improving survival. Phase 2: Significant differences were noted between high and low intensifiers in the utility of decision support and clinical trial summaries (Table). Conclusions: Decision support tools and databases of post-treatment options may help address barriers to TI and improve guideline-concordant care. Resource, mean COH (±SD) Academicn = 81 Nonacademicn = 221 High intensifiersn = 184 Low intensifiersn = 118 Database of post-treatment options 1.89(0.38) 1.80(0.38) 1.94(0.39) 1.65(0.36) Decision support tool linking patient characteristics to first-line treatment options 1.60(0.53) 1.75(0.53) 1.45*(0.52) 2.12*(0.51) Summaries of key clinical trial data 1.39(0.40) 1.25(0.44) 1.55*(0.44) 0.88*(0.37) Cross-specialty treatment guidelines 0.57(0.26) 0.59(0.25) 0.48(0.22) 0.75(0.30) Information comparing clinical outcomes of first-line vs later TI 0.41(0.21) 0.37(0.18) 0.40(0.19) 0.36(0.19) Tools to reduce administrative burden 0.13(0.06) 0.23(0.11) 0.18(0.10) 0.25(0.11) COH, coefficient of helpfulness (scaled to have average value of 1, i.e., &gt;1: above average utility; &lt;1: below average utility). * P &lt; 0.05 from bootstrap testing of subgroup averages.
Impact of bleomycin shortage in patients with advanced testicular non-seminoma germ-cell tumors: A middle-income country cancer center experience.
Authors: Nora Sobrevilla-Moreno, Josette Staufert-Gutiérrez, Ruben Rodriguez-Bautista, Diego Lopez, Jorge Chamorro-Chamorro, Carlos Arturo Gonzalez Nuñez, Maritza Ramos-Ramirez, Paula Anel Cabrera Galeana, Miguel Jimenez Rios, Anna Scavuzzo
Journal: Journal of Clinical Oncology (2025)

623 Background: Standard of care for advanced NSGCTs is BEP (bleomycin, etoposide, cisplatin). Social, epidemiologic and economic factors can impact drug availability. In our institution, the COVID-19 pandemic limited accessibility to several antineoplastic drugs, including bleomycin. This analysis describes the frequency of BEP modifications and its impact in prognosis of intermediate (IP) and poor (PP) NSGCT treated at the National Cancer Institute in Mexico. Methods: Retrospective observational study performed from 2018 to 2022. Clinical characteristics and chemotherapy modifications were retrieved from electronic charts. Survival curves were built with Kaplan-Meier method and compared log-rank test to demonstrate effects of different clinicopathological variables on survival. Statistically significant variables in univariate analysis were included in multivariate Cox regression. Results: 179 patients included. Median age 23 (16-56). 33% had IP and 66% PP; 32% had non-pulmonary visceral metastases (NPVM). 60% had at least one dose modification. Median dose of bleomycin was 67.5 IU (IQR, IU 0-90) per cycle. 42% of patients received the full-dose of bleomycin (Bleo360) dose. 55.8% of bleomycin modifications were due to drug shortage. 88% who received Bleo360 didn´t have other chemotherapy drug modifications (p&lt;.001). Median Progression Free Survival (mPFS) was 17.4 months (95% Confidence Interval (CI), 11.8-23.1). Median Overall Survival (mOS) was 73.6 months (95% CI, 20.6-126.7). Univariate and multivariate analysis are described in the table. Conclusions: Oncology drug shortages may have serious consequences for patient’s survival. In our cohort the dose-modifications of bleomycin had a deleterious impact in the survival of IP/PP NSGCTs patients. Policy modifications and stakeholders awareness is paramount to decrease shortage of “vintage” oncological therapies. Univariate and multivariate analysis. Univariate Multivariate Variable PFS HR(IC 95%) p OS HR(IC 95%) p PFS HR(IC 95%) p OS HR(IC 95%) p IPPP 0.34(0.21-0.56) &lt;0.0001 0.3(0.2-0.5) 0.0001 Ref.2.4(1.4-4.2) 0.002 Ref.2.8(1.5-5.5) 0.002 NPVMNoYes 0.53(0.36-0.78) 0.001 0.5(0.4- 0.9) 0.011 Ref.1.3(0.9-2) 0.2 Ref.1.1(0.7-1.9) 0.6 Bleo360YesNo 0.6(0.66-0.98) 0.04 0.63(0.39-1.0) 0.06 Ref.1.3(0.9-2.0) 0.1 Ref.1.3(0.8-2.1) 0.3 Log Tumor MarkerFavorableUnfavorable 0.51(0.30-0.84) 0.009 Ref.2.1(1.2-3.7) 0.008 Ref.1.6(0.9-2.9) 0.1
Evaluating the therapeutic role of lymph node dissection in variant histology bladder cancer.
