Real-World Evidence for Qizhen Yiliu Formula in Nonfunctional Pancreatic Neuroendocrine Tumors after Radical Resection: A Multicenter, Retrospective Study with Propensity Score Matching

Objective: Despite radical resection, postoperative recurrence of nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) remains common, particularly among high-risk patients. This study evaluates the adjuvant therapeutic potential of Qizhen Yiliu Formula (QZYL) in a multicenter real-world cohort. Methods: We retrospectively analyzed patients with NF-PanNETs treated at five tertiary centers in China between 2010 and 2022. Patients were divided into QZYL and control groups based on receipt of QZYL as postoperative adjuvant therapy. Baseline differences were adjusted using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) sensitivity analysis. 385 eligible patients were analyzed, with 112 matched pairs. Results: QZYL treatment was associated with longer recurrence-free survival (RFS) compared with controls (median: 78.0 vs. 71.9 months; HR = 0.60, P = 0.027), with higher 24-, 36-, and 60-month RFS rates (90.92% vs. 80.36%, 86.14% vs. 70.07%, 64.97% vs. 55.56%, respectively). Subgroup analyses demonstrated trends favoring QZYL across high-risk strata (Ki-67 index 10%–20%, tumor size ≥4 cm, lymph node metastasis, and pathological invasion), although statistical significance varied between PSM and IPTW analyses. Among patients receiving other adjuvant therapies, QZYL use was associated with improved outcomes (HR = 0.56, P = 0.070). Safety analysis indicated that QZYL did not increase the overall incidence of adverse events ( P = 0.847) and was associated with a lower incidence among patients receiving other adjuvant therapies ( P = 0.010). Conclusions: QZYL use was associated with a reduced risk of postoperative recurrence in patients with high-risk NF-PanNET, suggesting its role in postoperative management. Prospective validation is warranted.