Circulating Tumor Cell Infiltration of Major Vessels Influences Cancer Prognosis

Despite the prevalence of cancer and the identification of numerous molecular targets, the pathophysiological mechanisms that ultimately lead to death from cancer have not been fully elucidated. In a retrospective study of 108 patients with solid malignancies who died of tumor complications, 88% had tumor emboli within the cardiovasculature, and 59% showed signs of macrovascular infiltration. Thus, Newcomer and colleagues performed an observational, prospective study on 21 patients with cancer and a control group of 10 patients without signs of malignancy to characterize circulating tumor cells (CTC) dynamics and cancer-related events in the major vessels (macrovascular infiltration) in palliative care settings until death. An increase in the number and cluster size of CTCs was found in patients with cancer immediately before death. From the same vessels where samples were taken for CTC analysis, blood clots were analyzed in patients both with and without cancer. As expected, cancer cells were not detected in patients without malignancies, while 38% of patients with cancer had infiltrating masses that had colonized veins and arteries, supported by CT imaging. To determine the prognostic value of macrovascular infiltration, univariate and multivariate survival analyses were performed among patients with metastases. Validation of the observations was performed in an independent cohort (n = 1,250) comprising several cancer types, including hepatocellular carcinoma, lung, colorectal, pancreatic, and ovarian cancer, in which patients with macrovascular infiltration exhibited shorter median overall survival compared to those without. Furthermore, when specific types of vessels were analyzed, invasion within the abdominal aorta and inferior vena cava, the largest artery and vein, respectively, resulted in the highest hazard ratios. Taken together, these data demonstrate that increased CTC cluster size and the presence of macrovascular infiltrations across cancer types, ages, and sexes are pivotal events in cancer progression, providing evidence that these measures may be a stronger predictor of survival than metastatic and resection status. In addition, these findings point to new therapeutic avenues to block tumor invasion of large vessels and the formation of CTC clusters to prevent the irreversible and catastrophic vascular consequences observed in patients with soli tumors.Newcomer K, Bifolco A, Reeves S, Pontecorvi G, Asawa S, Sznurkowska MK, et al. Macrovascular tumor infiltration and circulating tumor cell cluster dynamics in patients with cancer approaching the end of life. Nat Med 2025 Oct 16 [Epub ahead of print].Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at https://aacrjournals.org/cdnews.