DISCUSSION
death, necrotic, regional disease, Extranodal extension, HNSCC, tumors, T2 tumors
RECURRENCE, SOFT TISSUE METASTASIS, NECROTIC, HYPOXIC, PRIMARY TUMOR, TUMORS, DISEASE
Extranodal extension in HNSCC has long been recognized as a poor prognostic factor since 1970.In our study, encompassing a series of HNSCC cases, approximately 50% of the cases were classified as pN2a, 16.9% as pN3b, and TDs were observed in 29.6% of cases (21 patients), slightly higher than reported in other studies. However, TDs are often compared with involved nodes, and their comparison with ENE is less frequent, as they are typically analyzed together.ENE has been associated with advanced T stages in HNSCC; however, our findings reveal that it can also occur in smaller tumors. We found ENE to be present in 16.9% of T1 tumors and 23.9% of T2 tumors, aligning with previous studies conducted by Ghadjar et al., who reported ENE in 7% of T1 stage tumors,The overall incidence of TDs in HNSCC ranges between 7% and 24% and they are more prevalent in advanced stages.Disease recurrence within the first 3 years is the primary cause of death in patients with HNSCC.Recent studies have reported that ENE is linked to an increased risk of mortality, recurrence, and DM in patients with HPV‐positive oropharyngeal squamous cell carcinoma (OPSCC).In the present research, the estimated HR between ENE and TDs in a Cox multivariate analysis, was significant (Exp (B) 4.341; When assessing the effect of TDs on survival, several authors consider ENE as a confounding factor, as the two are often analyzed together.In our series, TDs remained the variable closest to significance in the multivariate analysis, even after excluding six patients with both ENE and TDs. This observation suggests that patients with TDs may have a lower likelihood of survival compared to those with ENE, indicating that TDs may possess some prognostic value, although the statistical significance did not reach the conventional threshold of 0.05. Moreover, it is important to highlight that further reducing our sample size could increase the risk of false‐negative results, potentially underestimating the prognostic value of TDs. Therefore, despite the Cox multivariate analysis not showing statistical significance after excluding cases with simultaneous ENE and TDs, TDs should still be considered as a potential prognostic factor in future studies with a larger sample size. These findings align with the research conducted by Violaris et al., who similarly demonstrated that patients with TDs have a worse prognosis compared to those with ENE, a conclusion supported by several subsequent studies.ENE can be observed in a significant proportion of metastatic LNs that are smaller than 1 cm, indicating the aggressive nature of the primary tumor.Performing an initial ND approach might be a strategy to control regional disease by removing necrotic or hypoxic bulky neck nodes before CTX‐RT.Considering TDs a potential adverse high‐risk factor, adjuvant intensification therapy would be recommended. However, even with this approach, the prognosis remains poor. Prabhu et al. observed significantly worse OS in 15 patients with soft tissue metastasis (corresponding to grade 4 of the Lewis scale) despite the association of CTX with RT.While this study provides valuable insights, there are certain limitations that should be acknowledged. Firstly, the sample size is relatively small, and the retrospective design lacks randomized patient groups. In addition, our results may have been affected by potential confounding factors that were not included in the analysis, such as surgical margins, vascular invasion, nerve invasion, and histopathologic grade. These clinical and pathological factors could have an impact on the prognostic significance of ENE and TDs in HNSCC, and should be considered in future research. Nevertheless, the strength of this study lies in the analysis of an equally staged, treated, and monitored population.To our knowledge, this study is the first to examine the AJCC's proposal to distinguish pN2a‐ENE from pN3b‐ENE, as well as the prognostic implications of TDs, highlighting the need to consider TDs as a distinct entity. However, larger studies are necessary to identify the most effective treatment for these clinical scenarios and to validate our results. At present, the optimal therapeutic approach remains unclear.