Abstract
BACKGROUND: The development of reliable biomarkers for evaluating bevacizumab responsiveness following neoadjuvant therapy (NAC) could enable rapid identification of non-responding ovarian cancer patients, who may then be redirected promptly to alternative therapies with higher efficacy potential. Given that microvascular density (MVD) serves as a well-established surrogate marker for tumor angiogenesis, this study specifically investigated its potential role as a predictive biomarker for bevacizumab treatment outcomes in advanced ovarian cancer patients undergoing neoadjuvant regimens. PATIENTS AND METHODS: We conducted a multicenter, retrospective study to investigate the prognostic and predictive value of the tumor marker MVD in a real-world clinical setting. The study included 142 patients selected from five institutions. These patients had been treated with platinum-based neoadjuvant chemotherapy (NAC), with or without bevacizumab, followed by interval debulking surgery (IDS). Subsequently, they received adjuvant chemotherapy combined with bevacizumab, which was then transitioned to bevacizumab maintenance monotherapy. MVD was evaluated by immunohistochemical (IHC) staining of CD34 in post-NAC surgical specimens. RESULTS: Using a cutoff value of 33.8 microvessels/high-power field (HPF), which was determined based on the median of all measured MVD values, patients were stratified into high and low MVD subgroups. In the high MVD subgroup, the supplementation of standard platinum-based neoadjuvant chemotherapy with bevacizumab demonstrated significant survival benefits. This combination therapy achieved a 50% reduction in progression risk (HR: 0.500; 95% CI, 0.258-0.972; P = 0.041) and a 51% decrease in mortality risk (HR: 0.490; 95% CI, 0.225-0.819; P = 0.010), translating to clinically meaningful survival extensions of 4.7 months in median progression-free survival (P = 0.037) and 5.7 months in median overall survival (P = 0.008). Conversely, in the low MVD subgroup, bevacizumab augmentation of platinum/paclitaxel-based neoadjuvant chemotherapy failed to demonstrate statistical significance in either progression-free survival (HR: 0.620; 95% CI, 0.339-1.135; P = 0.121) or overall survival (HR: 0.664; 95% CI, 0.377-1.169; P = 0.156). CONCLUSIONS: Our real-world study provides preliminary evidence that bevacizumab may confer differential prognostic benefits in AOC patients undergoing NAC followed by IDS, contingent upon tumor MVD quantified via CD34 immunohistochemistry, though it is important to acknowledge the lack of independent external validation for these findings. This potential biomarker-driven therapeutic heterogeneity preliminarily underscores the possibility of developing adaptive treatment algorithms that stratify patients based on angiogenic susceptibility profiles, which may lay a foundation for exploring precision administration of anti-VEGF therapy in a cost-effective paradigm.