Longitudinal change of circulating tumor cell level and its relationship with immune checkpoint inhibitor-based treatment benefits in unresectable, metastatic colorectal cancer patients

Circulating tumor cell (CTC) exerts diagnostic and prognostic value in colorectal cancer (CRC) patients. This study intended to further investigate the longitudinal change of CTC count, and its correlation with the prognosis of immune checkpoint inhibitor (ICI)-based treatments in unresectable, metastatic CRC patients. Fifty-six unresectable, metastatic CRC patients receiving ICI-based treatments were enrolled. CTC count was assessed by the CellSearch system at baseline and month (M)2 in their peripheral blood samples. Forty-one (73.2%) and sixteen (28.5%) patients had CTC count ≥1 and ≥5 at baseline, respectively. Meanwhile, CTC count at M2 was decreased versus that at baseline (median (interquartile range): 1.0 (0.0–3.0) versus 3.0 (0.0–5.0)) (<i>p</i> &lt; 0.001). Besides, increased CTC count at baseline (<i>p</i> = 0.009) and M2 (<i>p</i> = 0.006) associated with a reduced overall response rate. Baseline CTC count ≥5 related to worse progression-free survival (PFS) (<i>p</i> = 0.007), but baseline CTC count ≥1 did not; additionally, baseline CTC count ≥1 (<i>p</i> = 0.043) and ≥5 (<i>p</i> = 0.016) linked to shorter overall survival (OS). Furthermore, M2 CTC count ≥1 (<i>p</i> = 0.002) and ≥5 (<i>p</i> &lt; 0.001) both correlated with poor PFS; meanwhile, M2 CTC count ≥1 (<i>p</i> = 0.006) and ≥5 (<i>p</i> &lt; 0.001) also related to worse OS. After adjustment, only CTC count at M2 ≥ 5 independently associated with unsatisfactory PFS (hazard ratio (HR)=3.218, <i>p</i> = 0.011) and OS (HR = 3.229, <i>p</i> = 0.038). CTC count is decreased during ICI-based treatments, its reduction represents satisfactory treatment outcomes in unresectable, metastatic CRC patients. Notably, the CTC count at 5 as a cutting threshold after a two-month treatment has an impressive prognostic value.