Longitudinal Interaction Between Frailty and Postoperative Symptom Burden in Older Adults Undergoing Colorectal Cancer Surgery: A Random Intercept Cross-Lagged Panel Model Study

Background/Objectives: Frailty and postoperative symptom burden are common in older adults undergoing colorectal cancer surgery, but their temporal associations remain unclear. This study examined longitudinal associations between frailty and two symptom dimensions, symptom severity and symptom interference, using the Random Intercept Cross-Lagged Panel Model (RI-CLPM). Methods: This prospective longitudinal study enrolled 242 older adults (≥60 years) undergoing CRC surgery. Frailty and symptoms were assessed before surgery and at 1 week, 1 month, 3 months, 6 months, and 12 months postoperatively. Separate RI-CLPMs were estimated for frailty with symptom severity and symptom interference. Sensitivity analyses compared results with conventional CLPMs, adjustment for time-varying albumin and body mass index, and a worst-case missing-data scenario. Results: Frailty and both symptom dimensions increased at 1 week after surgery, then generally declined. At the between-person level, frailty was strongly correlated with symptom severity and symptom interference. At the within-person level, higher symptom severity was associated with higher subsequent frailty from 1 to 3 months (β = 0.27, p = 0.033) and from 3 to 6 months (β = 0.38, p = 0.004), with the latter association remaining relatively stable across sensitivity analyses. Higher frailty was associated with higher subsequent symptom interference from before surgery to 1 week after surgery (β = 0.34), which was also relatively consistent across model specifications. Several other interval-specific paths changed after covariate adjustment or under the worst-case missing-data assumption. Conclusions: Frailty and postoperative symptom burden were closely associated at the between-person level, whereas within-person longitudinal associations were phase-specific and symptom-dimension-dependent.