tbuckley/cabot-search huggingface dataset:
The prognostic significance of circulating tumor DNA in prostate cancer: A systematic review and meta-analysis.
Authors: Haolin Liu
Journal: Journal of Clinical Oncology (2025)

214 Background: Circulating tumor DNA (ctDNA) has attracted increasing interest as a biomarker in multiple cancers. This study aimed to perform a systematic review and meta-analysis to evaluate the prognostic value of ctDNA in prostate cancer (PCa). Methods: An electronic search of PubMed, Embase, and the Cochrane library was conducted to identify eligible studies. Hazard ratios (HRs) and corresponding 95% confidence intervals (95%CIs) for progression-free survival (PFS) and overall survival (OS) were extracted for pooled analysis. Data were pooled using a fixed-effects or random-effects models based on the study heterogeneity. Subgroup analyses were performed according to disease status, study design, treatment regimen, and sequencing method. R software (version 4.2.2) was used for statistical analysis. Results: A total of 13 studies comprising 1946 patients with PCa were included. The pooled analysis showed that higher baseline ctDNA levels were associated with shorter PFS (HR 2.88, 95%CI 1.98-4.19, P&lt;0.001) and OS (HR 2.57, 95%CI 1.66-3.97, P&lt;0.001) in overall PCa patients. Subgroup analysis further indicated that the prognostic value of ctDNA levels remained consistent across different study designs, systemic treatment regimens, and sequencing methods. Additionally, elevated ctDNA levels were significantly correlated with shorter PFS (HR 2.56, 95%CI 1.69-3.87, P&lt;0.001) and OS (HR 2.76, 95%CI 1.76-4.33, P&lt;0.001) in the metastatic castration-resistant prostate cancer (mCRPC) setting. Conclusions: Our systematic review and meta-analysis demonstrated that higher ctDNA levels were associated with poorer survival outcomes in patients with PCa, suggesting that ctDNA may serve as a valuable prognostic biomarker in PCa.
Boosting survival in advanced urothelial carcinoma: The power of CBM588 probiotic and pembrolizumab combination.
Authors: Hirofumi Yoshino, Hideki Enokida
Journal: Journal of Clinical Oncology (2025)

774 Background: Immune checkpoint inhibitors (ICIs) is now standard cares for locally advanced or metastatic Urothelial Carcinoma (UC). One of the probiotics, CBM588 (MIYAIRI 588), is widely used in clinical practice and regulates the intestinal microbiota. Recently, the relationship between ICIs and probiotics in cancer therapy has attracted attention with prolonged prognosis reported in lung and renal cancers when combined with CBM588. However, there are no reports on the usefulness in UC. Methods: We retrospectively evaluated the effect of pembrolizumab plus CBM588 in patients with unresectable UC treated with pembrolizumab as second-line therapy at our institution, with and without CBM588. The analysis was divided into two groups: those taking CBM588 (n=33) and those not taking CBM588 (n=11) at the time of pembrolizumab initiation. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. Results: The median follow-up was 12.0 months in the pembrolizumab alone group versus 12.2 months in the CBM588 group. The median PFS was 3.9 months in the pembrolizumab alone group versus 10.2 months in the CBM588 group. On multivariate analysis, the hazard ratio for the CBM588 arm was 0.074. The median OS was 12.2 months in the CBM588 arm versus 12.0 months in the pembrolizumab alone arm. On multivariate analysis, the hazard ratio for the CBM588 arm was 0.105 (95% CI 0.022-0.533, P=0.0056). Conclusions: The combination of CBM588 with pembrolizumab may prolong progression in UC. Although the sample size and follow-up period are limited, the positive outcomes observed emphasize the necessity for further studies to confirm these findings and investigate the underlying causes. Multivariate analysis of PFS and OS. Multivariate Analysis-PFS Multivariate Analysis-OS Variables Groups Hazard ratio 95% CI P-value Hazard ratio 95% CI P-value Treatment PEM reference reference PEM with CBM588 0.074 0.016-0.340 0.0008 ** 0.105 0.022-0.533 0.0056 * Age 0.947 0.901-0.995 0.030 * 0.992 0.944-1.043 0.738 Sex male reference reference female 1.410 0.546-3.643 0.4786 0.717 0.292-1.985 0.513 ECOG-PS 0 - 1 reference reference 2 - 4 0.338 0.136-0.837 0.0191 * 1.067 0.400-2.712 0.894 Tumor location (primary) Lower urinary tract reference reference Upper urinary tract 1.455 0.577-3.662 0.426 0.666 0.228-1.986 0.461 T stage (primary) 0 - 2 reference reference 3 3.634 1.340-9.835 0.011 * 1.210-8.763 0.019 * unknown 7.623 1.291-45.00 0.025 * 6.368 1.069-37.93 0.042 * N stage 0 reference reference 1 0.976 0.380-2.505 0.958 1.328 0.521-3.389 0.552 M stage 0 reference reference 1 1.407 0.298-6.652 0.666 1.579 0.313-7.944 0.579 Lung metastasis 1 0.871 0.297-2.55 0.801 0.497 0.151-1.633 0.249 Liver metastasis 1 5.465 1.516-19.70 0.0094 * 2.889 0.735-11.34 0.129 Bone metastasis 1 1.841 0.608-5.57 0.280 1.447 0.445-4.703 0.539 IrAE 1 0.133 0.03-0.586 0.0077 ** 0.277 0.056-1.359 0.114 *p &lt; 0.05; **p &lt; 0.008.