Authors: Syed Rahman, David Hesse, Michael Jalfon, Victoria Kong, Fady Ghali
Journal: Journal of Clinical Oncology (2025)

749 Background: Outcome benefit associated with lymph node dissection (LND) at time of radical cystectomy have been suggested in urothelial bladder cancer (BC), but have not been evaluated in variant subtype BC. Our objective was to characterize the impact of LND on survival outcomes across variant subtype BC. Methods: The National Cancer Database was queried for cases of variant histology bladder cancers using International Classification of Disease-O-3 morphologic codes managed with radical cystectomy between 2004 and 2020. Cases were stratified by variant subtype and LND status. Primary outcome was overall survival associated pathologic nodal status and receipt of LND. Kaplan Meier analysis and Cox proportional hazards analysis were performed for survival analyses. Results: A total of 30,911 patients with variant UC histology were included in our analysis. that were managed with radical cystectomy. Rates for the no-LND group (pNx) were 33.1% in the micropapillary subtype, 42.2% in sarcomatoid, 68.4% in squamous, 48.9% in adenocarcinoma, and 56.2% in the neuroendocrine subtype. Median OS was higher in those that received a nodal dissection for squamous (91.3 [89.9, 92.7] vs. 62.8 [60.1, 65.6] months p&lt;0.001) and adenocarcinoma (83.6 [73.1, 92.1] vs. 56.3 [43.5, 69.0] months p=0.020). On Cox proportional hazards regression, in T1/2 stage disease LN dissection was associated improved OS for sarcomatoid (0.50 [0.23-0.96] p=0.048), squamous (0.67 (0.61-0.76) p&lt;0.001), adenocarcinoma (0.45 [0.23-0.85) p=0.015), and neuroendocrine (0.425 [0.21-0.85) p=0.017) variant histologies. In T3/4 disease, nodal dissection was statistically significant improved OS only for squamous histology (0.68 [0.59-0.77] p&lt;0.001 and 0.70 [0.59-0.83] p&lt;0.001 respectively). The survival benefit of LND appears to be attenuated following receipt of NAC across most histologic subtypes including micropapillary and sarcomatoid histologies. Conclusions: Our data highlights the varying degrees of therapeutic benefit across variant BC. LND particularly in sarcomatoid, neuroendocrine, and adenocarcinoma VHBC is correlated with improved survival, particularly in low clinical stages. The benefit also appears to be attenuated with receipt of NAC. These data help inform a variant subtype-informed surgical approach.
Prevention, diagnosis, and management of penile cancer in the LGBTQ+ community: A systematic review and meta-analysis.
