The role of liquid biopsy in predicting post-operative recurrence of non-small cell lung cancer.

Abstract

Radical resection is the cornerstone for patients with early stage of non-small cell lung cancer (NSCLC). However, fatal disease recurs in about 30-70% of resected cases. The circulating tumor cells (CTCs) is one of the main causes of recurrence of cancer. Circulating tumor DNA (ctDNA) is also a potential predictive biomarker of recurrence in patients with early stage NSCLC. A meta-analysis was conducted to identify the prognostic value of the CTCs and ctDNA in predicting the disease recurrence after surgery of NSCLC patients. Electronic databases were comprehensively searched for eligible studies. A random effects model was used. The primary endpoint was the hazards ratio (HR) for the disease-free survival (DFS) between CTCs/ctDNA positive and negative groups. The relative risks (RR) of one and two-year recurrence rate between CTCs/ctDNA positive and negative groups were also calculated. A total of 5 studies involving 351 patients were included, in which 3 were studies on CTCs and 2 were ctDNA. Our result revealed that positive peripheral blood CTCs (HR, 3.37; 95% CI: 2.28-4.96; P<0.001) and ctDNA (HR, 8.15; 95% CI: 2.11-31.50; P=0.002) indicated poor prognosis for DFS. One (68% vs. 18.2%; RR 3.28; P<0.001) and two (76% vs. 44%; RR 1.80; P=0.06) years recurrence rate were higher in CTCs positive group compared with the negative group, respectively. The same result was also observed in ctDNA positive versus negative groups of 1 (77.9% vs. 8.3%; RR 9.05; P=0.001) and 2 (85.6% vs. 8.3%; RR 9.63; P<0.001) years recurrence rate. Both postoperative CTCs and ctDNA are promising predictive biomarkers of early tumor recurrence in NSCLC patients. In addition, detection based on ctDNA seems to be more sensitive than CTCs.