Ready for Safe Cancer Treatment (RESET): Protocol for a Large-Scale Randomized Controlled Trial of an Integrated...

Background: Prolonged hospitalization, postoperative complications, and unplanned readmission remain major problems after major surgery. RESET evaluates a continuous perioperative pathway integrating individualized prehabilitation, coordinated inpatient care, enhanced-recovery principles, discharge planning, and transitional care in adults undergoing oncological surgery and patients aged 70 years or older undergoing non-oncological surgery. Methods: RESET is a prospective, two-center, two-arm randomized controlled study (NCT07727876). Up to 12,800 patients will be screened and approximately 8960 randomized 9:1 to RESET or standard care, including about 5740 oncological and 3220 non-oncological participants. The three primary outcomes are prolonged index hospitalization (≥14 days), unplanned readmission within 30 days after discharge, and postoperative complications within 30 days after surgery. Each outcome is evaluated separately in both clinical populations, yielding six primary hypothesis tests. Holm's procedure will control the family-wise error rate at α = 0.01 across all six tests, with endpoint- and population-specific confirmatory conclusions. Secondary outcomes include length of stay, multidomain health status, satisfaction, adherence, organizational effectiveness, and direct healthcare costs. Conclusions: RESET will evaluate the clinical and implementation effects of an integrated perioperative pathway across two surgical populations.