Predicting Pathologic Lymph Node Positivity in cN0 Pharynx and Larynx Cancers in the Modern Imaging Era

Abstract

<h3>Purpose/Objective(s)</h3> Neck dissection is a standard of care for pharynx and most larynx cancer patients undergoing surgery even with clinically node-negative (cN0) necks. This is based largely on historical series showing high rates of occult pathologic node-positivity (pN+) in cN0 patients. However, in the modern era with more sensitive imaging modalities, it is possible that certain patients with sufficiently low risk of pN+ could have elective neck dissection omitted, thereby reducing toxicity. <h3>Materials/Methods</h3> Patients with cN0 oropharynx, larynx (excluding T1-2 glottic), and hypopharynx cancers diagnosed from 2010-2015 and undergoing primary surgery were identified in the National Cancer Data Base. Multivariable logistic regression was performed to assess predictors of pN+. Predictive nomograms based on these predictors were generated. <h3>Results</h3> 4117 cN0 patients met inclusion criteria, including 2033 larynx (L), 293 hypopharynx (HP), 503 HPV(-) oropharynx (OP), and 1288 HPV(+) OP patients. The overall rate of pN+ among cN0 patients was 29.4%. Probability of pN+ was > 25% for all anatomic subsites (L: 26.9%; HP: 27.6%: HPV(-) OP: 32.4%; HPV(+) OP: 32.7%). In multivariable logistic regression, the presence of lymphovascular invasion (LVI) was the strongest predictor of pN+ (odds ratio [OR] = 4.19, 95% confidence interval [CI] 3.56-4.93, <i>P</i> < 0.001). Histologic grade also strongly predicted pN+ (high- vs. low-grade: OR 2.58, 95% CI 1.88-3.59, <i>P</i> < 0.001; intermediate- vs. low-grade: OR 1.90, 95% CI 1.40-2.62, <i>P</i> < 0.001). However, increasing pT-classification was not associated with increased rate of LN positivity. A nomogram predicting the probability of pN+ for cN0 patients was created. Using this nomogram, < 2% of patients had an estimated pN+ risk below 10%, < 10% of patients had pN+ risk below 15%. <h3>Conclusion</h3> LVI and histologic grade are the strongest predictors of pN+ among patients with cN0 pharynx and larynx cancers. Even with modern imaging, pN+ rates are high for cN0 patients, and the benefits of neck dissection likely outweigh the risks in virtually all patients undergoing surgery.