tbuckley/cabot-search huggingface dataset:
Assessing racial disparities in testicular cancer survival: Evidence from a nationwide cohort.
Authors: Kylie Margaret Morgan, Paul Riviere, Kshitij Margaret Pandit, Tyler Nelson, Daniel Sabater Minarim, Margaret Meagher, Dhruv Puri, Nuphat Margaret Yodkhunnatham, Frederick E. Millard, Rana R. McKay, Brent S Rose, Aditya Bagrodia
Journal: Journal of Clinical Oncology (2025)

621 Background: Testicular cancer is one of the most common and curable malignancies in young men, with a 5 year survival rate of 95%. Limited research has explored long-term survival outcomes among Black men, given rarity of disease among this demographic. Our study aims to assess potential racial differences in overall survival (OS) and cancer-specific mortality (CSM) among testicular cancer patients using a large, equal access nationwide Veterans Affairs (VA) database, focusing on self-identified Black and White race. Methods: This retrospective study analyzed Black and White testicular cancer patients from the VA database utilizing Veterans Informatics and Computing Infrastructure (VINCI). Self-identified race was obtained from the VA Cancer Registry, with OS and CSM as the primary outcomes. CSM was identified using the National Death Index (NDI). NDI data is available through 12/31/2020, after which date all patients with continued follow-up were censored. Cox proportional hazard models were applied to examine the associations of race on OS and CSM, adjusting for relevant clinical factors such as cancer staging, Charlson Comorbidity Index (CCI), and receipt of adjuvant chemotherapy or radiation. All time to event analyses were done from time of testicular cancer diagnosis to outcome of interest. Results: We compared 1799 White patients to 118 Black patients. A total of 431 (22.49%) patients died, of whom 405 were White and 26 were Black. There was no statistically significant difference in survival at 10 years between Black and White individuals (80.4% vs 81.6%, p = 0.68). The multivariable cox-regression analysis showed no statistically significant difference between Black and White men. Of the 431 deaths, 72 were identified as CSM (71 White, 1 Black). There was no significant difference in 10-year cumulative incidence of CSM in Black and White individuals (0% vs 4.1%, p=0.12). Similarly, no significant differences were found for CSM between Black and White men in the multivariable analysis. Conclusions: Our study found no significant racial disparities in OS or CSM between Black and White testicular cancer patients in the VA healthcare system. As the VA represents an equal access to care setting, these findings may not be generalizable to the broader U.S. population, where disparities in care are more notable. Conversely, access to care may overcome known sociodemographic disparities that drive worse clinical outcomes. The analysis is limited by the small number of patients experiencing the event of interest. Future research should be conducted to validate the association between self-identified race and survival outcomes in more diverse healthcare settings.
Comprehensive bladder cancer molecular profiling and monitoring based on mutational, epigenomic, and expression data from real-world patients.
Authors: Alan Tan, Yong Huang, Giancarlo Bonora, Binggang Xiang, Chao Dai, Fang Liu, Ziqi Zhu, Shidong Jia, Pan Du
Journal: Journal of Clinical Oncology (2025)

860 Background: Bladder cancer poses considerable therapeutic challenges, particularly in the context of bladder preservation strategies that aim to balance maintaining quality of life with achieving optimal survival outcomes. Traditional treatments, such as radical cystectomy, often have profound impact on patient morbidity. However, recent advances in molecular profiling -- including mutational, epigenomic, and gene expression analyses -- offer promising avenues for personalized cancer treatment approaches. Despite these advances, comprehensive studies leveraging detailed analysis of molecular profiling and urine-based monitoring in bladder cancer are lacking. Methods: A cohort of 30 real-world patients with bladder and upper tract urothelial carcinoma (UTUC) of various subtypes were included in this study. Standard treatment modalities employed were neoadjuvant chemotherapy, trimodality therapy (TMT) for bladder preservation, and systemic chemotherapy or immunotherapy in the metastatic setting. PredicineCOMPLETE is an integrated assay that interrogates genomic alterations such as mutations, copy number variations (CNVs), and gene fusions – as well as DNA methylation and transcriptomic profiles. All samples had previously undergone the PredicineBEACON urine MRD test, which covers mutation/CNV/fusion analysis. We further performed whole-transcriptome sequencing (WTS) on baseline urine cell pellet (UCP) samples, and the PredicineEPIC DNA methylation assay on all the follow-up timepoint samples. Results: The PredicineCOMPLETE assay generated significantly more comprehensive data compared to mutational panels alone, providing a rich molecular landscape of each patient’s tumor biology. Comprehensive correlation analysis between DNA methylation and RNA expression were conducted. Strong correlation was observed for some bladder cancer biomarker genes such as TERT and TP53. An AI model was trained using patients’ treatment decision (bladder preservation versus surgery), clinical features, and the comprehensive molecular data obtained. The trained AI model accurately matches the physician’s choices over 90% of the validation cases. Conclusions: This study demonstrates that comprehensive molecular profiling using the PredicineCOMPLETE assay helps us understand the underlying disease biology. Combined with machine learning and AI modeling, it can effectively assist in treatment decision-making for bladder cancer patients. While these initial results are encouraging, the limited sample size necessitates further validation in larger, independent cohorts to confirm the model’s efficacy and generalizability.
