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As IO enters a transformative era, the field must continue demonstrating value within the greater world of oncology, particularly through the study and application of surrogate endpoints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Surrogate Endpoint Definitions and Validation Criteria<\/jats:title>\n                    <jats:p>A central requirement for advancing IO is the\u00a0rigorous evaluation of\u00a0treatment outcomes through translational research. Surrogate endpoints, including imaging-based criteria and serum biomarkers,\u00a0expedite\u00a0therapeutic assessment, yet their validity as predictors of clinical benefit remains under scrutiny.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Regulatory and Methodological Challenges<\/jats:title>\n                    <jats:p>Experience from prior IO studies underscores\u00a0the complex interplay between surrogate endpoints, overall survival, and quality of life metrics. Variable regulatory acceptance, incomplete validation, and inconsistencies in endpoint definition and reporting continue to challenge their adoption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Primary Liver Tumors<\/jats:title>\n                    <jats:p>In hepatocellular carcinoma (HCC), surrogate endpoints have informed treatment evaluation; however, their predictive strength and reproducibility remain variable across studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Secondary Liver Malignancies<\/jats:title>\n                    <jats:p>Applications in metastatic liver disease similarly rely on imaging and serum-based surrogates, though performance and reliability remain heterogeneous.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Limitations<\/jats:title>\n                    <jats:p>Uncertainty persists regarding the ability of surrogate endpoints to reliably predict durable clinical outcomes, limiting their broader applicability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Future Directions<\/jats:title>\n                    <jats:p>Advancing IO will require\u00a0the integration of modern trial methodologies, synthetic control arms, radiomics, and artificial intelligence to strengthen surrogate endpoint validation and facilitate\u00a0broader clinical and regulatory acceptance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>By embracing its characteristically innovative spirit while maintaining a critical lens on data interpretation, the IO community can not only advance therapeutic development but also reinforce its indispensability in oncology. The beginning of a new quarter century brings a pivotal juncture, with an opportunity to reimagine IO\u2019s trajectory bridging technical ingenuity with the nuanced demands of modern cancer care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00270-025-04281-7","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T17:44:54Z","timestamp":1768585494000},"page":"862-868","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Survival and Surrogate Biomarkers in Interventional Oncology Trials: Pitfalls, Challenges, and Future Directions"],"prefix":"10.1007","volume":"49","author":[{"given":"Ana P.","family":"Gonzalez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Swersky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9745-1825","authenticated-orcid":false,"given":"Riad","family":"Salem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"issue":"8","key":"4281_CR1","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1016\/j.jvir.2013.04.024","volume":"24","author":"R Hickey","year":"2013","unstructured":"Hickey R, Vouche M, Sze DY, Hohlastos E, Collins J, Schirmang T, et al. 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