Treatment-Related Predictive and Prognostic Factors in Trimodality Approach in Stage IIIA/N2 Non-Small Cell Lung Cancer

Abstract

While there are no established pretreatment predictive and prognostic factors in patients with stage IIIA/pN2 non-small cell lung cancer (NSCLC) indicating a benefit to surgery as a part of trimodality approach, little is known about treatment-related predictive and prognostic factors in this setting. A literature search was conducted to identify possible treatment-related predictive and prognostic factors for patients for whom trimodality approach was reported on. Overall survival was the primary endpoint of this study. Of 30 identified studies, there were two phase II studies, 5 “prospective” studies, and 23 retrospective studies. No study was found which specifically looked at treatment-related predictive factors of improved outcomes in trimodality treatment. Of potential treatment-related prognostic factors, the least frequently analyzed factors among 30 available studies were overall pathologic stage after preoperative treatment and UICC downstaging. Evaluation of treatment response before surgery and by pathologic tumor stage after induction therapy were analyzed in slightly more than 40% of studies and found not to influence survival. More frequently studied factors—resection status, degree of tumor regression, and pathologic nodal stage after induction therapy as well as the most frequently studied factor, the treatment (in almost 75% studies)—showed no discernible impact on survival, due to conflicting results. Currently, it is impossible to identify any treatment-related predictive or prognostic factors for selecting surgery in the treatment of patients with stage IIIA/pN2 NSCLC.

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].…”

Multimodality Treatment including Surgery Related to the Type of N2 Involvement in Locally Advanced Non-Small Cell Lung Cancer

“…Various multimodality treatments are described, where the role of surgery is often being questioned. No predictors nor prognosticators were identified in a review on the management of stage IIIA-N2 disease, not facilitating the decision-making progress regarding the role of surgery in this subgroup [ 7 ]. Another difficult point remains the distinction between resectable and unresectable disease as no clear definitions exist.…”

“…Jeremic et al were unable to find treatment-related predictive and prognostic factors in the management of stage III disease, more specifically in identifying patients eligible for surgery. This was mainly due to heterogeneity in factors reported in different studies [ 7 ]. Concurrent chemoradiotherapy (CRT) has traditionally been suggested as the gold standard, especially in the unresectable stages.…”

Induction therapy with Erlotinib (E) and Gemcitabine/Platinum (GP) in stage III NSCLC

“…In contrast, the meta-analysis of Jeremić et al could not identify any treatment-related predictive or prognostic factors for selecting surgery in the treatment of patients with stage IIIA/ pN2 NSCLC. This result is limited by the fact, that factors, such as the degree of tumor regression, status of surgical margins, evaluation of response before surgery, or post-induction tumor status (ypT), were evaluated only in slightly more than 40% of all available studies [51].…”