Table 1 Overview of the secondary endpoints in adherence to the SANO-2 study protocol

Adherence and quality of active surveillance according to the protocol, including:

 ⦁ The proportion of patients who meet all eligibility criteria;

 ⦁ The proportion of appropriately timed diagnostic modalities (according to timing of CREs in Fig. 1);

 ⦁ The proportion of CREs that are performed in correct order (FDG-PET/CT one week prior to combined upper endoscopy and EUS);

 ⦁ The proportion of upper endoscopies with at least 4 bite-on-bite biopsies or regular biopsies taken;

 ⦁ The proportion of FNA performed in case of suspicious lymph nodes;

 ⦁ The proportion of complete endoscopic reports (anatomic landmarks should be described in cm from incisors, including upper and lower tumor boundary, upper esophageal sphincter, Z-line (i.e. squamo-columnar junction), esophagogastric junction (i.e. upper border of gastric folds) and diaphragm impression);

 ⦁ The number of biopsies taken and quality of the biopsies, defined as (non-)representative by the pathologist

Effectiveness of active surveillance outside the SANO trial, regarding the following endpoints:

 ⦁ Rate of distant relapse, defined as the proportion of all patients with cCR who develop distant metastases;

 ⦁ Rate of locoregional relapse, defined as the proportion of patients with cCR who develop locoregional relapse;

 ⦁ Progression-free survival (PFS), defined as the interval between cCR and the earliest occurrence of disease progression resulting in primarily (or peroperatively) unresectable disease, locoregional regrowth (after completion of therapy), distant dissemination (during or after completion of treatment) or all-cause death;

 ⦁ Overall survival (OS) of patients with cCR at CRE-2 (i.e. 10–12 weeks after completion of nCRT), defined from date of diagnosis to date of all-cause death or to last day of follow-up