Real-world survival outcomes of surgical patients with squamous cell carcinoma of unknown primary of the head and neck: A National Cancer Database analysis.

Abstract

e18142 Background: Squamous cell carcinoma of unknown primary (SC-CUP) of the head and neck is an infrequent disease, presenting with metastatic cancer in the cervical lymph nodes without an identifiable primary tumor site despite extensive work-up. Given the rarity of the disease, it is still unclear if conventional adverse prognostic factors in patients with head and neck squamous cell carcinoma with known primary, such as higher pathologic N stage, extranodal extension (ENE), lymphovascular invasion (LVI), perineural invasion (PNI), or positive resection margin, would similarly translate to those with SC-CUP. Therefore, we aim to explore this using an established real-world clinical registry from the National Cancer Database (NCDB). Methods: We included patients with SC-CUP of the head and neck with ICD-O-3 codes C00.0-C14.8 or C32.0-C32.9 in the 2022 NCDB registry who were diagnosed from 2004-2021. They must have a confirmed diagnosis of squamous cell carcinoma with pathologic T0, N1-3, and M0 stage with no prior cancer diagnosis, and have undergone wide, total, or radical excisions as part of the treatment. Patients with nasal cavity, middle ear, paranasal sinuses, or nasopharyngeal cancers, as well as those with clinical M1 disease, were excluded. Survival analysis was evaluated using univariate Cox regression analysis. Results: A total of 161 patients were included in the analysis. Most patients were male (85.1%) and White (91.3%). 54 patients received concurrent chemoradiation (CCRT), 48 received radiation therapy (RT) alone, and 40 received no chemotherapy or RT. For pathologic nodal staging, 115, 42, and 4 patients had N1, N2, and N3 disease, respectively. Patients with positive ENE or LVI had numerically poorer overall survival (OS) (hazard ratio (HR) for positive ENE 1.61, 95% confidence interval (CI) 0.69-3.75, p=0.27 and HR for positive LVI 1.67, 95%CI 0.18-15.25, p=0.65), along with those with pN3 disease (HR 1.70, 95% CI 0.22-12.91, p=0.61) and HPV-negativity (HR 4.96, 95% CI 0.45-55.04, p=0.19). However, patients with pN2 disease had outcomes similar to those with pN1 disease (HR 1.04, 95% CI 0.46-2.36, p=0.92). There was a trend toward improved OS in those who received radiation therapy alone (HR 0.43, 95% CI 0.13-1.38, p=0.16), whereas CCRT did not improve survival (HR 0.80, 95% CI 0.30-2.10, p=0.65). Of note, there is insufficient survival data on patients with positive resection margins or PNI for the analysis. Conclusions: This is the largest study to date that evaluated patients with surgically resected SC-CUP of the head and neck. Positive ENE, LVI, pN3, and HPV-negative disease are potential adverse risk factors. Adjuvant radiation therapy could potentially improve OS in this population, but concurrent chemotherapy with radiation was not beneficial. Further studies that evaluate the role of radiation therapy should be pursued.