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Risk factors and treatment outcomes of metachronous isolated distant metastasis in oral squamous cell carcinoma: A multicenter retrospective cohort study in Japan

Year: 2026

Type: article

Abstract: ABSTRACT Objectives Distant metastasis (DM) remains a significant challenge in oral squamous cell carcinoma (OSCC) management. This multicenter study aimed to identify risk factors for metachronous isolated DM and evaluate treatment outcomes in Japanese OSCC patients. Materials and Methods We retrospectively analyzed 2,166 OSCC patients who underwent curative surgery without preoperative therapy at seven Japanese institutions between January 2001 and December 2018. Risk factors for isolated DM were evaluated using multivariable Cox proportional hazards regression. Survival outcomes were compared among treatment modalities using Cox proportional hazards regression. Results Isolated DM developed in 129 patients (6.0%), with the lung being the predominant site (86.0%). Multivariable analysis identified four independent predictors of DM development: advanced T classification (T3-4; hazard ratio [HR]: 2.03, 95% confidence interval [CI]: 1.36-3.02), poor differentiation (HR: 2.14, 95% CI: 1.28-3.58), pathological nodal metastasis (pN+; HR: 3.87, 95% CI: 2.29-6.55), and extranodal extension (ENE; HR: 2.84, 95% CI: 1.80-4.46). Among patients with DM, local treatment of metachronous isolated DM was associated with significantly longer overall survival than systemic chemotherapy (adjusted HR: 0.38, 95% CI: 0.18-0.78, P=0.008) and best supportive care (adjusted HR: 0.15, 95% CI: 0.07-0.30, P<0.001), with a 3-year survival rate of 46.3%. Conclusion Advanced T stage, nodal involvement, ENE, and poor differentiation are significant predictors of metachronous isolated DM in OSCC. Local treatment of isolated DM was associated with longer survival in carefully selected patients with limited metastatic disease; prospective studies are needed to determine whether this reflects a treatment effect or patient selection.

Source: Oral Oncology Reports

DOI: 10.1016/j.oor.2026.100805