{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:07:03Z","timestamp":1791821223657,"version":"4.3.4"},"reference-count":58,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzhen","doi-asserted-by":"crossref","award":["SZSM202211011"],"award-info":[{"award-number":["SZSM202211011"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shenzhen High-level Hospital Construction Fund","award":["NCC201918A01"],"award-info":[{"award-number":["NCC201918A01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Esophageal cancer (EC) continues to pose a major global health burden, ranking as the ninth most common malignancy and sixth leading cause of cancer mortality, with over 600,000 new cases and 500,000 deaths annually as of 2025. While esophagectomy has long been the standard for curative intent in resectable disease, organ preservation strategies have advanced significantly, offering viable alternatives for patients with locally advanced esophageal squamous cell carcinoma (ESCC) or those unsuitable for surgery due to comorbidities. These approaches encompass definitive chemoradiotherapy (dCRT), neoadjuvant chemoradiotherapy (nCRT) followed by active surveillance (\u201cwatch-and-wait\u201d), and innovative integrations of immunotherapy and targeted therapies. This narrative review synthesizes evidence from recent clinical trials, systematic reviews, and international guidelines up to 2025, demonstrating that organ-sparing protocols can achieve comparable overall survival (OS) rates\u2014often exceeding 50% at 5 years in selected cohorts-while substantially enhancing quality of life (QoL) by preserving esophageal function. For instance, the SANO trial (2025) confirmed non-inferiority of active surveillance post-nCRT, with 2-year OS of 74% versus 71% for standard surgery. Key challenges include imprecise response assessment, locoregional recurrences (20\u201330%), and treatment-related toxicities such as esophageal strictures. Emerging trials like ESOSTRATE and PALACE3 are evaluating immunotherapy-enhanced regimens, potentially expanding organ preservation to esophageal adenocarcinoma (EAC). With genomic biomarkers and novel modalities like proton therapy, personalized organ preservation promises to broaden applicability, reduce morbidity, and improve outcomes across histological subtypes. Additionally, recent studies emphasize the role of liquid biopsies, such as circulating tumor DNA (ctDNA), in monitoring treatment response and guiding surveillance, potentially reducing the need for invasive procedures and improving detection of minimal residual disease. The aim of this review is not only to summarize recent trials but to synthesize them into an operational framework that clinicians and researchers can apply: a decision algorithm for selecting organ preservation candidates. This is the novel element that distinguishes this work from prior narrative reviews.<\/jats:p>","DOI":"10.3390\/cancers17213559","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:40:48Z","timestamp":1762180848000},"page":"3559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Organ Preservation in Esophageal Cancer: Current Strategies, Challenges, and Future Directions"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5921-4674","authenticated-orcid":false,"given":"Wenyi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China"},{"name":"Department of Thoracic Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China"},{"name":"Department of Thoracic Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, No. 283 Tongzipo Road, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunguang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longde","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhentao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqiang","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/cac2.12645","article-title":"Current Status and Perspectives of Esophageal Cancer: A Comprehensive Review","volume":"45","author":"Jiang","year":"2024","journal-title":"Cancer Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3108","DOI":"10.1097\/CM9.0000000000003420","article-title":"Global Esophageal Cancer Epidemiology in 2022 and Predictions for 2050: A Comprehensive Analysis and Projections Based on GLOBOCAN Data","volume":"137","author":"Qi","year":"2024","journal-title":"Chin. Med. