We assessed the clinical validity of circulating tumor cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data.
Nine European NSCLC CTC centers were asked to provide reported/unreported anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 - March 2017. We used Cox regression models, stratified by center, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinico-pathological models using likelihood ratio (LR) statistics and c-indices.
Seven out of nine eligible centers provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: HR 1.72, p<0·001; ≥5 CTCs: HR 2.21, p<0·001) and overall survival (≥2 CTCs: HR 2·18, p<0·001; ≥5 CTCs: HR 2·75, p<0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinico-pathological models (log-transformed CTCs p<0·001; ≥2 CTCs p<0·001; ≥5 CTCs p≤0·001 for both survival endpoints), while more moderate improvements were observed with the use of c-index models. There was some evidence of between-center heterogeneity especially when examining continuous counts of CTC.
These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC but also reveal some evidence of between-center heterogeneity. CTC count improves prognostication when added to full clinico-pathological predictive models.