At present, according to the latest t 8th (2015) edition TNM classification for lung cancer2, same as the 7th edition [12], SMPLC is still regarded as intrapulmonary metastasis in T and M stages. Multiple tumor nodules in the same lobe were classified as T3, in the different lobe but ipsilateral as T4 and in the bilateral lobe were classified as M1a (8th and 7th edition). In our study, the 1-year and 3-year DFS rates were 97.62% and 70.59%, respectively, and the 1-year and 3-year OS rates were 98.81% and 82.35%. These were basically consistent with other researches [2–7]. The research of Shintani, T. et al [13] found that in SMPLC patients only treated with stereotactic body radiotherapy (SBRT), the 3-year OS rate and DFS rate were 69.1% and 43.2%, far lower than the surgical-based comprehensive treatment. Other studies also supported this conclusion [14–15].Comprehensive studies had shown that the prognosis of patients with SMPLC was better than that of patients with lung cancer recurrence or metastasis [2–7]. Therefore, whether to treat multiple primary lung cancer as intrapulmonary metastasis for clinical staging remains to be further studied and discussed. At present, there is no systematic and authoritative treatment guideline for SMPLC, but our study showed that surgery can bring a great survival benefit. Therefore, for patients with SMPLC, it should never treat them as lung cancer recurrence or metastasis and give up surgery. Further research and discussion of clinical guidelines for SMPLC are still needed.
For DFS, vascular infiltration and postoperative chemotherapy were independent risk factors. For OS, postoperative chemotherapy was the only independent risk factor. The malignant tumors with vascular infiltration had a relatively high risk of vascular metastasis, so the patients had a relatively low DFS. However, the study did not find vascular infiltration was an influential factor for OS, which maybe because the patients underwent subsequent adjuvant therapy after discovering recurrence. But it was undeniable that vascular infiltration would affect the prognosis of patients. This study showed that postoperative chemotherapy reduced DFS and OS rates, which may be related to the toxic and side effects of chemotherapy drugs themselves. Some literatures have shown that postoperative chemotherapy can bring survival benefits [6, 16–17]. According to their research subjects, postoperative chemotherapy may benefit patients with late stage and positive lymph node metastasis. In our study, most of the primary tumors were in T1-2N0M0 stage. Only one tumor’s diameter was more than 5 cm and only one patient was in N1 stage. Therefore, for patients with early stage and negative lymph node metastasis, this study confirmed that postoperative chemotherapy was not conducive to the prognosis of patients. This problem still needs to be further studied, but in the process of operation, radical dissection of relevant lymph nodes should be performed, so as to perform accurate lymph node staging and guide the follow-up treatment.
Related studies had shown that tumor size was not conducive to the prognosis of patients6–7, 18. According to their research subjects, the reason may come from the fact that there were many late stage tumors. While in our study, most of the subjects were in T1-2N0M0 stage, so the effect of tumor size on the prognosis was not significant.
It was found that the number of operations was not an adverse factor for DFS and OS in SMPLC patients. In our study, only 2 patients underwent bilateral surgery at the same time, and more patients chose surgeries in different times. The study of Peng, Y. et al [4] showed that simultaneous operation of bilateral lesions was feasible. There was no significant statistical difference in postoperative hospital stay between synchronous surgery and non-synchronous surgery. However, the study did not mention other postoperative conditions, such as extubation time and postoperative complications and the study was more based on clinical experience with no more significant statistical studies.
In the choice of surgical methods, the principle was radical resection of tumor and maximum preservation of pulmonary function at the same time. In our study, there was no significant difference in prognosis among patients who underwent multi lobectomy, lobectomy + sublobar resection and only sub lobectomy. The results may be due to the popularity of early screening in recent years, the early diagnosis and treatment of SMPLC make the prognosis difference small. The review of Chen, T. F. et al [19] suggested that sublobar resection was acceptable for patients with SMPLC at an early stage, with the equivalent prognosis to the standard resection and better pulmonary function preservation. While the study of Ishikawa, Y. et al [20] suggested that lobectomy was an independent risk factor for poor prognosis. In our study, considering the relatively small sample size, it is not considered that multi sublobar resection can achieve the same survival time as multi lobectomy.
Gene detection is using specific molecular markers or gene mutation sites to differentiate SMPLC and intrapulmonary metastasis. In our study, a total of 26 (28.89%) patients underwent postoperative gene detection but only the main tumor was detected without detected separately which may relate to the high price of gene detection. Because of the intratumoral heterogeneity cannot be avoided in PCR or DNA sequencing analysis, the diagnosis of SMPLC cannot completely rely on molecular genetic characteristics. However, some studies still show that there were different gene mutations in different lesions of the same patient, and molecular gene detection can be used for the diagnosis of SMPLC [4, 21–22].
This study has not found that age, preoperative symptomatic, family history of cancer, preoperative tumor markers, tumor laterality, tumor location, surgical type, surgical frequency and visceral pleural invasion have no significant impact on the prognosis of SMPLC, which still need further study.
Limitations: First of all, the sample size is insufficient, and there is a bias in the selection of patients. Patients with high pT stage and positive lymph node metastasis are not enough in the study. The number of SMPLC patients with more than 5-year survival is less, so we did not count the 5-year survival rate. Secondly, we did not compare patients with SMPLC who underwent surgery with patients who only received non-surgical treatment (such as chemotherapy, radiotherapy, targeted therapy, etc.)