Surgery As Needed for Oesophageal Cancer - 2

Study Overview
=================
Brief Summary
-----------------
A prospective cohort study on active surveillance after neoadjuvant chemoradiation for oesophageal cancer: SANO-2 study.

Detailed Description
-----------------
An active surveillance approach after completion of neoadjuvant chemoradiotherapy for locally advanced oesophageal cancer is being investigated in the SANO (Surgery As Needed for Oesophageal cancer) trial, that completed patient inclusion in December 2020. First long term results are expected end 2023. Based on current retrospective studies and short term results of the SANO, to date there is no evidence that active surveillance is unsafe. Within the follow-up of the SANO trial, the safety of active surveillance is continuously monitored. Based on a high participation rate (>90%) in the SANO trial and on the view of the Dutch patient federation for cancer of the digestive tract (SPKS) to offer active surveillance as an alternative treatment option in a controlled setting, there is a demand for a tailored surgery approach after neoadjuvant chemoradiotherapy until results of the SANO trial are available. When patients request active surveillance outside the SANO trial, it is of the utmost importance to set up a prospective cohort study (extension study) in order to monitor safety, implementation and effectiveness of active surveillance outside the SANO trial before the final results of the SANO trail are available.

Official Title
-----------------
A Prospective Cohort Study on Active Surveillance After Neoadjuvant Chemoradiation for Oesophageal Cancer: SANO-2 Study

Conditions
-----------------
Cancer of Esophagus

Intervention / Treatment
-----------------
* Other: Active surveillance


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Operable patients who are planned to undergo or who recently underwent neoadjuvant chemoradiotherapy according to CROSS followed by surgical resection for histologically proven oesophageal squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophago-gastric junction Age ≥18 Written, voluntary, informed consent. Exclusion Criteria: Non-FDG-avid tumour at baseline PET-CT scan Initial treatment with endoscopic resection Patients who underwent of who are planned to undergo definitive chemoradiotherapy Language difficulty, dementia or altered mental status prohibiting the understanding and giving of informed consent.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Active surveillance|Patients will undergo two clinical response evaluations (CREs) after nCRT. During CRE-1 (5-6 weeks) patients will undergo oesophagogastroduodenoscopy (OGD) with bite-on-bite biopsies. During CRE-2 (10-12 weeks) patients will undergo positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) plus fine-needle aspiration (FNA). If cancer is detected, surgery will be performed. Patients with cCR are eligible for active surveillance where regular CREs are performed to detect regrowth of cancer. Delayed oesophagectomy will be offered to patients with highly suspected or profen locoregional regrowth, without distant metastases. The safety and feasibility of active surveillance depends on several factors monitored in the SANO trial. So far, these stopping rules have not been met. In case one of the stopping rules is reached, further inclusion in the SANO-2 study will be stopped and surgical resection is offered.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of active surveillance (including delayed surgery), measured by the number of patients with adverse events | Including: Complications from OGD with bite-on-bite biopsies, EUS-FNA and PET-CT Unresectable or incurable (T4b or R2) regrowth Microscopically non-radical (R1) resection Postoperative mortality (90 day- or in-hospital mortality) Postoperative hospital stay of >60 days Postoperative complications, defined by the Esophagectomy Complications Consensus Group (ECCG) Development of distant metastases | after the procedure/surgery and at least up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of distant and locoregional relapse | Defined as the proportion of all patients with cCR who develop distant metastases either locoregional relapse | at least up to 2 years | 
| 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 | From cCR until the date of first documented disease progression or date of death from any cause, whichever came first, assessed at least up to 2 years | 
| Overall survival (OS) | Patients with cCR at CRE-2, defined from date of diagnosis to date of all-cause death or to last day of follow-up | From cCR until the date of death from any cause, assessed at least up to 2 years | 
| The proportion of patients in the active surveillance strategy that opted for decision counseling | Decision counseling is a conversation with a trained physician who can elicit, examine, and discuss the patient's preferences in such a way that the patients are enabled to reflect on all aspects of his/her preference | at least up to 2 years | 
| The proportion of patients that opted for decision counselling as well as the proportion of patients who switched from preferring active surveillance to preferring immediate surgery or vice versa. |  | at least up to 2 years | 
| Fear of recurrence of cancer | Assessed with the validated Cancer Worry Scale, including 8 items rated on a 4-point Likert scale ranging from never to almost always. Scores range from 8 to 32. Higher scores indicate more frequent worries about cancer. | at least up to 2 years | 
| Regret of the decision to undergo active surveillance | Measured by the validated Decision Regret Scale, including 5 items rated on a 5-point Likert scale ranging from 1 (strongly agree) to 5 (strongly disagree). Two of the statements (items 2 and 4) were phrased in the negative direction to avoid yea-saying bias. Scoring consisted of reversing the scores of the 2 negatively phrased items, then taking the mean of the 5 items. These means were converted to a score ranging from 0 to 100 by subtracting 1 and multiplying by 25. A score of 0 means no regret; a score of 100 means high regret. | at least up to 2 years | 
| Regret of the decision to undergo surgery | Measured by the validated Decision Regret Scale, including 5 items rated on a 5-point Likert scale ranging from 1 (strongly agree) to 5 (strongly disagree). Two of the statements (items 2 and 4) were phrased in the negative direction to avoid yea-saying bias. Scoring consisted of reversing the scores of the 2 negatively phrased items, then taking the mean of the 5 items. These means were converted to a score ranging from 0 to 100 by subtracting 1 and multiplying by 25. A score of 0 means no regret; a score of 100 means high regret. | at least up to 2 years | 
| The proportion of participating patients in the SANO-2 study who meet all eligibility criteria |  | after the procedure and at least up to 2 years | 
| The proportion of performed diagnostic modalities performed at appropriate time | According to the SANO-2 study algorithm | after the procedure and at least up to 2 years | 
| The proportion of all performed CREs performed in correct order | Defined as PET-CT within 1 week followed by combined OGD and EUS | after the procedure and at least up to 2 years | 
| The proportion of all performed endoscopies with at least 4 bite-on-bite biopsies taken | When taking bite-on-bite biopsies, a second biopsy is taken exactly at the same location of the first biopsy. | after the procedure and at least up to 2 years | 
| The proportion of performed FNA in case of suspected lymph nodes | Suspected lymph nodes are defined as round, hypoechoic and larger than 5 mm. | after the procedure and at least up to 2 years | 
| The proportion of performed endoscopic reports which are complete | OGD for anatomical landmarks which should be described, such as locations of the upper and lower tumour boundary, upper oesophageal sphincter, Z-line (where the squamous epithelium of the oesophagus meets the columnar epithelium), oesophagogastric junction (upper border of gastric folds) and diaphragmatic impression. | after the procedure and at least up to 2 years | 
| The number of biopsies taken and quality of the biopsies |  | after the procedure and at least up to 2 years |