Survival in advanced prostate cancer (PCa) patients with visceral metastasis: A population-based SEER study.
Authors: Salman Ayub Jajja, Syed Arsalan Ahmed Naqvi, Muhammad Ali Khan, Muhammad Umar Afzal, Muhammad Umair Anjum, Ammad Raina, Prateek Jain, Fnu Swati, Zaryab Bin Riaz, Daniel S Childs, Ewan Kemar Cobran, Alan Haruo Bryce, Yousef Zakharia, Parminder Singh, Irbaz Bin Riaz
Journal: Journal of Clinical Oncology (2025)

134 Background: Prostate cancer patients with visceral metastases at diagnosis are often treated using one-size-fits-all approach. For example, CHAARTED criteria treats any visceral metastasis as high volume. Therefore, we aimed to assess overall survival (OS) by site of visceral involvement in patients with metastatic PCa. Methods: Surveillance, Epidemiology, and End Results (SEER) database (2010-2021) was queried to obtain case listing data on metastatic PCa patients from 17 registries. The patients were categorized into three groups based on visceral metastasis at diagnosis: lung metastasis, liver metastasis, and others. Kaplan-Meier survival analysis was performed to estimate median OS with 95% confidence interval (CI). Log-rank test was conducted to assess if survival was significantly different among the groups. Cox proportional hazard regression analysis was performed to assess the magnitude of difference among the groups. P-value &lt;0.05 established statistical significance. Results: This analysis included 21,007 metastatic PCa patients (lung: n=319; liver: n=123; brain: 107; bone: 20538). Metastatic PCa population with lung metastasis exhibited a median OS of 60 months (95% CI: 48-72) compared to 24 months (95% CI: 12-36) in population with liver metastases and to 36 months (95% CI: 36-36) in population with other metastases. The difference in OS among the groups was statistically significant (p &lt; 0.001). Compared to population with lung metastasis, those with liver (HR: 1.91; 95% CI: 1.41-2.57) but not those with other metastases (1.16; 0.97-1.39) had significantly worse OS adjusting for Gleason score, PSA and race (Table). Conclusions: In metastatic PCa, patients with lung-only metastasis have significantly better overall survival and should be considered differently in prognostication to liver metastases. Consideration of site of visceral metastasis is critical for treatment intensification decisions. Limitations of this analysis include lack of accounting for confounding relationships at individual patient level. Variable Hazard Ratio (95% CI) Metastases (Lung) REFERENCE Metastases (Liver) 1.91 (1.41-2.57) Metastases (Other) 1.16 (0.97-1.39) Gleason score≥8 REFERENCE Gleason score &lt;8 0.68 (0.64 -0.72) PSA - ng/dL 1.01 (1.00 – 1.01) Race (White) REFERENCE Race (Black) 0.99 (0.94 – 1.05) Race (Asian or Pacific Islander) 0.70 (0.64 – 0.76)
Clinicopathological characteristics of cancer of unknown primary (CUP) with renal profile using gene expression profiling (GEP) based cancer classification.
