Examining the link between obesity, inflammation, and exercise in patients with metastatic prostate cancer?An interim analysis from the ExPeCT trial

Background: Globally, prostate cancer (PrCa) is the fourth most common cancer type. Obesity and inflammation have been shown to play significant roles in PrCa disease progression. Obesity and a high body mass index (BMI) are associated with increased PrCa‐specific mortality in patients with advanced disease. Furthermore, proinflammatory cytokines can aid metastatic potential and promote angiogenesis. The ExPeCT (Exercise, Prostate Cancer and Circulating Tumor Cells) trial seeks to examine the effectiveness of a structured exercise program in modulating inflammatory mediators and obesity in patients with metastatic PrCa. Methods: ExPeCT (CTRIALIE 15‐21 (ClincalTrials.gov identifier NCT02453139)) is a multicenter, randomized trial for patients with metastatic PrCa (n=67). Participants were randomized to either control or exercise arms. Participants in the exercise arm completed six months of prescribed aerobic exercise, which was monitored using percentage heart‐rate reserve. Serum samples were collected for all participants at baseline (T0), three months (T3), and six months (T6), and assayed for 16 interlinked adipokines and cytokines using the Meso Scale Discovery platform. An interim statistical analysis was performed (n=26) comparing median change in serum analyte levels between control (n=13) and exercise (n=13) arms using non‐parametric Wilcoxon rank‐sum tests. Results: Among 26 patients included in our interim analysis, mean age at baseline was 71 years, median BMI was 29.1 kg/m2, and median waist circumference (WC) was 107 cm, with no significant differences between arms (all p>0.3). Between T0 and T6, WC decreased by a median of 3.8 cm in the exercise group and 2.6 cm in the control group (p=0.412), with a similar trend for BMI. Interim serum cytokine analysis showed a 3‐fold increase in IL‐10 levels in the exercise arm at T3 when compared to the control arm (p=0.036). No significant change in IL‐10 levels was recorded at T6 between arms (p=0.776). Similarly, CXCL8 (IL‐8) levels were increased by 1.8‐fold at T3 in the exercise arm in comparison to the control arm (p=0.017), with no significant change reported at T6 (p=0.191). While changes were evident in serum TNFα, IL‐6, VEGF, IL‐17a, MMP9 and CCL5 (RANTES) levels, these did not reach significance. Differences in levels of adipokines leptin and resistin were also reported. A 1.5‐fold increase in resistin expression was observed in the exercise arm at T6; however, it was not significant (p=0.293). A 2‐fold decrease in leptin in the control arm relative to the exercise arm at T6 was also detected (p=0.676). Analysis of adiponectin, MMP2, and CCL2 is ongoing. Conclusion: Our interim analysis of ExPeCT trial participants demonstrated a significant increase in serum CXCL8 and IL‐10 levels after three months of a supervised exercise intervention. These preliminary data suggest that a structured exercise program has the potential to modify inflammatory status in patients with metastatic PrCa.