Validation of new prognostic factors for relapse in patients with clinical stage I seminoma.
Authors: Tim Nestler, Angelina Strauch, Justine Schoch, Hans Schmelz
Journal: Journal of Clinical Oncology (2025)

625 Background: Patients with clinical stage I (cSI) seminomatous testicular germ cell tumors (GCT) have a relapse risk of 5 - 30% under surveillance after orchiectomy, depending on tumor size and rete testis infiltration. Recently, two studies introduced new prognostic risk models to improve clinical decision-making: the Danish Testicular Cancer database (DaTeCa) and an Individual Patient Data Analysis by the European Association of Urology (EAU) Testicular Cancer Guidelines Panel and Guidelines Office. This study aimed to validate these new prognostic risk models in an independent cohort of cSI seminoma patients. Methods: We included patients with unilateral cSI seminoma (retroperitoneal lymph nodes &lt;10 mm in short-axis diameter), normalized serum tumor markers post-orchiectomy (β-human chorionic gonadotropin (β-hCG) and lactate dehydrogenase (LDH)), and no adjuvant therapy. All patients had at least 12 months of follow-up. Cox regression analysis was applied to evaluate the proposed prognostic factors and relapse probabilities were estimated using the Kaplan-Meier method. Results: Among 139 patients, 25 (18%) relapsed within a median follow-up of 37 months (CI 47.9–63.1). In multivariate analysis, only rete testis infiltration was confirmed as an independent predictor of relapse (p=0.039). The other prognostic factors of DaTeCa (lymphovascular invasion, elevated pre-orchiectomy β-hCG and LDH) and EAU (tumor size and lymphovascular invasion) could not be confirmed. The 5-year relapse risk according to DaTeCa risk groups was consistent with our cohort (no risk factors: 4% vs. 6%; all four risk factors: 67% vs. 62%). Similarly, the EAU classification showed comparable 5-year relapse risks for low (13% vs. 8%) and intermediate (22% vs. 20%) groups. However, the high-risk group showed a greater discrepancy (67% vs. 44%), although our study included only a limited number of high-risk patients (n=6, 4.3%). Conclusions: The risk classification models from DaTeCa and EAU demonstrated good overall reproducibility in our cohort. These models may aid in identifying seminoma patients at high-risk for relapse who might be candidates for adjuvant therapy. However, the proposed prognostic factors were mainly not independently confirmed in the multivariate analysis in our study cohort.
Prospective COTRIMS (Cologne trial of retroperitoneal lymphadectomy in metastatic seminoma) trial: Final results.
Authors: Axel Heidenreich, David Pfister, Pia Paffenholz
Journal: Journal of Clinical Oncology (2025)

618 Background: Radiation or chemotherapy represent the standard treatment in clinical stage IIA/B seminoma. Despite high cure rates both modalities are associated with significant long-term toxicities. The COTRIMS trial evaluated the oncological and functional efficacy of primary retroperitoneal lymphadenectomy (RPLND) without adjuvant chemotherapy in CS IIA/B seminomas. Methods: 34 patients with CS IIA/B pure semimomas were prospectively recruited. Exclusion criteria were adjuvant chemotherapy following orchiectomy, CS IIC, previous retroperitoneal surgery or radiation, positive tumor markers. All patients underwent nerve sparing RPLND with a unilateral template; no adjuvant chemotherapy was delivered. Follow-up was done according to EAU guidelines. In 22 patients miR371 was evaluated preoperatively and correlated with pathohistology of lymph nodes. The primary endpoint of the study was a relapse-free rate of &lt; 20% at 3 years. Results: Median age is 34.2 (21-54) years, mean and median follow-up is 41.5 (4-73) and 33.4 (13-56) months. 22 and 12 pts had CS IIA and CS IIB, resp. Mean OR-time, blood loss and hospitalisation were 131 (105-195) min, &lt; 150ml and 4 (3-9) days. 4 (11.7%) pts experienced Clavien Dindo 3a complication. Antegrade ejaculation was preserved in 88%. A mean of 19 (7-57) lymph nodes were dissected. Mean number of positive lymph nodes was 1.4 (1-2), mean diameter was 2.3 (0.8-4.1) cm. Seminoma was present in 85%, non-malignancy and nonseminoma were found in 8.9% and 5.9%. miR371 was positive in 17/18 pts with metastases und negative in 3/3 with benign lesions. 4 (11.7%) pts relapsed after 4, 6, 9 and 12 months and all were salvaged by chemotherapy. Conclusions: RPLND results in high cure rates associated with low frequency of surgery – related complication even after a follow-up of about 3 years. Nearly 90% of patients can be managed without systemic chemotherapy. RPLNSD should be included in the treatment options for CS IIA/B seminomas. miR371 appears to be a valid biomarker to predict presence of lymph node metastases. Clinical trial information: DRKS00025384 .
