Recently, thoracic surgery has been considered to be helpful as local consolidative therapy in advanced stage NSCLC [8,10]. Some authors reported performing salvage surgery in advanced stage NSCLC and viewed it as one part of multidisciplinary management [6,9]. Thoracic surgery for primary lung cancer may improve survival in selected advanced stage NSCLC [6-11]. In addition, EGFR TKI therapy in advanced stage NSCLC is a critical treatment with excellent tumor response and improvement of PFS [3,4,13,28]. Many clinical trials have assessed EGFR TKI as a neoadjuvant or adjuvant therapy in early stage NSCLC [14-17], while other reports used EGFR TKI as a neoadjuvant therapy followed by thoracic surgery in advanced stage NSCLC [21-27].
In our study, we retrospectively reviewed our advanced stage EGFR-mutation positive lung adenocarcinoma patients receiving neoadjuvant TKI therapy followed by thoracic surgery. The tumor sizes decreased significantly after neoadjuvant TKI therapy. The difference in tumor sizes may be an effect of the high response rate of EGFR TKIs in EGFR-mutation patients [3,13]. Because tumor size is a risk factor that patients may receive thoracotomy or convert from VATS to thoracotomy . The benefit of decreased tumor size may let patients receive minimally invasive thoracic surgery as feasible. Although two patients in our study still received thoracotomy due to tumors respectively measuring 5.6 cm and 6.0 cm in maximal diameter, the tumor sizes were decreased after receiving neoadjuvant TKI therapy. The most patients received VATS uneventfully. Our study showed that advanced stage EGFR-mutation positive lung adenocarcinoma patients receiving neoadjuvant TKI therapy may experience decreased tumor size, allowing for the use of VATS as possible instead of thoracotomy.
Many clinical trials have shown that median PFS gradually decreases as disease progresses from early stage to advanced stage [3,13-17,30]. Median PFS in the advanced stage was around five to fourteen months associated with different types of management [3,13]. However, there is an issue that what kind of adjuvant management is feasible for the patients receiving neoadjuvant TKI therapy followed by thoracic surgery. In our study, the median PFS of all patients was 9.2 months, similar to previous clinical findings. The mean neoadjuvant TKI interval in the group receiving adjuvant TKI therapy and adjuvant chemotherapy was 107.2 days and 73 days, respectively. The difference was not significant (p value = 0.7177). Our patients received adjuvant TKI therapy or adjuvant chemotherapy after operation, the median PFS in the group receiving adjuvant TKI therapy was 14.0 months. The result was significantly better than the group receiving adjuvant chemotherapy. Previous studies in stage II to IIIA NSCLC reported the superior results in adjuvant TKI therapy versus adjuvant chemotherapy . There was also the same trend in our patients with the advanced stages of stage IIIB and IVA. The result might give us a hint that advanced stage lung adenocarcinoma patients with EGFR mutation receiving TKI as a neoadjuvant and adjuvant therapy might be an acceptable multidisciplinary management with comparable PFS. In addition, some studies have shown that patients harboring exon 19 deletion have better PFS than those with exon 21 L858R mutation, while others show different findings [13,28,32-33]. However, PFS showed no significant difference between exon 19 deletion and exon 21 L858R mutation in our study.
Generally, median OS and five-year survival rate gradually decreased corresponding to staging [1,2,30]. In our study, the 5-year survival rate was 66.7%. OS differences between patients treated with TKI or chemotherapy were not statistically significant in many studies and remain uncertain [3,13,28,32-33]. Our study also showed the same result. Although the 5-year survival rate of our patients seem to be superior to general population of advanced NSCLC patients, we could not explain where the benefit on OS coming from. Many factors involved during a whole course of treatment and influenced a result of OS. Multidisciplinary management might be a trend to deal with advanced stage NSCLC patients. No single management would be a critical role in treating advanced stage cancer patients. Besides, OS results reported by some studies show patients harboring exon 19 deletion treated with TKI have longer survival than patients harboring exon 21 L858R mutation . However, our OS results were not different between these two mutations. Not all patients received adjuvant TKI therapy and 26.7% patients received adjuvant chemotherapy. This might be a factor to influence the result of OS in our study.
Our study is retrospective and is limited to a small number of patients, thus being prone to have selection bias. The neoadjuvant TKI interval is not consistent nor definitely rule-based. Our result revealed that the tumor size was decreased after neoadjuvant TKI therapy, but we could not get the conclusion how long interval should patients take neoadjuvant TKI therapy. There is also a bias in adjuvant chemotherapy. The doublet regime of adjuvant chemotherapy was cisplatin-based not totally uniform due to a retrospective study. Because our patient number was small that we could not get the conclusion in OS between two mutation statuses even the patients harboring exon 19 deletion have the trend of superiority.