Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Background: Non-invasive (NI) disease margins are commonly encountered in the oral cavity during surgery for invasive cancer, and are defined by the presence of dysplastic tissue at the resection margins. Positive NI margins are classified on a spectrum from mild to high-grade/severe dysplasia, or carcinoma in situ. This varies greatly between centers with respect to pathological interpretation and reporting. The risks associated with positive NI surgical margins following primary resection of oral cavity squamous cell carcinoma (OCSCC) remain unclear, with a paucity of studies on this topic
Materials and Methods: All patients treated surgically for primary OCSCC in the Department of Head and Neck Surgery at Roswell Park Comprehensive Cancer Center between 2000 and 2023 were identified. Patients who achieved negative invasive margins following primary surgical management were included. Exclusion criteria included a history of radiation therapy (RT) to the head and neck and positive invasive margins. Patients were also excluded if their surgical pathology report did not comment on the presence (or absence) of a non-invasive/in situ disease component at either the resection margins or in the gross specimen. Disease-free survival (DFS) and overall survival (OS) analysis were performed using the log-rank test. With statistical significance defined as p = 0.05, univariate and multivariate Cox regression were used to identify significant and independent predictors, respectively.
Results: A total of 162 patients were included. Fifty-nine percent (95/162) had stage I/II disease. The majority of patients had primary tongue tumors (51%). Tumors of the gingiva, floor of mouth, and buccal mucosa/retromolar trigone each represented 14% of cases. Current and former tobacco use was documented in 33% and 36% of patients, respectively. Of the 117 patients who underwent neck dissection, 42 (36%) had metastatic nodal disease on final pathology. Negative (>5 mm), close (1-4 mm), and positive (<1mm) non-invasive margins were reported in 76, 34, and 30 patients, respectively. The presence of a component of NI disease that did not extend to the surgical margin had no impact on DFS or OS.
On univariate analysis a positive NI margin significantly predicted worse DFS (HR 2.145, 95% CI 1.150-3.999, p = 0.016) and closely approached significance for worse five-year OS (HR 2.080 95% CI 0.978-4.423], p = 0.057). On multivariable regression analysis, a positive NI margin independently predicted both DFS (HR [95%]: 3.061 [1.251-7.490], p = 0.014) and OS (HR [95%]: 3.632 [1.172-11.258], p = 0.025), even when controlling for T-stage, N-stage, histological grade, lymphovascular invasion, perineural invasion, extranodal extension. Adjuvant RT did not improve DFS or OS, even when controlling for high-risk pathological findings (e.g. perineural invasion, nodal disease).
Conclusion: In our cohort, a positive NI margin is a strong predictor of worse DFS on univariate analysis, and independently predicts worse DFS and OS when controlling for confounding factors. This is the first study to demonstrate an adverse effect of positive NI margins in patients with OCSCC. More studies are needed to determine their impact in specific subsites of OCSCC, which can improve our understanding of their management.