ImpRovEd Care After eSophageCtomy Using an Algorithm for postoperativE Complications - RESCUE Trial

The primary outcome measure is the incidence of severe complications (i.e. Clavien-Dindo ≥ 3b). Severe complications are defined as a composite endpoint with one or more of the following criteria within 90 days after esophagectomy:

• The complication was treated under general anaesthesia.
• Postoperative mortality.
• Escalation of care due to new onset or progressive organ failure (i.e. patients requiring vasopression, dialysis, (re-)intubation, (re)admission to a medium care or intensive care unit).

General quality of life, as measured using the validated EuroQol EQ-5D-5L questionnaire. Assessment will be performed at 6 weeks and 3, 6 and 12 months.

Time to functional recovery, defined as when a patient does not need intravenous fluid, has adequate pain control with oral analgesia (Numeric Rating Scale ≤4), restored mobility to an independent level (e.g. walk to the toilet with(out) walking aids and transfer bed/chair) or back to the previous functioning level of mobilization, sufficient caloric intake (minimum of 50% of the required calories), no signs of an active infection (no fever and declining CRP levels).

Comprehensive Complications Index, a measure for the severity of all complications together.

Failure to rescue, defined as the rate of mortality in patients with a complication within 90-days after esophagectomy.

Length of hospital and ICU stay, defined as the amount of days the patient stays in the ICU and in the hospital during 90 days postoperatively.

succes of implementation (i.e. proportion of patients' days in which the algorithm was not followed)

Cost-efficacy analysis will be performed from a societal perspective, including both medical and non-medical costs. Economic evaluation will be performed at 12 months follow-up. Medical resource use will be recorded from hospital records, including length of stay, laboratory and diagnostics use and treatment of complications. Medical resource use as well as out-of-pocket expenses will be recorded using iMTA Medical Consumption Questionnaire (iMCQ). [26] Resource use will be multiplied by associated unit costs to obtain total costs. Standard cost prices from the 'Dutch Guidelines for Cost Analyses' and www.medicijnkosten.nl will be used. Volumes of care will be multiplied by the cost price of each volume to calculate costs.

Productivity losses will be measured using the iMTA Productivity Cost Questionnaire (iPCQ).

Budget Impact Analysis (BIA) will be performed to assess the financial consequences of implementing the algorithm-based care, wherein the internationally accepted principles of ISPOR for the design, implementation and reporting of the BIA will be used. The third party payer perspective will be adopted to inform a business case for reimbursement companies.

Cancer-specific quality of life, as measured using the validated EIRTC QLQ-C30 questionnaire. Assessment will be performed at 6 weeks and 3, 6 and 12 months.

Esophageal cancer-specific quality of life, as measured using the validated EORTC QLQ-OG25 questionnaire. Assessment will be performed at 6 weeks and 3, 6 and 12 months.