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According to Global Cancer Statistics 2020, lung cancer accounts for one in ten new cases (11.4%) and one in five cancer-related mortalities (18.0%), making it the deadliest and the second most frequently diagnosed cancer. Despite curative treatment, around 30–55% of patients relapse, primarily at distant sites, and 50% succumb to lung cancer, suggesting the early dissemination of malignant cells. Circulating tumor cells (CTC) get dislodged from the primary tumor or metastatic sites and circulate in the bloodstream. The dissemination of CTC may precede the formation of metastases and even primary tumors itself.
Prior meta-analysis on NSCLC showed that CTC positivity (CTC+) was associated with poor overall survival (OS) and disease-free survival (DFS). CTC counts significantly increase in the pulmonary vein after surgical manipulation of the tumor or even endoscopic biopsy. However, the prognostic implication of CTC+ in the pulmonary vein is variable. The data on the predictive value of postoperative CTC are discordant. Variable follow-up periods, numerous detection methods, inconsistent CTC cut-off values, and a relatively small patient cohort may influence the outcome. Resolution of these issues will aid in the bench-to-bedside transition of CTC in resectable NSCLC.
A systemic review and metaanalysis of eighteen prospective studies by Wankhede et al. published Cancers in 2022, showed that CTC status was highly predictive of the survival outcomes of patients with early-stage NSCLC. Specifically, CTC+ status had a negative impact on OS, regardless of time and source of blood collection, detection methods, and follow-up duration. Meta-analytic data showed that CTC status was highly predictive of the survival outcomes and had a negative impact on DFS, regardless of time and source of blood collection, detection methods, and follow-up duration. In addition, it was found that the pathological stage was associated with CTC status, with stage III patients more likely to be CTC+, whereas stage I was at a lower risk. Although significant heterogeneity was observed among the included studies; however, sensitivity analyses revealed stable results.
These findings are consistent with the growing body of evidence that demonstrates that CTCs are promising prognostic markers for resectable cancers and resolve various issues revolving around the bench-to-bedside transition of CTC in early-stage NSCLC. An interesting pattern emerged during the stage assessment. As the stage progressed from early to advanced, the likelihood of CTC+ increased accordingly. Stage I disease was least likely to be associated with CTC resembling the classical view of the impact of the stage on CTC. Moreover, CTC count correlated with the pathologic stage in a similar way.
These findings hint towards the increased shedding of CTC from the bulky tumor and multiple nodal metastases. This result also conforms to the current evidence on the association of CTC to tumor size and lymph node metastasis.
To conclude, CTC could be a valid prognostic indicator for OS and DFS. Pre- and Post-OP CTC analysis can guide percision therapy. Timing of surgery and neo-adj. or adj. therapy can be based on CTC values. CTC could be used as a marker for recurrence survelience and response to therapy.
References
https://doi.org/10.3390/ cancers14246112
| Keywords | CTC, NSCLC, Resection |
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