Prostate carcinogenesis with diabetes and androgen-deprivation-therapy-related diabetes: an update

Prostate cancer and the androgen deprivation therapy (ADT) thereof are involved in diabetes in terms of diabetes-associated carcinogenesis and ADT-related metabolic disorder, respectively. The aim of this study is to systematically review relevant literature. About 218,000 men are estimated to be newly diagnosed with prostate cancer every year in the United States. Approximately 10% of them are still found with metastasis, and in addition to them, about 30% of patients with nonmetastatic prostate cancer recently experience ADT. Population-based studies have shown that dissimilar to other malignancies, type 2 diabetes is associated with a lower incidence of prostate cancer, whereas recent large cohort studies have reported the association of diabetes with advanced high-grade prostate cancer. Although the reason for the lower prevalence of prostate cancer among diabetic men remains unknown, the lower serum testosterone and PSA levels in them can account for the increased risk of advanced disease at diagnosis. Meanwhile, insulin resistance already appears in 25-60% of the patients 3 months after the introduction of ADT, and long-term ADT leads to a higher incidence of diabetes (reported hazard ratio of 1.28-1.44). Although the possible relevance of cytokines such as Il-6 and TNF-α to ADT-related diabetes has been suggested, its mechanism is poorly understood.