tbuckley/cabot-search huggingface dataset:
Optimizing the strategies to perform prostate biopsy in MRI-positive patients: A systematic review and network meta-analysis.
Authors: Qiyou Wu, Xiang Tu, Bo Tang, Yige Bao, Qiang Wei
Journal: Journal of Clinical Oncology (2025)

340 Background: Prostate cancer (PCa) is the most commonly diagnosed cancer in men, and early detection is crucial for better patient outcomes. This study aimed to thoroughly compare existing biopsy schemes for patients with suspicious lesions. Methods: This study conducted a systematic review and network meta-analysis following PRISMA guidelines, evaluating 13 biopsy schemes for detecting PCa in MRI-positive patients. Data from PubMed, Embase, and Cochrane databases were examined to assess the efficacy of biopsy schemes in detecting clinically significant (csPCa) and clinically insignificant (ciPCa) prostate cancer. Results: The analysis included 188 studies involving 64637 individuals. When compared with the combination of systematic biopsy (SB) and targeted biopsy (TB) (SB+TB), ipsilateral SB with TB (ips-SB+TB) and saturation TB (≥ 6 cores TB with or without perilesional cores) had comparable detection rate of csPCa (ips-SB+TB: RR 0.94, 95%CrI 0.87, 1.0; saturation TB: RR 0.94, 95%CrI 0.89, 1.0). While, saturation SB+TB and SB saturation (&gt; 20 cores SB) detected slightly more csPCa than SB+TB (saturation SB+TB: RR 1.04, 95%CrI 0.97, 1.11; saturation TB: RR 1.09, 95%CrI 0.93, 1.29). And TB and SB alone detected significantly less csPCa than SB+TB (TB: RR 0.86, 95%CrI 0.84, 0.88; SB: RR 0.74, 95%CrI 0.72, 0.76). Saturation SB also did not show significant superiority in detecting csPCa. Additionally, saturation TB and ips-SB+TB also decrease the detection of ciPCa. (ips-SB+TB: RR 0.87, 95%CrI 0.73, 1.04; saturation TB: RR 0.81, 95%CrI 0.70, 0.94). The SUCRA results are detailed (Table). Conclusions: The network meta-analysis underscores that saturation SB+TB and SB+saturation TB can detect the most PCa. While, ips-SB+TB and saturation TB are effective biopsy strategies for MRI-positive PCa patients, offering a more targeted approach, improving diagnostic accuracy. Ranking probability of different biopsy schemes. PCa csPCa ciPCa Biopsy schemes Cumulative Probability Biopsy schemes Cumulative Probability Biopsy schemes Cumulative Probability 1 SB+saturation TB 0.936 SB+saturation TB 0.954 SB+saturation TB 0.958 2 saturation SB+TB 0.920 saturation SB+TB 0.922 saturation SB+TB 0.910 3 SB+TB 0.840 SB+TB 0.842 saturation SB 0.768 4 ips-SB+TB 0.621 ips-SB+TB 0.682 SB+TB 0.739 5 saturation SB 0.590 saturation TB 0.675 ips-SB+TB 0.520 6 saturation TB 0.536 non-targeted SB+TB 0.549 con-SB+TB 0.427 7 non-targeted SB+TB 0.524 saturation SB 0.489 non-targeted SB+TB 0.424 8 con-SB+TB 0.470 con-SB+TB 0.487 SB 0.392 9 TB 0.240 TB 0.401 saturation TB 0.381 10 SB 0.229 SB 0.250 ips-SB 0.306 11 ips-SB 0.096 ips-SB 0.143 con-SB 0.089 12 con-SB 0.000 adjacent sextant SB 0.108 TB 0.085 13 con-SB 0
Pilot study evaluating duplex sequencing of urinary DNA as a biomarker for recurrence in non-muscle invasive bladder cancer.
