tbuckley/cabot-search huggingface dataset:
Final overall survival of ARIES trial evaluating first line avelumab monotherapy for patients with advanced urothelial cancer (aUC) unfit for cisplatin and outcome analysis based on baseline characteristics.
Authors: Denis Occhipinti, Chiara Ciccarese, Matteo Santoni, Silvia Puglisi, Consuelo Buttigliero, Claudia Mosillo, Sebastiano Buti, Luciano Stumbo, Emanuele Naglieri, Luca Galli, Elena Verri, Emanuela Fantinel, Stefania Di Girolamo, Rocco De Vivo, Laura Milesi, Elisa Biscaldi, Chiara Ligato, Matteo Brunelli, Giampaolo Tortora, Roberto Iacovelli
Journal: Journal of Clinical Oncology (2025)

797 Background: ARIES trial evaluated avelumab monotherapy in PD-L1+ve aUC patients (pts) not eligible to cisplatin-based chemotherapy, reaching its primary endpoint (Iacovelli R et al. ASCO-GU 2022). Treatment landscape for aUC has changed since enfortumab-vedotin and pembrolizumab (EV+P) has become the new standard for platinum-eligible pts reporting also a mPFS of 10.6 mos and 1-y OS rate of about 80% in cisplatin ineligible (carboplatin-eligible) pts. Unfortunately, up to 20% of pts are not eligible to platinum-based chemotherapy (PBC) and guidelines continue to recommend immunotherapy alone. Methods: Pts with PDL1+ve aUC and not eligible for cisplatin-based chemotherapy were enrolled and treated with avelumab until progression of disease. Here we reported the final OS, and we evaluated the baseline differences between pts with longer PFS compared to those who immediately progressed. Baseline characteristic included in this analysis were sites of metastases, performance status, body mass index (BMI), haematological values and the Neutrophils-to-Lymphocytes Ratio (NLR). Results: 71 pts were enrolled, the median age was 75 years (range 38 – 88); bladder cancer was the primary tumour in 73.2% of cases, 25.3% had liver metastases, 31% had ECOG=2 and 31% had renal function &lt;50ml/min. After a median FU of 52 mos, the median OS was 10.3 mos (95%CI 5.3 – 15.3) and the median PFS was 2.1 mos (95%CI 1.8 – 2.4). 26 pts (37%) received subsequent therapies, with gem+carbo as most frequently used (15 pts, 21%). A total of 18 pts (25%) had a PFS ≥9 mos while 44 (62%) had a PFS ≤3 mos. Significant differences between these two groups were the presence of liver mets (11% vs. 36%; p=0.047), the presence of node only disease (39% vs 5%; p&lt;0.001) and the rate of pts with NLR&gt;4 (22% vs. 61%; p=0.005). At multivariable analysis only NLR&gt;4 and liver mets were confirmed to be independent prognostic factors. The 27 pts (38%) without liver mets and with NLR&gt;4 had significantly (p=0.001) prolonged mPFS (7.7 vs. 1.9 mos), mOS (20.4 vs. 5.7 mos), and 1y OS rate (67% vs. 32%). Conclusions: ARIES trial confirmed the activity of avelumab in cisplatin-ineligible aUC pts including those not eligible to PBC. This analysis also identified the absence of liver mets and low values of NRL as potential markers of significant benefit from immunotherapy alone. This evidence can be used for a personalized approach in the evolving treatment landscape of aUC. Clinical trial information: NCT03891238 .
Immune checkpoint inhibitors in patients with testicular cancer: A systematic review.
