tbuckley/cabot-search huggingface dataset:
Association of statin use with overall survival and cardiac adverse events in patients with advanced prostate cancer treated with apalutamide: A pooled analysis of TITAN and SPARTAN.
Authors: Zeynep Irem Ozay, Scott C. Morgan, Kim N. Chi, Eric J. Small, Shawn Malone, Christopher J.D. Wallis, Michael Ong, Amar Upadhyaya Kishan, Angela Y Jia, Nicholas George Zaorsky, Umang Swami, Yilun Sun, Daniel Eidelberg Spratt, Simon Chowdhury, Neeraj Agarwal, Fred Saad, Soumyajit Roy
Journal: Journal of Clinical Oncology (2025)

137 Background: The impact of statins on overall survival (OS) in patients (pts) with advanced prostate cancer is not fully understood. We performed a pooled analysis of the TITAN and SPARTAN trials to determine if exposure to statins had an independent effect on OS and grade ≥3 cardiac adverse events (AE) in pts treated with androgen deprivation therapy (ADT) with/without apalutamide (APA). Methods: TITAN and SPARTAN randomized pts to receive ADT with/without APA either in metastatic hormone-sensitive or in non-metastatic castration-resistant prostate cancer, respectively. Pts had at least some duration of statin exposure during the assigned treatment which could have started before and ended during or after the assigned treatment. A stratified (for the trial) multivariable Cox proportional hazard model was applied to determine the association of statin use with OS. Adjusted (adj) OS was estimated for pts in each trial, separately. A multivariable stratified logistic regression model was applied to determine the association of statin exposure with grade ≥3 cardiac AE. Results: Out of 2190 pts included in this study, 1288 received APA (TITAN 517; SPARTAN 771) and 484 were exposed to statins. Statin exposure was associated with significantly superior OS among all APA-treated pts (adjusted hazard ratio [HR]: 0.58; 95% CI: 0.45-0.75) while the OS benefit was not significant among ADT-treated pts (adjusted HR: 0.83 [0.62-1.11]). Adjusted 3-year OS in pts with and without statins were 82% and 67% (adjusted difference: 15%; 95% CI: 6-24) in the APA arm of TITAN and 86% and 78% (adjusted difference: 8% [3-13]) in the APA arm of SPARTAN. Adjusted 3-year OS among pts with and without statins was 71% and 58% (adjusted difference: 13% [3-24]) in the ADT arm of TITAN and 77% and 75% (adjusted difference: -2% [-10 to 6]) in the ADT arm of SPARTAN. Statin exposure was associated with a higher risk of grade ≥3 cardiac AE in pts treated with APA (adjusted odds ratio [OR]: 2.92 [1.56-5.47]) and ADT (adjusted OR: 3.06 [1.18-7.89]). Conclusions: In this exploratory analysis, exposure to statins was associated with significantly improved OS in all APA-treated patients but not in ADT-treated patients. Statin exposure was also associated with a higher risk of grade ≥3 cardiac AE in all pts (APA and ADT), which could be attributed to pre-existing cardiac comorbidities requiring these patients to start statin.
Reduction of systemic chemotherapy by primary retroperitoneal lymph node dissection in low volume metastatic seminoma.
Authors: David Pfister, Pia Paffenholz, Constantin Rieger, Axel Heidenreich
Journal: Journal of Clinical Oncology (2025)

626 Background: Still, standard treatment of low-volume metastatic semimoma is either systemic chemotherapy or radiotherapy. Both options are associated with significant acute and long-term toxicities including mortality due to secondary malignancies in long-term follow-up. We calculated the number of potentially unnecessary chemotherapy cycles per hundred patients undergoing primary RPLND or Chemotherapy. Methods: In long-term follow-up of the COTRIMS-trial, 34 (12%) patients developed outfield relapses after a median follow-up of 41 months. All relapsing patients were cured by salvage PEB-chemotherapy. The base of our calculation are 12 recurrences on 100 Pts compared to 100 patients receiving chemotherapy upfront. Short term side effects of chemotherapy are from a historic patient cohort. Results: 12 relapsing patients received 36 cycles of PEB instead of 300 cycles of chemotherapy if given as first-line treatment. Significant PEB-associated acute toxicities mostly affect haematoxicity with neutropenia in 4 and 37 patients, resp., and febrile neutropenia in 1.7 and 14 patients, resp.. Based on our previous studies (Paffenholz P et al., World J Urol 2019; 37:1907), thrombembolic venous or arterial events are expected in 1.2 and 0.8 , resp. versus 10 and 7 patients, resp.. Therapy associated mortality would be expected in 0.2 and 2 patients, resp.. No data on long-term toxicities are available. Conclusions: All patients with relapses after primary RPLND can be cured by salvage chemotherapy. The number of chemotherapy cycles can be reduced by 88% without impairing oncological efficacy if surgery is performed in an experienced reference center. Thus overall acute toxicity rate affecting patients quality of life and even treatment associated deaths can be reduced dramatically. Although the reduction of long-term toxicities associated with cytotoxic therapy cannot be anticipated today, we strongly recommend to include primary nsRPLND in the therapeutic armentarium of clinical stage IIA/B seminomas.
