ADT-induced inflammation linked to fatigue in patients with prostate cancer

An increase in circulating interleukin 6 (IL‐6), an inflammation marker, among patients with prostate cancer receiving androgen-deprivation therapy (ADT) was linked to increased fatigue, according to research published in the journal Cancer.^1,2

“Interleukin-6 is a pro-inflammatory cytokine that is often associated with disruption of sleep and therefore fatigue,” Aasha Hoogland, PhD, lead study author and an applied research scientist in the Health Outcomes & Behavior Program at Moffitt Cancer Center, stated in a press release.

“Studies have shown testosterone can suppress the effects of IL-6, but ADT limits testosterone production in the body, which is why we may be seeing increased levels in this patient group,” added Hoogland.

Previous research established an associated between ADT and increased levels of fatigue, depressive symptomatology, and cognitive impairment in patients. However, no studies had focused on whether ADT-induced inflammation contributed to the development of these symptoms.

“This is the first study that we know of that examines the association between inflammation and symptoms of fatigue, depression, or cognitive impairment in prostate cancer patients receiving ADT,” Heather Jim, PhD, corresponding author and co-leader of the Health Outcomes & Behavior Program at Moffitt, stated in the press release.

“Because the blocking of testosterone can increase inflammation in the body, we believe that inflammation may also be contributing to these symptoms,” added Jim.

The Moffitt investigators assessed 2 groups of men. The first comprised 47 patients with prostate cancer who were treated with ADT. Patients were assessed at the start of ADT and then at 6 and 12 months following treatment initiation. The second group comprised a cohort of 82 age- and education-matched men without a history of cancer who were assessed at similar time points.

The researchers' strategy was to examine circulating markers of inflammation in patients receiving ADT and explore a potential connection between these markers and increases in fatigue, depression, and cognitive impairment related to ADT.

The circulating markers of inflammation assessed included interleukin 1 receptor antagonist (IL‐1RA), IL‐6, soluble tumor necrosis factor receptor II (sTNF‐RII), and C‐reactive protein (CRP).

Fatigue was assessed with the Fatigue Symptom Inventory, depression was assessed with the Center for Epidemiological Studies Depression Scale, and cognitive impairment was evaluated using a battery of neuropsychological tests.

The results showed a significant increase over time in fatigue, depressive symptomatology, and serum IL‐6 among patients receiving ADT versus the cancer-free group. “Rates of cognitive impairment also changed significantly between the groups,” the author wrote.

Over time, there were no significant changes detected in IL‐1RA, sTNF‐RII, or CRP.

The researchers established an association between increases in IL-6 and increased fatigue; however, no such connection was established between IL-6 increases and increases in depressive symptomatology or cognitive impairment.

The next steps, according to the Moffit investigators, are additional studies examining whether specific interventions, such as exercise and anti-inflammatory treatments, can mitigate fatigue and depression in patients with prostate cancer receiving ADT.

References

1. Inflammation from Androgen Deprivation Therapy May Cause Fatigue in Prostate Cancer Patients. Published online January 4, 2020. https://bit.ly/391Yl6I. Accessed January 4, 2020.

2. Hoogland AI, Jim HSL, Gonzalez BD, et al. Systemic inflammation and symptomatology in patients with prostate cancer treated with androgen deprivation therapy: Preliminary findings [published online December 30, 2020]. Cancer. doi: 10.1002/cncr.33397