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/S0140-6736(12)60643-6","article-title":"Oesophageal Carcinoma","volume":"381","author":"Pennathur","year":"2013","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100074","DOI":"10.1016\/j.cson.2025.100074","article-title":"A Comprehensive Narrative Review on Paradigm Shift in the Treatment of Esophageal and Rectal Cancer","volume":"4","author":"Chatziisaak","year":"2025","journal-title":"Clin. Surg. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1001\/jama.281.17.1623","article-title":"Chemoradiotherapy of Locally Advanced Esophageal Cancer: Long-Term Follow-up of a Prospective Randomized Trial (RTOG 85-01). Radiation Therapy Oncology Group","volume":"281","author":"Cooper","year":"1999","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1200\/JCO.20.03614","article-title":"Ten-Year Outcome of Neoadjuvant Chemoradiotherapy plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial","volume":"39","author":"Eyck","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1097\/SLA.0000000000003941","article-title":"Definitive Chemoradiotherapy Compared to Neoadjuvant Chemoradiotherapy with Esophagectomy for Locoregional Esophageal Cancer: National Population-Based Cohort Study","volume":"275","author":"Kamarajah","year":"2022","journal-title":"Ann. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dermine, S., L\u00e9vi-Strauss, T., Abou Ali, E., Belle, A., Leblanc, S., Bibault, J.-E., Barr\u00e9, A., Palmieri, L.-J., Brezault, C., and Dhooge, M. (2020). Organ Preservation after Endoscopic Resection of Early Esophageal Cancer with a High Risk of Lymph Node Involvement. Cancers, 12.","DOI":"10.3390\/cancers12123598"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nguyen, T.-M., Traeger, L., Fitzsimmons, T., Thomas, M., and Sammour, T. (2025). Functional Outcomes and Quality of Life in Patients Managed with Organ Preservation Following Total Neoadjuvant Therapy for Rectal Cancer\u2014A Historical Cohort Study. ANZ J. Surg., 1\u20138.","DOI":"10.1111\/ans.70309"},{"key":"ref_10","unstructured":"Ajani, J.A., D\u2019Amico, T.A., Bentrem, D.J., Chakrabarti, S., Corvera, C.U., Das, P., Enzinger, P.C., Enzler, T., Gerdes, H., and Gibson, M.K. (2025, September 30). NCCN Clinical Practice Guidelines in Oncology: Esophageal and Esophagogastric Junction Cancers (Version 4.2025). Available online: https:\/\/www.nccn.org\/guidelines\/guidelines-detail?category=1&id=1433."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104134","DOI":"10.1016\/j.esmoop.2025.104134","article-title":"ESMO Clinical Practice Guideline Interim Update on the Treatment of Locally Advanced Oesophageal and Oesophagogastric Junction Adenocarcinoma and Metastatic Squamous-Cell Carcinoma","volume":"10","author":"Leong","year":"2025","journal-title":"ESMO Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"JCO2500948","DOI":"10.1200\/JCO-25-00948","article-title":"Recurrence Patterns of Esophageal Adenocarcinoma in the Phase III ESOPEC Trial Comparing Perioperative Chemotherapy with Preoperative Chemoradiotherapy","volume":"10","author":"Hoeppner","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"50","DOI":"10.3892\/mco.2025.2845","article-title":"Advances in the Treatment of Unresectable Locally Advanced Esophageal Squamous Carcinoma (Review)","volume":"22","author":"Wang","year":"2025","journal-title":"Mol. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ijrobp.2023.05.025","article-title":"Late Toxicity and Health-Related Quality of Life Following Definitive Chemoradiotherapy for Esophageal Cancer: A Systematic Review and Meta-Analysis","volume":"117","author":"Pape","year":"2023","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1200\/JCO.19.02503","article-title":"Randomized Phase IIB Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced Esophageal Cancer","volume":"38","author":"Lin","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s00268-018-04901-z","article-title":"Definitive Chemoradiotherapy Versus Trimodality Therapy for Resectable Oesophageal Carcinoma: Meta-Analyses and Systematic Review of Literature","volume":"43","author":"Voeten","year":"2019","journal-title":"World J. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1159\/000493435","article-title":"Towards an Organ-Sparing Approach for Locally Advanced Esophageal Cancer","volume":"36","author":"Eyck","year":"2019","journal-title":"Dig. