A retrospective multicenter study on prognosis of oral squamous cell carcinoma patients with regional lymph node metastasis

Author(s)：

YANAMOTO Souichi¹, UEDA Michihiro², YAMASHITA Tetsuro², OTA Yoshihide³, OTSURU Mitsunobu³, KURITA Hiroshi⁴, KAMATA Takahiro⁴, OKURA Masaya⁵, AIKAWA Tomonao⁵, KOMORI Takahide⁶, SHIGETA Takashi⁶, KIRITA Tadaaki⁷, YAMAKAWA Nobuhiro⁷, UMEDA Masahiro¹

Affiliation(s)：

1 Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences
2 Department of Oral and Maxillofacial Surgery, Keiyukai Sapporo Hospital
3 Department of Oral and Maxillofacial Surgery, Division of Surgery, Tokai University School of Medicine
4 Department of Dentistry and Oral Surgery, Shinshu University School of Medicine
5 First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University
6 Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine
7 Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University

Background
Multiple pathologically regional lymph node metastases (pN+), extracapsular spread (ECS), and the presence of positive margins are recognized as major adverse prognostic factors for survival in head and neck squamous cell carcinoma (HNSCC). Patients with these prognostic factors are considered at high risk for recurrence and survival benefit of postoperative adjuvant therapy in HNSCC. However, the postoperative recurrent high-risk factors specifically for oral squamous cell carcinoma (OSCC) are still unclear. The purpose of this study was to design a prognostic model and understand the prognostic impact in OSCC patients with pN+ to identify high-risk patients who need adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT).
Patients and Methods
We examined 491 pN+ patients who underwent neck dissection (ND). The 5-year disease-specific survival (DSS) and overall survival (OS) rates served as the main outcome measures. The optimal cutoff line for the number of pN+ yielded the highest statistical significance in terms of 5-year DSS and OS rates.
Results
The 5-year survival rates for 491 pN+ patients treated with ND were as follows: DSS, 58.2%; and OS, 52.2%. Multivariable analysis showed that variables independently prognostic for DSS were T-stage (hazard ratio [HR] = 1.77, 95% confidence interval [95% CI] = 1.27-2.47; P < 0.001), ECS (HR = 2.36, 95% CI = 1.71-3.26; P < 0.001), and ipsilateral lower neck metastasis (level IV/V) (HR = 1.82, 95% CI = 1.27-2.62; P = 0.001). We identified the followed three risk groups based on the number of pN+ and the presence of ECS: group 1, number of pN+ 1 and ECS-; group 2, number of pN+ 2-5 and ECS-; and group 3, number of pN+ 6≤ and/or ECS+. In univariate analysis, neoadjuvant chemotherapy or chemoradiotherapy did not improve outcomes in OSCC patients with pN+. Postoperative adjuvant RT/CCRT improved outcomes only in group 3; however, the patients in this group did not benefit from the addition of chemotherapy to RT.
Conclusions
To our knowledge, this multicenter study is the largest to date in which pN+ has been retrospectively analyzed in OSCC patients. We found that the patients with pN+ 6≤ and/or ECS+, the so called "super high-risk" group, required postoperative adjuvant RT/CCRT. In this super high-risk group, however, the addition of chemotherapy to RT would not improve the outcomes.