Strengthening the Frail: Multimodal Prehabilitation and Clinical Resilience in Geriatric Gastric Cancer Surgery

Highlights

• Multimodal prehabilitation significantly reduces overall postoperative complications (17.2% vs 28.7%) in frail older patients undergoing radical gastrectomy.
• Interventions lasting as little as two weeks can meaningfully increase functional capacity, measured by a mean +24m improvement in the 6-minute walk test (6MWT).
• Prehabilitation acts as a biological primer, modulating chronic low-grade inflammation and enhancing surgical resilience beyond standard ERAS protocols.
• High compliance rates (93.75%) in supervised settings suggest that structured pre-surgical optimization is both feasible and tolerable for the geriatric population.

Background

Gastric cancer (GC) remains a significant global health burden, particularly among the elderly. As the population ages, a growing proportion of patients presenting for radical gastrectomy exhibit “frailty”—a clinical state characterized by diminished physiological reserve and increased vulnerability to external stressors. Frailty is a potent independent predictor of adverse outcomes, including prolonged hospitalization, increased morbidity, and functional decline following major abdominal surgery.

While Enhanced Recovery After Surgery (ERAS) pathways have revolutionized perioperative care by standardizing postoperative management, they are inherently reactive. “Prehabilitation” represents a paradigm shift, focusing on proactive optimization before the surgical stressor occurs. By integrating physical exercise, nutritional support, and psychological counseling, prehabilitation aims to bolster a patient’s functional capacity, potentially shifting them above the threshold for surgical complications.

Key Content

The GISSG+2201 Randomized Clinical Trial

The landmark GISSG+2201 trial (Sun et al., 2026) provides the most robust evidence to date for prehabilitation in this niche. This multicenter RCT conducted in China randomized 368 frail patients (aged 65–85 years) to either standard ERAS care or ERAS combined with at least two weeks of supervised multimodal prehabilitation. The study utilized the Geriatric 8 (G8) screening tool to identify frailty, ensuring a high-risk cohort was targeted.

Primary and Secondary Outcomes: The results demonstrated a clear superiority of the prehabilitation group (PG). The overall complication rate was 17.2% in the PG versus 28.7% in the standard group (SG) (P=0.01). Notably, the benefit was most pronounced in minor and medical complications, which often drive prolonged recovery in the elderly. Furthermore, the PG showed a significant improvement in the 6-minute walk test (6MWT) change (+24m) before surgery, whereas the standard group often experienced decline or stagnation.

Components of Effective Multimodal Prehabilitation

Evidence from GISSG+2201 and related studies (such as the PERIOP-OG trial and pulmonary-specific studies) suggests that a comprehensive approach is required:

• Physical and Respiratory Training: High-intensity pulmonary exercise and aerobic training are critical. A 2024 study showed that even short-term (5-day) intensive pulmonary training can significantly diminish postoperative pulmonary complications (PPCs) and reduce hospital costs.
• Nutritional Support: Addressing the nutritional depletion common in esophagogastric cancers is vital for muscle protein synthesis and wound healing.
• Psychosocial Treatment: Reducing surgical fear and enhancing self-efficacy are associated with better Quality of Recovery (QoR) scores.

Comparison with Traditional ERAS and Analgesic Protocols

While ERAS alone improves recovery—as shown in studies comparing ERAS to conventional care in distal gastrectomy (Ann Surg Oncol 2018)—the addition of prehabilitation addresses the “pre-surgical gap.” Furthermore, the choice of intraoperative management remains critical. Recent evidence (BMC Anesthesiol 2025) suggests that Erector Spinae Plane Blocks (EspB) may provide superior recovery profiles compared to traditional epidural anesthesia (EDA) in elderly patients, indicating that prehabilitation should be nested within a high-quality, minimally invasive surgical and analgesic environment.

Translational Insights: Inflammation and Resilience

A key finding from GISSG+2201 was the modulation of chronic low-grade inflammation. Prehabilitation appears to reduce the systemic inflammatory response usually exacerbated by surgery. By enhancing “surgical resilience,” patients are not only less likely to suffer a complication but are also better equipped to return to baseline functional status 4 weeks post-surgery, a milestone that the standard ERAS group often fails to reach.

Expert Commentary

The success of the GISSG+2201 trial hinges on its 93.75% compliance rate, which was achieved through supervised interventions. This raises a critical question regarding clinical implementation: Can these results be replicated in home-based, unsupervised settings? The PERIOP-OG trial (2024) noted that optional home-based programs were less effective in improving physical activity levels, suggesting that for frail patients, supervision is the key differentiator.

Clinicians must also consider the timing. A two-week window is often sufficient for physiological priming without delaying oncological treatment (such as neoadjuvant chemotherapy). However, the integration of prehabilitation into the neoadjuvant window (the “window of opportunity”) remains a complex logistical challenge that requires a multidisciplinary team approach involving surgeons, geriatricians, nutritionists, and physiotherapists.

Conclusion

Supervised multimodal prehabilitation is no longer a theoretical benefit but a clinically proven intervention for reducing morbidity in frail older patients with gastric cancer. By enhancing physiological reserve and modulating the inflammatory response, prehabilitation transforms the surgical journey from a period of vulnerability to one of managed resilience. Future research should focus on optimizing the “dose” of prehabilitation and exploring the long-term oncological impacts of improved perioperative health.