Clinical Outcomes in Patients with Cystic Fibrosis-Related Chronic Rhinosinusitis Treated with Functional Endoscopic Sinus Surgery or Triple Highly Effective Modulator Therapy: A Monocentric Retrospective Experience

Background: Cystic Fibrosis (CF) is an autosomal recessive inherited disease caused by mutations of the CF–transmembrane conductance regulator (CFTR), leading to impaired chloride ion trafficking, thickened secretions, and chronic rhinosinusitis (CF-CRS). CF-CRS was historically managed with intranasal corticosteroids (INCS) and endoscopic sinus surgery (ESS). Nowadays, the triple highly effective modulator therapy elexacaftor–tezacaftor–ivacaftor (ETI) is showing promising results in improving CF-CRS. Methods: This is a monocentric, retrospective study comparing Sinonasal Outcome Test-22 (SNOT-22), Nasal Polyps Score (NPS), modified Lund–Kennedy score (mLKS), sniffin’ sticks identification test (SSIT), and Lund–Mackay score (LMS) in patients affected by CF-CRS and treated with ESS or ETI. ETI patients were further subdivided based on previous surgery. Results: A total of 25 patients were surgically treated, and 54 were treated with ETI (specifically, 17 surgically naïve and 37 post-FESS patients). Patients undergoing ESS and those receiving ETI experienced statistically significant improvements in SNOT-22, SSIT, and LMS with no differences between groups and regardless of genetic or demographic characteristics. Conversely, ESS patients experienced significantly higher mean changes in NPS and mLKS. Conclusions: ETI and FESS were safe and effective in reducing the symptomatologic burden of CF-CRS. Even in the ETI epoch, surgery may play a crucial role in managing CF-CRS, particularly in patients not eligible for ETI or experiencing severe disease not adequately controlled with medical therapy alone.