Impact of adherence to a remote exercise program on health-related quality of life in prostate cancer patients undergoing treatment: A prospective study in Brazil.
Authors: Paulo Gustavo Bergerot, Cristiane Decat Bergerot, Jonas Ribeiro Gomes Silva, Marcos V S Franca, Dr. Paulo Sergio Lages, William Hiromi Fuzita, Enrique Soto Pérez de Celis, Narjust Florez, Kathryn H. Schmitz, Sumanta Kumar Pal
Journal: Journal of Clinical Oncology (2025)

130 Background: Patients with metastatic prostate cancer (mPCa) undergoing treatment often experience declines in health-related quality of life (HRQoL) and increased symptom burden. Exercise interventions are known to mitigate these effects, but adherence to such programs remains a challenge. This study aimed to assess the impact of adherence to a remote, home-based exercise program on HRQoL and symptom burden among patients with mPCa in a joint cancer practice in Brazil. Methods: This prospective study recruited patients with mPCa undergoing active treatment for both hormone sensitive and hormone resistant disease. Patients were assessed at baseline (T1) and after 12 weeks (T2) using the Functional Assessment of Cancer Therapy-General (FACT-G; scale: 0-108) and the Edmonton Symptom Assessment System (ESAS; scale: 0-90). Eligible participants received weekly exercise guidance through WhatsApp and performed prescribed exercise regimens (3 to 5 hours per week of combined resistance and aerobic training), with proper techniques demonstrated using the Vedius platform. Adherence was categorized as moderate to high (MH) ≥6 weeks of exercise, or low (L) ≤5 weeks. The primary outcomes included changes in HRQoL and symptom burden. Results: A total of 35 patients were recruited. The median age of participants was 74 years (range 58-91), with a majority being white (65.7%), married (82.9%), highly educated (88.6%), and retired (85.7%). All patients were receiving ADT plus abiraterone (34.3%), or docetaxel (25.7%), or enzalutamide (22.8%), or chemotherapy + abiraterone (14.3%). At 12 weeks, patients with moderate to high adherence demonstrated significant improvements in HRQoL (MH Mean T2 =94.9, L Mean T2 =88.7, P=0.01), particularly in physical (MH Mean T2 =25.1, Mean T2 =23.6, P=0.03), functional (MH Mean T2 =22.8, L Mean T2 =20.7, P=0.03), and emotional (MH Mean T2 =22.2, L Mean T2 =20.28, P=0.03) well-being domains, compared to those with low adherence. Additionally, those with higher adherence reported a lower symptom burden (MH Mean T2 =9.1 vs L Mean T2 =14.7, P=01). Conclusions: This study demonstrates that adherence to a remote exercise program significantly improves HRQoL and reduces symptom burden in patients with prostate cancer undergoing treatment. These findings underscore the importance of promoting exercise adherence through accessible platforms, such as WhatsApp, to enhance patient outcomes in mPCa.
Patient perceptions about their treatment for muscle-invasive bladder cancer (MIBC) over the last decade.
