Prostate cancer is the most commonly diagnosed malignancy in US men and it is the second leading cause of cancer death in US men. A standard of care treatment for localized prostate cancer includes radiation to the prostate. Reactive oxygen species are an important contributor to the efficacy of radiation therapy, but they also initiate down-stream signaling which eventually leads to resistance of oxidative damage and thus resistance to radiation therapy. One way that this is accomplished is through up-regulation of NF-κB. Rel-B is a member of the NF-κB family and is found in high concentrations in the nuclei of prostate cancer cells of higher Gleason scores (GS). High levels of Rel-B protect prostate cancer from radiation and suppression of Rel-B leads to more radiosensitive tumors, as reported from preclinical studies. There is evidence that overexpression of Rel-B increases interleukin 8 (IL-8) in prostate cancer cell lines and animal models. Serum IL-8 was also found to be increased in men with bone metastases from prostate cancer. Thus IL-8 may be an important tumor marker with prognostic significance in prostate cancer especially with regard to its growth and response to therapy. We conducted a prospective cohort study to document the correlations between IL-8, PSA, inflammatory markers such as C-reactive protein (CRP), clinical stage, and time to progression. Males with biopsy-proven prostate cancer were enrolled prior to definitive treatment. Patients were treated according to the standard of care. Physical exams were performed and blood was collected at baseline and at every follow-up to measure serum PSA, IL-8, and inflammatory markers such as CRP. Imaging studies were performed at diagnosis and then as clinically indicated. One-hundred-and-forty-nine patients were evaluable. Six patients had pathologic/radiologic evidence of disease progression. We found that stage group and baseline CRP is significantly related to time to progression (p=0.0280 and p= 0.0295, respectively). Baseline IL-8 levels significantly predicted stage group (p=0.021). We also found that age was significantly correlated with baseline CRP and GS at diagnosis (correlations: -0.19 & 0.20, p=0.0226&p=0.0134, respectively) and that baseline PSA was significantly related to GS at diagnosis (correlation=0.31, p=0.0002). IL-8 and CRP are tumor markers with potential prognostic significance. IL-8 predicted stage group successfully and CRP was related to time to progression. These discoveries may help build better models to understand prognosis and develop potential precision therapeutic strategies with regard to prostate cancer.