Authors: Fady Ghali, Ondrej Blaha, Hung-Ming Lam, Scott Kennedy, Jonathan L. Wright
Journal: Journal of Clinical Oncology (2025)

865 Background: The detection of tumor-associated urinary DNA (uDNA) as a biomarker for non-muscle invasive bladder cancer (NMIBC) has shown promise, but is significantly limited in sensitivity due to replication errors inherent in next-generation sequencing (NGS). Duplex sequencing is an ultrasensitive/accurate sequencing technology which may provide a solution to this problem. We present a pilot study applying duplex sequencing technique to uDNA in NMIBC for use as a biomarker of recurrence. Methods: Urine samples from a total of 30 patients with NMIBC were collected following complete transurethral resection of bladder tumor and prior to intravesical therapy (pre-tx) and following six weeks of intravesical therapy (post-tx). Detection of ten commonly mutated NMIBC genes was carried out using next generation duplex sequencing. Results were correlated with recurrence of tumor. Results: Median age for our cohort was 71 [41, 88] and 80% were male. A total of 16 (53.3%) of the cohort experienced a recurrence within the first year, with a median time to recurrence of 10 months. Tumor-associated uDNA was successfully detected to variant allele fraction (VAF) below 0.001. Presence of any pathogenic variant in the pre-tx urine &gt;0.006 VAF was associated with a 72.7% sensitivity and 78.9% specificity for recurrence within one year. The highest VAF of pathogenic variant in uDNA trended with time-to-relapse. Post-tx uDNA assessment did not correlate with recurrence. Further analysis is limited by small sample size. Conclusions: This pilot study demonstrates potential utility of ultrasensitive duplex sequencing on NMIBC uDNA in the detection of recurrence.
Avelumab first-line maintenance (1LM) in patients (pts) with advanced urothelial carcinoma (aUC) with or without diabetes mellitus (DM): Long-term outcomes from JAVELIN Bladder 100.
Authors: Shilpa Gupta, Petros Grivas, Se Hoon Park, Daniel P. Petrylak, Karin Tyroller, Jason Hoffman, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2025)

869 Background: In the JAVELIN Bladder 100 phase 3 trial, avelumab 1LM + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone in pts with aUC that had not progressed with 1L platinum-based chemotherapy (PBC). In some cancers, the presence of DM has been associated with reduced efficacy of immunotherapy; however, data in UC are limited. We report post hoc exploratory analyses from JAVELIN Bladder 100 in pts with or without DM at randomization. Methods: Eligible pts with unresectable locally advanced or metastatic UC without progression after 1L PBC were randomized 1:1 to receive avelumab + BSC or BSC alone. The primary endpoint was OS measured from randomization; secondary endpoints included PFS measured from randomization and safety. Results: At randomization in the avelumab + BSC (n=350) and BSC alone (n=350) arms, 55 (15.7%) and 59 (16.9%) pts had documented controlled DM, and 295 and 291 pts did not have documented DM, respectively. Median follow-up in both arms was ≥38.0 months (data cutoff, June 4, 2021). In pts with or without DM, OS and PFS (investigator assessed) were prolonged with avelumab + BSC vs BSC alone (Table). In the safety analysis set of avelumab-treated pts with (n=54) or without (n=290) DM, respectively, treatment-related adverse events (AEs) of any grade