Bevacizumab-Based Therapy Is Associated with Prolonged Progression-Free Survival in Patients with Peritoneal Mucinous Metastatic Colorectal Cancer

Objective: In metastatic colorectal cancer (mCRC), mucinous histology has been associated with poor clinical outcomes, particularly in the presence of peritoneal metastasis. However, it remains unclear whether mucinous histology exerts a context-dependent effect on treatment outcomes by modifying the efficacy of anti-vascular endothelial growth factor (VEGF)-based therapies independently of metastatic dissemination patterns and chemotherapy backbone. Methods: We retrospectively analyzed 250 patients with mCRC treated with bevacizumab-containing systemic therapy. Tumors were classified as mucinous (n = 52) or non-mucinous (n = 198). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Cox proportional hazards regression models were applied for univariate and multivariate analyses. Predefined subgroup analyses were conducted according to peritoneal metastasis status and chemotherapy backbone (oxaliplatin- or irinotecan-based). A 6-month landmark analysis was performed to reduce early progression bias. Interaction analyses evaluated potential effect modification between histology, peritoneal metastasis, and chemotherapy backbone. Results: Mucinous tumors were more frequently right-sided and strongly associated with peritoneal metastasis. In the overall cohort, mucinous histology was associated with significantly longer median PFS compared with non-mucinous histology (22.9 vs. 11.9 months; p < 0.001). This benefit was driven by patients with peritoneal metastasis, in whom mucinous histology was associated with markedly prolonged PFS (23.9 vs. 8.7 months; p < 0.001). No significant PFS difference according to histology was observed in patients without peritoneal metastasis. On multivariate analysis, mucinous histology remained independently associated with improved PFS (HR 0.44; 95% CI 0.25–0.78; p = 0.005), an effect preserved in the landmark cohort (HR 0.39; 95% CI 0.26–0.59; p < 0.001). A significant interaction between mucinous histology and peritoneal metastasis was observed (p for interaction = 0.040), indicating that the prognostic impact of histology differed according to metastatic pattern. No significant PFS difference or interaction was detected according to chemotherapy backbone within the mucinous subgroup. Conclusions: Among bevacizumab-treated patients with mCRC, mucinous histology—particularly in the presence of peritoneal metastasis—is associated with a pronounced PFS advantage independent of chemotherapy backbone. These findings suggest that mucinous peritoneal mCRC represents a biologically and clinically distinct subgroup that may derive context-specific and disproportionate benefit from anti-VEGF-based strategies, warranting prospective validation.