{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:23:16Z","timestamp":1790461396150,"version":"4.1.0"},"reference-count":27,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Serum tumor markers (STMs), including alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), are currently used in management of patients with germ cell tumors (GCTs). STMs in a substantial proportion of patients are normal or falsely elevated. We evaluated circulating tumor DNA (ctDNA) as a prognostic biomarker in patients with GCTs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>Longitudinal ctDNA testing was performed on a multi-institutional cohort of patients with GCTs using a clinically validated, personalized, tumor-informed 16-plex multiplex PCR-NGS ctDNA assay (Signatera, Natera Inc). ctDNA was evaluated preorchiectomy and during the molecular residual disease (MRD; 1-12 weeks postorchiectomy) and surveillance windows (&gt;12 weeks postorchiectomy, after retroperitoneal lymph node dissection [RPLND], or postchemotherapy). The correlation between ctDNA status and event-free survival (EFS) was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      ctDNA testing was performed for 74 patients (324 plasma samples) with clinical stages I to III GCTs. The median age was 34 years (IQR, 27-39), and the median follow-up was 17 months (IQR, 12-25). Disease management postorchiectomy included surveillance in 23% (17\/74), RPLND in 7% (5\/74), chemotherapy in 41% (30\/74), and chemotherapy + RPLND in 29% (22\/74) of patients. Preorchiectomy ctDNA was detectable in 14 of 15 patients. During the MRD (N = 42) and surveillance (N = 51) windows, patients who were ctDNA-positive versus ctDNA-negative showed a significantly inferior EFS during MRD (hazard ratio [HR], 5.11 [95% CI, 1.31 to 19.95];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .019) and surveillance windows (HR, 12.45 [95% CI, 4.32 to 35.85];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001). By contrast, elevated versus normal STM was not associated significantly with worse EFS (MRD: HR, 2.97 [95% CI, 0.68 to 13.05];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .149. surveillance: HR, 1.74 [95% CI, 0.75 to 4.02];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .194).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Tumor-informed ctDNA analysis shows promise for MRD detection in patients with GCTs. With further study, ctDNA monitoring may be useful in clinical decision making. Larger prospective trials are planned to establish clinical utility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00176","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T19:59:12Z","timestamp":1758743952000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Longitudinal Evaluation of Circulating Tumor DNA as a Prognostic Biomarker to Detect Molecular Residual Disease in Germ Cell Tumors"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8997-890X","authenticated-orcid":true,"given":"Rebecca","family":"Hassoun","sequence":"first","affiliation":[{"name":"Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7946-7145","authenticated-orcid":true,"given":"Reuben","family":"Ben-David","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai New York, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Sfakianos","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai New York, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9205-8258","authenticated-orcid":true,"given":"George","family":"Laliotis","sequence":"additional","affiliation":[{"name":"Natera, Inc, Austin, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8483-0647","authenticated-orcid":true,"given":"Cherry","family":"Au","sequence":"additional","affiliation":[{"name":"Rush University Medical Center, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5324-6475","authenticated-orcid":true,"given":"Clint","family":"Cary","sequence":"additional","affiliation":[{"name":"Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Masterson","sequence":"additional","affiliation":[{"name":"Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1992-0782","authenticated-orcid":true,"given":"Kevin","family":"Manage","sequence":"additional","affiliation":[{"name":"Natera, Inc, Austin, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0166-498X","authenticated-orcid":true,"given":"Punashi","family":"Dutta","sequence":"additional","affiliation":[{"name":"Natera, Inc, Austin, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4149-0486","authenticated-orcid":true,"given":"Neeraja","family":"Tillu","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai New York, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivaram","family":"Cumarasamy","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai New York, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3413-451X","authenticated-orcid":true,"given":"Jennifer","family":"King","sequence":"additional","affiliation":[{"name":"Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Rich","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai New York, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Rock","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5990-298X","authenticated-orcid":true,"given":"Tanya","family":"Dorff","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukti","family":"Patel","sequence":"additional","affiliation":[{"name":"Rush University Medical Center, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Sharma","sequence":"additional","affiliation":[{"name":"Natera, Inc, Austin, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3409-583X","authenticated-orcid":true,"given":"Adam C.","family":"ElNaggar","sequence":"additional","affiliation":[{"name":"Natera, Inc, Austin, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8206-5232","authenticated-orcid":true,"given":"Minetta