Authors: Deepro Chowdhury, Andrea B Apolo, Di Maria Jiang, Eila C. Skinner, Stephanie Chisolm, Rick Bangs, Manjula Maganti, Gary D. Steinberg, Matthew Kaag, Jason A. Efstathiou, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2025)

765 Background: The Bladder Cancer Advocacy Network (BCAN) is a national patient advocacy organization that has promoted awareness about the signs, symptoms, diagnosis, treatment and need for a multidisciplinary approach to the care of patients with MIBC. To better understand the impact of these efforts, and patients’ perceptions of their care, we surveyed bladder cancer patients initially in 2013 and again in 2023 through the BCAN website. Methods: We developed a 32-question survey with input from physicians, nurses, patients and caregivers. The survey was posted on the BCAN website 06/13-10/14 (Cohort A) and again from 06/23-04/24 (Cohort B). Questions focused on time from initial symptoms to diagnosis and treatment; proportion seeing a medical oncologist (MO) or radiation oncologist (RO); and treatments offered/received. Results: Overall, 337 (243 and 94) patients completed the survey. Respondents were self-selected and most were from the US/Canada, male, white, and had at least an undergraduate education. Median age was 61 (cohort A; range 31-93) and 63 (cohort B; range 38-87), respectively, at the time of diagnosis. The most common presenting symptom was hematuria (88% vs 78%, p=0.05). Overall, 35% vs 30% (p=0.56) waited &gt; 3 months to seek medical attention; in 38% and 43% it took &gt; 3 months to obtain a pathologic diagnosis (p=0.76). Men were more likely than women to be diagnosed within 1-2 months of seeking medical attention: Cohort A (68% vs 47% p=0.03) and Cohort B (70% vs 37%, p=0.03). In both cohorts, prior to surgery, approximately 50% saw a medical oncologist and were offered neoadjuvant chemotherapy; however, less than 10% saw a radiation oncologist and were offered bladder sparing approaches. Most patients reported having all the necessary information, knowing the right questions to ask, and were satisfied with their choices. A higher proportion in Cohort A vs Cohort B felt they had enough time to make their decisions (77% vs 67%, p=0.004). Conclusions: Despite nearly two decades of advocacy, there are ongoing areas of unmet need in MIBC. These include reducing time to definitive diagnosis and treatment, especially in women, and increasing multidisciplinary assessments prior to definitive surgery. Respondents were self-selected, had access to the BCAN website, and were highly educated, potentially limiting the generalizability of these results.
Evaluating the spectrum of disease within Gleason grade group 3: Results from a large institutional cohort.
Authors: Kevin Shee, Janet E Cowan, Lufan Wang, Chien-Kuang Cornelia Ding, Samuel L Washington, Katsuto Shinohara, Hao Nguyen, Matthew R. Cooperberg, Peter Carroll
Journal: Journal of Clinical Oncology (2025)

361 Background: A biopsy diagnosis of Gleason Grade Group (GG) 3 prostate cancer (PCa), also known as Gleason 4+3, automatically risk stratifies patients into at least unfavorable intermediate-risk by major guidelines including the AUA and NCCN, for which definitive treatment such as surgery or radiation is warranted. We hypothesized that GG3 prostate cancers represent a spectrum of disease, and that there may be GG3 PCa patients with lower risk of disease that may benefit from more conservative management. Methods: The Urologic Outcomes Database (UODB) at the University of California San Francisco (UCSF) was queried for men with localized, non-metastatic PCa diagnosed after 2000 who underwent radical prostatectomy (RP). Pre-biopsy clinicodemographic factors and biopsy and surgical pathology data were obtained, and Cancer of the Prostate Risk Assessment (CAPRA) and post-surgical CAPRA (CAPRA-S) scores were calculated. Outcomes were recurrence after surgery, defined as either biochemical failure (two PSA ≥0.2 ng/ml) or second treatment, and development of new metastasis. Multivariable Cox proportional hazards regression models were used to calculate associations with risk of recurrence and development of metastases, adjusting for year of diagnosis, age at diagnosis, percentage of positive biopsy cores (PPC), PSA density (PSAD), PSA before RP, Gleason pattern 4 histology, genomic risk score, prostate MRI findings, with or without CAPRA-S. Results: 5262 men from the UODB database who underwent RP were included in the study. Of these, 904 (17%) men were diagnosed with GG3 on diagnostic biopsy. The number of GG3 diagnoses over time increased from 8.5% between 2000-2004 to 27% between 2020-2023. Among patients with initial diagnoses of GG3, pathologic GG after RP showed an increasing proportion of patients with upgrade to ≥GG4 and a decreasing proportion of patients with downgrade to &lt;GG3 over time. Post-RP CAPRA-S scores overall increased over time, but remained broadly distributed. On multivariable analysis, favorable biopsy Gleason pattern 4 histology was strongest pre-operative factor associated with decreased recurrence after RP (HR 0.54, 95% CI 0.35-0.85, p&lt;0.01). Increased PPC was the only factor associated with risk of metastasis after RP (HR 1.13, 95% CI 1.00-1.27, p=0.04). Conclusions: Patients with GG3 on diagnostic biopsy are a heterogenous group, with post-surgical grade and risk scores both broadly distributed and increasing over time. These data suggest that certain GG3 patients, such as those with favorable biopsy histology and lower PPC, may not be as unfavorable as guidelines suggest and may benefit from more conservative management.
