The Number of Radiographically Positive Lymph Nodes is Predictive of Survival in HPV-Associated Oropharyngeal Cancer and Further Stratifies Outcomes Beyond Clinical Staging Alone

Abstract

<h3>Purpose/Objective(s)</h3> HPV-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) requires further study to optimize patient selection for treatment de-escalation. We aim to present an alternative stratification within the cN1 category for patients with HPV(+)OPSCC undergoing surgical therapy using radiographically positive lymph nodes (LNs). <h3>Materials/Methods</h3> 260 patients were enrolled from two prospective clinical trials at a high-volume referral center. Patients without pathologic data available for assessment were excluded. Patients underwent primary tumor resection and lymphadenectomy, followed by either standard of care (60 Gy in 30 fractions) +/- cisplatin (40 mg/m² weekly) or de-escalated radiotherapy (30 Gy in 20 bid fractions) with concomitant 15 mg/m2 docetaxel once weekly. Imaging studies were independently reviewed by a blinded neuroradiologist classifying radiographic extranodal extension (radENE) and involved LNs. <h3>Results</h3> Patients had a median of 2 radiographically positive LNs (range: 0-12) and 107 (41%) had radENE. All 3 forms of nodal categories (clinical, radiographic, and pathologic) predicted for PFS (p<0.0001 for each), as did radENE (p=0.0014). Both radN and cN categories were equivalent to the final pN category in over 80% of cases. For the entire cohort, stratification by the number of radiographically positive LNs alone predicted for PFS (p=0.003). Among only cN1 patients, stratifying by radiographically positive LNs 1-2 vs. 3-4 vs. > 4 also predicted for PFS (p=0.017), with 2-year PFS rates of 96%, 88%, and 81%. More than 2 radiographically positive LNs was identified as a significant threshold for PFS (p=0.0055) and overall survival (OS) (p=0.029). Lymph node size was not predictive of PFS. <h3>Conclusion</h3> The number of radiographically positive LNs is predictive of PFS for surgically managed HPV(+)OPSCC. Among cN1 patients, increasing radiographically positive LNs is predictive of worse PFS, and > 2 such LNs portends decreased OS. cN1 patients with 0-2 radiologically positive LNs could be categorized as cN1a, patients with 2-4 radiologically positive LNs categorized as cN1b, and patients with > 4 radiographically positive LNs categorized as cN1c.