Authors: Akshit Chitkara, Fnu Anamika, Atulya Aman Khosla, Sakshi Bai, Arshia Adib, Rushin Patel, Rohit Singh
Journal: Journal of Clinical Oncology (2025)

2 Background: Penile cancer is a rare but significant malignancy with unique prevention, diagnosis, and treatment challenges within the LGBTQ+ community. This systematic review and meta-analysis aims to evaluate the existing evidence on penile cancer for LGBTQ+ individuals, addressing disparities and unique needs to improve clinical outcomes. Methods: Following PRISMA 2020 guidelines, a systematic search was conducted across PubMed, Embase, Scopus, and clinical trial registries up to September 2024. Studies were included if they involved penile cancer prevention, screening, or treatment in LGBTQ+ populations, with no restrictions on study design or language. Data extraction focused on epidemiological patterns, risk factors (e.g., HPV infection), screening practices, diagnostic approaches, treatment modalities, and outcomes. The risk of bias was assessed using the Newcastle-Ottawa Scale for cohort studies and the Cochrane risk-of-bias tool for randomized controlled trials. The meta-analysis used a random-effects model to pool prevention and treatment outcomes data. Results: Of the 872 studies screened, 18 met the inclusion criteria, encompassing 1,232 LGBTQ+ patients. High-risk populations included men who have sex with men (MSM) and transgender women with elevated rates of HPV-associated penile cancer. HPV vaccination was underutilized in these populations despite its potential to prevent penile cancer. Early diagnosis was often delayed due to stigma, lack of awareness, and healthcare access barriers. Treatment outcomes varied, with higher rates of post-surgical complications and psychological distress reported. Meta-analysis revealed that HPV vaccination reduced the risk of penile cancer by 60% (pooled relative risk: 0.40, 95% CI: 0.25-0.64), while early surgical intervention improved 5-year survival rates by 45% (HR: 0.55, 95% CI: 0.32-0.79). Conclusions: Penile cancer prevention and management in LGBTQ+ populations require tailored strategies, including increased HPV vaccination coverage, early screening, and culturally competent healthcare. Addressing barriers related to stigma and healthcare access could significantly improve outcomes. Further research is needed to optimize treatment protocols and incorporate LGBTQ+-specific considerations in penile cancer care. Summary of meta-analysis results. Outcome Measure Number of Studies Pooled Effect Estimate 95% Confidence Interval (CI) Heterogeneity (I²) % HPV Vaccination Effectiveness 8 Relative Risk (RR): 0.40 0.25–0.64 42 Barriers to Early Diagnosis 5 Odds Ratio (OR): 2.25 (higher risk) 1.45–3.51 38 Post-Surgical Complication Rate 4 Risk Ratio (RR): 1.30 (higher rate) 1.12–1.50 27 Psychological Distress Post-Treatment 3 Standard Mean Difference (SMD): 0.75 0.50–1.00 60 5-Year Survival Improvement with Early Surgery 6 Hazard Ratio (HR): 0.55 0.32–0.79 49
Comprehensive modalities of kidney-sparing treatment in a carefully selected cohort of localized high-risk upper tract urothelial carcinoma: A potential paradigm shift.
Authors: Zeyu Chen, Jianjun Ye, Xiang Tu, Xinyang Liao, Qihao Wang, Lei Zheng, Kai Chen, Qiang Wei, Yige Bao
Journal: Journal of Clinical Oncology (2025)

794 Background: This study aims to assess the efficacy and safety of comprehensive modalities of kidney-sparing treatment in a carefully selected cohort of patients with localized high-risk upper tract urothelial carcinoma (UTUC). Methods: This study was initiated in January 2019 and is ongoing. Selected localized high-risk UTUC patients, characterized by conditions such as solitary kidney, bilateral tumors, impending renal insufficiency or patient refusal/ineligibility for radical nephroureterectomy (RNU), were included. Systemic therapy regimens were tailored to patient characteristics, tumor pathology and biomarkers, and included platinum-based chemotherapy, Disitamab Vedotin, and immune checkpoint inhibitors (ICIs). After endoscopic biopsy and attempted laser ablation, patients received four cycles of systemic induction therapy, followed by maximal endoscopic laser ablation or segmental ureterectomy. Postoperatively, a one-year course of immunotherapy maintenance was administered. The co-primary endpoints were disease-free survival (DFS) and conversion-free survival (CFS). Secondary endpoints included metastasis-free survival (MFS), renal function changes, ureteral stricture and treatment safety. Results: 68 patients were enrolled, with a follow-up of 18 months. 54 patients underwent endoscopic thulium laser tumor ablation, while 14 underwent segmental ureterectomy. The induction therapy comprised Disitamab Vedotin for 32 patients, platinum-based chemotherapy for 9, and immunotherapy for 37. Urothelial tract recurrence was observed in 28 patients with a 1-yr DFS rate was 58.82%, who subsequently underwent repeat endoscopic laser ablation. Salvage RNU was performed in 9 patients, yielding a 1-yr CFS rate of 93.7% and a 2-yr CFS rate of 88.9%. No distal metastasis was reported. Postoperative renal function impairment was noted in 15 patients (22.06%). Mean eGFR improvements were observed at various time points: 3.15 ml/min/1.73m 2 at 1 months, 5.07 ml/min/1.73m 2 at 3 months, 2.41 ml/min/1.73m 2 at 6 months, and 3.97 ml/min/1.73m 2 at 12 months. Ureteral stricture on the affected side was a common complication, which was more likely to occur in patients who underwent 3 or more times of ureteroscopy (9/27). Notably, no grade 3 or higher systemic toxicities were observed. Conclusions: Preliminary findings indicate that our comprehensive modalities of kidney-sparing treatment demonstrated promising tumor control and satisfactory renal function preservation in a carefully selected cohort of localized high-risk UTUC. Its definite application strategy and value should be further evaluated in future clinical practice.
