With the advancement in early detection technology of lung cancer and the close postoperative follow-up of lung cancer patients, the detection rate of second primary lung cancer (SPLC) has been growing. The efficacy and safety of surgical treatment for second primary non-small cell lung cancer (SP-NSCLC) patients have also been demonstrated in several studies (1–7). For the patients with resectable early-stage NSCLC, lobectomy remains the accepted standard surgical procedure (8). However, with the continuous improvement of medical technology and treatment concept, the treatment of lung cancer has become individualized and standardized. Two “maxima”, namely, maximum removal of tumor and maximum preservation of normal lung tissue, have become the development direction of lung tumor surgery. For lung cancer patients with previous lung cancer-directed surgery, in addition to having less lung tissue, they would also have a higher risk of developing another new primary lung cancer than the general population (9). Clinically, it may be difficult to accurately identify the second tumor as primary, recurrent, or metastatic. Since 1975, when Martini and Melamed came up with the diagnostic criteria (10) for multiple primary lung cancer (MPLC), there have been more and more reports on MPLC. In the SEER database, there is also a dataset on multiple primary events. The relevant information can be available to us from this website (https://seer.cancer.gov/tools/mphrules/). As with the Martini–Melamed criteria (10), SEER also considers tumor histology, location, and time since initial diagnosis to determine multiple primary events. However, there are still no clear treatment guidelines and plans for MPLC. For patients with SPLC with previous lung cancer-directed surgery, especially for patients who are elderly, have severe cardiopulmonary diseases, or are unwilling to undergo surgery, the limited residual lung tissue makes them more cautious when they face the surgical removal of the second tumor lesion. Radiotherapy, especially stereotactic radiotherapy, may be a good option for such patients (11). Compared with surgical resection, stereotactic radiotherapy has the advantages of non-invasive treatment, the immediate recovery of activity after treatment, and the treatment of multiple lesions simultaneously. However, everything has two sides. Radiotherapy-related toxicities, such as bronchial stenosis, necrosis, and esophageal ulcers, have increased the concern (12). Surgery, to our knowledge, is still currently the only treatment offering potential cure and long-term survival in patients with SPLC. Despite significant breakthroughs in the diagnosis and treatment of lung cancer, it has not been determined whether lobectomy has a better survival advantage than wedge resection for patients with early-stage SP-NSCLC, especially those with a history of radical surgery for the first primary lung cancer (FPLC). A recent SEER-based study (13) has reported that SPLC demonstrated similar survival with lobectomy and wedge resection. However, the study did not delve into the differences in survival between the two procedures in various specific circumstances. Faced with the complexity of patients’ clinical situation, further stratified analysis is still necessary. Thus, combining with a variety of methods, this study compared the survival after lobectomy and wedge resection using overall survival (OS) and lung cancer-specific mortality as outcomes.

At present, there is no uniform standard for the surgical method of MPLC. Some scholars (14–16) have reported that lobectomy should be the first choice for the second primary tumor, followed by segment or wedge resection. However, sublobectomy, including segmentectomy and wedge resection, has also been studied as the main surgical method (3, 17). At the cost of damaging more pulmonary functional reserve compared with segmentectomy or wedge resection, lobectomy can remove more intrapulmonary lymph nodes and significantly reduce the recurrence rate of tumor (8), which can undoubtedly affect the postoperative quality of life of patients, especially those with a history of lung cancer-directed surgery. For stage IA SP-NSCLC patients with previous lung cancer-directed surgery, to date, it has not been fully understood whether lobectomy is more conducive to survival than wedge resection. Although several retrospective studies (18–20) and a recent SEER-based study (13) have found that lobectomy did not show a significant survival advantage over sublobectomy for SPLC patients, these studies still lacked an in-depth study on SPLC patients who have undergone radical surgery for primary lung cancer. To better solve this problem and provide references for further clinical research and practice, we carried out this study.

