Neoadjuvant mFOLFOXIRI plus bevacizumab reduces peritoneal tumor burden in colorectal cancer patients.

To investigate the efficacy and safety of mFOLFOXIRI combined with bevacizumab plus cytoreductive surgery (CRS) in patients with resectable peritoneal metastasis of colorectal cancer (CRC). A single-center, prospective randomized controlled design was conducted. Inclusion criteria: confirmed synchronous or metachronous peritoneal metastasis of CRC, aged >18 years, adequate organ function and tolerance to chemotherapy, resectable peritoneal lesions with peritoneal cancer index (PCI) <20, Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1, and tolerance to CRS. Exclusion criteria: intolerance or inefficacy to oxaliplatin, distant unresectable metastasis, emergency surgery, active malignancy, history of thromboembolism, pregnancy or lactation, and other severe comorbidities. Between August 2022 and December 2024, eligible patients with resectable peritoneal metastasis of CRC treated at the Sixth Affiliated Hospital, Sun Yat-sen University were enrolled and randomly assigned at a 1:1 ratio to the neoadjuvant therapy group (mFOLFOXIRI plus bevacizumab followed by CRS) or the direct CRS group. The primary endpoint was the 1-year progression-free survival rate. Secondary endpoints included the response to neoadjuvant therapy, completeness of cytoreduction (CC) score, length of postoperative hospital stay, and postoperative complications. A total of 53 patients who underwent surgery were included, with 19 in the neoadjuvant therapy group and 34 in the direct CRS group. There were no statistically significant differences between the two groups in age, sex, BMI, primary tumor location, pathological type, pattern of peritoneal metastasis (synchronous/metachronous), extraperitoneal metastasis, history of prior systemic therapy, baseline radiological PCI score, or tumor markers (CEA, CA19-9, CA125) (all >0.05). In the neoadjuvant therapy group, post-treatment radiological PCI score was significantly lower than baseline [(,): 6.0 (4.0, 12.0) vs. 8.0 (5.0, 12.0), =-3.086, =0.002], and CEA was significantly reduced [3.9 (2.8, 7.3) μg/L vs. 7.7 (4.1, 16.1) μg/L, =-2.809, =0.005]. Hemoglobin and albumin levels were also decreased [107.0 (97.5, 117.0) g/L vs. 134.0 (118.0, 140.5) g/L, =-3.019, =0.003;35.9 (34.9, 39.3) g/L vs. 40.0 (37.3, 42.9) g/L, =-2.213, =0.027], with all differences statistically significant (all <0.05). CA19-9 and CA125 showed a downward trend, but the differences were not statistically significant (all >0.05). There were no significant between-group differences in CC grade (proportion of CC 0-1: 17/19 vs. 88.2% [30/34]), length of postoperative hospital stay [10.0 (7.0, 13.0) days vs. 13.0 (9.3, 14.0) days], or incidence of severe postoperative complications (8/19 vs. 38.2%[13/34]) (all >0.05). The proportion of 1-year progression-free survival in the neoadjuvant therapy group was 10/19, which was higher than that in the direct CRS group (29.4%), but the difference was not statistically significant (²=2.797, =0.096). Neoadjuvant therapy with mFOLFOXIRI plus bevacizumab can reduce peritoneal tumor burden without increasing surgical risk, and may improve progression-free survival. However, due to the small sample size and short follow-up duration, long-term benefits need to be confirmed by further follow-up.