The prognostic significance of serum levels of tumour necrosis factor- alpha and interleukin-6 and their association with cachexia in patients with prostate cancer

Abstract

4743 Background: The complex syndrome of cancer cachexia is multifactorial in origin and several cytokines may be involved in its aetiology. The present study was undertaken to evaluate the relationship between serum tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and cachexia in patients with prostate cancer (CaP), and their prognostic significance. Methods: The levels of TNF-α and IL-6 were determined in serum samples from 26 patients with organ-confined CaP, from 54 patients with advanced or metastatic CaP and from 38 controls. High sensitive commercially available (ELISA) assays were used to determine cytokine levels. Serum IL-6 and TNF-α levels were correlated with serum albumin levels, hemoglobin levels, body mass index, clinicopathological variables and patient survival. The prognostic significance of the above parameters was assessed using univariate and multivariate Cox's proportional hazards model analyses. Results: Weight loss more than 10% over a 3–6 month period was seen in 7 of 54 patients (13%) with advanced CaP. The median levels of TNF-α and IL-6 were significantly elevated in cachectic patients with advanced prostate cancer (9.3 pg/ml and 6.7 pg/ml respectively) compared with patients with localized disease (1.3 pg/ml, and 1.9 pg/ml p< .001), or healthy subjects. The serum albumin levels, hemoglobin levels, and body mass index of the patients with elevated serum TNF-α and IL-6 levels were significantly lower (p< 0.001) than the corresponding values in patients with very low levels of both cytokines. TNF-α levels correlated with IL-6 levels, but there was no correlation between PSA levels and cytokine levels. With a median follow-up of 48 months, patients with elevated serum levels of both cytokines and cachexia had a significantly higher mortality rate (p < 0.05) than those with undetectable serum levels. Conclusions: These results suggest that TNF-α and IL-6 levels were correlated with significant cachexia and related to survival in patients with advanced prostate cancer, and could provide potential targets for the treatment of cancer cachexia. No significant financial relationships to disclose.