Abstract
INTRODUCTION: Increased efforts to optimize outcomes for early stage NSCLC through the investigation of novel perioperative treatment strategies are ongoing. An emerging question is the role of pathologic response and its association with long-term clinical outcomes after neoadjuvant therapy. METHODS: To investigate the association of pathologic complete response (pCR) and event-free survival (EFS) and overall survival (OS), we performed a systematic review and meta-analysis identifying studies reporting on the prognostic impact of pCR after neoadjuvant chemotherapy or chemoradiotherapy. To evaluate this prognostic value, an aggregated data (AD) meta-analyses was conducted to estimate the pooled hazard ratios (HRs) of EFS and OS for pCR. Using reconstructed individual patient data (IPD), pooled Kaplan-Meier curves were obtained to estimate this association in a more granular fashion. Subgroup analyses were conducted to further explore the impacts of study-level characteristics. RESULTS: A total of 28 studies comprising 7011 patients were included in the AD meta-analysis, of which, IPD was available for 6274 patients from 24 studies. Results from our AD meta-analysis revealed a pooled pCR rate of 18% (95% confidence interval [CI]: 15%-21%), including significant improvements in OS (HR = 0.50, 95% CI: 0.45-0.56) and EFS (HR = 0.46, 95% CI: 0.37-0.57) on the basis of pCR status. Our IPD analysis revealed a 5-year OS rate of 63% (95% CI: 59.6-67.4) for patients with a pCR compared with 39% (95% CI: 34.5-44.5) for those without a pCR. CONCLUSIONS: pCR after neoadjuvant chemotherapy plus or minus radiotherapy is associated with significant improvements in EFS and survival for patients with resectable NSCLC.