Updated Clinical Nodal Staging System for p16+ Oropharyngeal Squamous Cell Carcinoma Associated with Loss of Prognostic Data

Abstract

<h3>Purpose/Objective(s)</h3> Due to human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) having significantly improved prognosis, the American Joint Committee on Cancer (AJCC) introduced a distinct staging system for p16+ OPSCC in its 8^th edition. The clinical nodal staging system removed multiple pathologic factors present in the 7^th edition, including nodal quantity and extracapsular extension (ECE). This study aimed to characterize whether the simplification of the staging system resulted in the loss of prognostic value by using the National Cancer Database (NCDB). <h3>Materials/Methods</h3> The NCDB was queried for patients diagnosed with p16+ OPSCC. Patients with no staging information, metastatic disease, who did not receive definitive surgery or radiation, or had unknown follow-up were excluded. The prognostic impact of nodal size, nodal quantity, nodal laterality, and ECE on overall survival (OS) were assessed using survival analysis with the Kaplan Meier method, univariable, and multivariable Cox proportional hazards regression. <h3>Results</h3> A total of 21,868 patients met inclusion criteria. On Kaplan Meier analysis, patients with more than one positive lymph node had significantly inferior OS (p<0.001; 5-yr OS: 82% vs 86%). Patients with ECE also had inferior outcomes (p<0.001; 5-yr OS: 82% vs 75%). Patients with contralateral or bilateral nodal involvement also had inferior OS (p<0.001; 5-yr OS: 71% vs 84%). Lastly, a largest nodal size of >6 cm was also associated with inferior OS (p<0.001; 5-yr OS: 66% vs 82%). Interestingly, a nodal size of ≤3 cm was also associated with inferior OS compared to 3-6 cm (p<0.001; 5-yr OS: 81% vs 84%). On multivariable Cox regression, having more than one positive node (p<0.001; HR [95% CI]: 1.17 [1.07-1.28]), ECE (p<0.001; HR [95% CI]: 1.20 [1.04-1.38]), and a node >6 cm (p<0.001; HR [95% CI]: 1.52 [1.30-1.79]) remained associated with inferior OS. Node laterality was no longer significant (p=0.99). There was no longer a significant difference between ≤3 cm nodes and 3-6 cm nodes (p=0.63), but only when the model included T stage. Other factors associated with OS included age, Charlson Deyo score, insurance type, T stage, and lymphovascular invasion (LVSI). <h3>Conclusion</h3> Although incorporation of p16 status in OPSCC staging was an important addition to the AJCC 8^th edition, the associated simplifications in the current staging system result in loss of valuable prognostic information in nodal staging, including nodal quantity and ECE, which could limit risk stratification of patients with node-positive OPSCC. Although all of these factors needn't necessarily be included in the staging system, and could instead be used as additional prognostic and predicative considerations, further work evaluating the impact of the updated clinical nodal staging for p16+ OPSCC prognostication and treatment selection is warranted, and should be considered for future iterations of the AJCC staging system.