occurred in 75.9% and 78.6% (grade ≥3 in 24.1% and 18.6%) and led to avelumab discontinuation in 9.3% and 12.1%; immune-related AEs of any grade occurred in 31.5% and 32.4%. Limitations include the exploratory nature of the analysis and the potential for missing DM diagnosis. Conclusions: In exploratory analyses, avelumab 1LM was associated with long-term efficacy and consistent safety in pts with aUC with or without DM. Clinical trial information: NCT02603432 . Pts with DM Pts without DM Avelumab + BSC (n=55) BSC alone (n=59) Avelumab + BSC (n=295) BSC alone (n=291) Median OS (95% CI), months 20.8 (18.0-32.4) 14.5 (11.7-21.3) 24.7 (19.9-30.0) 15.8 (13.3-18.7) 2-year OS (95% CI), % 44.5 (30.7-57.3) 34.1 (22.2-46.3) 50.7 (44.8-56.4) 39.4 (33.6-45.2) 3-year OS (95% CI), % 33.1 (20.4-46.4) 20.3 (10.8-31.9) 36.6 (30.6-42.6) 31.9 (26.3-37.7) Hazard ratio (95% CI) 0.60 (0.37-0.95) 0.78 (0.64-0.96) Median PFS (95% CI), months 5.6 (3.7-9.3) 2.0 (1.9-3.7) 5.4 (3.8-7.2) 2.1 (1.9-3.5) 2-year PFS (95% CI), % 18.5 (9.1-30.6) 9.2 (3.4-18.6) 24.3 (19.3-29.7) 6.5 (3.8-10.2) 3-year PFS (95% CI), % 13.5 (5.5-25.1) 5.5 (1.4-13.8) 16.3 (11.7-21.6) 5.3 (2.9-8.9) Hazard ratio (95% CI) 0.50 (0.33-0.77) 0.54 (0.45-0.65)
Efficacy and safety of CAR-T cell therapy in penile and urethral carcinomas: A meta-analysis of preliminary clinical trials and case studies.
Authors: Hashim Talib Hashim, Ahmed Qasim Mohammed Alhatemi, Atif Hussain Sarwar, Muhammad Nabeel Saddique, Sheena Shamoon
Journal: Journal of Clinical Oncology (2025)

655 Background: Penile and urethral carcinomas are rare and aggressive cancers with limited treatment options, often leading to poor prognoses. Chimeric Antigen Receptor T-cell (CAR-T) therapy has shown promise in various malignancies, but its efficacy and safety in penile and urethral carcinomas remain under-explored. This meta-analysis aims to evaluate the preliminary clinical trials and case studies on CAR-T cell therapy in treating these rare carcinomas. Methods: The PubMed, Embase, Scopus and Cochrane databases were systematically searched from inception until June 2024 using relevant keywords. We performed proportional meta-analysis of untransformed proportions using Random Effects model in OpenMeta (version 5.3). The I 2 and X 2 statistics were used to evaluate inter-study heterogeneity. An I 2 value of &gt;50% was considered significant heterogeneity. Subgroup analyses were performed to identify factors influencing treatment outcomes. Results: A total of 15 studies, including 10 clinical trials and 5 case reports, comprising 230 patients were included in the meta-analysis. The pooled overall response rate (ORR) was 42% (95% CI: 30%-55%), with a complete response rate (CRR) of 15% (95% CI: 8%-25%). Common adverse effects included cytokine release syndrome (CRS) (35%) and neurotoxicity (20%). Pre-existing comorbidities and prior treatments were significant factors affecting outcomes. No treatment-related mortality (TRM) was reported. Conclusions: CAR-T cell therapy demonstrates encouraging efficacy in penile and urethral carcinomas, with manageable safety profiles. While preliminary results are promising, larger and more comprehensive studies are needed to validate these findings and optimize treatment protocols.
CTC and AR-V7 analysis in the ECOG-ACRIN 8153 (CHAARTED2) randomized trial: Abiraterone (Abi) with or without cabazitaxel (Abi-Cabazi) in extensive mCRPC following docetaxel.
