Background: We aimed to develop and validate a risk-scoring system for distant metastases (DM) in oral cavity carcinoma (OCC). Methods: In this IRB-approved retrospective study, OCC patients treated at 4 tertiary cancer institutions with curative surgery +/- postoperative radiation/chemo-radiation (PORT/PO-CRT) were divided into discovery and validation cohorts (randomly selected in 3:2 ratio). Staging was reviewed based on TNM 8^th edition. Predictors of DM identified on multivariable analysis in discovery cohort were used to develop DM risk-score model to classify patients into risk groups using Contal and O’Quigley method for cut-off optimization. The utility of risk classification was subsequently evaluated in validation cohort. C-index was used to assess predictive ability of the continuous risk score. Results: Overall 2749 patients were analyzed (Table). Predictors (risk score coefficient) of DM in discovery cohort were: pT3-4 (0.4), pN+ (N1:0.8; N2:1.0; N3:1.5), histologic grade 3 (G3, 0.7) and lymphovascular invasion (LVI, 0.4). The DM risk groups were defined by cumulative sum of risk score coefficients: high risk (sum >2), intermediate risk (sum=1-2), and standard risk (sum<1). In the discovery cohort, 5-yr DM for high vs intermediate vs standard risk groups was 33% vs 19% vs 6%, p<0.001 (C-index=0.79). Similarly, in the validation cohort, 5-yr DM for high vs intermediate vs standard risk groups was 36% vs 23% vs 7%, p<0.001 (C-index=0.77). When applied to entire study population, this predictive model showed excellent discriminative ability in predicting DM only without locoregional failure (29% vs 18% vs 3%, p<0.001), late (>2 yr) DM (11% vs 5% vs 3%; p<0.001), DM in patients treated with surgery only (26% vs 11% vs 6%, p<0.001), PORT (37% vs 23% vs 7%, p<0.001), and PO-CRT (42% vs 29% vs 9%, p<0.001). Finally, 5-yr OS for high vs intermediate vs standard risk groups in the overall cohort was 24% vs 38% vs 66%, p<0.001. Conclusions: A predictive-score model for DM utilizing pT3-4, pN1/2/3, G3 and LVI demonstrated a validated utility in identifying patients at higher risk of DM who may be evaluated for individualized risk-adaptive treatment escalation and/or surveillance strategies.

^@variables included in multivariable analysis: age, gender, smoking history, subsite, pT, pN, grade, LVI, PNI, margin status, pN+ at level IV/VB, PORT and PO-CRT.