Standardized treatment for ENB has not been well established due to the relative rarity of these tumors and associated lack of clinical trials. Surgical resection is generally accepted as first line treatment in the care of ENB patients  and the attainment of negative margins is an independent prognostic factors for improved survival [4, 12, 13]. In recent years, endoscopic endonasal techniques have been increasingly used, and some series have reported an improvement in OS and progression-free survival in ENB patients undergoing an endoscopic endonasal craniofacial resection as compared to the traditional open craniofacial resection [11, 14]. Regardless of approach, it is challenging to attain a gross total resection and negative surgical margins in ENB patients due to the locoregional extension of the tumor and complex neurovascular anatomy of the anterior cranial base . Our findings confirmed that GTR could only be obtained in one-third of patients and 16% of patients had tumor biopsies only. Furthermore, large tumor size, tumor extension, nodal, and distant metastases at presentation may affect the success of surgical eradication. Morita et al. showed that GTR offers more survival benefits than STR and biopsy ; however, our results indicate that GTR and STR added survival advantage to ENB patients as compared to patients managed nonoperatively but there was no survival difference between GTR and STR (Fig. 1).
ENB is known to be radiosensitive and radiotherapy plays an important role in ENB management [11, 17] which was further confirmed in this study. It is most commonly used in the adjuvant setting to mitigate recurrence risk following surgery but has also been described in the neoadjuvant setting to reduce tumor burden prior to surgery or even as sole therapy with or without chemotherapy in patients with unresectable disease. [12, 14, 17–21]. In our study, radiotherapy was performed in about two-thirds of patients with biopsy alone and STR, which is lower than the GTR group. Of note, it may be difficult to orient surgical sinonasal specimens, complicating pathologic examination of the surgical margins. Because of uncertain resection margin status, postoperative radiation treatment seems justified in all patients to minimize the risk of locoregional relapse. Furthermore, while a combination of surgery and radiation yields the best outcome in low- and intermediate-risk patients , the treatment algorithm for advanced cases has not been well established. [19, 21, 22].
Several studies have suggested a survival benefit of chemotherapy in ENBs, especially in high-grade tumors [20, 23–25]. Also, preoperative chemotherapy might be effective for tumor reduction and improving surgical resection, especially in advanced diseases [21, 22, 26]. However, the use of chemotherapy in ENB patients may also increase mortality risk [20, 27, 28]. Our study also demonstrated a negative effect of chemotherapy regardless of tumor stage, which is in line with previous studies [20, 29]. While chemotherapy is not routinely recommended in the treatment for ENB it is important to consider the possibility of confounding variables such as selection bias for very advanced or aggressive disease. Ultimately, its role should be further examined alongside important parameters such as the Kadish staging, Dulguerov’s modified TNM staging, and Hyams grading systems, which are missing in the SEER database.
The survival rates of carcinomas of the nasal cavity and paranasal sinuses have been improved over the years with the developments of new techniques for early diagnoses and advanced treatment modalities [10, 30–32]. However, our study indicated that there has been no improvement in the survival of ENB patients over the last 20 years. As mentioned, obtaining negative margins is one of the vital prognostic factors for ENB survival [15, 27, 33] and despite the introduction of new surgical techniques and improved visualization using endoscopic endonasal techniques, it is still challenging to achieve margin-negative resections, either macroscopically or microscopically. This is largely a result of patients with ENB presenting with advanced stage of disease at diagnosis due to a relative paucity of symptoms early on in addition to diagnostic delays from attributing early symptoms to ‘allergies’ or ‘sinusitis'. In fact, up to 62% of patients with ENB have advanced stage disease (Kadish stage C and D)  at diagnosis. Taken together, ENB is a difficult tumor to clinically diagnose at early stages and there is little consensus on standard of care for this rare tumor entity, especially for high-risk individuals given the lack of large prospective cohort studies or clinical trials resulting in heterogenenous care across treatment centers and over time which may help explain the lack of survival improvement over the past two decades.
There are limitations of our study that need to be discussed. Firstly, several important markers of ENB are not included in the SEER program including Kadish staging, Dulguerov’s modified TNM staging, Hyams grading, surgical margins, surgical approach, and chemoradiotherapy regimens. Some of these factors contribute to whether or not a lesion is resectable which would help explain why certain patients underwent a biopsy alone and/or any selection bias for administration of chemotherapy. Next, patients undergoing STR or GTR may share different characteristics related to their age, performance status, and medical comorbidities than those who had biopsy only, which could contribute to survival differences. There are also very likely to be other biological tumor heterogeneities in this patient population.
In conclusion, our study demonstrates the utility of surgical resection followed by adjuvant radiotherapy in improving survival of ENB patients, whereas the role of chemotherapy remains somewhat unclear in this study population. Despite the evolution of diagnostic and treatment methods, there was no remarkable survival improvement of ENB patients over the past two decades, highlighting an urgent need to refine the standards of care for these patients and identify new therapeutic targets.