Authors: Christos Kyriakopoulos, Yu-Hui Chen, Robert Jeraj, Fenghai Duan, Abhishek Tripathi, David Kosoff, Rohan Garje, Russell Kent Pachynski, Rahul Atul Parikh, Andrea Harzstark, Nabil Adra, Benjamin L. Maughan, Yousef Zakharia, Paul Gettys Corn, Glenn Liu, Michael A Carducci, Jun Luo, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2025)

181 Background: The CHAARTED2 trial showed improved PFS with Abi-Cabazi over Abi-alone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who previously received docetaxel for metastatic castration-sensitive disease. Here, we evaluated the prognostic and predictive impact of CTC and AR-V7 circulating biomarkers. Methods: The modified AdnaTest (Qiagen) was used to define CTC detection (+ vs –) and AR-V7 detection (+ vs –) at baseline, C5D1, as well as at the time of progression. We first assessed the prognostic value of baseline and C5D1 CTC and AR-V7 status in the two arms. We also assessed the predictive potential of baseline and C5D1 CTC and AR-V7 status to explore if these biomarkers may aid in treatment selection. Logrank test and Cox proportional hazards models were used to assess for associations between clinical outcomes and baseline biomarker status. Landmark analysis was performed to evaluate associations at C5D1. Results: A total of 223 pts were randomized between the two arms. CTC data were evaluable for 94/112 and 94/111 pts in the Abi-alone and Abi-Cabazi arms, respectively. Baseline CTC detection was prognostic for worse PFS in both the Abi-alone (7.1 vs 31.7 months, HR 3.64, P &lt;0.001) and the Abi-Cabazi (9.6 vs 36.9 months, HR 4.13, P &lt;0.001) arms. Likewise, baseline AR-V7 detection portended worse PFS in the Abi-alone (4.1 vs 12.8 months, HR 3.34, P &lt;0.001) and the Abi-Cabazi (6.9 vs 15.1 months, HR 3.17, P &lt;0.001) arms. At C5D1, there was a higher rate of CTC(-) conversion (60 vs 46%) and AR-V7(-) conversion (69 vs 58%) in the Abi-Cabazi arm. CTC(-) and AR-V7(-) status at C5D1 was prognostic of improved PFS in both arms (all P ≤0.02). In terms of predictive impact, PFS was numerically but not statistically longer in the Abi-Cabazi arm in all biomarker groups; the greatest relative PFS benefit to Abi-Cabazi was in the baseline AR-V7(+) group (HR 0.68, 95%CI 0.36–1.3, P =0.2). Similarly, at C5D1, the greatest relative PFS benefit to Abi-Cabazi was in pts remaining AR-V7(+) (HR 0.57, 95%CI 0.15–2.16, P =0.4). Conclusions: Baseline CTC and AR-V7 detection were both prognostic for inferior PFS in both study arms. PFS outcomes were broadly longer in the Abi-Cabazi vs Abi-alone arm in all biomarker groups. The presence of AR-V7 at baseline and at C5D1 was the strongest relative predictor of Abi-Cabazi benefit, but did not meet statistical significance. Clinical trial information: NCT03419234 .
A prognostic model for survival of patients with metastatic upper tract urothelial carcinoma with first-line systemic therapy.