Relationship of spatial transcriptomic analyses with distance-associated transcriptomic spectrum and morphology-specific signatures of localized prostate cancer.
Authors: Brendan Raizenne, Hanbing Song, Nancy Greenland, Maggie Tsui, Jared Khan, Taiqi Li, Chih-Hao Chang, Matthew R. Cooperberg, Franklin W. Huang
Journal: Journal of Clinical Oncology (2025)

422 Background: Current clinical management and classification of prostate cancer is dependent upon specimen morphology assessment. Limited studies have focused on identifying and mapping transcriptomic signatures within morphological variants. Additionally, the impact of transcriptomic distance-relationship between benign and tumor glands has yet to be identified. In this analysis, we profiled and derived signature gene sets for morphological variants and assessed the spatial impact of distance from the adjacent tumor areas on surrounding benign tissues. Methods: Four (three African American and one European ancestry) formalin fixed paraffin embedded prostate cancer samples were obtained via radical prostatectomy and underwent the GeoMx DSP workflow with gene expression level counts. The four patients each had different dominant morphologic features on the slide used, with one patient with extensive foamy gland morphology, one with extensive atrophic morphology, one with extensive mucinous morphology, and one with extensive Gleason pattern 5 carcinoma. Other regions of interest (ROIs) were benign (including benign glands, benign stromal) or mixed tumor/benign. Transcriptomic analysis was performed on these ROIs to derive the morphology-specific gene signatures. Additionally, distance-based spectrum of proximity of benign ROIs to tumor ROIs was constructed to identify genes that are significantly associated with distance to the nearest tumor ROI. Results: 96 ROIs from four patients (denoted by the dominant morphological tumor features) were annotated. In total, 95 ROIs and 8,102 genes passed quality control for analyses. A distance-based spectrum analysis revealed that benign ROIs that are closer to tumor ROIs were highly enriched in transcriptomic androgen signature and MYC signature and endothelial or club-like features were enriched in benign ROIs further from tumor ROIs. Moreover, distinct gene set signatures were established for each morphological feature. Conclusions: Benign ROIs closer to the tumor are more tumor-like and enriched in androgen receptor pathways and MYC signatures. We identified transcriptomic differences among the morphological tumor features that demonstrate inter-patient and intra-patient tumor heterogeneity.
First next-generation sequencing (NGS) testing at the end of life in patients with metastatic prostate cancer.
