Differential Cytokine Profiles in Prostate Cancer Under Treatment: Implications for Prognosis and Synergistic Therapy Design

<b>Background/Objectives</b>: Localized prostate cancer may be treated with total cryotherapy, focal cryotherapy, stereotactic body radiotherapy (SBRT), or radical prostatectomy (RP). However, the immune response to these therapies is not fully understood despite its potential importance in determining extent and timing of recovery, disease control and cancer recurrence rate. This exploratory study measured cytokine expression changes in the urine and blood of prostate cancer patients as a means of monitoring immune response to these four alternative treatments. <b>Methods</b>: Urine and blood multiplex ELISA cytokine assays were performed in 37 men with histologically confirmed prostate adenocarcinoma before, 2 weeks after, and 3 months after therapy. <b>Results</b>: Treatment method alone significantly affected levels of plasma but not urine cytokines. Both plasma and urine showed significant changes across visit number and significant interactions between treatment and visit number for some cytokines. In plasma, SBRT was associated with the highest cytokine levels when compared to RP and cryotherapy. Urinary IL-8 levels increased over time following cryoablation, whereas they remained relatively stable across visits after SBRT and RP (β = 1.51, 95% CI [0.89-2.13], <i>p</i> < 0.001). Urinary IL-6 levels reached their highest point at visit three following both SBRT and cryoablation, whereas after RP, the peak occurred earlier at visit two (β = 0.07, 95%CI [0.04-0.11], <i>p</i> < 0.001). The pattern of plasma levels of IL-10 differed by time elapsed after treatment depending upon treatment group (β = -0.05, 95%CI [-0.08--0.01], <i>p</i> = 0.005). <b>Conclusions:</b> These findings show that the prostate cancer treatment method employed may affect post-operative inflammatory mechanisms. This small study encourages expansion to determine the prognostic utility of urine and plasma cytokine expression patterns based on prostate cancer treatment and time elapsed following treatment. Understanding these changes may inform a personalized medicine approach to prostate cancer immunotherapies.