Prostate Cancer and General Medicine
Prostate adenocarcinoma is the most common non-cutaneous cancer and the second leading cause of cancer death in men in the US, with an annual incidence of over 200,000 cases per year and an annual mortality of over 30,000 deaths per year.
PSA based screening for prostate cancer is controversial. While a large European randomized trial showed a decreased risk of prostate cancer mortality, a US similar randomized trial did not.
Two agents (finasteride and dutasteride; both 5α-reductase inhibitors) have been shown to reduce the incidence of prostate cancer in placebo-controlled randomized trials. However, these drugs were not approved by the FDA for prostate cancer chemoprevention, due to concerns about toxicities as well as an increased detection of high-grade prostate cancers in men taking the 5α-reductase inhibitors.
Localized prostate cancer is curable in 30-70% of patients. Selection of the optimal local therapy is guided by the clinical stage (determined by digital rectal exam), the Gleason score, and the serum PSA level. These three parameters can be used to classify patients risk as: low, intermediate, or high.
In men with recurrent prostate cancer after maximal local therapy as evidenced by a rising PSA alone without radiographic evidence of distant metastases, time to metastatic progression and overall survival are most strongly influenced by the PSA doubling time. Management of these patients with biochemical recurrence is controversial and includes observation, androgen deprivation therapy, and clinical trial participation.
In men with metastatic prostate cancer, androgen deprivation therapy (ADT) is the most effective initial treatment, although a recent trial has demonstrated improved survival with the addition of docetaxel chemotherapy to ADT, particularly in men with high-volume disease. Nevertheless, most men develop resistance to androgen suppression within 12-48 months (median 18 months). When this occurs, the disease transforms to a new state known as castration-resistant prostate cancer, which is invariably fatal.
There are six FDA-approved treatment modalities for metastatic castration-resistant prostate cancer (mCRPC) that have resulted in survival improvements in such patients. These include two chemotherapy drugs (docetaxel and cabazitaxel), one therapeutic vaccine (sipuleucel-T), one radiopharmaceutical (radium-223 dichloride), and two androgen-modulating drugs (abiraterone and enzalutamide).
In patients with castration-resistant bone metastases, two osteoclast-inhibiting agents have gained FDA-approval for the prevention of skeletal related events: the bisphosphonate agent zoledronic acid, and the receptor activator of nuclear-factor kappa-B (RANK) ligand inhibitor denosumab.