Authors: Zeynep Irem Ozay, Yeonjung Jo, Chadi Hage Chehade, Nicolas Sayegh, Georges Gebrael, Micah Ostrowski, Edwin Lin, Gliceida M Galarza Fortuna, Blake Nordblad, Haoran Li, Vinay Mathew Thomas, Ryon P Graf, Irbaz Bin Riaz, Avirup Guha, Benjamin L. Maughan, Soumyajit Roy, Rana R. McKay, Emmanuel S. Antonarakis, Umang Swami, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2025)

90 Background: Poly(ADP) ribose polymerase inhibitors and pembrolizumab are approved for patients with metastatic prostate cancer (mPC) with susceptible genomic alterations based on NGS testing. We recently reported that the rate of NGS testing in mPC remains low at 29.3% in the United States (1). Herein, we investigated the rates of NGS testing at the end of life in a real-world patient population. Methods: This study utilized the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Eligibility: diagnosis of mPC, with information on receipt of NGS testing (blood/tissue) and recorded date of death. The time between each patient’s first NGS testing result date and date of death was measured and categorized into 3 groups: NGS test results delivered more than 3 months (mo) before death, within 3 mo of death, and delivered after death. Frequencies and percentages of these 3 categories were reported, also by the year of death. Results: Out of 24,105 patients with mPC in the database, 3,397 had both a recorded date of death and underwent NGS testing and were eligible and included. The median age was 74 (IQR 67–80), 70% were White non-Hispanic, and 83% were treated in a community-based practice. In these patients, 2,901 (85.4%) NGS results were reported more than 3 mo before death, 457 (13.5%) within 3 mo of death, and 39 (1.1%) after death. From 2015 to 2024, the percentage of patients receiving their result more than 3 mo before death increased from 27% to 91%, while those receiving it within 3 mo before death decreased from 55% to 8.5%, and the percentage of NGS results reported after death declined from 18% to 0.6%. Baseline characteristics (including race-ethnicity, insurance plan, practice type [academic vs. community]) in these categories will be presented at the meeting. Conclusions: Despite the availability of life-prolonging targeted therapies based on NGS testing results for patients with mPC, in ∼14% of patients, the first NGS testing results were reported within 3 mo before death or after death. The lack of timely NGS testing limits patients' access to life-prolonging personalized treatments in earlier settings, resulting in missed opportunities for improved outcomes. 1. Hage Chehade, Swami, JAMA Network Open, 2024.
Stage II embryonal predominant NSGCT: Minimizing treatment burden.
Authors: Jiping Zeng, Parth Thakker, Timothy A. Masterson, Tareq Salous, Jennifer King, Nabil Adra, Lawrence H. Einhorn, Clint Cary
Journal: Journal of Clinical Oncology (2025)

634 Background: Embryonal carcinoma predominance (ECP) in the orchiectomy specimen is linked to a higher risk of retroperitoneal and systemic relapse. Both chemotherapy and primary retroperitoneal lymph node dissection (RPLND) are recommended options for stage II disease, but the approach that minimizes treatment burden remains unclear. Methods: We queried the Indiana University Testicular Cancer Database to identify patients with non-seminomatous germ cell tumors (NSGCT) and ECP &gt;50% in the orchiectomy specimen, stage II with retroperitoneal adenopathy &lt;5 cm, and normal serum tumor markers. Patients with malignant transformation (n=3) or bilateral cancer (n=3) or receiving 1-2 cycles of BEP after orchiectomy were excluded (n=14). Treatment courses and outcomes were compared. Results: Between 2005 and 2022, 142 patients met the criteria. Of 67 patients who underwent primary RPLND, 62 had active EC in final pathology. Adjuvant chemotherapy (2 cycles of EP or BEP) was given to 5 patients. After a median follow-up of 37.7 months, 10 recurred, with a recurrence-free survival (RFS) of 85.1%. Following induction chemotherapy for documented recurrence, 9 patients were disease-free, with 1 disease-related death. Disease-free survival (DFS) was 98.5%. There were no in-field recurrences in the primary RPLND group. Of the 75 patients who received chemotherapy, 25 required post-chemotherapy (PC) RPLND, which revealed either teratoma or necrosis, and no active cancer was found. One recurred and needed re-do RPLND. Five patients who achieved complete remission after chemotherapy recurred, requiring second-line and high-dose chemotherapy. The RFS was 92%, with a median follow-up of 34.1 months. DFS was 97.3%. Univariate analysis showed pre-orchiectomy AFP &gt;100 ng/mL (OR 7.6, 95% CI 1.6–54.9) and teratoma &gt;5% in the orchiectomy specimen (OR 4.1, 95% CI 1.3–13.2) were associated with the need for PC-RPLND, but no parameters were predictive in multivariate analysis. Conclusions: Primary RPLND achieved complete remission as a single treatment modality in 85% of patients, compared to 67% for chemotherapy. Primary RPLND may reduce treatment burden in early-stage II ECP NSGCT in well-selected patients.