Adjuvant vs neoadjuvant chemotherapy in resectable NSCLC: is that the real question?

Besse and Le Chevalier provide us with an excellent and comprehensive review of available literature summarizing the current state of the art relating to both adjuvant and neoadjuvant (or induction) chemotherapy in resectable non-small-cell lung cancer (NSCLC).[1] They review the efficacy of adjuvant and neoadjuvant treatment in randomized clinical trials (RCTs) that employ cisplatin-based chemotherapy in stages I, II, and IHA NSCLC, as well as meta-analyses of these RCTs. They present what they believe to be the pros and cons of each approach. Ultimately, the authors are unable to answer the question they are asking - whether adjuvant or neoadjuvant chemotherapy provides the greater benefit in this setting. This is not a criticism of their manuscript, because such an answer is not available on the basis of existing data. Moreover, it may not represent the key question that needs to be addressed at this time. In a section entitled "Adjuvant Chemotherapy Milestones," the authors review seven cisplatin-based RCTs addressing the value of adjuvant chemotherapy in various stages of resectable NSCLC.[2-8] These include three highly influential RCTs that reported positive overall results among populations randomized to adjuvant chemotherapy. [4-6] However, in each of these seminal trials only certain subgroups appeared to benefit, while other "milestone" studies were quite negative.[2,3,81 For this reason, the authors depend heavily on recent meta-analyses to justify their conclusions regarding the efficacy of adjuvant chemotherapy. In the treatment of breast cancer, several RCTs have compared adjuvant and neoadjuvant approaches. The best known individual RCT is the National Surgical Adjuvant Breast and Bowel Project (NSABP) B- 18 protocol reported a decade ago by Fisher et al. [27] In general, these RCTs have shown that survival was not significantly different when adjuvant or neoadjuvant chemotherapy was used. A similar conclusion was reached with a meta-analysis of nine RCTs that compared adjuvant and neoadjuvant chemotherapy in breast cancer. [28] This reviewer suspects that adjuvant and neoadjuvant therapy is likely to provide similar outcome in appropriately selected patients. In lung cancer, two ongoing RCTs are directly comparing neoadjuvant and adjuvant chemotherapy. One is the NATCH (Neoadjuvant- Adjuvant Taxol Carboplatin Hope) trial, a threearm study comparing neoadjuvant or adjuvant paclitaxel and carboplatin to surgery alone in stage IB, II, and III