Authors: Joelle Allam, Li Ma, Jianping Zhao, Jeannelyn Estrella, Victoria Higbie, Anneleis Willett, Aurelio Matamoros, Elizabeth A Lano, Kai Treuner, Kanwal Pratap Singh Raghav, Ryan W Huey
Journal: Journal of Clinical Oncology (2025)

456 Background: CUP is a rare and heterogenous clinicopathologic syndrome with unidentifiable origin at time of diagnosis. Based on immunophenotyping, specifically PAX8 staining, CUP with Renal profile (RCUP) is emerging as a distinct clinical subset. In addition to clinical presentation and immunohistochemistry (IHC), molecular profiling for tissue of origin may aid defining CUP subsets. Precision in diagnosis impacts therapeutics given that cytotoxic chemotherapy options for CUP do not overlap with tyrosine kinase inhibitors or checkpoint inhibitors used for renal cell carcinoma. Methods: We retrospectively (2018-2022) evaluated patients with CUP composed of cases (renal profile, N=100, clear cell or papillary) or controls (non-renal, N=200) identified using the 92-gene assay (CancerTYPE ID), a validated classifier for predicting tissue of origin. Clinicopathologic data including IHC and molecular profiling results were collected using pathology specimens and reports. Results: Baseline characteristics (age, gender, tumor grade) of cases and controls were comparable, except for histology, wherein adenocarcinoma was less common with RCUP (27% vs 48%, p&lt;0.001). Median number of IHC stains performed was 11 (range 0-30) vs 9 (0-29) (p=0.04) in RCUP vs non-renal cases, respectively. While PAX8 was tested in 64% vs 39% (p&lt;0.001) of cases, it was found to be strongly or focally positive in 87.5% vs 21.8% (p&lt;0.001), respectively. In contrast to non-renal CUP, RCUP patients were more likely to have bone biopsies (24% vs 11.5%, OR 2.4, p=0.007), less likely to have high-TMB (2.8% vs 28.2%, OR 0.07, p=0.001), and had a lower proportion of TP53 mutations (18.8% vs 89.2%, OR 0.028, p&lt;0.001), KRAS mutations (13.3% vs 77.4%, OR 0.045, p&lt;0.001) and BRAF mutations (0% vs 42%, OR 0, p=0.015). Conclusions: RCUP appears to be a distinct subset of CUP with variable diagnostic workup. Critical IHC markers may be omitted in a considerable number of cases and despite positivity, may still confer an uncertain diagnosis. Key molecular factors appear to be different and may require tailored therapeutic approaches. This study further supports the clinical utility of GEP-based cancer classification with the 92-gene assay to predict RCUP and may be an important adjunct to IHC to improve diagnostic accuracy for CUP and to guide treatment selection for better clinical outcomes. RCUP (N=100) Non-renal CUP (N=200) IHC Cases Tested (%) Cases Positive (%) Cases Tested (%) Cases Positive (%) CK7 83 47 81 75* CK20 75 11 77 24* PAX8 64* 88* 39 22 Napsin 29 28* 25 8 RCC 26* 31 4 13 Vimentin 17 94 5.5 73 *Significantly (p&lt;0.05) greater proportion of cases.
Clinical utility of measuring steady-state plasma level of lenvatinib in advanced renal cell carcinoma.
Authors: Sang Yoon Kim, James Checkley, Mirjana Radovanovic, Peter Galettis, Alison Yan Zhang, Howard Gurney
Journal: Journal of Clinical Oncology (2025)

486 Background: As a multitarget tyrosine kinase inhibitor, lenvatinib (LEN) efficacy and toxicity are dose-dependent, and dose adjustment is common for toxicity. A therapeutic level of LEN has not been defined in renal cell carcinoma (RCC), leading to uncertainty whether the patient is on an effective dose. LEN is also widely used in combination with immune checkpoint inhibitor (ICI), adding complexity due to overlapping toxicity. In this investigator-initiated study, we aimed to assess: A) inter- and intra-patient variability in LEN steady-state plasma level (C ss ) after dose adjustment for target toxicity; and B) associations between C ss and health-related quality of life (HRQoL) outcomes and treatment-related toxicity (trAE). Methods: Patients on LEN for advanced RCC underwent C ss assessment – first when LEN dose was stable after adjusting for target of CTCAE grade 1 to 2 toxicities for at least 6 weeks prior; and another 6 weeks or more later to assess for intra-patient variation. HRQoL and trAE data were collected at the time of phlebotomy. Additional C ss samples were taken when patients required dose interruption due to significant trAE, as determined by the treating clinician. Bivariate linear regression model was used to analyse association between C ss and HRQoL (EORTC-QLQ-C30 Summary Score and QL2 domain), plus C ss and CTCAE Composite Score (CTCAE grade multiplied by number of days the event was present during preceding 30 days). Results: Between Apr 2023 – Jun 2024, 47 plasma samples from 19 RCC patients were collected and analysed. Patients were predominantly male (95%; 18/19) with clear cell subtype (74%; 14/19). At time of first sample collection: 13/19 (68%) patients have been on their LEN dose for more than 6 months (median time on dose 348 days), and 14/19 (79%) patients were on combination systemic therapy (10 with ICI; 1 with belzutifan; 3 with ICI+belzutifan). The median daily LEN dose was 14 mg (range 8-20). Median C ss was 17.9 µg/L (interquartile range, IQR, 14.3-23.0). The median intra-patient variation was low at 1.09% (IQR -11.9 to 11.9%). Moderate correlation was observed between C ss and QLQ-C30 Summary Score reflecting overall symptom burden (b= -0.713, R 2 =0.387, p&lt;0.0001). Similar correlation was also observed between C ss and QLQ-C30 QL2 domain reflecting global health status (b= -1.20, R 2 =0.456, p&lt;0.0001). There was little correlation between C ss and CTCAE Composite Score (b= 2.06, R 2 =0.105, p=0.030). Conclusions: LEN C ss after dose adjustment for a target toxicity showed minimal intra-patient variation. Our study indicates that after dose adjustment, LEN C ss correlates with patient-reported symptom burden and global health status. Future prospective studies to evaluate recommended therapeutic range, and integration of therapeutic drug monitoring in real-world clinical settings may ensure patients are receiving an effective dose.
