{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:10:47Z","timestamp":1773655847798,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>(1) Background: Treatment of esophageal cancer (EC) traditionally consists of neoadjuvant radiochemotherapy (RCT) followed by resection; however, esophagectomy is associated with substantial morbidity, particularly in patients with relevant comorbidities. Therefore, a watchful waiting (WW) strategy has been increasingly adopted for patients achieving a complete response to RCT. This study aimed to identify independent predictors and recurrence patterns in EC patients managed with WW. (2) Methods: We retrospectively analyzed all patients with potentially curable EC and complete response to RCT treated at a tertiary university hospital between 2014 and 2022. Comprehensive staging and restaging were performed using computed tomography, endoscopy with ultrasound and biopsies, and positron-emission tomography, followed by structured surveillance. Recurrence patterns and associated clinical and tumor-related factors were assessed using multivariate regression analysis. (3) Results: Among 50 included patients, 30 (60%) developed recurrence after a median of 202 days. Patients with initially nodal-negative disease did not develop distant recurrence, whereas nodal-positive patients showed metastatic recurrence in 26% and local regrowth in 16%. (4) Discussion: Adenocarcinoma, circumferential tumor extent greater than 50%, dysphagia, fatigue, and deterioration of general condition at restaging were independently associated with recurrence. These findings support risk-adapted surveillance and may facilitate personalized management in EC patients undergoing WW.<\/jats:p>","DOI":"10.3390\/curroncol33030170","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T08:41:26Z","timestamp":1773650486000},"page":"170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Predictors and Patterns of Recurrence After a Watchful Waiting Approach following Clinical Complete Response to Neoadjuvant Radiochemotherapy for Esophageal Cancer"],"prefix":"10.3390","volume":"33","author":[{"given":"Sarah","family":"Gerber","sequence":"first","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9224-7104","authenticated-orcid":false,"given":"Martin D.","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4426-6188","authenticated-orcid":false,"given":"Hossein","family":"Hemmatazad","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8033-4179","authenticated-orcid":false,"given":"Pauline","family":"Aeschbacher","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8736-6619","authenticated-orcid":false,"given":"Dino","family":"Kr\u00f6ll","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Candinas","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1997-0675","authenticated-orcid":false,"given":"Yves","family":"Borb\u00e9ly","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/1759-7714.14745","article-title":"Epidemiology of esophageal cancer in 2020 and projections to 2030 and 2040","volume":"14","author":"Liu","year":"2022","journal-title":"Thorac. Cancer"},{"key":"ref_2","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","first-page":"69","article-title":"Global cancer statistics","volume":"61","author":"Jemal","year":"2011","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1016\/S0140-6736(17)31462-9","article-title":"Oesophageal cancer","volume":"390","author":"Lagergren","year":"2017","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"van Heijl, M., van Lanschot, J., Koppert, L., Henegouwen, M.v.B., Muller, K., Steyerberg, E., van Dekken, H., Wijnhoven, B., Tilanus, H., and Richel, D. (2008). Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS). BMC Surg., 8.","DOI":"10.1186\/1471-2482-8-21"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1056\/NEJMoa1112088","article-title":"Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer","volume":"366","author":"Hulshof","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/S1470-2045(15)00040-6","article-title":"Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): Long-term results of a randomised controlled trial","volume":"16","author":"Shapiro","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1016\/S0140-6736(18)32557-1","article-title":"Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2\/3 trial","volume":"393","author":"Homann","year":"2019","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.annonc.2022.07.003","article-title":"Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"33","author":"Alsina","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ijsu.2020.03.020","article-title":"Critical appraisal of gastric conduit ischaemic conditioning (GIC) prior to oesophagectomy: A systematic review and meta-analysis","volume":"77","author":"Kamarajah","year":"2020","journal-title":"Int. J. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1007\/s11605-019-04346-2","article-title":"Mortality After Esophagectomy: Analysis of Individual Complications and Their Association with Mortality","volume":"24","author":"Linden","year":"2020","journal-title":"J. Gastrointest. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1097\/SLA.0b013e31815c4037","article-title":"Extended Transthoracic Resection Compared with Limited Transhiatal Resection for Adenocarcinoma of the Mid\/Distal Esophagus","volume":"246","author":"Omloo","year":"2007","journal-title":"Ann. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41416-021-01485-9","article-title":"Advances in the curative management of oesophageal cancer","volume":"126","author":"Bolger","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1097\/SLA.0000000000002611","article-title":"Benchmarking Complications Associated with Esophagectomy","volume":"269","author":"Low","year":"2019","journal-title":"Ann. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.athoracsur.2023.05.033","article-title":"Determinants of Long-term Survival Decades After Esophagectomy for Esophageal Cancer","volume":"116","author":"Chaar","year":"2023","journal-title":"Ann Thorac Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1007\/s12672-024-01567-z","article-title":"Survival outcomes fifteen years after minimally invasive esophagectomy","volume":"15","author":"Orabi","year":"2024","journal-title":"Discov. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1097\/SLA.0000000000004794","article-title":"on behalf of the NOGCA project team AUGIS. The AUGIS Survival Predictor: Prediction of Long-Term and Conditional Survival After Esophagectomy Using Random Survival Forests","volume":"277","author":"Rahman","year":"2021","journal-title":"Ann. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1200\/JCO.2011.38.9791","article-title":"Health-Related Quality of Life Among 5-Year Survivors of Esophageal Cancer Surgery: A Prospective Population-Based Study","volume":"30","author":"Derogar","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s12957-018-1330-9","article-title":"The change of health-related quality of life after minimally invasive esophagectomy for esophageal cancer: A meta-analysis","volume":"16","author":"Zhang","year":"2018","journal-title":"World J. Surg. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hipp, J., Nagavci, B., Schmoor, C., Meerpohl, J., Hoeppner, J., and Schmucker, C. (2021). Post-Neoadjuvant Surveillance and Surgery as Needed Compared with Post-Neoadjuvant Surgery on Principle in Multimodal Treatment for Esophageal Cancer: A Scoping Review. Cancers, 13.","DOI":"10.3390\/cancers13030429"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/s13014-021-01947-7","article-title":"Omitting surgery in esophageal cancer patients with complete response after neoadjuvant chemoradiotherapy: A systematic review and meta-analysis","volume":"16","author":"Park","year":"2021","journal-title":"Radiat. Oncol."},{"key":"ref_23","first-page":"467","article-title":"Chemoradiotherapy Followed by Active Surveillance Versus Standard Esophagectomy for Esophageal Cancer","volume":"275","author":"Eyck","year":"2021","journal-title":"Ann. Surg."},{"key":"ref_24","first-page":"1009","article-title":"Active Surveillance Versus Immediate Surgery in Clinically Complete Responders After Neoadjuvant Chemoradiotherapy for Esophageal Cancer","volume":"274","author":"Noordman","year":"2019","journal-title":"Ann. Surg."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/jso.24429","article-title":"Salvage esophagectomy after failure of definitive radiochemotherapy for esophageal cancer","volume":"114","author":"Farinella","year":"2016","journal-title":"J. Surg. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.athoracsur.2012.05.106","article-title":"Salvage Esophagectomy After Failed Definitive Chemoradiation for Esophageal Adenocarcinoma","volume":"94","author":"Marks","year":"2012","journal-title":"Ann. Thorac. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1067\/mtc.2002.119070","article-title":"Salvage esophagectomy for recurrent tumors after definitive chemotherapy and radiotherapy","volume":"123","author":"Swisher","year":"2002","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1053\/j.gastro.2019.10.039","article-title":"Circulating Tumor DNA Analysis for Detection of Minimal Residual Disease After Chemoradiotherapy for Localized Esophageal Cancer","volume":"158","author":"Azad","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101664","DOI":"10.1016\/j.eclinm.2022.101664","article-title":"Use of a non-endoscopic immunocytological device (Cytosponge\u2122) for post chemoradiotherapy surveillance in patients with oesophageal cancer in the UK (CYTOFLOC): A multicentre feasibility study","volume":"53","author":"Jones","year":"2022","journal-title":"eClinicalMedicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/dote\/dox100","article-title":"Active surveillance in clinically complete responders after neoadjuvant chemoradiotherapy for esophageal or junctional cancer","volume":"30","author":"Noordman","year":"2017","journal-title":"Dis. Esophagus"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1245\/s10434-025-18531-y","article-title":"Accuracy of Predicting Residual Disease and Disease Progression During Active Surveillance for Esophageal Cancer","volume":"33","author":"Panday","year":"2025","journal-title":"Ann. Surg. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13014-025-02637-4","article-title":"Preoperative chemoradiotherapy for esophageal or gastroesophageal junction cancer: Results from a retrospective study using extended CROSS regimen","volume":"20","author":"Haltmeier","year":"2025","journal-title":"Radiat. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"znaf286","DOI":"10.1093\/bjs\/znaf286","article-title":"Health-related quality of life of patients undergoing active surveillance versus standard surgery for oesophageal cancer (SANO trial)","volume":"113","author":"Panday","year":"2025","journal-title":"Br. J. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"111171","DOI":"10.1016\/j.ejso.2025.111171","article-title":"Long-term outcome of patient choice of surgery or active surveillance following a clinical complete response to neoadjuvant chemoradiotherapy for oesophageal cancer","volume":"52","author":"Smyth","year":"2025","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17266","DOI":"10.1002\/cam4.6308","article-title":"Esophageal cancer patients\u2019 need for information and support in making a treatment decision between standard surgery and active surveillance","volume":"12","author":"Hermus","year":"2023","journal-title":"Cancer Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"znae118.069","DOI":"10.1093\/bjs\/znae118.069","article-title":"Overall Survival in Patients with Esophageal Cancer and Clinical Complete Response after Radiochemotherapy: Should a Watchful Waiting Strategy be the New Standard of Care? Abstract only","volume":"111","author":"Gerber","year":"2024","journal-title":"BJS"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s10120-024-01556-9","article-title":"Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer","volume":"28","author":"Iden","year":"2024","journal-title":"Gastric Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1245\/s10434-023-13194-z","article-title":"Tumor Burden Monitoring with Circulating Tumor DNA During Treatment in Patients with Esophageal Squamous Cell Carcinoma","volume":"30","author":"Morimoto","year":"2023","journal-title":"Ann. Surg. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/path.6016","article-title":"Detection of circulating tumour DNA after neoadjuvant chemoradiotherapy in patients with locally advanced oesophageal cancer","volume":"259","author":"Eyck","year":"2022","journal-title":"J. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3451","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":"43","author":"Hoeppner","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1056\/NEJMoa2503701","article-title":"Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer","volume":"393","author":"Janjigian","year":"2025","journal-title":"N. Engl. J. Med."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/3\/170\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T09:33:49Z","timestamp":1773653629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/3\/170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,16]]},"references-count":43,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["curroncol33030170"],"URL":"https:\/\/doi.org\/10.3390\/curroncol33030170","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,16]]}}}