With the improvement of diagnostic techniques and treatment options, the OS and CSS rates of patients with non-metastatic NSCLC continue to increase. However, in terms of metastasis, the time from the occurrence of the primary tumor to the determination of metastasis is not certain. It is generally believed that this process requires a certain amount of time for the appropriate conditions to develop and interactions within the tumor microenvironment. Altorki et al's research shows that before metastasis, immune cells[11], organ-specific inducing substances, growth factors, inflammatory factors and extracellular matrix-modified proteins create a more favourable microenvironment for metastatic tumour cells. The method by which metastatic tumour cells interact with the host organ microenvironment is complex. Different types of interactions may lead to unique patterns of transfer events. The Vieira et al study found that most patients with lung sarcomatoid carcinoma have a high vascular invasion rate and a high recurrence rate after surgical resection, which indicates that this type of tumour has a high metastasis rate and poor prognosis characteristics[12, 13]. In previous research, we found that approximately 71.9% of patients with lung sarcomatoid carcinoma are smokers. Such a high smoking rate is related to the occurrence of tumours, but smoking status has no significant effect on the prognosis and survival of patients with lung cancer[12, 14]. At the same time, the formulation of chemotherapy programmes has been reported for different lung cancer subtypes and stages, and the effects of single and combined targeted therapy applications have also been reported[15-17]. We studied the effect of chemotherapy on the CSS rate of GCLC through PSM. Some of the clinicopathological parameters showed significant differences between the chemotherapy set and the nonchemotherapy set. It was found that patients younger than 71 years old had a good prognosis after chemotherapy, and patients older than 71 years old had no difference in prognosis, regardless of whether they received chemotherapy or not; this may be related to the body's cardiopulmonary functional reserve, the tolerance to toxicity and the side effects of chemotherapy drugs. It is reported that the proportion of patients aged 80 and above who undergo systemic chemotherapy has decreased significantly, which is consistent with our previous PSM data. There were 184 people who were 71 years old or older and did not receive chemotherapy. The possible reason is that elderly patients and their families may be unwilling to undergo this treatment. Therefore, due to the side effects, we prefer to suggest a milder treatment for advanced cancer in elderly patients[18]. There are also studies showed that few elder patients receive further treatment after relapse or metastasis[19]. Our data from the PSM analysis show that T stage, N stage, metastatic factors, surgery and chemotherapy are statistically significant factors, but the differences in outcomes related to chemotherapy, race and sex are not obvious. Interestingly, there was no significant difference in the effect of radiotherapy in our study, either within or between sets. Martin et al's study showed that the benefits of postoperative radiotherapy have not been shown to improve the survival rate of patients with typical lung sarcomatoid carcinoma[20]. According to previous research, platinum-based palliative chemotherapy strategies are less effective for the treatment of lung cancer, and the results for GCLC as a subtype in our study are slightly different from those in this previous report. We found that patients receiving chemotherapy had improved CSS compared with that of patients not receiving chemotherapy. An analysis within the chemotherapy set showed that patients with lung,brain, and bone metastases had a significantly better CSS than those in the nonchemotherapy set. The analysis between sets showed that chemotherapy had no significant effect on the prognosis of patients with or without metastasis. A possible reason is that the systemic chemotherapy does not convey additional benefits in patients without metastasis. Local treatments, including stereotactic body radiation therapy (SBRT), and other treatments, can also be utilized. A multicentre, randomized, controlled phase 2 study showed that local consolidation therapy in oligometastatic NSCLC can significantly prolong the survival duration while delaying the appearance of new metastatic foci[21].Patients with single-site metastases with only brain or intra-pulmonary metastases have better CSS with chemotherapy.Previous studies have many controversial aspects, and one study showed that palliative chemotherapy used in NSCLC is not effective for advanced lung sarcomatoid carcinoma. No patients achieved an effective response after chemotherapy, and the median OS was only 5 months. Lung sarcomatoid carcinoma has a higher rate of local recurrence after surgery and a higher incidence of metastases at diagnosis[6]. The Vieira et al study showed that patients receiving platinum chemotherapy had a prolonged OS while with no difference in PFS[22]. Chaft et al's research suggests that not all lung sarcomatoid carcinomas are refractory to chemotherapy. Due to the poor prognosis after recurrence of sarcomatoid carcinoma, relapse should be prevented and delayed as much as possible. Neoadjuvant or adjuvant chemotherapy could be used in patients with resectable lung cancer. In addition, according to Wang et al's research, when NSCLC has a high degree of vascular invasion, the relative risk of recurrence and death is 4 and 2 times higher. Therefore, it is recommended that NSCLC patients receive systemic chemotherapy rather than palliative chemotherapy[23, 24]. However, the analysis within the set showed that the prognosis of patients with liver metastases was worse than that of the other metastatic sets[25], and the effect of chemotherapy was poor. The results of the Wu et al study identified that patients with liver metastases had significantly lower PFS and OS. Rong et al showed that the effect of chemotherapy in early bone metastasis was significant; however, in this retrospective analysis, the effect of chemotherapy on bone metastasis was not beneficial as expected. The analysis between sets showed that chemotherapy had no significant effecton patients with 2 or more metastases. The possible reason is thatan increased tumor burden leads to chemotherapy being ineffective. The Joss study found that patients with two or more metastases in distant organs had a lower chemotherapy response rate than patients with less tumor burden (patients with local disease or a metastatic disease in an extrathoracic organ); the reason may be that a larger tumor burden results in more cell populations that are resistant to multiple drugs[26].
Overall, the prognosis of GCLC patients is unsatisfactory. At present, an army of clinical prediction models are showing a hot trend, but most of the clinical prediction models are general studies of NSCLC, and do not involve the prognosis prediction of GCLC[27-29].In order to express this screening and integration data more concretely, we constructed this nomogram for clinical practice conveniently, which predicted its 1 and 3 year survival probability. Contemporarily, with the sustainable basic study and the development of cure strategies[30, 31], and the novel detection techniques appeared[32],The new prediction model we have established opens up a novel way for the prognosis prediction of GCLC patients through the independent prognostic factors screened. The evaluation of this model has a well accuracy and calibration. The C-index value for predicting the survival probability was 0.768,The Area Under Curve of ROC was 0.877,which was statistically higher than that TNM 8th Edition[33].
The strange thing is that radiotherapy is not included in the nomogram model. We suspect that this may be related to the dose and location of radiotherapy. According to Johnson's point of view, the increase in dose compared with the standard dose of radiotherapy can improve the survival rate. A high dose of cardiac radiotherapy is an important independent prognostic factor to reduce survival rate[34].
Our research still has many shortcomings. For example, the relationship between chemotherapy and the time of surgery in the SEER database is not clear; second, the description of the type of surgery is slightly unclear, and it is not clear whether the surgery performed was a lobectomy or lung segment resection. In addition, data on complications and costs of treatment are minimal, the sample size for tumor data is small, and the tracking time is short. The abovementioned limitations may introduce a degree of uncertainty in our results. The data in the SEER database are common, and it lacks the unique data contained in databases in other regions, but the SEER database does provide many types of valid and reliable data for retrospective analysis. Our data compilation is expected to provide a better treatment results for patients with GCLC.