1. Introduction
Non-small cell lung cancer (NSCLC) is a frequent malignancy and the most common cause of cancer-related death among males and females in the world, resulting in a large social and economic burden [1]. The National Comprehensive Cancer Network (NCCN) guidelines recommended surgery followed by adjuvant chemotherapy (AC) for cT2-4N0-1 NSCLC with a supplementary instruction that neoadjuvant chemotherapy (NAC) followed by surgery should also be considered for these patients [2]. The use of adjuvant chemotherapy for surgically resectable NSCLC has been well established by several randomized trials and meta-analysis which demonstrated clear survival benefits over surgery alone [3]-[6].
Despite similar overall survival (OS) and disease-free survival (DFS), evidence is not very robust with regard to the benefits of NAC. The original purposes of administering chemotherapy before surgery included: improving operability by reducing tumor tissue size, increasing the likelihood of administering the maximal planned dose of chemotherapy, and reducing the likelihood of micro-metastasis and uncomplete resection (R1/R2) [7][8]. At the same time, there were several potential risks of NAC including delaying operation, increasing the postoperative complication for the postoperative toxicity, and making the tumor unresectable [9]. Thus, there is widespread debate in the use of NAC and adjuvant chemotherapy (AC) with NSCLC patients.
The comparative effectiveness of NAC versus AC in terms of DFS and OS remains controversial. The study by Brandt et al. aims to evaluate whether treatment strategy of NAC or AC is better for cT2-4N0-1 NSCLC patients through a propensity score match analysis [10]. They analyzed 92 matched-pair patients and ultimately demonstrated that there was no significant difference in DFS and OS between treatment cohorts. Previous investigators have tried to answer this question. The NATCH trial recruited 624 patients with stage Ⅰ-ⅢA, N0-N1 NSCLC to compare the effect of tree therapeutic strategies (NAC, AC and surgery alone) [3]. The three arms trial found that there was no significant difference in DFS and OS between those treatments. The open label randomized trial by Westeel et al. showed the same conclusion in early stage NSCLC patients [11]. Coincidentally, the meta-analysis of trials also did not demonstrate differences in OS and DFS between NAC and AC [12][13].
Although they show similar clinical outcomes, most of the previous literature supports the use of adjuvant chemotherapy over neoadjuvant chemotherapy. However, there are some theoretical difference that have not been specifically addressed or adequately studied. Firstly, administration of NAC could have the potential to reduce tumor size before surgery and increase the complete resection rate [9]. Secondly, the patients who received NAC might have higher surgery complications and mortality rate, due to the preoperative chemotherapy toxicity [7]. Thirdly, patients who received NAC had better chemotherapy tolerance than the patients who underwent AC [3][10].
These theoretical differences of AC and NAC may impact the cost associated with caring for NSCLC patients. What’s more, under the circumstances, there was no robust evidence on the outcomes of NAC versus AC in terms of OS and DFS. Cost-effectiveness analyses may contribute to decision-making among NSCLC patients for whom the optimal therapeutic regimen is unclear. Until now, cost-effectiveness research comparing the NAC and AC treatment protocols in lung cancer, was absent. The previous cost-effectiveness studies about neoadjuvant chemotherapy versus adjuvant chemotherapy, focused only on ovarian cancer and head neck cancer [14]-[19]. Therefore, we compared the cost effectiveness of AC and NAC treatment strategies in the case of NSCLC, through a decision tree-modeled cost effectiveness analysis from the perspective of the payer.