Combined modality therapy in Stage IIIA non–small cell lung cancer: clarity or confusion despite the highest level of evidence?

Abstract

Recent years have witnessed a number of clinical trials in Stage IIIA non–small cell lung cancer (NSCLC) comparing (A) induction chemotherapy (CHT) with induction CHT and radiotherapy (RT), each followed by surgery; (B) either induction CHT or induction RT-CHT, each followed by surgery, with definitive RT-CHT (no surgery). Due to the heterogeneity of patient, tumor and treatment characteristics across these trials, various meta-analyses (MAs) have been performed to define the optimal treatment approach in this setting for this clinical presentation. Six such MAs exist. In spite of the differences between MAs, it appears that RT does not add extra benefit to induction CHT administered before surgery, and that a trimodality (i.e. including surgery) regimen is not superior to definitive concurrent RT-CHT. While one can consider both induction CHT followed by surgery and exclusive concurrent RT-CHT as feasible in this setting, lack of pre-treatment predictive factors identifying patients who might preferentially benefit from a surgical approach limits its use to well-planned clinical trials.

Real-world Treatment Patterns of Lung Cancer- experience of Resource Restricted Country

“…Recent data on the use of modern postoperative TRT [22] seem to overcame negative impact of historic data [23,24], since it enabled effectively concentrating on patients harboring high risk features. In Stage IIIA NSCLC, less than a half of the institutions would still consider surgical multimodality approach likely due to a number of group/society guidelines and recommendations [25,26] in spite of the fact that serious criticism and a number of aws and fallacies have been highlighted in recent years [27][28][29][30]. In, inoperable cases, the vast majority of departments would prefer concurrent RT-CHT, following highest level of evidence existing for more than a decade [31][32][33].…”

Resectable IIIA-N2 Non-Small-Cell Lung Cancer (NSCLC): In Search for the Proper Treatment

“…Moreover, two phase II trials comparing chemotherapy plus surgery to surgery alone found a similar significant improvement in median survival with chemotherapy [11,12]. In the last years, clinicians' attention has shifted to the role of surgery following neoadjuvant therapy, since no published study has established the superiority of this approach over dCR, yet and the main concern is the potential for increase surgical morbidity and mortality [13]. Definitive concurrent CR is the standard treatment, as shown in a metanalysis by Auperin et al [14]; by comparing six randomized trials about outcomes of concomitant over sequential dCR in patients with locally advanced NSCLC, concomitant combination increases 3-years overall survival (OS) of a 5.7% and 5-years OS of a 4.5%.…”

Neoadjuvant Treatment for Resectable, Stage IIIA Non-Small Cell Lung Cancer

“…There was no difference in 5-year OS (40% vs. 44%, p = 0.34) or PFS (35% or 32, p = 0.75) between the CHRT and surgical arms, respectively [39]. Results of these studies were the subject of four meta-analyses/systematic reviews [31,[40][41][42] which were summarized by Jeremic et al [43] who clearly showed that there is no place for surgery in a multimodality treatment in these patients. The most recent meta-analysis of Pottgen et al also analyzed randomized trials comparing surgery with definitive RT as local curative treatment options within the framework of different multimodality treatments for patients with locally advanced (LA-NSCLC).…”