Predictors of Occult Nodal Involvement in Clinically Node Negative Primary Parotid Carcinoma: An NCDB Analysis

Abstract

<h3>Purpose/Objective(s)</h3> Primary Parotid Carcinomas (PPC) comprise a wide array of histologies, each with varying propensity for local invasion and cervical nodal involvement. Upfront surgical excision of the primary tumor constitutes the standard of care for PPC, but there exists little consensus regarding management of the clinically negative neck (cN0). We conducted a clinicopathologic correlative analysis of the National Cancer Database (NCDB) to identify predictors of occult nodal involvement in PPC to guide elective neck management. <h3>Materials/Methods</h3> The NCDB was queried for adults with a first malignant diagnosis of cN0M0 cancer of the parotid who underwent adequate surgical resection (defined as subtotal to radical parotidectomy with ³18 nodes examined) without pre-surgical treatment. Pathologic T-classification, tumor size, histology, grade, lymphovascular space invasion (LVSI), gender, and age at diagnosis were specified <i>a priori</i> as variables of interest. The primary outcome, occult nodal positivity (<i>i.e.</i> cN0 but pN+), was assessed by univariable (UVA) and multivariable (MVA) logistic regression analysis, depicted as odds ratios (OR) and corresponding 95% confidence intervals (95% CI) with a prespecified threshold for statistical significance of <i>p</i>£0.05. Recursive partitioning analysis (RPA) was subsequently performed to categorize patients according to their calculated risk of occult nodal disease. <h3>Results</h3> From an initial cohort of 41,445 patients with PPC 978 met inclusion criteria and were included for analysis, of whom 331 (33.8%) had occult nodal involvement. By UVA, the incidence of occult nodal positivity was significantly higher in male patients, those aged 72 and older, patients with high grade disease, pT4 classification, adenocarcinoma histology, a >4cm tumor, and those with positive LVSI. On MVA, tumor size, age, and gender were no longer significantly associated with occult nodal involvement; however, LVSI (OR 6.1, 95% CI 4.3-8.8), carcinoma ex-pleomorphic adenoma (OR 5.6, 95% CI 2.1-14.8), adenocarcinoma (OR 5.1, 95% CI 2.6-9.9), salivary duct (OR 4.0, 95% CI 1.8-8.6), or mucoepidermoid (OR 2.3, 95% CI 1.2-4.3) histology, pT3 (OR 2.0, 95% CI 1.1-3.7) or pT4 (OR 3.9, 95% CI 2.1-7.3) status, and high grade (OR 2.0, 95% CI 1.4-3.0) remained significant. LVSI, histology, pT status, and grade were further evaluated with RPA, which identified LVSI as the strongest predictor of occult nodal involvement (57.1% vs 42.9%, <i>p</i><0.01). <h3>Conclusion</h3> LVSI appears to supersede tumor histology, grade, size, and pT status as the strongest risk factor for occult nodal involvement in PPC. To our knowledge, this is the largest series to evaluate this pathologic feature. Further research into this heretofore underappreciated risk factor and its implications for management of the cN0 neck is warranted.