{
    "abstract": "Cisplatin-based chemotherapy has been a cornerstone of therapy for advanced/metastatic urothelial cancer (mUC). However, no genomic characteristics have been validated as prognostic biomarkers for this therapy. We sought to identify prognostic biomarkers using plasma cell-free (cf)DNA collected in a phase 3 cooperative group trial.\nWe analyzed pretreatment cfDNA from a cohort nested in CALGB 90601 (Alliance), a first-line trial of gemcitabine/cisplatin with bevacizumab or placebo in mUC. We examined associations between cfDNA features and overall survival (OS), progression-free survival (PFS), and treatment response.\nBaseline cfDNA was sequenced from 201 patients with mUC. There was no statistically significant association between alterations in DNA damage response (DDR) genes and response to cisplatin-based chemotherapy (12/24; 50% response rate in DDR+ vs 60/145; 41% response rate in DDR-; \nAmong patients with mUC treated with cisplatin-based chemotherapy, high pretreatment VAF in ctDNA and alterations in the \nWe looked at the link between tumor DNA present in blood and outcomes after chemotherapy for patients with advanced bladder cancer. Higher amounts of tumor DNA in blood and mutations in specific cancer genes were linked to worse survival. The results may help in the design of new studies to improve survival for patients with advanced bladder cancer.This trial is registered on ClinicalTrials.gov as NCT00942331.",
    "authors": [
        {
            "affiliation": "James P. Wilmot Cancer Institute, University of Rochester, Rochester, NY, USA.",
            "firstname": "Brendan J",
            "initials": "BJ",
            "lastname": "Guercio"
        },
        {
            "affiliation": "Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
            "firstname": "Karissa",
            "initials": "K",
            "lastname": "Whiting"
        },
        {
            "affiliation": "Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
            "firstname": "Ronak H",
            "initials": "RH",
            "lastname": "Shah"
        },
        {
            "affiliation": "Department of Quantitative Health Sciences, and Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, USA.",
            "firstname": "Karla V",
            "initials": "KV",
            "lastname": "Ballman"
        },
        {
            "affiliation": "Department of Biostatistics and Bioinformatics, and Alliance Statistics and Data Management Center, Duke University, Durham, NC, USA.",
            "firstname": "Susan",
            "initials": "S",
            "lastname": "Halabi"
        },
        {
            "affiliation": "Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
            "firstname": "Ashley M",
            "initials": "AM",
            "lastname": "Regazzi"
        },
        {
            "affiliation": "Marie-Jos\u00e9e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
            "firstname": "Jennifer H",
            "initials": "JH",
            "lastname": "Milbank"
        },
        {
            "affiliation": "Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.\nDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.",
            "firstname": "Dean F",
            "initials": "DF",
            "lastname": "Bajorin"
        },
        {
            "affiliation": "Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.",
            "firstname": "Himisha",
            "initials": "H",
            "lastname": "Beltran"
        },
        {
            "affiliation": "Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.\nDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.",
            "firstname": "Michael J",
            "initials": "MJ",
            "lastname": "Morris"
        },
        {
            "affiliation": "Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.\nGenitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.\nMarie-Jos\u00e9e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.\nDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.",
            "firstname": "David B",
            "initials": "DB",
            "lastname": "Solit"
        },
        {
            "affiliation": "Marie-Jos\u00e9e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.\nDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
            "firstname": "Michael F",
            "initials": "MF",
            "lastname": "Berger"
        },
        {
            "affiliation": "Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.\nDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.",
            "firstname": "Gopa",
            "initials": "G",
            "lastname": "Iyer"
        },
        {
            "affiliation": "Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
            "firstname": "Venkatraman",
            "initials": "V",
            "lastname": "Seshan"
        },
        {
            "affiliation": "Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.\nDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.",
            "firstname": "Jonathan E",
            "initials": "JE",
            "lastname": "Rosenberg"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2025 The Author(s).",
    "doi": "10.1016/j.euros.2025.03.009",
    "journal": "European urology open science",
    "keywords": [
        "Bladder cancer",
        "Cell-free DNA",
        "Chemotherapy",
        "Circulating tumor DNA",
        "Cisplatin",
        "Survival",
        "Urothelial cancer"
    ],
    "methods": null,
    "publication_date": "2025-04-21",
    "pubmed_id": "40256659\n29980530\n27310333\n25096233\n29742009\n32165095\n32235944\n27749842\n29259186\n28916750\n30380390\n18670422\n33989025\n34059130\n34145282\n25801821\n35939771\n21350629\n10506615\n22588877\n28988769\n37682528\n38823511\n35046520\n33420073\n28802642\n25636205\n0\n38754471\n38490358\n28137924",
    "results": null,
    "title": "Circulating Tumor DNA and Response to Cisplatin-based Chemotherapy in Patients with Metastatic Urothelial Carcinoma Enrolled in CALGB 90601 (Alliance).",
    "xml": "<Element 'PubmedArticle' at 0x7885038d6de0>"
}