Current Treatments for Metastatic Prostate Cancer
Most patients who have prostate cancer are diagnosed with early-stage disease that is localized to the prostate. These patients are able to benefit from many different treatment options that include active surveillance, radical surgery, cryotherapy of the prostate and radiation therapy. Most that undergo intervention for early stage disease are usually cured.
However, some of these patients can have recurrent disease which may progress and spread outside of the prostate, and others may be diagnosed with disease that has metastasized at the time of the initial diagnosis. The most common locations for spread of prostate cancer are local extension outside of the prostate, to local lymph nodes, and to bones. Unfortunately, spread outside of the prostate is associated with a decrease in long-term survival rates; however, there are several treatments that are available to help manage the spread of the disease.
A series of injectable medications known as LHRH agonists are commonly used with patients who have advanced disease. These medications induce a medical castration by indirectly decreasing the production of testosterone. Approximately 95 percent of testosterone is blocked by these medications. There are several medications in this category including Lupron, Eligard, Vantas, Trelstar, and dosing schedules vary from monthly to yearly. A LHRH antagonist known as Degarelix is now also available which has a slightly different mechanism of action, but also causes a medical castration.
Although these medications are highly effective with regards to controlling disease, over long periods of time, patients can develop hormonally-resistant forms of the disease. When this occurs, the medications are no longer effective and the disease can then progress. Side-effects of these drugs include loss of libido, osteoporosis, breast swelling (gynecomastia) and hot flashes.
Another recent Phase III study has shown that abiraterone has resulted in an improved 35 percent survival in patients who have advanced disease that has not responded to docatexel.
Some Urologists opt to have their patients undergo complete androgen blockade so that the additional 5 percent of testosterone is eliminated. This can be accomplished with the use of medications in the anti-androgen category, and include medications such as bicalutamide (Casodex), flutamide (Eulexin), and nilutamide (Nilandron).
A prostate cancer vaccine, sipuleucel-t (Provenge, Dendreon Corp) has recently been introduced. This treatment is the first autologous cellular immunotherapy to treat minimally symptomatic metatstatic castrate resistance prostate cancer by targeting and attacking cancer cells. Patients need to first have their white blood cells removed (leukapharesis). These cells are treated with a protein that is manufactured and found in most prostate cancer cells and linked to another substance that stimulates the immune system. The cells are then given back every two weeks for 3 infusions. The most common side effects of this treatment are flu-like symptoms including chills, fevers, fatigue, back pain and nausea.
This treatment has been shown to give the patients an approximately 4-month survival advantage when compared to patients who received the placebo. Now that the drug has been FDA approved and is being utilized clinically, the debate has begun as the treatment costs approximately $90,000. In this era of limited financial resources the question has certainly been raised as to whether given the relatively short survival advantage, is this a worthwhile use of these resources?
Skeletal related events, are either fractures that occur from bone metastasis from prostate cancer or bone pain that requires radiation to a painful area of the bone, both which are serious problems that arise in patients who have advanced prostate cancer.
Osteoclasts are cells that remove bone tissue by removing its mineralized matrix and breaking up the organic bone, resulting in resorption of bone. Rank ligand is a mediator of bone resorption and recently a new drug denosumab (Xygeva, Amgen Corporation), a monoclonal antibody has been introduced to help inhibit osteoclast activity and limit bone destruction. This drug has been shown to increase the time to when the first skeletal related event occurs. Compared to the previous drug that was available zoledronic acid (Zometa, Novartis Pharmaceutical), the time to the first skeletal related event as been extended to 21 months when compared to zoledronic acid. Side effects of this medication include hypocalcemia (low blood calcium levels) and osteonecrosis of the jaw.
Interim results from a clinical study of a new agent cabozantinib (Exelis Inc.) have also been promising, indicating a reduction or a stabilization of metastatic bone lesions. This is another promising new agent that should help manage the complications that arise in patients with advanced disease.
Docetaxel (Taxotere, Sanofi Aventis) and prednisone combination therapy is another approach for hormonally resistant prostate cancer with a reported 26% survival advantage at 3 years compared to mitoxantrone, a previously used agent. This treatment does not address the side effects but rather treats the disease itself. The most serious side effect of this treatment is neutropenia, a severe lowering of the white blood cell count, however anemia, neuropathy, mucositis, and anorexia can all be experienced.
Significant advances have been made in the treatment of advanced prostate cancer, however once the disease has spread, there is no cure. Treatments now can extend life, as well as improve the quality of life, however, early detection remains the key to curing this disease.
Jay Motola, MD, is a board-certified urologist and attending physician, Department of Urology, Mount Sinai West, and Assistant Professor of Urology, Icahn School of Medicine at Mount Sinai. Dr. Motola is a summa cum laude, Phi Beta Kappa graduate of Boston University, and earned his medical degree at the State University of New York at Stony Brook.