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/S1470-2045(18)30201-8","article-title":"Detection of Residual Disease after Neoadjuvant Chemoradiotherapy for Oesophageal Cancer (preSANO): A Prospective Multicentre, Diagnostic Cohort Study","volume":"19","author":"Noordman","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/j.ijrobp.2024.06.019","article-title":"Optimizing Organ-Preservation Strategies Through Chemotherapy-Based Selection in Esophageal Squamous Cell Carcinoma: Results from the CROC Multi-Institutional Phase 2 Clinical Trial","volume":"120","author":"Katada","year":"2024","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S1470-2045(25)00027-0","article-title":"Neoadjuvant Chemoradiotherapy Followed by Active Surveillance versus Standard Surgery for Oesophageal Cancer (SANO Trial): A Multicentre, Stepped-Wedge, Cluster-Randomised, Non-Inferiority, Phase 3 Trial","volume":"26","author":"Eyck","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.gie.2005.06.047","article-title":"Photodynamic Therapy with Porfimer Sodium for Ablation of High-Grade Dysplasia in Barrett\u2019s Esophagus: International, Partially Blinded, Randomized Phase III Trial","volume":"62","author":"Overholt","year":"2005","journal-title":"Gastrointest. Endosc."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Li, M., Jin, X., Zhou, R., Ying, Y., Wu, X., Jing, J., and Pan, W. (2024). Comparison of Interventions for Barrett\u2019s Esophagus: A Network Meta-Analysis. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0302204"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1200\/OP.22.00226","article-title":"Immunotherapy in the Management of Esophagogastric Cancer: A Practical Review","volume":"19","author":"Patruni","year":"2023","journal-title":"JCO Oncol. Pract."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.ejca.2020.11.039","article-title":"Preoperative Pembrolizumab Combined with Chemoradiotherapy for Oesophageal Squamous Cell Carcinoma (PALACE-1)","volume":"144","author":"Li","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.xjon.2021.11.003","article-title":"Preoperative Pembrolizumab Combined with Chemoradiotherapy for Esophageal Squamous Cell Carcinoma: Trial Design","volume":"9","author":"Zheng","year":"2022","journal-title":"JTCVS Open"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Goetze, T., Angermeier, S., Debus, J., Heuer, V., Homann, N., Kanzler, S., Kubicka, S., Liersch, R., Lorenzen, S., and Mahlberg, R. (2024). Organ Preservation with Durvalumab-Based Immunotherapy in Combination with Chemoradiation as Definitive Therapy for Early-Stage Esophageal Adenocarcinoma (PRESTO\/FLOT-AIO): Trial in Progress. J. Clin Oncol., 42.","DOI":"10.1200\/JCO.2024.42.3_suppl.TPS431"},{"key":"ref_27","unstructured":"ClinicalTrials.Gov (2025, September 30). Durvalumab Plus Chemotherapy and Chemoradiation for Organ Preservation in Early-Stage Esophageal Adenocarcinoma (PRESTO). Identifier: NCT05713838. Updated 2024, Available online: https:\/\/Clinicaltrials.Gov\/Ct2\/Show\/NCT05713838."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Li, W., Zhang, X., Du, Y., Zhang, Y., Lu, J., Hu, W., and Zhao, J. (2022). HER2-Targeted Advanced Metastatic Gastric\/Gastroesophageal Junction Adenocarcinoma: Treatment Landscape and Future Perspectives. Biomark. Res., 10.","DOI":"10.1186\/s40364-022-00416-x"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bonomi, M., Spada, D., Baiocchi, G.L., Celotti, A., Brighenti, M., and Grizzi, G. (2024). Targeting HER2 in Gastroesophageal Adenocarcinoma: Molecular Features and Updates in Clinical Practice. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073876"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1038\/s41591-023-02465-7","article-title":"Zolbetuximab plus CAPOX in CLDN18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma: The Randomized, Phase 3 GLOW Trial","volume":"29","author":"Shah","year":"2023","journal-title":"Nat. