Should All Nasopharyngeal Carcinoma with Paranasal Sinus Invasion Be Staged as T3 in the Intensity-Modulated Radiotherapy Era? A Study of 1811 Cases

Background: Currently, there is no uniform consensus regarding the appropriate staging for invasion of the paranasal sinuses in nasopharyngeal carcinoma (NPC). In the current AJCC staging system for NPC, paranasal sinus invasion is defined within the T3 classification. However, according to the Chinese 2008 staging system, which is also widely used in the regions where NPC is endemic in China, paranasal sinus invasion is classified as T4 disease. Methods: Patients (n = 1811) with non-metastatic, histologically-proven NPC treated with intensity-modulated radiotherapy (IMRT) were retrospectively analyzed. Results: Paranasal sinus invasion was identified in 289/1811 patients (16.0%). Multivariate analysis revealed ethmoid sinus invasion (HR, 2.889; 95% CI, 1.362-6.131; P = 0.006) and maxillary sinus invasion (HR, 3.110; 95% CI, 1.439-6.721; P = 0.004) were independent prognostic factors for local relapse-free survival (LRFS). T3 patients with ethmoid sinus or maxillary sinus invasion had similar 3-year LRFS (83.6% vs. 92.2%, P = 0.132) as T4 patients, and had poorer LRFS (83.6% vs. 98.3%, P = 0.006) than T3 patients with sphenoid sinus invasion alone. Also, T3 patients with sphenoid sinus invasion alone had similar 3-year LRFS (98.3 vs. 96.4%, P = 0.391) as T3 patients without paranasal sinus invasion, and a trend toward higher LRFS (98.3% vs. 92.2%, P = 0.065) than T4 patients. Conclusion: In patients underwent IMRT, tumors with ethmoid sinus or maxillary sinus invasion had a higher risk of local failure than those with sphenoid sinus invasion alone. Sphenoid sinus invasion alone should be classified as T3 disease and ethmoid sinus or maxillary sinus involvement as T4 disease in the current AJCC staging system for NPC.