DNM after oral cancer is a rare clinical phenomenon which the etiology has not been clearly identified. There are some literature and reviews about the event followed by OSCC of the tongue [5, 6, 8, 17, 18]. However, only few research was related to OSCC at other sites [9, 10]. According to previous studies, it is clear that neck metastasis is the most significant predictor of prognosis in cases of OSCC [11, 12]. The presence of neck metastasis results in approximately 50% reduction of the cure rate [23]. In consequence, the disease can significantly reduce the survival rate by more than 50% [22].

This study, conducted as a retrospective investigation into a highly rare phenomenon, holds clinical significance as it involved long-term tracking and analysis of patient data. Predicting the occurrence of DNM after surgery for OSCC is challenging, as it involves various host and tumor factors. Analyzing these factors is important for understanding the causes of DNM, which, in turn, plays a pivotal role in predicting patient prognosis and establishing appropriate treatment strategies. This study contains cumulative patient data of 17 years since 2006 to precisely analyze the relatively unreported field of DNM. Statistical analysis was based on demographic characteristics, patient factors, and tumor factors to estimate the prognosis of the disease.

Previous studies have suggested several patient and tumor factors related to the prognosis of OSCC. Some studies researched occult neck metastasis of node-negative cases [13, 24, 25]. Others suggested the risk factors and compared the survival rate of the patients [22]. Still, others have reported neck metastasis of the contralateral side associated with the risk factors [9, 10]. Such factors include demographic characteristics, size, pTNM stage, regional metastasis, neck dissection, depth of invasion, primary tumor site, clinical stage, and postoperative radiation therapy. However, DNM has not been reported frequently. Also, studies analyzing a direct correlation between risk factors and DNM and estimating survival rates based on significant factors were rare. Our findings did not reveal any significant difference in the occurrence of DNM concerning age, sex, distant metastasis, histopathological differentiation, perineural invasion, and lymphovascular invasion. Three factors that showed a significant correlation with DNM were pTNM stage, depth of invasion, and postoperative radiation therapy. A recent study has shown that the primary location of the tumor and pTNM stage are important predictors of neck metastasis [24, 25]. In case of survival, several studies have suggested that the pTNM stage at the time of diagnosis turned out to be a crucial factor [22, 26]. In our study, cumulative survival rates of patients with DNM and without DNM were estimated.

When comparing the CSR of patients who had DNM after the initial surgery and patients who remained disease-free, the latter group showed a better prognosis in survival. Also, the most important covariant related to the incidence of DNM turned out to be pTNM stage by the result of the Cox proportional hazard model. Although the result of this analysis indicates the significance of pTNM as an important factor contributing to the occurrence of DNM, it may not reveal how much more likely DNM is to occur in advanced stages compared to early stages. However, the result can imply the assertion made in previous studies, which indicates that as the pTNM stage advances, the likelihood of survival decreases [27, 28]. This implies that even in cases of DNM after primary surgery, the lower pTNM stage indicates a greater chance of successful treatment in OSCC. Also, the higher CSR of disease-free patients suggests that the recurrence of neck lymph nodes may be indicative of a higher cancer malignancy or a more rapid disease progression. Therefore, it can be said that rapid detection of recurrence is crucial for the prognosis of DNM.

In our study, the χ2 test has shown a significant correlation between DNM and depth of invasion. This result is coherent with previous studies that suggest the anatomical DOI is associated with nodal metastasis and reported to be a predictable factor of neck metastasis [29,30,31,32,33]. This factor can be predicted to be related to the pTNM stage mentioned above, because a malignant tumor that reveals higher DOI is likely to classify into a higher level of pTNM stage, in terms of either depth or size. However, when the DOI was evaluated considering the cumulative survival rate, it did not show a significant correlation with the occurrence of DNM in this study. This is speculated due to the small sample size, since numerous previous studies have verified the significance of the factor, indicating the need for further evaluation in future research.

Postoperative radiation therapy implies a positive or close margin in biopsy results. According to the treatment protocol, adjuvant therapy seems to be less effective due to the potential for localized or regional invasion in OSCC [22]. In this study, cross-analysis results revealed a higher tendency for patients undergoing radiation therapy to experience DNM. It is considered that when radiation therapy is administered due to the result of close margin after initial surgery or the high malignancy of the tumor, the likelihood of metastasis to other areas is increased. Therefore, it is believed that the obtained results are attributed to the elevated probability of DNM in such cases.

In order to explain the presence of DNM, the theory of field cancerization is considered. Field cancerization was first suggested in 1953 while pathologic tissue was found in clinically normal tissue around OSCC [34]. The findings led to a conclusion that the normal mucosa near OSCC has gone through changes in its characteristics due to exposure to carcinogens accelerating multiple foci development of malignant transformation [35]. This could be explained by molecular and genetic tissue alterations [36,37,38,39,40]. The nearby healthy mucosa exposed to carcinogens can also undergo abnormal molecular changes. The molecular alterations, identified as key signs of field cancerization, involve mutations in oncogenes and tumor suppressor genes, loss of heterozygosity, and genomic instability [37, 38]. Cells carrying these modifications are known to gain the capability to initiate and expand the pre-cancerous field. It is theorized that these altered, pre-cancerous cells may eventually replace the normal mucosal cells, making the epithelium more susceptible to further genetic alterations, thereby triggering the formation of tumors. This suggests that if a tumor arises from tissues which are altered by field cancerization, there is an increased likelihood of cancer cells spreading through the lymphatic vessels to nearby lymph nodes. This signifies that mutations are occurring over a wide area even before the tumor is detected. Regarding this theory, pre-surgical examinations such as sentinel node biopsy should be performed to identify entrapped tumor-suppressing gene or oncogene [41]. The sentinel node is known to be the first group of lymph nodes in a regional lymphatic basin where cancer is likely to spread from the primary tumor site. Therefore, this procedure can determine the extent of cancer involvement and guide treatment decisions.

The limitations of this study include a relatively small sample size and a short follow-up period for patients who underwent initial surgery recently. Especially for patients who underwent surgery relatively recently, DNM can potentially occur at any time in the future. Additionally, there is a limitation in not considering cases such as local recurrence and second primary SCC, which could be directly related to neck failure. However, in the obtained sample for this study, the number of such cases was very limited, making it challenging to incorporate them into the statistical analysis. It is deemed essential to address these aspects in future research.