Objectives: Elevated circulating levels of interleukin 6 (IL-6) have been associated with cancer metastasis. IL-6 binds either to membrane or to soluble IL-6 receptor (IL-6sR), which then induces homodimerization of gp130 that activates downstream signaling. We tested the hypothesis that preoperative plasma IL-6 and IL-6sR levels are associated with prostate cancer stage, progression, and metastasis after radical prostatectomy.
Methods: Plasma levels of IL-6 and IL-6sR were measured in 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer, 44 healthy men without any cancer, 19 men with prostate cancer metastatic to the regional lymph nodes, and 10 men with prostate cancer metastatic to bone.
Results: Plasma IL-6 and IL-6sR levels were highest in patients with bone metastases (P <0.001). The preoperative IL-6 and IL-6sR levels were associated with the preoperative prostate-specific antigen (PSA) level (P </=0.041), prostatectomy tumor volume (P </=0.048), and final Gleason sum (P </=0.042). The preoperative IL-6 and IL-6sR levels and biopsy Gleason sum were independent predictors of PSA progression (P </=0.029). However, in a model that included both IL-6 and IL-6sR, only IL-6sR and the biopsy Gleason sum predicted progression (P </=0.040). In patients whose disease progressed, the preoperative IL-6 and IL-6sR levels were highest in those with presumed aggressive failure (P </=0.042).
Conclusions: Plasma IL-6 and IL-6sR levels were dramatically elevated in the men with prostate cancer metastatic to bone. In patients with clinically localized prostate cancer, the preoperative plasma IL-6 and IL-6sR levels independently predicted biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.