The effect of a structured exercise intervention on CTCs and platelet cloaking in patients with metastatic prostate cancer.

Abstract

243 Background: Physical activity has been described as an effective adjunct for improving quality of life in patients with metastatic prostate cancer (PrCa). Circulating tumor cells (CTCs) are a morphologically distinct set of cancer cells, involved in disease progression. Platelet cloaking, the surrounding and subsequent attachment of platelets to CTCs, has been proposed as effective in aiding extravasation, thus enhancing metastatic spread. The ExPeCT (Exercise, Prostate Cancer and Circulating Tumor Cells) trial aimed to examine the impact of a structured exercise intervention on the mechanisms of metastasis, including CTC cloaking, in patients with metastatic PrCa. Methods: ExPeCT was a multi-center, randomized trial for patients with metastatic PrCa (n=61). Participants were randomized to either control or exercise arms. Participants in the exercise arm (n=29) completed six months of prescribed aerobic exercise. Whole blood was collected for all participants at baseline (T0), three months (T3) and six months (T6), and analyzed for the presence of CTCs, CTC clusters and platelet cloaking. Results: No significant difference in CTC number between the exercise and control arms was observed (p=0.2630), however significant alterations in CTC number were observed within group over time (p<0.001). Platelet cloaking was modelled as a binary response (presence/absence). A trend towards higher levels of platelet cloaking in the control group was observed (p=0.1005). Further, all findings were compared to a range of clinical variables. CTC clusters were positively correlated with PSA levels (p=0.0393) and a positive correlation between CTC number and white blood cell count (p<0.001) was determined. Conclusions: No significant relationship between CTCs and physical activity was observed, however the exercise program was well tolerated by ExPeCT participants. This study has, for the first time, shown platelet cloaking of CTCs in metastatic PrCa, in addition to a significant positive correlation between CTCs and white blood cells. These findings provide critical insight into immune crosstalk and the metastatic cascade in metastatic PrCa. Clinical trial information: NCT02453139.