Shengjie Pan, Gang Wang
In older adults undergoing gastrointestinal cancer surgery, a multidomain physiological vulnerability phenotype was associated with postoperative morbidity, delayed recovery, and long-term survival outcomes. Longitudinal assessment revealed substantial heterogeneity in physiological recovery after surgical stress. PABI should currently be considered an investigational risk phenotype rather than a validated clinical prediction tool. External multicenter validation and future intervention studies are required to determine whether simplified assessments of physiological vulnerability can improve perioperative risk stratification and patient outcomes.
BACKGROUND: Chronological age and conventional clinical risk factors incompletely capture physiological heterogeneity among older adults undergoing major surgery. Multisystem vulnerability involving inflammation, nutritional reserve, physical function, sleep-circadian regulation, psychological status, and cognitive performance may influence postoperative recovery and long-term outcomes. Whether an integrated multidomain physiological vulnerability phenotype can characterize perioperative risk and recovery patterns remains uncertain.
METHODS: In this prospective cohort study, 450 adults aged ≥60 years undergoing curative gastrointestinal cancer surgery were enrolled and followed for 3 years. Multidomain assessments incorporating inflammatory status, nutri-immune function, sarcopenia-related measures, sleep-circadian and autonomic regulation, psychological vulnerability, and cognitive performance were performed before surgery and during postoperative recovery. A Perioperative Aging Burden Index (PABI) was developed using hierarchical principal component analysis to quantify multidomain physiological burden. PABI was designed as a clinically measurable physiological vulnerability phenotype rather than a molecular aging clock. Associations of baseline PABI and early perioperative changes in PABI with postoperative delirium, clinically significant complications, length of stay, disease-free survival (DFS), and overall survival (OS) were evaluated using multivariable regression and Cox proportional-hazards models. Longitudinal recovery patterns were characterized using trajectory modeling, and internal validation was performed using bootstrap resampling.
RESULTS: Among 450 enrolled patients, 441 contributed to baseline PABI derivation. Higher baseline PABI was independently associated with postoperative delirium (adjusted OR per 1-SD increase, 1.88; 95% CI, 1.43-2.47), clinically significant complications (adjusted OR, 1.55; 95% CI, 1.20-2.00), delayed discharge (adjusted HR, 0.77; 95% CI, 0.66-0.89), poorer DFS (adjusted HR, 1.42; 95% CI, 1.21-1.67), and poorer OS (adjusted HR, 1.36; 95% CI, 1.13-1.64). Longitudinal analyses identified three distinct recovery patterns: rapid recovery, intermediate recovery, and sustained high physiological burden. Addition of PABI to clinicopathologic models improved discrimination for 3-year DFS, with the optimism-corrected C-index increasing from 0.684 to 0.738 after bootstrap validation.
CONCLUSIONS: In older adults undergoing gastrointestinal cancer surgery, a multidomain physiological vulnerability phenotype was associated with postoperative morbidity, delayed recovery, and long-term survival outcomes. Longitudinal assessment revealed substantial heterogeneity in physiological recovery after surgical stress. PABI should currently be considered an investigational risk phenotype rather than a validated clinical prediction tool. External multicenter validation and future intervention studies are required to determine whether simplified assessments of physiological vulnerability can improve perioperative risk stratification and patient outcomes.