Authors: Carlos Eduardo Salazar-Mejía, Estefanía Guadarrama-Rendon, Andrea Sarahi Guerra-Garza, Karina Alicia Salazar-Salazar, Carlos de la Cruz-de la Cruz, Sofia Alejandra Alvarado-Ruiz, Ramiro Quiroz-Huerta, Neri Alejandro Alvarez-Villalobos, Oscar Vidal-Gutiérrez, Rosalaura Villarreal-Gonzalez
Journal: Journal of Clinical Oncology (2025)

638 Background: Germ cell tumors (GCT) are chemosensitive neoplasms with high cure rates, even in the metastatic setting. However, a small group of these patients will present tumors refractory to chemotherapy, with a dismal prognosis and very few effective management options. Although immune checkpoint inhibitors (ICIs) are approved for use in chemotherapy-refractory GCT for those tumors with a high microsatellite instability (MSI-H/dMMR) or high tumor mutational burden (TMB-H), the evidence supporting this indication is scarce. Methods: Original research studies, conducted on patients with GCT refractory to chemotherapy treated with ICI up to December 2023 were included. Comprehensive search strategies of 5 databases and MeSH keywords were used to locate eligible literature. Study characteristics, participant demographics, and oncological outcomes were recorded. Results: A total of 13 studies (n = 106) were identified for inclusion; 5 of which corresponded to single-patient case reports, one was identified as a retrospective cohort, 6 were phase II RCTs and we included a recent abstract from the preliminary results of a phase II RCT. Most of the studies evaluated did not request biomarkers as inclusion criteria. The median overall response rate across all patients included was 3.4% (range, 0-57), versus 0% (range 0-6) in those reported in retrospective cohort and phase II studies. Progressive disease as best clinical response was reported in most patients, with 75% (range, 0-82.9) in the overall population and 82% (range, 75 -83) in patients from retrospective cohort and phase II trials. Some of the most durable clinical responses documented in this systematic review corresponded to TMB-H or MSI-H/dMMR tumors. Conclusions: Analysis from retrospective cohorts and clinical trials evaluating ICIs for the treatment of chemotherapy-refractory GCT documented a limited activity of these drugs as a single intervention in patients not selected by biomarkers, with a tendency to better results described in those with TMB-H or MSI-H/dMMR tumors. Future prospective study designs should attempt to select patients by biomarkers to shed light on the determination of clinical and molecular factors that can predict response to ICIs in this scenario.
Risk factors of complications after inguinal lymph node dissection in patients with penile cancer.
Authors: Yilong Gao, Yanxiang Shao, Xiang Li
Journal: Journal of Clinical Oncology (2025)

6 Background: Inguinal lymph node dissection (ILND) is a crucial step in the management of patients with penile cancer, particularly for those with lymph node involvement. However, ILND is associated with a significant risk of postoperative complications, which can impact recovery and long-term outcomes. Identifying the risk factors that contribute to these complications may help in improving patients’ quality of life after ILND and perioperative management. Methods: We conducted a retrospective analysis of 192 penile cancer patients who underwent ILND between October 2008 and October 2023 at West China Hospital. 370 surgeries were conducted. Data on patient demographics, tumor characteristics, comorbidities, surgical details, and postoperative outcomes were collected. Complications were classified as minor or major based on the Clavien-Dindo classification. Multivariate logistic regression was performed to identify independent risk factors for each complications. Receiver operating characteristic (ROC) curves were used to analyze the relationship between certain risk factors and postoperative complications and find cut-off points for certain risk factors. Results: The overall complication rate was 87.5%, with most patients experiencing minor complications. Common complications included wound infections (35.4%), lymphatic fistula (50%), lymphocele (42.2%) and lower limb edema (28.6%). Except for the common risk factors, such as surgery type (conventional or minimally invasive, Odds Ratio (OR): 0.157, 95% Confidence Interval (CI): [0.036, 0.692], p =0.014) for wound infection, we additionally found that the shorter retention time of drainage tube (OR: 0.784, 95% CI: [0.724, 0.850], p &lt;0.001) is strongly correlated with subsequent lymphocele, with cut-off points of 6.5 days. And longer retention time of drainage tube (OR: 1.065, 95% CI: [1.031, 1.100], p &lt;0.001) is correlated with wound infection, with cut-off points of 10.5 days. Conclusions: Our study highlights several modifiable and non-modifiable risk factors associated with each complications following ILND in penile cancer patients. Optimizing perioperative care and conducting minimally invasive surgery when possible may reduce postoperative complication rate. And the duration of drainage tube retention is associated with both lymphocele and wound infection. Further prospective studies are warranted to validate these findings.
