Effects of postoperative antifungal therapy on the recurrence of Aspergillus infection after pulmonary aspergilloma resection: a prospective, randomized, controlled, single-center, 24-month, open-label, parallel group trial.

BACKGROUND: Surgical resection is considered the most effective therapeutic method for pulmonary aspergilloma (PA), while the necessity of postoperative antifungal therapy remains controversial. Previous studies have several shortcomings such as retrospective design and inadequate follow-up durations. In this study, we aim to address these evidence gaps by evaluating the effects of postoperative antifungal therapy on both Aspergillus infection recurrence and drug-related side effects. METHODS: We conducted a prospective, randomized, controlled, single-center clinical trial. Eligible patients with PA who underwent surgical resection at our institute were enrolled and randomly assigned to receive either a 3-month course of voriconazole (VRZ) tablet postoperatively or symptomatic treatment alone. Participants were evaluated for Aspergillus infection recurrence and drug-related side effects every 3 months for 2 years. Ultimately, 36 patients in the VRZ group and 14 patients in the control group were included in the analysis, with balanced baseline characteristics between groups. RESULTS: After a median follow-up of 27 months, no recurrence of Aspergillus infection was observed in either group. Symptomatic improvements (e.g., hemoptysis and white sputum) were comparable between groups. Although serum IgG level significantly increased by 2.22 g/L after VRZ treatment (p < 0.001), other parameters indicating immune activity (CD4+%, CD8+%, CD4+/CD8+ ratio, IgA, IgM and Aspergillus-specific IgG) and pulmonary function showed no significant intergroup differences at the final follow-up. Regarding safety, VRZ intervention was associated with a significant increase in aspartate aminotransferase level (20.9 ± 6.2 U/L to 26.5 ± 7.8 U/L, p = 0.023). Hypokalemia incidence was numerically higher in the VRZ group (21.4% vs. 0, p = 0.530), though not statistically significant. CONCLUSIONS: Our findings demonstrated that postoperative antifungal therapy did not reduce Aspergillus recurrence rate but posed potential safety risks. For immunocompetent patients undergoing complete resection without intraoperative fungal spillage, routine postoperative antifungal agents are not recommended. TRIAL REGISTRATION: Chinese Clinical Trial Registry Number: ChiCTR1800019990, registration date: December 11th, 2018.