Efficacy and safety of thymosin combined with anticancer therapy for colorectal cancer: a systematic review and meta-analysis of controlled studies

Objective To evaluate the efficacy and safety of thymosin preparations added to the same background anticancer treatment in patients with colorectal cancer. Methods We searched nine bibliographic and trial-registration sources through 1 October 2026. Randomized controlled trials (RCTs) and nonrandomized studies with concurrent controls were eligible. Risk of bias was assessed using RoB 2 and ROBINS-I. RCTs provided the primary evidence; nonrandomized studies were analyzed separately. Review Manager 5.4.1 calculated risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs), organized by treatment setting. Sensitivity analyses, GRADE and exploratory trial sequential analysis (TSA) assessed robustness and uncertainty. Results Thirty studies involving 2,514 participants comprised 25 RCTs (2,079 participants) and five nonrandomized studies (435 participants). In postoperative RCTs, CD4 percentage (MD 6.33, 95% CI 4.89 to 7.76), CD4/CD8 ratio (MD 0.25, 0.16 to 0.35) and NK-cell percentage (MD 6.41, 3.72 to 9.11) were higher with thymosin; CD3 and CD8 findings were inconclusive. KPS was higher in two postoperative RCTs (MD 8.50, 6.52 to 10.48) and two advanced or mixed-stage trials (MD 4.35, 1.90 to 6.80), with source-reporting concerns affecting the latter. Postoperative neutropenia was inconclusive in the RCT (RR 0.91, 0.82 to 1.01), whereas two nonrandomized studies reported a lower unadjusted risk (RR 0.65, 0.51 to 0.83). Comparable one-year survival evidence came from one trial. Certainty was low or very low. Conclusion This review identifies RCT-based signals in circulating immune indices and performance status and clarifies the contribution of nonrandomized evidence. These findings inform the selection of outcomes and treatment settings for future trials. Current evidence is insufficient to support routine clinical use of thymosin preparations in colorectal cancer. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261467566 , CRD420261467566.