Qu-yu-jie-du decoction maintenance therapy improves postoperative survival in metastatic colorectal cancer: a single-center randomized trial with 36-month follow-up

BACKGROUND: Qu-yu-jie-du (QYJD) decoction is an established traditional Chinese medicine (TCM) formulation. For over ten years, there has been empirical evidence in support of its benefits for colorectal cancer patients, yet RCT validation for it as a postoperative maintenance therapy is lacking. Despite achieving no evidence of disease (NED) status after curative-intent resection in metastatic colorectal cancer (mCRC), up to 60 % of patients relapse within five years, with no guideline-recommended maintenance therapy. PURPOSE: To determine whether QYJD decoction improves disease-free survival (DFS) and modulates inflammation/lactate metabolism in postoperative mCRC-NED patients. METHODS/DESIGN: In this single-center randomized trial, 140 stage IV mCRC patients achieving post-resection NED status were randomized at a ratio of 1:1 to either a QYJD group (200 mL/day for 2 years) or a control group (routine follow-up). Two patients per group withdrew consent prior to the intervention, resulting in an intention-to-treat (ITT) population of 136 patients (68 per group) for the final analysis. All received standard adjuvant chemotherapy. The primary outcome was DFS; secondary outcomes were OS, 1-/2-/3-year survival rates, adverse events, and inflammation/lactate metabolism markers. RESULTS: Compared to the control group, QYJD decoction significantly improved DFS throughout the observation period (HR = 0.515, p = 0.004). The 1-year DFS rate was 91.2 % (62/68) in the QYJD group versus 73.5 % (50/68) in the control group (p < 0.01); the 2-year DFS rate was 56.9 % (40/68) in the QYJD group versus 35.1 % (25/68) in the control group (p = 0.002); and the 3-year DFS rate was 47.4 % (32/68) in the QYJD group versus 32.4 % (22/68) in the control group (p = 0.03). Significant differences were observed across all time points (1-year, 2-year, and 3-year) for DFS. Regarding overall survival (OS), the 2-year OS rate was 95.4 % (65/68) in the QYJD group versus 85.1 % (58/68) in the control group (p = 0.01), and the 3-year OS rate was 68.7 % (47/68) in the QYJD group versus 57.7 % (39/68) in the control group (HR = 0.407, p = 0.019). QYJD also significantly reduced inflammatory markers and lactate dehydrogenase (LDH) (p < 0.05). The most common adverse events were grade 1 hematologic toxicity, anorexia, diarrhea, and nausea, which were generally mild and manageable. CONCLUSION: QYJD decoction significantly improves DFS and shows OS benefits in postoperative mCRC-NED patients. It also reduces systemic inflammation/LDH, and in terms of safety, only causes mild adverse events. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100053521, registered on November 24, 2021).