Predictors for Locoregional Recurrence for Clinical Stage III-N2 Non-small Cell Lung Cancer with Nodal Downstaging After Induction Chemotherapy and Surgery

Arya Amini,James Huang,Jack A Roth,Arlene M Correa,Randall Baldassarre,Andreas Rimner,Ara A Vaporciyan,Feiran Lou,Stephen G Swisher,Steven H Lin

doi:10.1245/s10434-012-2800-x

Abstract

PurposePathologic downstaging following chemotherapy for stage III-N2 NSCLC is a well-known positive prognostic indicator. However, the predictive factors for locoregional recurrence (LRR) in these patients are largely unknown.MethodsBetween 1998 and 2008, 153 patients with clinically or pathologically staged III-N2 NSCLC from two cancer centers in the United States were treated with induction chemotherapy and surgery. All had pathologic N0-1 disease, and none received postoperative radiotherapy. LRR were defined as recurrence at the surgical site, lymph nodes (levels 1–14 including supraclavicular), or both.ResultsMedian follow-up was 39.3 months. Pretreatment N2 status was confirmed pathologically (18.2 %) or by PET/CT (81.8 %). Overall, the 5-year LRR rate was 30.8 % (n = 38), with LRR being the first site of failure in 51 % (22/+99877943). Five-year overall survival for patients with LRR compared with those without was 21 versus 60.1 % (p < 0.001). Using multivariate analysis, significant predictors for LRR were pN1 disease at time of surgery (p < 0.001, HR 3.43, 95 % CI 1.80–6.56) and a trend for squamous histology (p = 0.072, HR 1.93, 95 % CI 0.94–3.98). Five-year LRR rate for pN1 versus pN0 disease was 62 versus 20 %. Neither single versus multistation N2 disease (p = 0.291) nor initial staging technique (p = 0.306) were predictors for LRR. N1 status also was predictive for higher distant recurrence (p = 0.021, HR 1.91, 95 % CI 1.1–3.3) but only trended for poorer survival (p = 0.123, HR 1.48, 95 % CI 0.9–2.44).ConclusionsLRR remains high in resected stage III-N2 NSCLC patients after induction chemotherapy and nodal downstaging, particularly in patients with persistent N1 disease.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-012-2800-x) contains supplementary material, which is available to authorized users.

Highlights

For patients with stage III NSCLC, multimodality therapy remains the standard of care
From February 1998 to December 2008, 153 patients with clinically or pathologically staged III-N2 NSCLC from two cancer centers in the United States were treated with induction chemotherapy followed by surgery and found to have pathologically downstaged nodal disease at the time of their surgery
This study evaluated the rate of locoregional recurrence in patients with a pathologic response following neoadjuvant chemotherapy

Summary

Introduction

For patients with stage III NSCLC, multimodality therapy remains the standard of care. The median time to local relapse comparing persistent pN2 versus pN0-1 was 14.4 versus 43.8 months In their most recent update, they reported 5-year locoregional failure (LRF) rates as high as 60 % in the entire study population, including those with or without nodal downstaging. In those patients with pathologic response to chemotherapy, there was a significant reduction in distant metastasis. We performed a retrospective analysis of the treatment outcomes of patients treated at two major cancer centers to determine predictors for locoregional recurrence for patients with clinical stage III-N2 disease who undergo nodal downstaging after induction chemotherapy at the time of surgery. We hypothesized that there are certain patient and tumor characteristics that would be predictive for higher local recurrence and may necessitate more aggressive local treatment, including PORT

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Conclusion