It is important to distinguish the T2N0 OSCC patients with poorer outcomes from the others, and subsequently guide them using the followed treatment.
PNI is widely considered to be a predictor of poor prognosis, and is related to aggressive tumor behavior, tumor recurrence, and poor clinical outcomes in oral cancer patients [9–12]. PNI is a way for tumor cell spread to occur in and along the nerve bundle beyond the local tumor. In a previous study, OSCC was recognized as a neurotropic cancer, where approximately 30% of patients had PNI positive [13]. In this study, we revealed that PNI was an independent prognostic factor of T2N0 OSCC patients.
Sparano et al. [14] showed that ALI was a predictor correlated to occult lymph node metastasis in clinical T1/T2N0 oral cancer patients. Additionally, Aires et al. [15] found that ALI was a predictor for distant metastasis. In this trial, we demonstrated that ALI positive patients had poorer DSS, and also tended to have poorer DFS. In our study, too few positive ALI patients may affect the ability to determine the difference between patients with ALI positive and patient with ALI negative.
Postoperative radiotherapy was scheduled for oral cancer patients who had experienced intermediate risk disease after surgery, while radiotherapy with concurrent chemotherapy was given to patients who had a high risk of disease after surgery. Previous studies [2–4] defined the adverse features, while isolating PNI as an intermediate risk factor. Nair et al. [16] demonstrated that PNI worsened survival rates and required patients to receive adjuvant therapy. For T2N0 oral cancer patients, the survival benefit of adjuvant therapy is controversial. Luryi et al. [17] reviewed stage I and II OSCC and revealed that adjuvant therapy did not improve survival. In the Luryi study, stage I disease was included and the team did not consider the pathologic adverse factors. For stage I disease, patients experienced a lower risk of disease relapse, with the treatment-related side effects possibly counteracting the benefits of adjuvant therapy. Rubin et al. [18] did not find any survival benefit of T2N0 oral cancer patients. In the Rubin study, pathological adverse factors such as PNI and ALI were not included in their analysis. In subgroup analysis in our study, we recruited 24 PNI positive patients and revealed that the patients who had received adjuvant therapy experienced both better DSS (100% vs. 35%, p = 0.005) and DFS (100% vs. 29.1%, p = 0.005). After several pathological and treatment factors were incorporated into multivariate analysis, we determined that adjuvant therapy offered better results.
This retrospective study did have certain limitations. First, margin status did not show any significant difference on DSS and DFS. We reviewed the pathology reports, but margin status may often be affected by different surgical procedures and re-excision in the surgery process. Second, the staging was according to the AJCC 7th edition, and did not consider tumor invasion depth, which is considered in the AJCC 8th edition. The first advantage of this study was that we selected T2N0 OSCC in order to exclude the effect of tumor size. The second advantage was that we excluded any patients who had a second malignancy in order to eliminate the influences between primary oral cancer and second malignancy. Further studies are still required in order to clarify the adverse features, as well as to find more patients who require adjuvant therapy so as to improve future clinical outcomes.