Cross resistance among novel androgen receptor axis-targeted agents in non-metastatic castration-resistant prostate cancer: A multi-institutional retrospective study.
Authors: Naoki Fujita, Fumiya Yoneyama, Yohei Kawashima, Ryuma Tanaka, Takuya Oishi, Hikari Miura, Kazutaka Okita, Chikara Ohyama, Shingo Hatakeyama
Journal: Journal of Clinical Oncology (2025)

395 Background: Previous studies reported a cross resistance among novel androgen receptor axis-targeted agents (ARATs) in patients with metastatic castration-resistant prostate cancer. However, the effects of sequential therapy with novel ARATs in non-metastatic castration-resistant prostate cancer (nmCRPC) remain unclear. Methods: This multi-institutional retrospective study included 56 patients with nmCRPC treated with second-novel ARATs after first-novel ARATs treatments, including apalutamide, enzalutamide, darolutamide, and abiraterone acetate between January 2014 and April 2024. The duration of novel ARATs treatment and PSA response were compared between first-use and second-use of novel ARATs. Results: The median age at nmCRPC diagnosis were 76 years. Of the 56 patients, 14 (25%), 16 (29%), 11 (20%), and 16 (29%) were treated with apalutamide, enzalutamide, darolutamide, and abiraterone acetate as second-novel ARATs. Median duration of novel ARATs treatment in second-use was significantly shorter than that in first-use (7.0 month vs. 14 month, respectively, P = 0.038). The rates of PSA decline ≥50% and ≥90% in second-use were significantly lower than those in first-use (25% vs. 73%, P &lt; 0.001; 9.1% vs. 36%, P = 0.004; respectively). The rate of patients who did not achieve any PSA response in second-use was significantly higher than that in first-line use (45% vs. 11%, P &lt; 0.001). Conclusions: A significant cross resistance among novel ARATs was observed in patients with nmCRPC. A further study is needed to evaluate the optimal candidates for sequential therapy with novel ARATs.
Efficacy outcomes 12 months after initiation of darolutamide in non-metastatic castrate resistant prostate cancer (nmCRPC) from the real world UK multi-centre RECORD study.
Authors: Amarnath Challapalli, Amit Bahl, Manreet Randhawa, Omi Parikh, Santhanam Sundar, Alison Jane Birtle, Jahangeer Malik, Mark Prentice, Dakshinmoorthy Muthukumar, Rajanee Bhana, Kamalram Thippu Jayaprakash, Isabel Syndikus, Anita Mitra, Thiraviyam Elumalai, Emma Gray, Hilary Glen, Mark Beresford, Vincent Khoo, Emily Foulstone, Paul White
Journal: Journal of Clinical Oncology (2025)

83 Background: Darolutamide has authorisation for treatment of non-metastatic Castrate Resistant Prostate Cancer (nmCRPC) based on the ARAMIS trial. The RECORD Study is a prospective real-world evaluation (RWE) of clinical outcomes in patients with nmCRPC treated with darolutamide in the UK. The study will improve understanding of treatment response and duration as well as inform regarding the use of next generation imaging (NGI) and effects of concomitant medication. Methods: Patients were enrolled from 19 centres over a 3-year period from November 2020. Data cut-off was 16 September 2024. Disease characteristics of patients and efficacy up to 12 months (m) after initiation of darolutamide are evaluated. Descriptive statistics will be used for patient demographics. Results: 257 patients were analysed with a median age of 77 (range 52-94) years (y). 52% have a Gleason score ≥8. 30 patients (11.7%) had NGI prior to initiation of darolutamide and 41 (15.8%) were on anticoagulant/antiplatelet medication. ECOG 0:35%, 1:59% and 2:6.2%. Median pre-treatment PSA was 9.7ng/mL and pre-treatment PSA doubling time (PSAdT) was 5 months. The greatest reduction in median PSA values was seen within the first 3m on darolutamide but was still decreasing slightly at 12m. PSA response was as follows: PSA 50 reduction at 3, 6, 9 and 12 months was 74%, 77%, 75% and 73% respectively and PSA 90 reduction at 3, 6, 9 and 12 months was 28%, 38%, 43% and 42% respectively. No differential effect on PSA reduction was seen with Gleason score (&lt;8, ≥8), PSAdT≤6m or &gt;6m, previous treatment (RT or prostatectomy), anticoagulant/antiplatelet medication or those who had NGI. Median duration of treatment on darolutamide did not significantly differ (p=0.067) in patients with PSAdT&gt;6m (104 patients) compared to those with PSAdT≤6m (135 patients). 