Over the past decade, insight into the biological basis of prostate cancer development and progression has influenced our approach to treating patients with the disease. While research efforts have historically focused on the prostate cancer epithelial cell, there is growing evidence that interactions between the host tissue microenvironment and the cancer epithelial cell are critical for tumorigenesis. For example, prostate cancer epithelial cells preferentially metastasize to bone by acquiring osteomimetic properties that usurp normal bone homeostasis maintained by osteoblasts, osteoclasts, endothelial cells, and other bone stromal elements. Understanding the bidirectional cancer cell-host interaction now dominates prostate cancer research. The knowledge gained from this effort has led to novel treatment strategies that target the bone microenvironment (eg, with antiangiogenesis inhibitors) in addition to the epithelial cell (eg, with chemotherapy).
Prostate cancers have recognizable clinical features that allow anticipation of their clinical behavior. Fortunately, the progression from localized, androgen-dependent disease to castration-resistant disease with bone-forming metastases occurs in only a minority of patients. To conceptualize the clinical heterogeneity displayed along this continuum, we assign patients to different prostate cancer "clinical states" to help structure treatment recommendations and therapy development. The goal of our research program at MD Anderson is to more reliably predict prostate cancer progression and apply therapy to only those patients who need it. This strategy will favorably improve the outcome of selected patients threatened by their disease while avoiding unnecessary morbidity to the majority who are not.
Prostate cancer is a major health care challenge in the United States (1). It is the second most common cancer in men (behind skin cancer) and the second leading cause of cancer death (behind lung cancer). In 2009, it is estimated that 192,280 men will be newly diagnosed with prostate cancer and 27,360 men will die from prostate cancer. There are a number of unique clinical features of prostate cancer that distinguish it from other solid tumor types:
Despite the high prevalence of prostate cancer, the majority of patients diagnosed with the disease eventually die from other causes. This is in striking contrast to lung cancer, where the majority of patients diagnosed with the disease die from it.
Cancer of the prostate often has a prolonged natural history. This is evidenced by a high incidence of occult malignancy in autopsy series of men who die from non–prostate cancer causes and in clinically normal prostates of men undergoing cystoprostatectomy for bladder cancer. Therefore, over the course of a normal lifetime, most men will develop "clinically occult" prostate cancer that will never produce symptoms, require treatment, or cause death.
The incidence of detected carcinoma increases with age.
Androgens are a major driving force in normal prostate development and are implicated in tumorigenesis.
Prostate cancer is typically multifocal, commonly presenting as synchronous carcinomas arising in multiple locations, and the malignant potential is determined by the sum of the primary and secondary grades (Gleason score). Thus, biologic heterogeneity is an inherent property ...