Predictors for locoregional recurrence for clinical stage III-N2 non-small cell lung cancer with nodal downstaging after induction chemotherapy and surgery.

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

doi:10.1200/jco.2012.30.15_suppl.7043

Abstract

7043 Background: Pathologic downstaging following induction chemotherapy in patients with 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. Methods: Between 1998-2008, 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 patients had pathologic N0-1 disease, and no one received postoperative radiotherapy. LRR were defined as disease recurrence at the surgical site, lymph nodes (levels 1-14 including supraclavicular) or both. Overall survival (OS) was calculated using the Kaplan and Meier method and comparisons were made using the log-rank test. Univariate and multivariate Cox proportional hazards model were used to assess the association of LRR and risk factors. Results: The median follow up time for survivors was 39.3 months. Baseline pretreatment N2 nodal involvement was staged by either pathologic confirmation (18.2%) or 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 of 43). The 5 year OS for patients with LRR compared to those without was 21% versus 60.1%, respectively (p<0.001). Using multivariate analysis, significant predictor for LRR was pN1 versus pN0 disease at time of surgery (p<0.001, HR 3.43, 95% CI 1.80-6.56) and trended for squamous histology (p=0.072, HR 1.93, 95% CI 0.94-3.98). The 5-year LRR rate for N1 versus N0 disease was 62% versus 20%, respectively. Neither single versus multistation N2 disease (p=0.291) nor initial staging by mediastinoscopy versus PET/CT (p=0.306) were predictors for LRR. We found that N1 status was also predictive for higher distant recurrence rate (p=0.021, HR 1.91, 95% CI 1.10-3.30) but only trended for poorer OS (p=0.123, HR 1.48, 95% CI 0.90-2.44). Conclusions: LRR remains high in resected stage III-N2 NSCLC patients after induction chemotherapy and nodal downstaging, particularly in patients with persistent N1 disease. Postoperative radiotherapy may be needed for these high-risk patients.

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

Methods

Results

Conclusion