Tislelizumab in combination with abiraterone/enzalutamide for metastatic castration-resistant prostate cancer with intraductal adenocarcinoma of the prostate after progression on prior androgen receptor pathway inhibitor.
Authors: Qiyu Zhu, Jinge Zhao, Pengfei Shen, Ming Zhang, Qian Wang
Journal: Journal of Clinical Oncology (2025)

TPS299 Background: Intraductal adenocarcinoma of the prostate (IDC-P) serves as an aggressive pathological pattern of prostate cancer. Previous retrospective study suggested limited therapeutic response of chemotherapy and androgen depriving therapy for patients with IDC-P. No standard of care treatment options are established for this type of tumor. IDC-P was characterized by genomic instability, high homologous recombination repair (HRD) scores and mutational enrichment of mismatch repair (MMR) pathway, which are predictive for response to immune checkpoint inhibitor. Tislelizumab, an investigative anti-PD-1 antibody, has demonstrated disease stabilization capacity to multiple advanced tumors. Thus in this study, we aim to investigated the efficacy and safety of tislelizumab in combination with androgen receptor pathway inhibitor (ARPI) in metastatic castration-resistant prostate cancer patients (mCRPC) after failure of first-line novel hormone therapy regimens. Methods: This is a phase II, multisite, open label study with one cohort. Eligible patients must have pathologically confirmed IDC-P. Patients with any component of neuroendocrine tumor are ineligible. Patients must have received one prior type of novel hormone therapy (e.g., abiraterone, enzalutamide) in mCRPC stage . Patients receiving chemotherapy in the mCRPC stage are excluded. Participants will receive tislelizumab 200mg IV every 21 days in combination with ARPI change (abiraterone 1000 mg PO QD+ prednisone 5 mg PO BID/enzalutamide 160 mg PO QD) for four cycles. The primary endpoint is prostate specific antigen progression-free survival (PSA-PFS) and radiographic PFS (rPFS), with key secondary endpoints including PSA response and overall survival (OS). Exploratory objectives include analyzing DNA and RNA sequencing of tumors, and measurement of ctDNA and TMB. Clinical trial information: ChiCTR2400085267 .
Integrating aggressive variant prostate cancer–associated tumor suppressor genes (AVPC-TSG) status to refine prognosis and predict androgen-receptor pathway inhibitors (ARPI) response in metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Martino Pedrani, Giuseppe Salfi, Sara Merler, Irene Testi, Chiara Maria Agrippina Clerici, Luis Castelo-Branco, Luigi Tortola, Fabio Turco, Ursula Vogl, Jean-Philippe Theurillat, Silke Gillessen, Ricardo Pereira Mestre
Journal: Journal of Clinical Oncology (2025)

243 Background: Alterations in AVPC-TSG (TP53, RB1, PTEN) are related with androgen insensitivity and aggressive disease. However, their role in mHSPC prognosis and treatment guidance is unclear. This retrospective study assesses the value of AVPC-TSG alterations in refining prognosis and predicting ARPI benefit in mHSPC. Methods: We included 158 mHSPC patients with available genomic tumor sequencing analysis undergoing treatment between 2013 and 2023. We compared patients with AVPC-TSGalt tumors (defined by ≥1 alterations in the TP53 gene, RB1 gene, or PTEN/PI3K/AKT pathway genes) to those without (AVPC-TSGwt tumors). Cox analyses were performed for progression-free survival (PFS) and overall survival (OS). Results: AVPC-TSGwt status was associated with improved PFS and OS in both univariate and multivariate (MV) analyses (MV PFS: HR 0.58, p=0.012; MV OS: HR 0.48, p=0.025). AVPC-TSGalt mHSPC patients seemed to derive no PFS benefit (PFS: HR 1.13, p=0.721) from the addition of an ARPI to ADT, while AVPC-TSGwt mHSPC patients did (PFS: HR 0.51, p=0.029). Integrating AVPC-TSG status with CHAARTED volume criteria enhanced prognostic and predictive