Comparative Effectiveness and Safety of Systemic Versus Intralesional Bevacizumab in the Management of Recurrent Respiratory Papillomatosis

ABSTRACT: Systemic and intralesional administration of bevacizumab have emerged as important therapeutic strategies for recurrent respiratory papillomatosis (RRP), a benign but aggressive disease characterized by frequent recurrences and surgical burden. This narrative review evaluated the comparative effectiveness and safety of systemic versus intralesional bevacizumab, synthesizing evidence from 18 eligible studies, including systematic reviews, prospective interventional studies, retrospective case series, and consensus statements. Systemic bevacizumab demonstrated complete remission rates ranging from 30% to 82%, with several studies reporting prolonged surgical intervals or elimination of further procedures. Improvements were consistently noted in Derkay severity scores, voice outcomes, and overall disease burden. However, systemic therapy was associated with a higher adverse event profile, including proteinuria, hypertension, and rare severe complications such as tracheoesophageal fistula and neutropenia. Intralesional bevacizumab, predominantly used in localized laryngeal disease, achieved complete remission in up to 40% of cases, significantly prolonged surgical intervals, and improved disease severity scores, with minimal or no drug-related adverse events reported. Comparative data between the two modalities were lacking, and outcome definitions varied across studies, limiting direct comparisons. Nonetheless, findings indicate systemic therapy may be better suited for refractory or disseminated disease, whereas intralesional delivery appears safe and effective for localized cases. Future randomized controlled trials directly comparing both approaches are essential to establish optimal treatment protocols and clarify long-term safety and efficacy. Keywords: Papillomatosis, Recurrent Respiratory Papillomatosis, Bevacizumab, Intralesional Injections, Systemic Therapy, Angiogenesis Inhibitors, Treatment Outcome, Safety