46 patients (17.9%) have come off treatment within 12m of initiation: 26 (10.1%) disease progression, 8 (3.1%) toxicity (most frequent being fatigue and diarrhoea), 12 other unrelated causes including 1 death. Conclusions: This RWE shows that patients with nmCRPC in clinical practice have comparable outcomes to the ARAMIS trial. Response rates, tolerability and discontinuation rates are similar and in particular only 3.1% discontinuing treatment due to toxicity. Gleason score &gt;8; PSAdT and the use of NGI had no differential impact on PSA response. This is valuable RWE enabling optimisation of treatment in nmCRPC.
The influence of body composition on the survival of patients with metastatic clear cell renal carcinoma (mccRCC) treated with nivolumab (nivo) + ipilimumab (ipi).
Authors: Kabir Grewal, Pankaj Kumar Chauhan, Sagar S Mukhida, Nizar M. Tannir, Neha Venkatesh, Amishi Yogesh Shah, Amado J. Zurita, Andrew Johns, Matthew T. Campbell, Sangeeta Goswami, Jianjun Gao, Eric Jonasch, Jennifer Leigh McQuade, Omar Alhalabi, Pavlos Msaouel, Andrew Warren Hahn
Journal: Journal of Clinical Oncology (2025)

545 Background: Over the last decade, immune checkpoint therapy (ICT) has become the cornerstone of first-line treatment for mccRCC. Despite the widespread use, there is heterogeneity in tumor response to ICT, and there is growing interest in how host factors modulate the tumor microenvironment. Recent studies in patients with mccRCC and other malignancies suggest that ICT may be more effective in patients with higher body mass index (BMI). Since BMI is an imperfect surrogate for distinct compartments of adipose tissue and muscle, we investigated the influence of body composition on outcomes with first-line (1L) nivo + ipi in patients with mccRCC. Methods: A retrospective analysis was conducted on patients with mccRCC at MD Anderson Cancer Center from June 2015 to Dec 2021 who received nivo + ipi as 1L treatment for advanced or mccRCC. Clinical data including demographics, BMI, and IMDC risk score were collected. Body composition was measured using an AI segmentation tool at the L3 vertebra from a pre-treatment CT scan obtained within 45 days of starting nivo + ipi. Efficacy endpoints of interest were time to treatment discontinuation (TTD), progression-free survival (PFS) and overall survival (OS). We constructed flexible multivariable Cox regression models guided by directed acyclic graphs to flexibly model the association of treatment outcomes with body composition measures as continuous variable, including nonlinear terms as cubic splines, and adjusting for IMDC risk and sarcomatoid dedifferentation as confounders. Results: 209 patients received 1L nivo + ipi (78.5% male, median age of 61 years, 59.3% and 32.5% IMDC intermediate- and poor-risk). Increasing skeletal muscle mass (SMMi) was associated with inferior PFS (HR 1.52, 95% CI 1.01 - 2.31 for 1-unit increase), whereas BMI and adiposity measures were not associated with PFS. Body composition measures were not significantly associated with OS, yet noteworthy trends were observed for visceral adiposity (VATi, HR 0.69, 95% CI 0.42 - 1.15 for 1-unit increase) and SMMi (HR 1.22, 95% CI 0.72 - 2.07). Conclusions: In a large cohort of patients with mccRCC, skeletal muscle mass was surprisingly associated with inferior PFS on 1L nivo + ipi. These results build upon conflicting body composition studies in mccRCC and suggest that future studies should investigate how skeletal muscle influences the tumor microenvironment.
