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Peer-reviewedCC BYOral Oncology Reports

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

  • Yasumasa Kakei
  • Takumi Hasegawa1
  • Takumi Imai2
  • Hiroshi Nakamura3
  • Nobuhiro Yamakawa3
  • Yusuke Yokota4
  • Masaya Okura5
  • Tomofumi Naruse6
  • Hiroshi Kurita7
  • Eiji Hirai8
  • Shin Rin9
  • Michihiro Ueda9
1 more authors
  • Masaya Akashi1
9 affiliations
  1. 1Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
  2. 2Clinical and Translational Research Center, Kobe University Hospital, Kobe, Japan
  3. 3Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, Kashihara, Japan
  4. 4Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, The University of Osaka, Osaka, Japan
  5. 5Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, The University of Osaka, Osaka, Japan; Department of Oral and Maxillofacial Surgery, Morinomiya Hospital, Osaka, Japan
  6. 6Department of Clinical Oral Oncology, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  7. 7Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Matsumoto, Japan
  8. 8Department of Oral and Maxillofacial Surgery, Oita Red Cross Hospital, Oita, Japan
  9. 9Department of Oral Surgical Oncology, Hokkaido Cancer Center, Sapporo, Japan
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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 2166 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.

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Cite

BibTeXRIS
BibTeX
@article{kakei2026risk,
  title = {{Risk factors and treatment outcomes of metachronous isolated distant metastasis in oral squamous cell carcinoma: A multicenter retrospective cohort study in Japan}},
  author = {Yasumasa Kakei and Takumi Hasegawa and Takumi Imai and Hiroshi Nakamura and Nobuhiro Yamakawa and Yusuke Yokota and Masaya Okura and Tomofumi Naruse and Hiroshi Kurita and Eiji Hirai and Shin Rin and Michihiro Ueda and Masaya Akashi},
  journal = {Oral Oncology Reports},
  year = {2026},
  month = oct,
  doi = {10.1016/j.oor.2026.100805},
  url = {https://doi.org/10.1016/j.oor.2026.100805},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Risk factors and treatment outcomes of metachronous isolated distant metastasis in oral squamous cell carcinoma: A multicenter retrospective cohort study in Japan
AU  - Yasumasa Kakei
AU  - Takumi Hasegawa
AU  - Takumi Imai
AU  - Hiroshi Nakamura
AU  - Nobuhiro Yamakawa
AU  - Yusuke Yokota
AU  - Masaya Okura
AU  - Tomofumi Naruse
AU  - Hiroshi Kurita
AU  - Eiji Hirai
AU  - Shin Rin
AU  - Michihiro Ueda
AU  - Masaya Akashi
PY  - 2026
DA  - 2026/10/30
JO  - Oral Oncology Reports
DO  - 10.1016/j.oor.2026.100805
UR  - https://doi.org/10.1016/j.oor.2026.100805
AB  - 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 2166 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.
SN  - 2772-9060
ER  -