Molecular evolution of HRR gene alterations in metastatic prostate cancer: A ctDNA-based study.
Authors: Chinmay Jani, Eli Tran, Nicole Zhang, Jill Tsai, Jianjie Dong, Elizabeth Pan, Justine Panian, Rana R. McKay
Journal: Journal of Clinical Oncology (2025)

255 Background: Homologous recombination repair (HRR) genes, including DNA repair genes, are increasingly recognized for impacting treatment resistance and prognosis of metastatic prostate cancer (mPC). Next-generation sequencing of circulating tumor DNA (ctDNA) enables non-invasive, longitudinal monitoring of molecular alterations in patients (pts) undergoing systemic therapies. This study explores the dynamic changes in ctDNA profiles in mPC, particularly focusing on the HRR alterations. Methods: We utilized GuardantINFORM, a clinical-genomics database containing de-identified ctDNA test results and commercial payer-claims data. Eligible pts had a diagnosis of mPC and underwent ctDNA testing pre (within 3 months before initiation) and post (within 3 months of discontinuation before initiating subsequent treatment) Androgen Receptor Pathway Inhibitors (ARPi), poly ADP-ribose polymerase inhibitors (PARPi), and taxane chemotherapy. Mann-Whitney test assessed the differences in mutations. We also examined the association between ctDNA burden and overall survival (OS). Results: From a database of 21,682 pts with mPC, 145 had ctDNA collected pre/post-ARPi, 54 pre/post PARPi and 115 pre/post taxane chemotherapy. Pre-to-post-ARPI, individual HRR alterations increased from 21 to 34, with the most common (%pre/%post) genes to be altered, including ATM (5.5/7.6), BRCA2 (3/6) and CDK12 (3/2). In the PARPi group, the most prevalent (%pre/%post) genes to be altered were ATM (28/22), BRCA2 (28/20) and BRCA1 (4/6). Although overall BRCA2 prevalence declined, 11 new unique alterations were detected post-PARPi, along with an increase in unique BRCA1 (2 to 4) and BRCA2 (16 to 21) alterations. Three of 25 patients (12%) who underwent serial testing pre- and post-PARPi exhibited BRCA reversion mutations. In the taxane group, notable (%pre/%post) HRR genes to be altered included ATM (4/3), BRCA1 (1/3), and BRCA2 (1/3). Patients with higher ctDNA burden in pre-treatment samples exhibited worse OS. Conclusions: This study reveals dynamic changes in HRR gene alterations in mPC using ctDNA profiling. We observed increased unique alterations in ATM, BRCA1, and BRCA2 post-treatment, along with BRCA reversion mutations, indicating potential treatment resistance mechanisms. These findings underscore the importance of tailoring therapeutic approaches based on HRR gene profiles in mPC.
Association between post-orchiectomy systemic inflammatory indexes and tumor characteristics in clinical stage I germ cell tumours.