Sarcopenia as a marker to assess the surveillance necessity after a 5-year cancer-free period in patients who undergo radical cystectomy: A multi-institutional retrospective study.
Authors: Naoki Fujita, Toshikazu Tanaka, Shogo Hosogoe, Noritaka Ishii, Masaki Momota, Takahiro Yoneyama, Hiroyuki Ito, Chikara Ohyama, Shingo Hatakeyama
Journal: Journal of Clinical Oncology (2025)

871 Background: Although continuous surveillance after a 5-year cancer-free period in patients with bladder cancer (BC) who undergo radical cystectomy (RC) is recommended, optimal candidates for continuous surveillance remain unclear. Sarcopenia is associated with unfavorable prognosis in various malignancies. Thus, we hypothesized that sarcopenia, characterized by low muscle quantity, might be a useful marker to assess the necessity of surveillance after a 5-year cancer-free period in patients who underwent RC. Methods: This multi-institutional retrospective study included 274 patients with muscle-invasive bladder cancer (MIBC) who had a 5-year cancer-free period after RC. Muscle quantity was evaluated using the psoas muscle index (PMI) using computed tomography images five years after RC. The optimal cut-off values for all-cause mortality were calculated separately for men and women using receiver operating characteristic curves. Patients with lower PMI values than the cut-off values were diagnosed with sarcopenia. Recurrence-free survival (RFS) and overall survival (OS) after a 5-year cancer-free period were evaluated using the Kaplan–Meier method and compared using the log-rank test. Moreover, univariable and multivariable Cox proportional hazards regression analyses were performed to evaluate the impact of sarcopenia on OS. Results: The median age and follow-up period after the 5-year cancer-free period were 73 years and 63 months, respectively. Of the 274 patients, 129 (47%) were diagnosed with sarcopenia five years after RC. By the end of the follow-up period after the 5-year cancer-free period, 14 (5.1%) and 77 (28%) patients experienced recurrence and died from any cause, respectively. The 10-year RFS rate was 93%. RFS was not significantly different between the two groups, whereas OS in the sarcopenia group was significantly shorter than that in the non-sarcopenia group. After adjustment for confounding variables, sarcopenia was significantly associated with shorter OS (Table). Conclusions: Patients with sarcopenia might not need continuous surveillance after a 5-year cancer-free period, considering the high mortality rate. Multivariable analysis for OS. Factor P value Hazard ratio 95% CI Age Continuous &lt;0.001 1.065 1.027–1.105 Performance status Continuous 0.012 1.829 1.145–2.922 Hypertension Positive 0.011 1.897 1.157–3.110 eGFR Continuous 0.168 0.990 0.976–1.004 Urinary diversion Neobladder 0.033 0.546 0.313–0.953 Sarcopenia Positive 0.025 1.801 1.076–3.012
Feasibility and efficacy of cisplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer in older patients: A retrospective French GETUG study.
