Prostate cancer growth is fueled by the male hormone, testosterone. Lowering testosterone levels will usually result in decrease in the growth of the cancer. Once the cancer has spread to other parts of the body, the first line of therapy used is hormone therapy. This involves lowering the patient’s testosterone levels and can be done surgically by removing the testicles or chemically through medications. The initial response to these treatments is usually favorable, but unfortunately, the median duration of response is 18 to 24 months.
Metastatic castration-resistant prostate cancer is the term used when the cancer has spread outside the prostate and is able to grow despite treatments to lower the amount of testosterone. A few years ago, the only other option for these patients was chemotherapy. Fortunately, there are now several treatment options for this group of men. For the most part, these therapies are tolerated well and offer promising results. Therapies include:
Provenge (sipuleucel-T)
Provenge is immunotherapy that uses a patient’s own immune cells to fight the prostate cancer. It is used for patients with a rising PSA on hormone therapy who are asymptomatic or minimally symptomatic and have good functional status.
Research data shows there is a 13 month survival advantage if Provenge is completed before the PSA reaches 22. The treatment requires only six appointments and is completed in about a month. Patients first go to a blood center for cell collection (leukapheresis) and then those cells are made into a dose that is specific for them. Patients return to the physician’s office about three days after cell collection to have their cells reinfused through an IV. This process is done three times, spaced a week apart. The procedures are usually tolerated very well with minimal, if any, side effects.
Oral Oncolytics
The approval of oral oncolytics, before the use of chemotherapy, has been a major step forward in treating metastatic castrate-resistant prostate cancer. The standard hormone therapy we use targets testosterone produced by the testicles. However, testosterone-like hormones are also produced by the adrenals and the tumor itself. Zytiga (abiraterone) and Xtandi (enzalutamide) are two oral agents that block testosterone signaling or production outside the testicles.
These drugs each have roughly a four month survival advantage over placebo. Furthermore, they delay disease progression on imaging studies and delay the beginning of chemotherapy. As with any oral medication, there are potential side effects, but most men deny significantly bothersome symptoms and are capable of continuing on with their daily living while on either of these medications.
Xofigo (Radium 223)
Xofigo is used for patients with metastatic spread to bones who are experiencing bone pain symptoms. When cancer invades the bones, it stimulates the bones to accelerate calcium uptake. Radium 223 is structurally similar to calcium. Therefore, it is absorbed by the bone cells and concentrated in areas of the bones where the cancer is most active.
Although it can improve pain symptoms, it is not just a palliative treatment. The primary role is to use it as another form of treatment to actually fight the prostate cancer. Xofigo, administered by an intravenous injection, is given once a month for six months. It has been shown to increase overall survival by 3.6 months compared to a placebo and delay time to first symptomatic skeletal events, such as pathologic bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, or need for external beam radiation to relieve pain.
Chemotherapy
Chemotherapy, of course, continues to be an option for metastatic castrate-resistant prostate cancer. Docetaxel (Taxotere) is the first chemo drug given in most cases. Treatment usually consists of six to ten total treatments.
The word “chemo” can be very frightening to patients, but thankfully, docetaxel is tolerated much better than most other forms of chemotherapy. Patients might experience some side effects, including fatigue and loss of appetite, but it generally does not cause the severe degree of toxicity associated with other chemotherapies. Recent studies have also shown increased benefit in early chemotherapy intervention and many are proceeding with this even before they become castrate-resistant.
Bone-Targeted Therapies
Another important component in treating these patients is addressing bone health. Hormone therapy alone puts patients at risk for loss of bone density and muscle mass. Once the cancer has spread to the bones, patients are even more susceptible to bone related complications such as fractures. Fortunately, there are therapies that can effectively decrease the risk of these complications. Denosumab, zoledronic acid, and Fosamax are commonly used bone supportive treatments that decrease such events. Years ago, nothing was being done on this front, but we now have more knowledge and ways to decrease bone complications, which gives patients longer quality of life.
It should be noted that the treatments above are additive. The months of survival advantage and delay in disease progression of one therapy adds to the next therapy, and so on. The combination of treatments gives patients a significantly extended live expectancy. Perhaps more importantly, since most of these treatments have minimal side effects, patients can also expect to maintain a good quality of life. When compared to the options just a few years ago, this is very exciting for metastatic castration-resistant prostate cancer patients. There are also several new treatments that are expected to be released in the near future that will build on what we already have available. There is certainly reason to have hope.
Vincent Michael Bivins, MD practices with Urology Centers of Alabama.