Authors: Jinchang Wei, Siming Li, Huayan Xu, Xiaowen Wu, Juan Li, Li Zhou, Xieqiao Yan, Bixia Tang, Lu Si, Chuanliang Cui, Zhihong Chi, Jun Guo, Xinan Sheng
Journal: Journal of Clinical Oncology (2025)

868 Background: Upper tract urothelial carcinoma (UTUC) presents distinct clinicopathological, molecular features, and biological behaviors compared to urothelial bladder carcinoma (UBC). Currently, no prognostic model exists for metastatic UTUC (mUTUC). This study aimed to develop a prognostic model for mUTUC patients receiving first-line systemic therapy. Methods: A total of 476 patients with mUTUC who received first-line systemic therapy at Peking University Cancer Hospital from January 2005 to March 2024 were included in the analysis. Patients were randomly assigned to development and validation cohorts in a 3:1 ratio, with potential prognostic factors recorded prospectively. Univariate Cox regression analysis identified clinical and laboratory factors significantly associated with median overall survival (mOS) in the development cohort, followed by multivariate Cox regression analysis to determine independent prognostic factors. These factors were utilized to develop a prognostic model. Internal validation was conducted using the validation cohort. Results: After a median follow-up of 51.8 months, 321 patients (67.4%) had died, with a mOS of 26.6 months. The median age at diagnosis was 63 years, with 58.4% males. Common visceral metastatic organs included lung (37.8%), liver (17.9%), and adrenal gland (7.4%). The most frequent first-line treatment option was platinum-containing chemotherapy (63.7%). The number of metastatic organs ≥ 3, Eastern Cooperative Oncology Group Performance Status (ECOG PS) &gt; 1, time to distant metastasis (TTDM) &lt; 12 months, white blood cell (WBC) count &gt; upper limit of normal (ULN), and alkaline phosphatase (ALP) level &gt; ULN were identified as independent prognostic risk factors for mUTUC (Table). A prognostic model for mUTUC was developed, in which the patients were stratified into three risk categories: favorable (0 risk factors, mOS 65.0 months [95% CI 35.5–94.6]), intermediate (1 risk factor, mOS 32.0 months [95% CI 25.8–38.2]), and poor (2+ risk factors, mOS 16.0 months [95% CI 12.1–19.9]) ( p &lt; 0.05). The model's concordance statistic (c-statistic) was 0.71 in the development cohort and 0.72 in the validation cohort. Conclusions: We developed and validated a prognostic model for mUTUC patients receiving first-line systemic therapy, which can inform future clinical practice and trial designs. Results of multivariate analysis. Variables P Hazard Ratio (95% CI) Reference Category TTDM &lt;0.01 3.01 (2.13 ~ 4.26) ≥ 12 months ECOG PS &lt;0.01 2.28 (1.30 ~ 3.97) ≤ 1 Number of Metastatic Organs 0.01 1.41 (1.04 ~ 1.91) &lt; 3 WBC &lt;0.01 1.89 (1.21 ~ 2.95) ≤ ULN ALP 0.02 1.71 (1.10 ~ 2.64) ≤ ULN
Concordance between clinical and pathologic staging of T2a–b and T3a renal cell carcinoma.
Authors: Taylor Goodstein, Rajvi R. Goradia, Arnav Srivastava, Akshay Sood, Shawn Dason, Viraj A. Master, Eric A. Singer
Journal: Journal of Clinical Oncology (2025)

600 Background: Among patients with renal cell carcinoma (RCC), 5–23% of those with cT1 and smaller cT2 tumors may be upstaged to pT3a disease after surgery. The pathologic restaging rate of larger or clinically more invasive tumors is understudied and has implications for perioperative systemic therapy clinical trial enrollment. We examined rates of pathologic restaging for cT2a-b and cT3a RCC after surgery. Methods: Using the National Cancer Database, we identified adult patients with cT2a, cT2b, and cT3a RCC undergoing partial or radical nephrectomy. We compared pathologic restaging rates between the clinical stage groups using a Chi-square test. Subgroup analysis of restaging rates was performed for histology (clear cell vs non–clear cell), clinical nodal status (cN1 vs cN0), and clinical metastatic status (cM1 vs cM0). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the overall cohort and subgroups. Multivariable logistic regression was performed to assess predictors of pT3a upstaging among patients with cT2a and cT2b tumors. Results: We identified 31,912 patients who met inclusion criteria (13,840 cT2a, 8,079 cT2b, and 9,993 cT3a). he overall rate of restaging was 47.4% for cT2a disease (10.7% downstaged and 36.7% upstaged) for a sensitivity and specificity of 89% and 72%, respectively. The overall rate of restaging was 52.5% for cT2b disease (10.6% downstaged and 41.9% upstaged), for a sensitivity and specificity of 85% and 96%, respectively. The overall rate of restaging was 9.5% for cT3a disease (5.1% downstaged and 4.4% upstaged), for a sensitivity and specificity of 55% and 94%, respectively (p &lt; 0.001). The positive predictive value was 52.5%, 47.5%, and 90.6%, and the negative predictive value was 95%, 97%, and 67% for cT2a, cT2b, and cT3a disease, respectively. On multivariable analysis, among patients with cT2 tumors, the presence of clinically node-positive (OR 2.8 [95% CI 2.43–3.17]) metastatic (OR 2.4 [95% CI 2.18–2.65]) or cT2b disease (OR 1.18 [95% CI 1.10–1.26]) was associated with pathologic upstaging (p &lt; 0.001). Conclusions: Restaging is common for patients with cT2a and cT2b tumors, but the specificity of cT3a staging is high. These findings suggests that opportunities exist to improve the accuracy of clinical staging for cT2 tumors, which will have implications for future adjuvant/perioperative RCC clinical trials.
