Development of Bone Metastases in Men With Prostate Cancer

Men with non-metastatic prostate cancer are commonly treated with androgen deprivation therapy (ADT) for various reasons including biochemical relapse after primary therapy. After a duration of response lasting between two and 10 years, many patients become resistant, developing what is referred to as castrate-resistant prostate cancer.

Over 80% of men with castrate-resistant prostate cancer will eventually develop bone metastases. These can lead to important clinical consequences, such as bone pain, functional impairment, and increased mortality.

Bone is a particularly fertile site for the development of metastases. Prostate cancer cells shed from the primary tumor enter the circulation and release growth factors, cytokines, and other proteins which promote adhesion and proliferation to the bone. Circulating prostate cancer cells initially adhere to cells lining blood vessels in bone marrow, following which these tumor cells are actively recruited to the bone microenvironment by multiple factors, where the cells preferentially adhere to areas of increased bone turnover.

Furthermore, interactions between tumor cells and the bone microenvironment foster the development of bone metastases. These interactions ultimately result in excessive osteoclast and osteoblast activity, which in turn releases multiple factors that may further stimulate tumor growth and bone destruction.