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.