{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:11:35Z","timestamp":1789668695219,"version":"4.0.1"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Surg Oncol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study aimed to evaluate whether pre-surgical tumor-informed circulating tumor DNA (ctDNA) predicts pathologic nodal status at radical cystectomy and its potential role in risk stratification for future biomarker-guided surgical strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study prospectively analyzed 40 patients with non\u2013muscle-invasive and muscle-invasive bladder cancer who underwent radical cystectomy with pelvic lymph node dissection (LND) and pre-surgical tumor-informed ctDNA testing. Compared with pathologic nodal findings, ctDNA status was classified as positive or negative. Diagnostic performance metrics with 95 % confidence intervals (CIs) were calculated. To assess reproducibility, data from a published cohort meeting comparable inclusion criteria were integrated for pooled descriptive analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 40 patients, 27 (68 %) were ctDNA-negative and 13 (32 %) were ctDNA-positive before cystectomy. Pathologic nodal metastases were identified in seven patients (18 %). For nodal metastases, ctDNA demonstrated a sensitivity of 86 % (95 % CI, 49\u201397 %), a specificity of 79 % (95 % CI, 62\u201389 %), and negative predictive value of 96 % (95 % CI, 82\u201399 %). In pooled descriptive analysis including 149 patients, the negative predictive value remained high at 92 % (95 % CI, 84\u201397 %). A simulated ctDNA-guided omission strategy may have avoided LND for 27 patients (68 %), with one false-negative case (3.7 %) that subsequently had recurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pre-surgical tumor-informed ctDNA showed high negative predictive value for nodal metastases at radical cystectomy. These findings supported prospective validation of ctDNA as a biomarker to identify patients at low risk of nodal metastases and inform future trials of biomarker-guided surgical strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1245\/s10434-026-20022-7","type":"journal-article","created":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T19:16:51Z","timestamp":1782069411000},"page":"9475-9482","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preoperative Tumor-Informed ctDNA for Prediction of Nodal Metastases at Radical Cystectomy in Bladder Cancer"],"prefix":"10.1245","volume":"33","author":[{"given":"Can","family":"Aydogdu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"McSweeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Pieretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Weight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Autorino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihad","family":"Kaouk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bukavina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,21]]},"reference":[{"key":"20022_CR1","unstructured":"van der Heijden AG, H.M.B., Carrion A, Cathomas R, Comp\u00e9rat EM, Dimitropoulos K, Efstathiou JA, et al., EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer. EAU Guidelines Office, Arnhem, 2025."},{"key":"20022_CR2","unstructured":"National Comprehensive Cancer Network. NCCN Clinical Practise Guidelines in Oncology (NCCN Guidelines), Bladder Cancer (version 1.2025). 2025 17.09.2025. Retrieved xxxx at https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/bladder.pdf."},{"key":"20022_CR3","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.eururo.2025.09.001","volume":"88","author":"MM Heck","year":"2025","unstructured":"Heck MM, et al. Long-term results from the LEA randomized trial: extended versus standard lymph node dissection in patients with bladder cancer undergoing radical cystectomy. Eur Urol. 2025;88:566\u201370.","journal-title":"Eur Urol."},{"key":"20022_CR4","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1056\/NEJMoa2401497","volume":"391","author":"SP Lerner","year":"2024","unstructured":"Lerner SP, et al. Standard or extended lymphadenectomy for muscle-invasive bladder cancer. N Engl J Med. 2024;391:1206\u201316.","journal-title":"N Engl J Med."},{"key":"20022_CR5","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1200\/JCO.18.02052","volume":"37","author":"E Christensen","year":"2019","unstructured":"Christensen E, et al. Early detection of metastatic relapse and monitoring of therapeutic efficacy by ultra-deep sequencing of plasma cell-free DNA in patients with urothelial bladder carcinoma. J Clin Oncol. 2019;37:1547\u201357.","journal-title":"J Clin Oncol."},{"key":"20022_CR6","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.euo.2025.05.019","volume":"8","author":"B Wang","year":"2025","unstructured":"Wang B, et al. Real-world experience with a commercial circulating tumor DNA assay in non\u2013muscle-invasive bladder cancer. Eur Urol Oncol. 2025;8:883\u20137.","journal-title":"Eur Urol Oncol."},{"key":"20022_CR7","unstructured":"Chatzkel J, et al. Urothelial cancer: leveraging circulating tumor DNA to avoid unnecessary bladder-directed and systemic therapies. Eur Urol Focus."},{"key":"20022_CR8","unstructured":"Tasios A, et al. In patients with muscle-invasive bladder cancer undergoing radical cystectomy, dynamics of circulating tumor DNA following cystectomy: association with patient outcomes. Eur Urol Focus."},{"key":"20022_CR9","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1016\/j.euo.2024.03.002","volume":"7","author":"R Ben-David","year":"2024","unstructured":"Ben-David R, et al. Longitudinal tumor-informed circulating tumor DNA status predicts disease upstaging and poor prognosis for patients undergoing radical cystectomy. Eur Urol Oncol. 2024;7:1105\u201312.","journal-title":"Eur Urol Oncol."},{"key":"20022_CR10","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.eururo.2018.09.047","volume":"75","author":"JE Gschwend","year":"2019","unstructured":"Gschwend JE, et al. Extended versus limited lymph node dissection in bladder cancer patients undergoing radical cystectomy: survival results from a prospective, randomized trial. Eur Urol. 2019;75:604\u201311.","journal-title":"Eur Urol."}],"container-title":["Annals of Surgical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1245\/s10434-026-20022-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1245\/s10434-026-20022-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1245\/s10434-026-20022-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:53:30Z","timestamp":1789667610000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1245\/s10434-026-20022-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,21]]},"references-count":10,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["20022"],"URL":"https:\/\/doi.org\/10.1245\/s10434-026-20022-7","relation":{},"ISSN":["1068-9265","1534-4681"],"issn-type":[{"value":"1068-9265","type":"print"},{"value":"1534-4681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,21]]},"assertion":[{"value":"30 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study received no funding","order":1,"name":"Ethics","label":"Funding","group":{"name":"EthicsHeading","label":"Ethics"}}]}}