Undoubtedly, our most significant discovery was that cT3/4N0 MS-SCC typically portended a poor prognosis, with death often being the result of local invasion, while regional recurrence was relatively infrequent. Although END did not prove advantageous in terms of RC or DSS when compared to ENI, it did offer superior outcomes with respect to appearance, chewing, and speech. Our findings have practical implications for the development of a more effective treatment plan for cT3/4N0 MS-SCC, aiding clinicians in providing optimal care for their patients.

The challenge of treating cT3/4N0 MS-SCC is further compounded by its low incidence, as well as ongoing debates regarding optimal neck management despite widespread agreement on primary tumor resection. Historically, due to the assumed low incidence of occult metastasis, emphasis was placed on local control, though recent evidence reveals that LN metastasis is more common than previously believed [4], with untreated necks experiencing regional failure in up to 33% of cases [13]. Through an analysis of oncologic outcomes among 777 N0 MS-SCC patients, Li et al. [7] demonstrated that those who underwent END displayed significantly improved overall survival and DSS compared to their counterparts who did not undergo END. Furthermore, when combined with radiotherapy, END was even more effective in promoting a favorable prognosis. Abu-Ghanem et al. [4], in a review of four retrospective studies comprising a total of 129 patients, determined that ENI significantly reduced the risk of regional nodal recurrence by nearly 80% compared to observation. Similarly, Faisal et al. [14], in an RC assessment of 255 patients with MS-SCC, found that positive LNs were present in 14.1% of the population, with regional relapse occurring in 3.7% of those who underwent elective neck treatment, compared to 26.4% in those who did not. Elective neck treatment, therefore, considerably reduced the risk of regional recurrence. In a multicenter study conducted in Japan [3], 111 patients were treated with curative intent, out of which 98 had cN0 neck disease and did not receive prophylactic neck irradiation. Subsequently, 11 patients (11.2%) were diagnosed with lymph node metastasis, of which eight formed part of the 83 patients with an N0 neck who had not undergone elective neck treatment. Taken together, these findings reveal that END and ENI deliver better prognoses compared to observation, however, the question as to whether END is superior to ENI remains unanswered until our current investigation, which shows no significant differences in terms of RC and DSS between END and ENI. The lower occurrence rate of occult metastasis in our study (11.1%) compared to earlier studies [4,5,6,7,8,9,10] may be attributed to the utilization of PET/CT to confirm cN0 status in most of our patients, thereby enabling prompt intervention to easily control the very few positive LNs through subsequent END or ENI [1].

Evaluating the impact of a therapeutic procedure on QoL is another crucial aspect to consider. While END may be technically mature and associated with minimal complications when carried out by an experienced practitioner, some patients have reported complaints of shoulder dysfunction [15]. Although radiation therapy techniques are constantly improving, it is important not to disregard potential complications such as dry mouth [16]. Our study may represent the first comparison of QoL in patients who underwent END and ENI, and we observed that those who received END reported higher scores with regards to appearance, chewing, and speech. Our findings are particularly intriguing, as they shed light on the critical role that the maxilla plays in maintaining both oral function and facial appearance. Notably, cT3/4 MS-SCC often necessitates extensive resection of the maxilla, which can result in facial collapse and the development of a communication between the oral and nasal cavities. Furthermore, it is worth noting that a small number of patients in the END group received neck radiotherapy, which could have had a significant impact on the differences in QoL observed between the two groups.

However, it is important to carefully consider the advantages and disadvantages of elective neck treatment. First, there is general consensus that surgery and/or radiotherapy on the neck is indicated for patients with clinically positive nodes. However, in patients with a tumor that has a low rate of LN metastases at presentation, preventive treatment of the neck may not be necessary. In fact, Cantù et al. [17] demonstrated that subsequent LN metastases in cN0 patients were rare and could be effectively treated with careful monitoring and follow-up. In their study, only 2 out of 182 patients with MS-SCC died from nodal metastases. Similarly, in the study by Patel et al., 15.4% of patients did not receive any treatment of the neck, 2.6% underwent an elective neck dissection (END), 69.2% received elective nodal irradiation (ENI) only, and 12.8% were treated with both END followed by radiotherapy. Notably, none of the patients with N0 necks had isolated regional recurrence regardless of neck management [1]. Second, it is important to remember that approximately 80–90% of cN0 patients may undergo unnecessary preventive neck treatment, despite potential complications associated with such treatment. Third, even with spinal accessory nerve-preserving neck dissections, patients may experience variable degrees of shoulder dysfunction and must be informed of the associated risks before undergoing treatment. Furthermore, while radiation therapy techniques are improving, potential complications such as dry mouth must not be ignored [18, 19]. Thus, it is imperative to identify the factors that can inform decision-making regarding elective neck treatment. Existing evidence suggests that lymph node (LN) metastases are more frequently observed in tumors involving the palate and upper gum, and that these tumors behave more similarly to tumors of the oral cavity than those of the maxilla [17, 20]. It is therefore essential to consider the site and characteristics of the primary tumor when determining the need for and extent of elective neck treatment, however, due to the retrospective nature of our study and its extended duration, accurately assessing invasion of the palate and upper gum may be challenging.

Poor differentiation and positive margin were the two most important prognostic factors. Wang et al. [21] also described that low differentiation was related to both additional increased 50% risk of overall death and cancer-caused death. Positive margin was common during surgical treatment of advanced stage MS-SCC, and it certainly predicted worse survival [22].

Limitation in current study must be acknowledged, first, there was inherent bias within retrospective study, second, the response rate of QoL questionnaire was not very satisfactory, it might decrease our statistic power, third, more external validation was required before clinical application.