Authors: Benjamin Combe, Clement Dumont, Guilhem Roubaud, Damien Pouessel, Elsa Lafitte, Manon De Vries, Brigitte Laguerre, Helen Jane Boyle, Aymeric Guilbert, Bérengère Narciso, Hakim Mahammedi, Delphine Borchiellini, Baptiste Abbar, Marine Gross-Goupil, Mathieu Laramas, Franck Bruyere, Julie Biogeau, Mathilde Cancel
Journal: Journal of Clinical Oncology (2025)

735 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy is the gold standard in localized muscle-invasive bladder cancer (MIBC), for fit patients. However, NAC is less prescribed in older patients, mainly due to safety concerns. This study aimed to evaluate the feasibility and efficacy of NAC for patients aged ≥ 75. Methods: We retrospectively included older patients, from 14 French GETUG centers. All patients had received at least one cycle of cisplatin-based NAC for localized MIBC, between 2010 and 2022. Primary outcome was NAC feasibility evaluated as the rate of patients that underwent optimal treatment, defined as at least 4 cycles of chemotherapy followed with local treatment (surgery or chemoradiotherapy). Secondary outcomes were NAC safety and efficacy. Results: 156 pts were included. Median age was 77 (from 75 to 96), with 20% aged ≥ 80. Patients were in good general condition: 54% were PS 0, with a median serum albumin level of 39 g/L, and 86% had a creatinine clearance ≥ 60 ml/min. 108 (69%) had a cT2N0 MIBC. 75 (48%) received dose dense MVAC (ddMVAC), 80 (51%) received gemcitabine-cisplatin (GC) and one patient received MVAC. 96 (62%) received an optimal treatment. 50 patients (32%) prematurely stopped NAC, due to death (3 pts, 2 from unknown causes), progressive disease (4), infection (3), toxicity (34 patients) mainly renal and hematological ones. Among them, 38 (76%) underwent local treatment. Among the 112 patients that underwent cystectomy, pathological complete response (pCR) was significantly more frequent when they received ≥ 4 cycles (36/78 = 46% versus 5/34 = 15%, p = 0.002). Median follow up from diagnosis was 28 months, with 97 patients (62%) that were still alive at the end of follow-up. Median disease-free survival was 3 years and 3 months. 2-years overall survival (OS) was 72%; 5-years OS was 56%. Conclusions: These data suggest that NAC for MIBC is feasible in selected older patients, even if toxicity was the main reason for cisplatin-based regimen discontinuation. Older patients who received optimal treatment were more often in pCR. OS in the this cohort of older patients was very similar to the results published in younger patients.
Prognostic significance of tumor immune microenvironment dynamics in prostate cancer induced by androgen deprivation therapy.
Authors: Yoshinori Yanai, Takeo Kosaka, Shuji Mikami, Masashi Arai, Yuto Baba, Keitaro Watanabe, Toshikazu Takeda, Kazuhiro Matsumoto, Makiko Yamashita, Shigehisa Kitano, Mototsugu Oya
Journal: Journal of Clinical Oncology (2025)

398 Background: The dynamics of the prostate cancer microenvironment through androgen regulation are unclear. In this study, we analyzed the relationship between the dynamics of the immune microenvironment and prognosis after androgen deprivation therapy. Methods: We retrospectively reviewed the patients who underwent radical prostatectomy at our institution. Among them, 104 patients received prostate needle biopsy and neoadjuvant androgen deprivation therapy at the same institution. These cases were compared before and after androgen deprivation therapy. Immune cell infiltration in the cancer areas was assessed using multiplex fluorescent immunohistochemistry. Transcriptome analysis and gene panel analysis by next-generation sequencing were used to systematically and comprehensively analyze the expression and mechanisms of the immune microenvironment. Results: Few immune cells were detected in the needle biopsies before androgen deprivation therapy. After androgen deprivation therapy, prostatectomy specimens showed a significant change in various immune cells, including CD4 + T cells, CD8 + T cells, Foxp3 + regulatory T cells, CD204 + macrophages, and CD20 + B cells (P&lt; 0.001). In particular, CD8 + T cells and CD20 + B cells were significantly increased compared to patients who did not receive androgen deprivation therapy followed by total prostatectomy (P&lt;0.001). Clustering analysis allowed stratification into three groups: One group had a predominant increase in CD8 + T cells after androgen deprivation therapy, another group had a predominant increase in CD20 + B cells, and the third group had no significant increase. The group with increased CD8 + T cells had a significantly higher 5-year biochemical recurrence rate of 56 % (P=0.045). Differences in the mechanisms of androgen metabolism were observed among these cases. Conclusions: Differences in immune induction after androgen deprivation therapy have an impact on the prognosis of prostate cancer.