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/S0140-6736(23)00620-7","article-title":"Zolbetuximab plus mFOLFOX6 in Patients with CLDN18.2-Positive, HER2-Negative, Untreated, Locally Advanced Unresectable or Metastatic Gastric or Gastro-Oesophageal Junction Adenocarcinoma (SPOTLIGHT): A Multicentre, Randomised, Double-Blind, Phase 3 Trial","volume":"401","author":"Shitara","year":"2023","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/jjco\/hyad137","article-title":"A Phase III Randomized Controlled Trial Comparing Local Field with Additional Prophylactic Irradiation in Chemoradiotherapy for Clinical-T1bN0M0 Esophageal Cancer: ARMADILLO Trial (JCOG1904)","volume":"54","author":"Sasaki","year":"2024","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hoeppner, J., Lordick, F., Brunner, T., Glatz, T., Bronsert, P., R\u00f6thling, N., Schmoor, C., Lorenz, D., Ell, C., and Hopt, U.T. (2016). ESOPEC: Prospective Randomized Controlled Multicenter Phase III Trial Comparing Perioperative Chemotherapy (FLOT Protocol) to Neoadjuvant Chemoradiation (CROSS Protocol) in Patients with Adenocarcinoma of the Esophagus (NCT02509286). BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2564-y"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7422","DOI":"10.1245\/s10434-023-13643-9","article-title":"Long-Term Postsurgical Outcomes of Neoadjuvant Chemoradiation (CROSS) versus Chemotherapy (FLOT) for Multimodal Treatment of Adenocarcinoma of the Esophagus and the Esophagogastric Junction","volume":"30","author":"Gebauer","year":"2023","journal-title":"Ann. Surg. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0140-6736(24)00745-1","article-title":"Doublet Chemotherapy, Triplet Chemotherapy, or Doublet Chemotherapy Combined with Radiotherapy as Neoadjuvant Treatment for Locally Advanced Oesophageal Cancer (JCOG1109 NExT): A Randomised, Controlled, Open-Label, Phase 3 Trial","volume":"404","author":"Kato","year":"2024","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1056\/NEJMoa2032125","article-title":"Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer","volume":"384","author":"Kelly","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"znaf004","DOI":"10.1093\/bjs\/znaf004","article-title":"Detecting Residual Disease after Neoadjuvant Chemoradiotherapy for Oesophageal Squamous Cell Carcinoma: The Prospective Multicentre preSINO Trial","volume":"112","author":"Yang","year":"2025","journal-title":"Br. J. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhang, X., Eyck, B.M., Yang, Y., Liu, J., Chao, Y.-K., Hou, M.-M., Hung, T.-M., Pang, Q., Yu, Z.-T., and Jiang, H. (2020). Accuracy of Detecting Residual Disease after Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma (preSINO Trial): A Prospective Multicenter Diagnostic Cohort Study. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-6669-y"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Sugawara, K., Oka, D., Hara, H., Yoshii, T., Ushijima, H., Kudo, S., and Fukuda, T. (2023). Survival Outcomes of Esophageal Cancer Patients with Recurrence after Curative Treatments. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11568-w"},{"key":"ref_40","first-page":"88","article-title":"Long-Term Outcomes of an Esophagus-Preserving Chemoradiotherapy Strategy for Patients with Endoscopically Unresectable Stage I Thoracic Esophageal Squamous Cell Carcinoma","volume":"30","author":"Suwa","year":"2021","journal-title":"Clin. Transl. Radiat. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"98974","DOI":"10.18632\/oncotarget.21940","article-title":"Pretreatment Nutritional Risk Scores and Performance Status Are Prognostic Factors in Esophageal Cancer Patients Treated with Definitive Chemoradiotherapy","volume":"8","author":"Song","year":"2017","journal-title":"Oncotarget"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e2410670","DOI":"10.1001\/jamanetworkopen.2024.10670","article-title":"Travel-Time Disparities in Access to Proton Beam Therapy for Cancer Treatment","volume":"7","author":"Burus","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1007\/s10388-019-00710-y","article-title":"Relationship between Psychological Distress and Health-Related Quality of Life at Each Point of the Treatment of Esophageal Cancer","volume":"17","author":"Ohkura","year":"2020","journal-title":"Esophagus"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1038\/s43018-025-00955-w","article-title":"Evolutionary and Immune Microenvironment Dynamics during Neoadjuvant Treatment of Esophageal Adenocarcinoma","volume":"6","author":"Barroux","year":"2025","journal-title":"Nat. