Prostate cancer accounts for 25 percent of all cancer diagnoses in American men (186,320 in 2008) as well as 10 percent of cancer deaths in men (28,660 in 2008) [1]. Although mortality has fallen by 25 percent over the past decade and the five-year survival is approaching 100 percent, several challenges to decreasing the morbidity and mortality from metastatic prostate cancer remain.

The end result of the process of metastasis in prostate cancer is clear; nearly 100 percent of men suffer from osteoblastic bone metastases at the time of death (Figure 41.1) [2–5]. The mechanisms by which prostate cancer metastasizes to bone sites remain obscure, but there is no doubt that forces that drive preferential seeding are at play. In 1889, Stephen Paget proposed the “seed-and-soil” theory to explain the nonrandom pattern of cancer metastasis [6]. His theory suggested that factors within the metastatic site promote growth, which is analogous to the tendency of seeds to grow in fertile soil (i.e., factors in the environment of the metastatic site could contribute to the proliferation of cancer cells). In 1928, James Ewing proposed that cancer cells grow at a particular site because they are directed to that site by the direction of blood flow and lymphatics [7]. It appears that both these theories have correct elements. Isaiah Fidler defined the modern “seed-and-soil” hypothesis as consisting of three principles [8]. First, cancerous tissues contain heterogeneous subpopulations of cells with different angiogenic, invasive, and metastatic properties.