Prospective monitoring of prostate specific membrane antigen (PSMA) –positive recurrent prostate cancer: Preliminary data from 6 months PSMA follow-up.
Authors: Ravi Amrit Madan, Melissa Lauren Abel, Esther Mena, Liza Lindenberg, Megan Hausler, Monique Williams, Amy Hankin, Jeanny B. Aragon-Ching, Laura Sena, Russell Kent Pachynski, Edwin Melencio Posadas, Helen Moon, Marijo Bilusic, Philip M. Arlen, Krishnan R. Patel, Deborah Jolissaint, Gregory T Chesnut, William Douglas Figg, Fatima Karzai, Peter L. Choyke
Journal: Journal of Clinical Oncology (2025)

45 Background: PSMA imaging can identify recurrent prostate cancer after definitive surgery/radiation prior to detection on computed tomography (CT) or bone scan. Radiation to PSMA+ findings is common but lacks clear data demonstrating long term benefit. PSMA+ recurrent prostate cancer (PSMArpc) is often defined and treated as metastatic castration sensitive prostate cancer (mCSPC), yet PSMA imaging alone as an eligibility criteria was never studied in the mCSPC trials. PSMArpc requires better understanding to define at-risk patients (pts). Methods: NCT05588128 enrolls pts after definitive and possibly salvage therapies. Pts are required to be 1 year removed from definitive therapy with a PSA≥0.5 ng/ml, testosterone≥100 ng/dL, and negative CT/bone scans. Lymph nodes (LNs) up to 1.5 cm and prior therapies are permitted. At enrollment pts have a baseline PSMA, which is repeated every 6 months (mos) if positive. If negative PSMA is done annually. CT and bone scans are also repeated annually. Pts are allowed to have radiation therapy or systemic therapies for ≤6 mos and remain on-study. Up to 350 pts will be enrolled and followed for up to 5 years. Results: Over 100 pts have enrolled since 3/2023 and 73 pts were evaluable after the 6-month PSMA scan/follow-up. The pts had a median age of 71 years, PSA=2.8, PSA doubling time=11.1 mos (30% less than 6 mos). In an overlapping descriptive analysis 10 pts were PSMA- and 15 pts had only local disease. For PSMA+ LNs, 15 pts had 1 LN, 8 pts had 2-3 LNs+, 4 pts had 4 LNs+, and 16 pts had 5+ LNs. 6 pts had bone findings, but negative bone scan. 3 pts had PSMA+ serosal nodules. After baseline PSMA 3 pts had radiation to solitary LNs, only 1 resolved/PSA declined. 1 pt elected androgen deprivation and 1 pt had salvage radiation. 4 pts enrolled in a clinical study at the NCI without androgen deprivation. At 6 mos PSMA scan only 2 pts had metastatic disease, both with bone scan findings, no pts had LNs beyond eligibility size criteria, and no pts had new visceral findings. Conclusions: These preliminary data from an ongoing study suggest PSMArpc is an indolent disease process and pts are at limited risk for clinically relevant progression within 6 mos. This study continues to accrue at the NCI and will seek to better define high-risk PSMArpc. These preliminary data may better inform the risks/benefits of aggressive treatment of PSMArpc and clinical studies in PSMArpc. Clinical trial information: NCT05588128 .
Real-world analysis of pembrolizumab utilization and characteristics of patients being prescribed treatment in early stage RCC.