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5263","DOI":"10.1007\/s00464-025-11951-7","article-title":"Gender, Racial, and Socioeconomic Disparities in the Management and Survival of Patients with Locally Advanced Esophageal Cancer: A SEER-Based Study","volume":"39","author":"Tran","year":"2025","journal-title":"Surg. Endosc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1016\/j.cgh.2023.02.011","article-title":"Socioeconomic Disparities Affect Outcomes in Early-Stage Esophageal Adenocarcinoma: A SEER Analysis","volume":"21","author":"Geng","year":"2023","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hoefnagel, S.J.M., Boonstra, J.J., Russchen, M.J.A.M., and Krishnadath, K.K. (2021). Towards Personalized Treatment Strategies for Esophageal Adenocarcinoma; A Review on the Molecular Characterization of Esophageal Adenocarcinoma and Current Research Efforts on Individualized Curative Treatment Regimens. Cancers, 13.","DOI":"10.3390\/cancers13194881"},{"key":"ref_48","first-page":"e934106","article-title":"A Review of Circulating Tumor DNA in the Diagnosis and Monitoring of Esophageal Cancer","volume":"28","author":"Jiang","year":"2022","journal-title":"Med. Sci. Monit."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"149","DOI":"10.35772\/ghm.2020.01083","article-title":"Proton Therapy for Patients with Esophageal Cancer: History, Characteristics, Clinical Outcome and Future Direction of Proton Beam Therapy","volume":"3","author":"Karube","year":"2021","journal-title":"Glob. Health Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.clon.2019.01.010","article-title":"Hypofractionated Radiotherapy in Oesophageal Cancer for Patients Unfit for Systemic Therapy: A Retrospective Single-Centre Analysis","volume":"31","author":"Jones","year":"2019","journal-title":"Clin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"101680","DOI":"10.1016\/j.gendis.2025.101680","article-title":"The Advancements in Organoids: Potential and Challenges in Researching the Esophagus and Esophageal Squamous Cell Carcinoma: ESCC Organoids Promote Drug Screening and Treatment Optimization","volume":"12","author":"Li","year":"2025","journal-title":"Genes Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1186\/s12967-025-06593-1","article-title":"Patient-Derived Esophageal Adenocarcinoma Organ Chip: A Physiologically Relevant Platform for Functional Precision Oncology","volume":"23","author":"Pal","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_53","unstructured":"Mostert, D.B. (2025, September 30). Nivolumab During Active Surveillance after Neoadjuvant Chemoradiation for Esophageal Cancer: SANO-3 Study, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05491616."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e70467","DOI":"10.1002\/cam4.70467","article-title":"Application of Esophageal Sponge Cytology in Screening Esophageal Squamous Cell Carcinoma in a High-Risk Region of China","volume":"14","author":"Huang","year":"2025","journal-title":"Cancer Med."},{"key":"ref_55","unstructured":"(2025, September 30). NRG Oncology Phase III Randomized Trial of Proton Beam Therapy (PBT) versus Intensity Modulated Photon Radiotherapy (IMRT) for the Treatment of Esophageal Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03801876."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lin, Y., Liang, H.-W., Liu, Y., and Pan, X.-B. (2023). Nivolumab Adjuvant Therapy for Esophageal Cancer: A Review Based on Subgroup Analysis of CheckMate 577 Trial. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1264912"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Kim, J.-S., Nam, H., Kim, E.C., Jeong, H.-J., and Lee, S.-J. (2025). Bioengineered Approaches for Esophageal Regeneration: Advancing Esophageal Cancer Therapy. Bioengineering, 12.","DOI":"10.3390\/bioengineering12050479"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Guedan, S., and Alemany, R. (2018). CAR-T Cells and Oncolytic Viruses: Joining Forces to Overcome the Solid Tumor Challenge. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02460"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/21\/3559\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T05:15:21Z","timestamp":1762319721000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/21\/3559"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":58,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["cancers17213559"],"URL":"https:\/\/doi.org\/10.3390\/cancers17213559","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]}}}