Thymic epithelial tumors (TETs) are relatively rare and occur most frequently in the anterior mediastinum. The age of onset of TETs is usually between 50 and 60 years (1, 2). They include two main pathological types; thymoma and thymic carcinoma. Thymomas are divided into five subtypes, A, AB, and B (1–3), and the latter is also known as subtype C (3). The incidence of thymic carcinoma is lower than that of thymoma, but its prognosis is worse, and the 5-year survival rate is approximately 50% (4–6). Surgery is the first-line treatment and main choice for early thymic tumors (Masaoka–Koga I and II). For TETs with Masaoka-Koga III and partial resectable IVA, comprehensive treatment based on surgery is the main treatment (7). There is no definitive and detailed treatment guideline for advanced TETs however, thus when lymph node and other organ metastasis are present the clinical guidelines recommend chemotherapy-based multidisciplinary treatment (7, 8). Previous studies indicate that surgery is beneficial for advanced TETs (9–11), but due to few cases of advanced TETs and the scarcity of reports, the role of surgery is still unknown (12, 13). The present study aimed to systematically analyze the role of surgery in advanced thymic tumors based on the Surveillance, Epidemiology, and End Results (SEER) database with a sufficient number of cases. A secondary aim was to clarify the prognostic value of surgery in advanced thymic tumors.

Thymic epithelial tumors with metastasis to lymph nodes or distant sites have a poor prognosis, and the 5-year survival rate is significantly worse compared to early-stage tumors (4, 18). In previous studies, the respective 5-year survival rates of stage IVA and stage IVB thymic tumors were only 56.3% and 38.2%, and there was an obvious difference in survival between stage IVA and IVB (19). Currently, the clinical treatment for early thymic tumors is clear radical resection. However, the value of surgery in advanced tumors has not been fully verified. Many previous studies explored the role of surgery in thymic tumors with stage IVA and the results showed that surgery could provide long-term survival. So surgery was preferred after deliberative clinic assessments if the tumor could be completely resectable before surgery or after neoadjuvant therapy in thymic tumors with stage IVA (7, 20–24). However, probably due to limited by the number of cases, there are few available reports about IVB thymic tumors. According to a clinical guideline, multidisciplinary discussion was necessary to determine the final treatment plan, and there was insufficient evidence to recommend (7). Meanwhile, a recent treatment guidelines from China stated that standard chemotherapy was the best choice for advanced thymic tumors (8). Hence, it is therefore imperative to define the role of surgery in advanced thymic tumors, which contributes to the formulation of clinical treatment.

In the current study, surgery was associated with significantly better survival time in thymoma patients and thymic carcinoma patients than in the control group. After PSM to reduce confounding factors, these result was further verified. We speculated that surgery played a positive role i n survival by reducing tumor burden and enhancing the effects of chemotherapy. In recent years, the application of surgery in advanced thymic tumors has gradually increased. Hiroyuki et al. reported a case with stage IVB thymic carcinoma that radical resection was performed after concurrent chemoradiotherapy and the patient had 30 months of recurrence-free survival (25); Coincidentally, a clinical team from Japan conducted a cure for a patient with locally recurrent, previously stage IV thymic small-cell carcinoma by surgery combined with perioperative chemotherapy and the tumor did not recur more than 2.5 years (26). Moreover, a retrospective study from Yusuke concluded that surgical intervention was a favorable factor for overall survival in patients with advanced thymic carcinoma (27). Combined with the present study, it is suggested that surgery may improve the survival of patients with advanced thymic tumors.

Furthermore, the resection status of the tumor may affect the patient’s prognosis and a macroscopic complete (R0/R1) was more beneficial to the survival of advanced patients. Markowiak et al. found that the median survival time after R2 resection was 25 months, which was significantly shorter than that after R0 or R1 resection (115 months) (28). Also in the current study, we got a similar result that total resection of the primary site was better than partial resection or debulking surgery concerning survival time. It was well known that R0 resection is almost impossible in patients with lymph nodes or distant metastases. As described in the previous report, a macroscopical R0/R1 resection can be achieved, similar to surgery for malignant pleural mesothelioma, with a significant reduction in tumor burden, which may result in a survival benefit. Interestingly postoperative radiotherapy(PORT) was a positive prognostic factor in univariate analysis, and its statistical significance was eliminated in a multivariate analysis. In fact, there had been many studies on whether postoperative radiotherapy could prolong the survival time of patients with thymic epithelial tumors based on SEER databases. In a study,postoperative radiotherapy had no significant effect on disease-specific survival but had a positive effect on overall survival time in patients with stage IV disease (15). Other studies have yielded different results, and the reason may be that the data processing was different—i.e., putting stages III and IV into one group (29–31). The role of postoperative radiotherapy is controversial in patients with advanced thymic tumors, but some reports have recommended it (32–34). Combined with the current research, considering that advanced thymic tumors cannot be completely resected, postoperative radiotherapy will benefit them. Of course, further studies will be needed to determine the role of postoperative radiotherapy in advanced thymic tumors in the future. Neither tumor size nor lymph node dissection was significantly associated with prognosis. In a multi-institutional analysis, lymph node dissection did not contribute to survival time in patients with thymic malignancies (35). Another article concluded that lymph node dissection was recommended for stage II and higher thymic tumors (36). As mentioned earlier, macroscopic R0/R1 resection was beneficial to the prognosis and coupled with the improved surgical level, it was recommended that positive or suspicious positive nodes should be resected as much as possible although controversial. In the end, thymic carcinoma and metastasis to distant sites were independent adverse factors in this study.

In a recent study based on the SEER database investigating the effects of surgery in Masaoka stage IV thymic carcinoma, it was concluded that surgery positively influenced prognosis (11). Unlike the aforementioned studies and thymic carcinomas, thymomas were also investigated in that study. More cases were analyzed due to an update of the SEER database.

The current study ha dsome limitations. There was no way to distinguish stages IVA and IVB because the SEER database lacked relevant information. We could not acquire detailed information about surgery, such as types of surgical access, resection margins in surgery, and so on. This rendered our findings incomplete and biased. Outcome variables did not include information on tumor recurrence. Lastly, as a retrospective study, while PSM was performed, selection bias strongly influenced the study. Prospective studies are needed for further validation.

In conclusion, in the present study based on the SEER database surgery significantly improved survival time in advanced thymoma and advanced thymic carcinoma patients who could accept surgery. Total resection of the primary site was the most advantageous form of surgery. This study provides a basis for the clinical treatment of advanced thymic tumors.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

WQ provided the acquisition, analysis, and interpretation of data, statistical analysis, and writing; HT provided the study conception and design. All authors contributed to the article and approved the submitted version.