Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial

作者：on behalf of the SANO-study group, Bo Jan Noordman, Bas P. L. Wijnhoven, Sjoerd M. Lagarde, Jurjen J. Boonstra, Peter‐Paul L. O. Coene, Jan Willem T. Dekker, Michael A. Doukas, Ate van der Gaast, Joos Heisterkamp, Ewout A. Kouwenhoven, Grard A. P. Nieuwenhuijzen, Jean-Pierre E. N. Pierie, Camiel Rosman, Johanna Wilhelmina van Sandick, Maurice J.C. van der Sangen, Meindert Nico Sosef, Manon C.W. Spaander, Roelf Valkema, Edwin S. van der Zaag, Ewout Willem Steyerberg, J. Jan B. van Lanschot · 发表于：BMC Cancer · 年份：2018 · DOI：10.1186/s12885-018-4034-1 · 被引用次数：248 · 研究领域：Esophageal Cancer Research and Treatment、Pancreatic and Hepatic Oncology Research、Esophageal and GI Pathology

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. METHODS: This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The dura...