discrimination in mHSPC. Three distinct subgroups were identified: "good-risk" (AVPC-TSGwt and low-volume), "intermediate-risk" (either AVPC-TSGalt or high-volume), and "poor-risk" (AVPC-TSGalt and high-volume) with median PFS of 46.8, 28.2, and 15.7 months, respectively. Among them, only the "intermediate-risk" subgroup seemed to derive PFS benefit (HR 0.36, p=0.002) from addition of an ARPI. Conclusions: Integrating AVPC-TSG status with clinical prognostic variables refines prognostication and may predict PFS benefits from the addition of an ARPI in patients with mHSPC. Patients with AVPC-TSGalt mHSPC should be considered for clinical trials exploring alternative treatments, as they may not benefit from current standard approaches. Patient characteristics. AVPC-TSGaltn=63(39.9%) AVPC-TSGwtn=95(60.1%) p-value mHSPC treatmentADT aloneADT+ARPIADT+DocetaxelADT+ARPI+Docetaxel 23(36.5%)28(44.5%)8(12.7%)4(6.3%) 32(33.6%)49(51.6%)7(7.4%)7(7.4%) p=0.64 1 De Novo disease 43(68.3%) 57 (60%) p=0.29 1 CHAARTED High Volume 36(57.1%) 52(54.7%) p=0.77 1 AVPC-TSG 1 altAVPC-TSG 2-3 alt 56(88.9%)7(11.1%) 00 p&lt;0.012 1 median PFS (months)median OS (months) 20.568.2 39.6NR p=0.010 2 1 Pearson, 2 Log-rank test.
Efficacy and safety of fruquintinib combined with serplulimab as 1 <sup>st</sup> line treatment in metastatic or unresectable non-clear cell renal cell carcinoma (nccRCC): Updated results from a single-arm, multicentre clinical trial.
Authors: Jiwei Huang, Xiaoyi Hu, Hang Wang, Jianming Guo, Wei Xue
Journal: Journal of Clinical Oncology (2025)

542 Background: For advanced non-clear cell renal cell carcinoma (nccRCC), systemic therapy is the main option but the treatment standard remains unclear. In the past decade, promising results have emerged from clinical trials with vascular endothelial growth factor receptor (VEGFR) inhibitors, or anti-programmed death-1 (PD-1) antibodies. Fruquintinib (FRU) is a potent VEGFR inhibitor approved for metastatic colorectal cancer. This trial aims to evaluate the efficacy and safety of FRU combined with serplulimab (an anti-PD-1 antibody) in patients (pts) with advanced nccRCC. Methods: This is a multicentre single-arm prospective trial planning to enroll 39 pts with pathologically confirmed metastatic or unresectable nccRCC. Eligible patients were 18 to 80 years old with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, and had not received prior systemic therapy. All pts received FRU (5mg, qd, po, 2w on/1w off) plus serplulimab (4.5mg/kg, d1, i.v.gtt, q3w). The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), safety, etc. Results: As of Sep.20 th , 2024, 16 nccRCC pts were enrolled. The median age was 63.5 years (range 24-78) and 75.0% were male. Seven (43.8%) pts had an ECOG PS of 2. Histologically, papillary subtype was the most prevalent (12, 75.0%), followed by chromophobe (2, 12.5%), 1 collecting duct carcinoma and 1 unclassified subtype, and sarcomatoid features were observed in 5 (31.3%) patients. The metastatic sites were primarily lymph nodes (56.3%), lungs (37.5%), peritoneum (25.0%) and abdominal cavity (25.0%). Among the 16 evaluable pts, 8 achieved partial response and 6 had stable disease, resulting in an ORR of 50.0% (95% CI: 25.5%-74.5%) and a DCR of 87.5% (95% CI: 61.7%-98.4%). Three pts experienced rapid progression, all with sarcomatoid features (2 papillary, 1 chromophobe). The median PFS was not reached. The most common treatment-related adverse events (TRAEs) were rash (37.5%), fever (31.3%), ALT increased (25.0%), AST increased (25.0%), hypertension (18.8%), hypothyroidism (18.8%), fatigue (18.8%) and most were grade 1/2 except 1 pt experiencing grade 3 AST increased. Conclusions: The preliminary data showed promising efficacy and tolerable toxicity of FRU combined with serplulimab in pts with metastatic or unresectable nccRCC. Clinical trial information: NCT05831891 .