Integrated perioperative host-response optimization improves functional recovery and survival after ultra-low anterior resection: A randomized controlled trial.

BACKGROUND

Ultra-low anterior resection for low rectal cancer is associated with profound perioperative physiologic stress and systemic inflammation, contributing to impaired functional recovery and adverse long-term outcomes. Whether the perioperative host response can be effectively modulated to improve both recovery and survival remains unclear.

METHODS

In this single-center, randomized controlled trial, 194 patients with stage I-III low rectal adenocarcinoma undergoing curative ultra-low anterior resection were assigned to standard enhanced recovery after surgery care or enhanced recovery after surgery plus an integrated perioperative host-response optimization program. The intervention combined structured perioperative optimization strategies targeting stress regulation, sleep normalization, and individualized nutritional support, delivered from the preoperative period through postoperative month 6. Primary outcomes included postoperative functional recovery, assessed by validated measures of bowel, sleep, psychological, and sexual function. Secondary outcomes comprised postoperative inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor-α), short-term recovery metrics, and 24-month disease-free survival and overall survival.

RESULTS

Compared with standard enhanced recovery after surgery care, the intervention group demonstrated significantly attenuated systemic inflammation on postoperative day 7 (C-reactive protein, interleukin-6, and tumor necrosis factor-α; all P < .001), accompanied by a faster return of bowel function and a shorter hospital stay. Functional recovery across bowel, sleep, psychological, and sexual domains was significantly improved and exceeded prespecified minimal clinically important difference thresholds. At 24 months, disease-free survival was 92.8% in the intervention group vs 77.3% in controls, and overall survival was 95.9% vs 83.5%, respectively. In multivariable Cox models adjusted for age, TNM stage, baseline depressive symptoms, and postoperative inflammatory markers, the intervention was independently associated with improved disease-free survival (hazard ratio, 0.44; 95% confidence interval, 0.22-0.87) and overall survival (hazard ratio, 0.39; 95% confidence interval, 0.17-0.89).

CONCLUSION

Integrated perioperative optimization targeting the host inflammatory and stress response significantly improves functional recovery and is associated with superior disease-free survival and overall survival after ultra-low anterior resection for rectal cancer. These findings support perioperative host-response modulation as a clinically actionable strategy to enhance both short- and long-term surgical outcomes.