Extreme bipolar androgen therapy: Alternating darolutamide and testosterone cypionate in patients with metastatic castration-resistant prostate cancer (mCRPC; ExBAT trial/LACOG 0620).
Authors: Pedro Isaacsson, Andrey Soares, Denis Leonardo Fontes Jardim, Fernando Cotait Maluf, Igor Alexandre Protzner Morbeck, Daniel da Motta Girardi, Mariane Fontes Dias, Vinicius Carrera Souza, Adriano Goncalves E Silva, Rafaela Gomes de Jesus, Gustavo Werutsky, Taiane Rebelatto, Diogo Assed Bastos
Journal: Journal of Clinical Oncology (2025)

178 Background: Sequencing androgen-receptor signaling inhibitors (ARSi) has limited activity in metastatic castration-resistant prostate cancer (mCRPC). Bipolar Androgen Therapy (BAT), consisting of supraphysiological doses of exogenous testosterone, followed by a decline to castrate levels, has shown benefit in a subset of patients (pts) with mCRPC, by the downregulation of AR levels, a therapeutic vulnerability which led to resensitization to ARSi in trials. We hypothesize that BAT could significantly enhance the efficacy of subsequent ARSi darolutamide in pts who had progressed to abiraterone. Methods: The ExBAT/LACOG 0620 ( NCT04558866 ) study is a phase II, single-arm, multi-center trial investigating a pre-planned regimen of alternating BAT and darolutamide in mCRPC pts after progression on abiraterone. Prior docetaxel for hormone-sensitive disease was allowed. Pts received intramuscular testosterone cypionate 400 mg on day 1, followed by oral darolutamide 1200 mg/day from day 29 to day 56, followed by a washout period of 7 days, in 63-day cycles. The primary endpoint was radiographic progression-free survival (rPFS) at 12 months. Secondary endpoints include median rPFS, PSA50 response, overall survival (OS), quality of life (QoL) and safety. Results: From Jun2021 to Mar2023, 51 pts were enrolled in 9 centers and 48 pts were eligible for efficacy analysis. Median age was 69y (range, 48-92), 23.5% had received abiraterone on castration-sensitive setting and 76.5% on mCRPC. The rPFS rate at 12 months was 40.9% (95% CI, 26.3 – 55.0) and median rPFS was 9.0 months (95% CI, 3.9 – 12.9). PSA50 response was 16.7% (95% CI, 7.4–30.2) and median OS was 23.0 months (95% CI, 17.7 – not reached). At cut-off date (22Mar24), 10 pts remained on treatment. QoL was maintained during the treatment. Treatment-related adverse events (TRAEs) rates of any grade and grade 3-4 were 64.7% and 9.8% respectively, and no grade 5 TRAE was reported. The most common AEs were bone and breast pain. Conclusions: ExBAT study demonstrated durable (12 months or more) antintumor activity of alternating BAT and darolutamide in around 40% of pts, with manageble safety profile. Further studies evaluating ExBAT are needed to identify biomarkers of response and the impact of ARSi sequencing in subsequent lines of therapy. Clinical trial information: NCT04558866 .