Authors: Peter Lesko, Michal Mego
Journal: Journal of Clinical Oncology (2025)

643 Background: Approximately 25-30% of clinical stage I (CSI) GCT patients will experience disease relapse after orchiectomy. Adding adjuvant treatment will decrease relapse rate, however, on the contrary leads to over-treatment. Prognostic biomarkers such as lymph-vascular invasion (LVI) and/or embryonal carcinoma (EC) in non-seminoma (NSGCT) and rete testis invasion (RTI) and/or primary tumor size (PTS) in seminoma (SGCT) add limited value in treatment decision making. The aim of this study is to assess systemic inflammatory (SI) indexes and lactate-dehydrogenase (LDH) with clinico-pathological findings along with their prognostic impact. Methods: This is retrospective study, which included 159 diagnosed CSI GCT patients, who underwent active surveillance (AS) from June 2004 to November 2023. Medical records and pathology reports were collected retrospectively. Blood drawn must have been done less than 3 months since orchiectomy had been done. For survival analysis we used dichotomized values of studied biomarkers to “low” and “high” based on median value. Results: Median follow-up was 61 months (ranging from 1-230 months), with 2-years relapse free survival (RFS) 81.3% and 69.0% in SGCT and NSGCT respectively. We confirm inferior RFS among LVI presence compared to LVI absence in NSGCT ([HR]= 2.59, 95%CI (0.74-9.07), p=0.04). Trend to inferior RFS in NSGCT patients with EC predominance (≥50%) was observed as well ([HR]= 2.59, 95%CI (0.98-6.85), p=0.06). Prognostic impact of RTI and PTS(&gt;4cm) in SGCT was not observed, p=0.24 and p=0.51, respectively. SI indexes were assessed among population, where higher neutrophil to lymphocyte ratio (NLR) value was associated with LVI presence and with advanced tumor stage in NSGCT. In SGCT, higher systemic inflammatory index (SII) level was associated with LVI presence as well as with advanced pathological stage. PTS (&gt;4cm) was associated with higher LDH level among cohort of all studied patients, without significance among SGCT nor among NSGCT. Higher LDH value in NSGCT was also associated with EC predominance (≥50%). Conclusions: Our study for the first-time revealed associations of post-orchiectomy systemic inflammatory indexes and/or LDH in CSI GCT. Those new associations deserve further evaluation on larger cohort of CSI GCT to elucidate, whether, its associations in certain histology subgroups will improve stratification of risky population.
Interpretable machine learning for prostate biopsy: Cohort study.
Authors: Jindong Dai, Jinge Zhao, Pengfei Shen, Hao Zeng
Journal: Journal of Clinical Oncology (2025)

333 Background: The objective of this study is to develop prediction models and provide diagnostic results for prostate biopsy among patients. Methods: This paper presents an improved tree model, called the Light gradient boosting machine model, for building a prostate cancer (PCa) risk prediction model. The research data used in this study (Waves 2008-2022) are obtained from 1987 patients who underwent transperineal biopsy at West China Hospital. All patients had biopsy indications (high levels of prostate specific antigen (PSA), suspect lesions in magnetic resonance imaging (MRI) suspect lesions). A total of 13 baseline variables were considered as candidate features, and eight machine learning models were compared in the experiment. Shapley additive explanations (SHAP) was used for explaining the prediction model. Results: The Light gradient boosting machine model demonstrated the best performance, achieving an area under the receiver operating characteristic (ROC) curve of 0.76 (CatBoost=0.71, KNN=0.65, LDA=0.61, CART=0.67, SVM=0.64, NB=0.55, XGBoost=0.71). According to the interpretable analysis, the apparent diffusion coefficient (ADC) of MRI was identified as the most important feature in the prediction model. Other important features included prostate volume, red blood cell count, neutrophil count, and platelet count. Conclusions: This study suggests that optimal models show promise in screening out patients at high risk for PCa in prostate biopsies. The decisions regarding prostate biopsies should specifically focus on the ADC of MRI, prostate volume, and blood routine indices such as RBC count, platelet count, and neutrophil count. Baseline characteristic of all patients. Mean (SD) Pca (n=1001) Non-Pca (n=986) P Age (years) 68.68(9.29) 67.99(9.32) 0.901 Blood routine RBC (10 12 /L) 4.66(0.62) 4.65(0.61) 0.56 Hemoglobin (g/L) 141.46(19.72) 141.84(17.21) 0.149 Platelet (10 9 /L) 188.49(64.65) 193.46(69.12) 0.02 WBC (10 9 /L) 6.76(6.36) 6.6(1.95) 0.56 Neutrophil count (10 9 /L) 4.15(1.52) 4.19(1.71) 0.026 Lymphocyte count (10 9 /L) 1.89(5.73) 1.75(0.76) 0.405 Monocyte count (10 9 /L) 0.48(0.16) 0.47(0.17) 0.626 Eosinophil count (10 9 /L) 0.16(0.16) 0.15(0.16) 0.781 Basophil Cell Count (10 9 /L) 0.25(1.21) 0.36(1.47) &lt;0.001 PSA (ng/ml) 65.02(346.16) 11.32(23.01) &lt;0.001 Prostate volume (ml) 43.96(27.66) 51.24(26.85) 0.007 PSAD (ng/ml 2 ) 1.82(12.88) 0.28(0.544) 0.001 ADC 733.13(172.09) 756.93(181.31) 0.004