Authors: Robert Uzzo, Rituparna Bhattacharya, Manojkumar Bupathi, Aymen Elfiky, Alisha Monnette, Karen Todoroff, Paul R. Conkling, Murali Sundaram
Journal: Journal of Clinical Oncology (2025)

480 Background: In the United States, adjuvant pembrolizumab was approved on November 17, 2021, for patients with RCC with intermediate-high (T2N0M0-G4, T3N0M0, any grade) or high risk (T4, any grade; N+, any T, any grade; and M1NED patients) of recurrence following nephrectomy. This study aims to assess adoption of adjuvant pembrolizumab in routine practice and demographic and clinical characteristics of post nephrectomy RCC patients who received this therapy. Methods: This retrospective study included adult patients with non-metastatic localized RCC who underwent nephrectomy between November 17, 2021, and December 31, 2022, and were seen in the U.S. Oncology Network. Patients were excluded if they were treated for other documented primary cancer diagnoses or enrolled in clinical trials. Descriptive analyses were conducted to evaluate demographic, clinical, and treatment characteristics overall, and for patients who received adjuvant pembrolizumab monotherapy and those who did not. Multivariate logistic regression was used to identify factors associated with adjuvant pembrolizumab use. Results: In total, 178 patients were included. The mean age was 62 years (SD 11.8), with a majority being male (66.3%, n=118), and a median follow-up of 7.9 months (Q1,Q3: 4.1,9.8). The majority had intermediate-high risk (n=86, 57.5%), clear cell (cc) RCC (n=147, 82.6%) and received adjuvant pembrolizumab monotherapy (n=118, 66.3%). Among those who received adjuvant pembrolizumab, 90.7% had ccRCC, 62.5% were intermediate-high risk (T2N0G4: 8 (55.1%), T3N0 All Grades: 53 (44.9%)), 27.5% were N+ with a median follow-up of 8.3 (Q1, Q3: 6.0, 10.1) months. Median time to the start of adjuvant pembrolizumab post nephrectomy was 1.6 months (Q1, Q3: 1.3,2.1). The median time to treatment discontinuation was 11.5 months (Q1, Q3: 9.0, 11.5) (the recommended duration of treatment for adjuvant pembrolizumab is: 12 months at 17 cycles at 200mg/ Q3W or 9 cycles at 400mg/Q6W). Multivariate analysis showed that patients with non ccRCC histology were 93% less likely (p-value: &lt;0.0001) and those whose with first oncologist visit &gt;=2 months post nephrectomy were 60% less likely (p-value:0.035) to receive adjuvant pembrolizumab treatment. Conclusions: This study demonstrated notable uptake of adjuvant pembrolizumab among post-nephrectomy RCC patients in this community setting following FDA approval. RCC histology and the timing of oncologist visits post nephrectomy were significant factors influencing the receipt of adjuvant pembrolizumab. Future research should focus on examining referral patterns, and identifying the drivers and barriers to treatment adoption, with the goal of developing strategies to enhance its integration. Additionally, future research may explore long-term outcomes and real-world effectiveness of adjuvant pembrolizumab.
Impact of tumor burden on treatment patterns and outcomes in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) treated with avelumab first-line maintenance (1LM).
Authors: Helen Moon, Mairead Kearney, Seyed Hamidreza Mahmoudpour, Chiemeka Ike, Valerie A. Morris, Andrew Rava, Sonia Kim, Haiyan Sun, Allison Dillon, Marty Masek, Jocelyn Sun
Journal: Journal of Clinical Oncology (2025)

764 Background: With the evolving treatment (tx) landscape in la/mUC, patient (pt) clinical characteristics are increasingly important when selecting systemic anticancer tx. This study describes pt characteristics, tx patterns, and clinical outcomes by tumor burden in pts with la/mUC treated with avelumab 1LM following 1L platinum-based chemotherapy (PBC) with no progressive disease (PD). Methods: In this noninterventional retrospective study, pts with la/mUC were identified using Flatiron Health’s electronic health record database. Inclusion criteria were pts aged ≥18 years diagnosed with la/mUC between Jan 1, 2019, and Jul 31, 2023, treated with 1L PBC with no PD, followed by avelumab 1LM on/after Jul 1, 2020. Pt characteristics at 1LM initiation, tx patterns, and real-world overall response rate (rwORR) were reported using descriptive statistics. Real-world overall survival (rwOS), progression-free survival (rwPFS), time to next tx (TTNT), and time to tx discontinuation (TTD) were assessed using Kaplan-Meier methods. Subgroup analyses by disease burden were conducted reported: visceral (bone and other visceral) vs nonvisceral metastases (bone only) and lymph node only (includes distant lymph node) vs distant metastases. Results: Of 290 pts included, 156 (53.8%) were still receiving avelumab 1LM at data cutoff (Jul 31, 2023). Median age was 71 years; most pts were male (75.9%), White (70.7%), and had ECOG performance status 0/1 (78.3%). Median follow-up from 1LM initiation was 8.7 months. Among 266 pts with metastases, these were visceral in 142 (53.4%), nonvisceral in 124 (46.6%), distant in 183 (68.8%) and lymph node only in 83 (31.2%). 1L PBC was cisplatin-based in 52.4% and carboplatin-based in 47.6%. Median rwPFS and rwOS from avelumab 1LM initiation were 5.0 (95% CI, 3.9-5.8) and 22.0 (95% CI, 18.2-24.8) months, respectively. In pts with tumor assessment during avelumab 1LM (n=236), rwORR was 34.7%. Outcomes by disease burden are shown in the table. Conclusions: These results provide insights into clinical outcomes by tumor burden in pts with la/mUC treated with avelumab 1LM. Pts with nonvisceral and/or lymph node-only metastases had more favorable outcomes, consistent with the JAVELIN Bladder 100 trial. Outcome from 1LM start, median (95% CI), months Pts with metastases (n=266) Nonvisceral (n=124) Visceral (n=142) rwPFS 5.6 (4.1-7.8) 3.6 (3.1-5.0) rwOS 23.8 (15.4-NE) 19.1 (12.5-23.8) TTNT 6.6 (6.6-9.8) 6.0 (4.3-7.4) TTD 5.3 (4.2-10.1) 4.4 (3.5-5.7) Lymph node only (n=83) Distant (n=183) rwPFS 8.7 (5.0-NE) 3.6 (3.1-4.6) rwOS 24.3 (20.7-NE) 16.5 (12.5-22.6) TTNT 8.1 (6.2-23.8) 5.2 (4.3-6.7) TTD 10.1 (4.9-NE) 4.2 (3.3-5.5) NE, not estimable.
Impaired renal function and cisplatin-based regimens as risk factors for neoadjuvant chemotherapy-induced acute kidney injury in muscle-invasive bladder cancer: A multicenter retrospective study.
Authors: Naoki Fujita, Shogo Hosogoe, Toshikazu Tanaka, Noritaka Ishii, Masaki Momota, Hiroyuki Ito, Takahiro Yoneyama, Chikara Ohyama, Shingo Hatakeyama
Journal: Journal of Clinical Oncology (2025)

760 Background: Neoadjuvant chemotherapy (NAC)-induced acute kidney injury (AKI) is one of the frequent complications in patients with muscle-invasive bladder cancer (MIBC) and we previously have reported the negative impact of NAC-induced AKI on oncological outcomes. However, its risk factors remain unclear. Methods: This multi-institutional retrospective study included 517 patients with MIBC who received 2–4 cycles of NAC followed by radical cystectomy. AKI was defined according to the KDIGO criteria. Patients were divided into two groups: patients who developed any stage AKI during NAC (AKI group) and patients who did not (non-AKI group). Multivariable logistic regression analysis was performed to identify the risk factors for NAC-induced AKI. The predictive abilities for AKI were evaluated using the area under the receiver operating characteristic (ROC) curve. Results: The median age was 69 years. Of the 517 patients, 188 (36%) received cisplatin-based regimens and 92 (18%) developed any stage AKI. Approximately 86% AKI were stage 1 AKI. eGFR in the AKI group was significantly lower than that in the non-AKI group ( P &lt;0.001). The rate of AKI development in patients who received cisplatin-based regimens was significantly higher than that in patients who received carboplatin-based regimens ( P &lt;0.001). In the multivariable analysis, hypertension, impaired renal function, and cisplatin-based regimen were independently and significantly associated with increased risk of AKI (Table). The optimal cutoff value of estimated glomerular filtration rate for AKI was 65.0 mL/min/1.73m 2 . ROC analysis showed that the area under the curve (AUC) of hypertension plus eGFR &lt;65.0 mL/min/1.73m 2 plus cisplatin-based regimen was 0.748 (95% confidence interval: 0.697–0.799). Conclusions: Hypertension, impaired renal function, and cisplatin-based regimens were risk factors for NAC-induced AKI in patients with MIBC. Multivariable analysis for AKI development. Factor P value Odds ratio 95% CI Age Continuous 0.462 0.989 0.959–1.019 Hypertension Presence 0.016 1.894 1.128–3.179 eGFR Continuous &lt;0.001 0.955 0.939–0.971 Cisplatin-based regimens Positive &lt;0.001 6.530 3.725–11.45