Biomarker-Guided Inflammatory Control and Multidimensional Recovery After Abdominoperineal Resection: A Prospective...

Patients undergoing abdominoperineal resection (APR) for rectal cancer frequently experience persistent inflammation, nutritional decline, and psychosocial distress, which may adversely affect postoperative recovery and longer-term clinical trajectories.

In this single-center, prospective nonrandomized cohort, 200 patients with stage I-III rectal adenocarcinoma undergoing APR received either standard Enhanced Recovery After Surgery (ERAS) care (n = 100) or a biomarker-guided program (n = 100) integrating inflammatory modulation and immunometabolic/nutritional support. Supplements (sodium butyrate, multi-strain probiotics, omega-3 fatty acids) were Good Manufacturing Practice-certified and titrated to predefined C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) thresholds. The prespecified primary endpoint was change in Beck Depression Inventory-II (BDI-II) score over 24 months, selected to reflect patient-centered psychosocial recovery after APR. Secondary endpoints included sleep (Pittsburgh Sleep Quality Index, PSQI), sexual function (IIEF-5/FSFI), QLQ-C30 role/emotional functioning, inflammatory and immune markers, skeletal muscle index, and exploratory disease-free survival (DFS) and overall survival (OS). The present report should be interpreted as an interim medium-term analysis rather than a definitive long-term oncologic evaluation. The study was approved by the institutional ethics committee, and the protocol and statistical analysis framework are disclosed in the Supporting Information to enhance transparency.

Compared with controls, the intervention group showed greater 24-month improvements in BDI-II (-5.1 vs. -1.9), PSQI (-3.6 vs. -1.2), IIEF-5/FSFI (+5.3/+5.9 vs. +1.7/+2.1), and QLQ-C30 role/emotional (+11.1/+12.7 vs. +3.4/+4.1; all q < 0.01), meeting minimal clinically important difference in ≥ 2 domains in 65.6% versus 31.2% (p < 0.001). POD7 CRP, IL-6, and TNF-α were lower, and CD4⁺/CD8⁺ ratio recovered faster. Exploratory survival analyses also showed associations with reduced recurrence or death (DFS HR 0.43 [95% CI 0.23-0.81]; OS HR 0.39 [95% CI 0.18-0.84]). However, immune recovery beyond the current observation window was not evaluated in this analysis. Compliance was 85.6%, and adverse events were mild (8.1%).

A perioperative, biomarker-guided integrative program targeting inflammatory and immunometabolic vulnerability was associated with improved psychosocial and functional recovery after APR, with favorable effects on immune restoration and exploratory survival outcomes, and with excellent safety and adherence. Longer follow-up will be required to determine whether the observed immune and survival benefits remain durable over time.