C.","family":"Liu","sequence":"additional","affiliation":[{"name":"Natera, Inc, Austin, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6350-5917","authenticated-orcid":true,"given":"Alan","family":"Tan","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence H.","family":"Einhorn","sequence":"additional","affiliation":[{"name":"Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-8329","authenticated-orcid":true,"given":"Nabil","family":"Adra","sequence":"additional","affiliation":[{"name":"Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5205-4527","authenticated-orcid":true,"given":"Alexander","family":"Chehrazi-Raffle","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_7_2_2","first-page":"381","article-title":"Advances in the treatment of testicular cancer","volume":"4","author":"Ehrlich Y","year":"2015","unstructured":"Ehrlich Y, Margel D, Lubin MA, et al: Advances in the treatment of testicular cancer. Transl Androl Urol 4:381-390, 2015","journal-title":"Transl Androl Urol"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000488284"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1997.15.2.594"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2019.01.001"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2010.04.007"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-020-0043-5"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241210230"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-1860"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.0528"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02615"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-024-00653-3"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03642-9"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2018.05.030"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2200075"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2023.06.007"},{"key":"e_1_3_7_17_2","volume-title":"An Integrated Phase 2\/3 and Phase 3 Trial of MRD-Based Optimization of ADjuvant ThErapy in URothelial CaNcer","author":"MODERN","year":"2023","unstructured":"MODERN: An Integrated Phase 2\/3 and Phase 3 Trial of MRD-Based Optimization of ADjuvant ThErapy in URothelial CaNcer. 2023"},{"key":"e_1_3_7_18_2","volume-title":"A Phase III, Double-Blind, Multicenter, Randomized Study of Atezolizumab (Anti-PDL1 Antibody) versus Placebo as Adjuvant Therapy in Patients with High-Risk Muscle-Invasive Bladder Cancer Who Are ctDNA Positive Following Cystectomy","year":"2020","unstructured":"A Phase III, Double-Blind, Multicenter, Randomized Study of Atezolizumab (Anti-PDL1 Antibody) versus Placebo as Adjuvant Therapy in Patients with High-Risk Muscle-Invasive Bladder Cancer Who Are ctDNA Positive Following Cystectomy. 2020. https:\/\/clinicaltrials.gov\/study\/NCT04660344NCT04660344"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.56.0607"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15030694"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.4481"},{"key":"e_1_3_7_22_2","first-page":"1","article-title":"Role of biochemical markers in testicular cancer: Diagnosis, staging, and surveillance","volume":"4","author":"Milose JC","year":"2011","unstructured":"Milose JC, Filson CP, Weizer AZ, et al: Role of biochemical markers in testicular cancer: Diagnosis, staging, and surveillance. Open Access J Urol 4:1-8, 2011","journal-title":"Open Access J Urol"},{"key":"e_1_3_7_23_2","first-page":"1915","article-title":"The clinical significance of circulating tumor DNA for minimal residual disease identification in early-stage non-small cell lung cancer","volume":"13","author":"Verlicchi A","year":"2023","unstructured":"Verlicchi A, Canale M, Chiadini E, et al: The clinical significance of circulating tumor DNA for minimal residual disease identification in early-stage non-small cell lung cancer. Life (Basel) 13:1915, 2023","journal-title":"Life (Basel)"},{"key":"e_1_3_7_24_2","first-page":"JCO1800210","article-title":"Questioning the value of fluorodeoxyglucose positron emission tomography for residual lesions after chemotherapy for metastatic seminoma: Results of an international Global germ cell cancer group Registry","author":"Cathomas R","year":"2018","unstructured":"Cathomas R, Klingbiel D, Bernard B, et al. Questioning the value of fluorodeoxyglucose positron emission tomography for residual lesions after chemotherapy for metastatic seminoma: Results of an international Global germ cell cancer group Registry. J Clin Oncol. 2018;JCO1800210.","journal-title":"J Clin Oncol"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)64458-8"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.01480"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.02057"},{"key":"e_1_3_7_28_2","volume-title":"Testicular Teratoma, StatPearls","author":"Farci F","year":"2024","unstructured":"Farci F, Shamsudeen S. Testicular Teratoma, StatPearls. Treasure Island, FL, StatPearls Publishing LLC., 2024. StatPearls Publishing Copyright \u00a9 2024"}],"updated-by":[{"DOI":"10.1200\/po-26-00181","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000}}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO-25-00176","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T20:59:40Z","timestamp":1772917180000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO-25-00176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":27,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1200\/PO-25-00176"],"URL":"https:\/\/doi.org\/10.1200\/po-25-00176","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1200\/PO.26.0128","asserted-by":"subject"}]},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-30","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2500176"}}