In the present study, wedge resection demonstrated equivalent OS to lobectomy, both before and after PSM. Similar results were observed in all clinical subgroups. Unlike the previous studies (4, 16, 17, 21), participants in this study were patients with stage IA SP-NSCLC with previous lung cancer-directed surgery. Moreover, the sublobectomy mentioned in their studies included not only wedge resection, but also other surgical methods such as segmental resection. To our knowledge, although wedge resection and segmentectomy were classified as sublobectomy, there were significant differences between them. Wedge resection was defined as non-anatomical resection of the lung parenchyma, and was not necessary to determine the histological structure of bronchus and pulmonary vessels, while segmentectomy was the anatomical resection of the lung parenchyma, and required the disconnection of segmental bronchus, segmental vessels, and segmental parenchyma. In view of the different anatomical pathways of wedge resection and segmentectomy, it was necessary to discuss the two surgical methods separately. Therefore, this study emphasized the difference in survival between wedge resection (rather than segmentectomy and/or wedge resection) and lobectomy. This study further confirmed that stage IA SP-NSCLC patients with previous lung cancer-directed surgery demonstrated similar OS with lobectomy and wedge resection.

In clinical practice, the relative location of two primary tumors had an extremely important influence on the final selection of surgical procedure. Generally speaking, when two tumor lesions were in the ipsilateral different lobes, lobectomy for the second lesion tended to lead to pneumonectomy, which was a risk factor affecting the prognosis of patients (4, 16, 20). This study found that when the two lesions were in the ipsilateral different lobes, wedge resection demonstrated equivalent OS to lobectomy. Thus, we believe that in this case, lobectomy for the second lesion may not result in a greater survival benefit than wedge resection. In agreement with our research, Ishigaki and his colleagues (4) suggested that if FPLC and SPLC were on the same side of the lung and FPLC received lobectomy, sublobectomy should be a priority for the SPLC. Additionally, surgical choice regarding the optimal extent of resection for a second primary tumor on the contralateral side is also controversial. Yang et al. (18) reported that a limited resection (sublobectomy) for the contralateral second tumor did not have a negative effect on OS in these patients with stage I bilateral MPLC. This was also confirmed by the findings of this study. Similarly, other previous studies (1, 16, 19, 20) did not demonstrate a significant difference in prognosis with respect to lobectomy versus sublobectomy for the second tumor. The choice of surgery for the second primary tumor is challenging for thoracic surgeons, especially for patients with a history of lobectomy or pneumonectomy. In addition to the maximum preservation of pulmonary functional reserve, maximum tumor resection is also an oncological principle to be followed. An adequate margin (>2 cm or the tumor diameter) is a prerequisite for sublobectomy. In a number of studies (19, 22), sublobectomy has been proved to have similar therapeutic effect to lobectomy for patients with early single primary lung cancer. Therefore, we believe that under strict patient screening criteria, sublobectomy including wedge resection is worthy of choice for thoracic surgeons.

Overall, this study provided evidence that wedge resection produced similar survival rate to lobectomy in stage IA SP-NSCLC patients with previous lung cancer-directed surgery, and wedge resection and lobectomy had similar lung cancer-specific mortality in most cases. A correct understanding of the difference in OS and lung cancer-specific mortality between the two surgical approaches might help clinicians make more reasonable choices.

This study still has the following limitations. First, much of the detailed information (such as imaging findings, pulmonary function index, and related basic diseases), which may be an important reference for clinicians to make treatment decisions, is not available in the SEER database. Second, the number of patients with stage IA SP-NSCLC included in this study was still relatively small, and the postoperative follow-up time was also short. Third, the nature of a retrospective study and the strict screening criteria in this study inevitably resulted in selection bias. Considering the deficiency of retrospective analysis, further prospective analysis is recommended.

In conclusion, wedge resection demonstrated equivalent survival to lobectomy in Stage IA second primary NSCLC patients with lung cancer-directed surgery. Considering the limitations of the present study, relevant prospective studies are still necessary.

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

The SEER database is a public database with free access to data, so ethics committee approval is not required for this study. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

CS designed the study and reviewed relevant literature and drafted the manuscript. CS, ZL, and DL conducted all statistical analyses. All authors contributed to the article and approved the submitted version.

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81770095, 81700093, and 8210082163), the Fundamental Research Funds for the Central Universities (No. 2042021kf0081), and Science Fund for Creative Research Groups of the Natural Science Foundation of Hubei Province (No. 2020CFA027).

This study used the Surveillance, Epidemiology, and End Results (SEER) database. We acknowledge the efforts of the National Cancer Institute in the creation of the database. We also thank Weidong Hu, Sheng Li, Zhiquan Wu, Donghu Yu, Zixin Guo, Qingwen Wang, Yujin Wang, and Jingyu Huang for our preliminary revision, review, and constructive comments. They have made great and selfless contributions to this paper.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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