Kathleen Li

Background/Objectives: 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. Methods: 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. Results: 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], p < 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], p < 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], p = 0.005). Conclusions: 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.

Androgen deprivation therapy (ADT) is a mainstay treatment for metastatic prostate cancer, improving progression-free survival. ADT suppresses the production of testosterone and reduces circulating levels of the hormone. Luteinizing hormone-releasing hormone (LH-RH) agonists are the most commonly used ADT modality. They can be given alone or in combination with androgen synthesis inhibitors or androgen receptor antagonists. An estimated 40% of prostate cancer patients will receive ADT as part of their therapy during their lifetime. However, ADT has numerous adverse effects, including an increased cardiovascular risk that impacts quality of life. Relugolix is an alternative form of ADT. It is the only oral gonadotropin-releasing hormone antagonist, circumventing injection site reactions, making it easier for patients to take, and thus increasing compliance. Testosterone suppression with relugolix is excellent and testosterone recovery after discontinuation is rapid. This paper reviews the ADT and anti-androgen treatment options for men with prostate cancer and the cardiovascular effects of these therapies. There is accumulating evidence that cardiovascular risk with relugolix is lower than with other ADT medications and also lower than with androgen synthesis inhibitors and androgen receptor antagonists. This paper provides insight into the use of different ADT regimens based on the cardiovascular status and circumstances. It explores strategies to mitigate negative cardiovascular consequences and highlights the need for further study.