Host-Response Optimization Trial After Ultra-Low Anterior Resection

Key Takeaways

• Twenty-four-month disease-free survival and overall survival were both higher in the intervention group than in the standard ERAS group.
• Functional recovery was better with the integrated program across bowel, sleep, psychological, and sexual domains, with gains exceeding prespecified minimal clinically important difference thresholds.
• Postoperative day 7 inflammatory markers were lower, alongside faster bowel recovery and a shorter hospital stay.

For patients undergoing curative ultra-low anterior resection for low rectal cancer, an integrated perioperative program was associated with a 15.5-point higher 24-month disease-free survival rate. In a single-center randomized trial of patients with stage I–III low rectal adenocarcinoma, investigators compared standard enhanced recovery after surgery care with the same pathway plus host-response optimization. They tracked postoperative recovery measures, inflammatory signals, and 24-month oncologic outcomes after surgery.

Researchers randomized 194 patients, with 97 assigned to each arm, in a prospective single-center parallel-group trial at the First Affiliated Hospital of Soochow University. Enrollment ran from May 2019 through May 2021 in Suzhou, China, among patients with stage I–III low rectal adenocarcinoma undergoing curative ultra-low anterior resection. All participants underwent curative surgery without neoadjuvant therapy and received either standard ERAS care or ERAS plus optimization from before surgery through postoperative month 6. The added program centered on stress regulation, sleep normalization, and individualized nutritional support, while outcomes included functional recovery, inflammatory markers, short-term recovery, disease-free survival, and overall survival. The same randomized cohort was followed for both early recovery outcomes and 24-month survival.

The primary endpoint of functional recovery favored the integrated program across bowel, sleep, psychological, and sexual domains. Gains exceeded prespecified minimal clinically important difference thresholds in each of those areas. By postoperative day 7, CRP, IL-6, and TNF-α were all lower in the intervention group, with all comparisons reported at P < .001. Return of bowel function was faster, and hospital stay was shorter.

At 24 months, disease-free survival was 92.8% with host-response optimization and 77.3% with standard ERAS care. Overall survival at the same time point was 95.9% versus 83.5%, respectively. In adjusted Cox models, the intervention was associated with improved disease-free survival, with a hazard ratio of 0.44 and a 95% confidence interval of 0.22 to 0.87. Overall survival showed a similar association, with a hazard ratio of 0.39 and a 95% confidence interval of 0.17 to 0.89. Follow-up at 24 months was completed by 91.8% of the intervention group and 89.7% of controls.