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

Branislav Jeremić,Francesc Casas,Nikola Čihorić,Ivan Igrutinovic,Antonio Gomez-Caamano,Pavol Dubinsky,Gregory Videtic

doi:10.3389/fonc.2018.00030

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.

Highlights

Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease presentation based on the range of patient and tumor characteristics included under its heading
While little is known about treatment-related factors, the aim of the present study is to identify if potential treatment-related predictive and prognostic factors exist that can help optimize the selection of patients for a trimodality approach for their stage IIIA/pN2 disease
Five studies compared concurrent RT-CHT vs a trimodality approach, one compared surgery alone with a trimodality approach, while the remaining seven studies compared induction CHT followed by surgery with induction RT-CHT followed by surgery

Summary

Introduction

Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease presentation based on the range of patient and tumor characteristics included under its heading. Treatment regimens consisting of surgery alone or in combination with adjuvant CHT- and/or RT have been historically among the most common approaches used, Stage IIIA NSCLC with recent decades showing a trend for induction regimens followed by surgery. The latter have included induction CHT followed by surgery [4,5,6,7], and, in more recent years, induction RT-CHT followed by surgery [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34]. When tested in prospective randomized phase III studies, preoperative RT (PORT)-CHT (with or without preceding CHT) followed by surgery brought no improvement in overall survival (OS) or local control compared to definitive concurrent RT-CHT, and was associated with an increase in treatment-related mortality [8, 10, 35, 36]

Objectives

Methods

Results

Conclusion