The Influence of Smoking and Age on Pathologic Features and Outcomes in Oral Cavity Squamous Cell Cancer: A Multi-institutional Collaborative Study

Abstract

To evaluate the impact of smoking and age on the frequency of pathological risk factors and outcomes for surgically staged oral cavity squamous cell carcinoma (OCSCC) in a multi-institutional analysis. A collaborative database of patients with primary OCSCC among 6 academic medical centers encompassing non-metastatic cases diagnosed between 2005 and 2015 was constructed. All cases were treated with surgery +/- adjuvant radiation therapy (RT) +/- concomitant chemotherapy (CRT) according to risk factors. Patients were categorized based on smoking history and age and the resultant groups were compared for demographic data, pathologic features and treatment modalities using t-test and Chi-squared tests. Kaplan-Meier curves and Log-rank p-values as well as multivariate analysis (MVA) for recurrence free survival (RFS). We identified 1055 cases that met our inclusion criteria after excluding 227 patients with unknown smoking history and incomplete records. Median age was 61 years, 60% of cases were men, 88% were White; and oral tongue (22%) followed by floor of mouth (18%) were the most common sub-sites. The median follow up time was 40 months (15-195 months). Surgery alone, surgery + RT and surgery + CRT were utilized in 32%, 37% & 31% of cases respectively. Smokers either during or at any point before diagnosis (“Ever Smoked”) were 730 cases (69%), whereas “Never Smoked” constituted the remaining 31% (n=325). Smoking was significantly associated with male sex, heavy alcohol use (38% vs 3%) and floor of mouth location (28% vs 6%) (p<0.001 for all). Adverse pathologic features were similar in both groups including grade, AJCC stage, lymphovascular (LVI) and extracapsular space invasion (ECE); except for perineural invasion (PNI) that was detected more in smokers (48% vs 37%; p=0.003). Three and 5 years RFS were not influenced by smoking (62.8% & 57.7% for Ever Smoked vs. 62% & 56.2% for Never Smoked; p=0.553). Even when we further categorized our study population into current (36%), former (33%) and never smokers (31%) similar results were attained both for risk features and RFS and the same occurred within different AJCC stages. RFS for patients younger than 50 years (n=193; 18%) was also not significantly different when compared to older ones 50-70 (n=584; 56%) and > 70 years (n=278; 26%) with 3-year RFS of (67%, 74% & 51%) and 5-year RFS of (64%, 73% & 51%) for the three groups respectively (p=0.74). On MVA, classical factors namely higher AJCC stage, PNI, LVSI, ECE and positive final margins were independently associated with worse RFS (p<0.05 for all). Both smoking and young age were not associated with any detrimental effect. In our multi-institutional analysis that included one of the largest cohorts to date for oral cavity squamous cell carcinoma treated with modern modalities with adequate follow up, smoking history and young age did not skew outcomes. Smoking was not correlated with any adverse risk feature except for perineural invasion.