Recurrent Prostate Cancer
When prostate cancer has been detected or has returned following initial treatment with surgery, radiation therapy and/or hormonal therapy, it is said to be recurrent or relapsed.
The course of treatment for relapsed prostate cancer depends on what treatment a patient has previously received and the extent of the cancer. Some patients have only a rise in PSA level as evidence of recurrent cancer. Other patients will have evidence of recurrent cancer on x-rays or scans. Patients who have prostate cancer that continues to grow despite hormone therapy are referred to as having hormone-refractory prostate cancer.
A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.
The following is a general overview of the treatment of recurrent prostate cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.
Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.
RECURRENT PROSTATE CANCER AFTER SURGERY
If the cancer shows signs of returning after prostatectomy, decisions about additional treatment depend in part on whether or not the cancer has metastasized (spread) to other parts of the body. Cancer that is thought to be confined to the area of the prostate may be treated with radiation therapy (with or without androgen-deprivation therapy).
If the cancer is thought to have spread to other locations in the body, androgen-deprivation therapy (ADT) is the primary approach to treatment and may be used with or without radiation therapy. ADT slows or stops cancer growth by reducing levels of male hormones such as testosterone. Recurrent prostate cancer usually can be controlled with ADT for a period of time, often several years. Eventually, however, most prostate cancers continue growing despite the hormone therapy.
RECURRENT PROSTATE CANCER AFTER RADIATION THERAPY
Once a patient has received radiation therapy to the prostate gland, more radiation therapy typically cannot be given to the same area safely. Rarely, surgeons have removed the prostate gland for persistent cancer after radiation therapy. Other surgeons have used cryosurgery, which is a local treatment where the prostate gland is frozen with a probe. Complications of surgery or cryosurgery, however, tend to be more frequent in patients previously treated with radiation therapy. If a patient is not a candidate for these types of local therapies, treatment commonly involves androgen-deprivation therapy.
HORMONE-REFRACTORY PROSTATE CANCER
For patients treated with androgen-deprivation therapy, the treatment may control the growth of the cancer for several years. Eventually, however, most prostate cancers stop responding to this treatment and begin to grow again. Cancers that grow in spite of ADT are called hormone-refractory. Treatment options for hormone-refractory prostate cancer include chemotherapy, immunotherapy, additional hormonal therapy, local radiation therapy for the purpose of alleviating symptoms, or participation in clinical studies evaluating new treatments.
Chemotherapy: The chemotherapy drug Taxotere® (docetaxel) has been shown to improve survival and reduce cancer symptoms in men with metastatic, hormone-refractory prostate cancer. If the cancer progresses in spite of treatment with Taxotere, Jevtana® (cabazitaxel)—a newer chemotherapy drug—may provide benefits.
Immunotherapy: Provenge® (sipuleucel-T) is an immunotherapy that prompts the body’s immune system to respond against the cancer. It may be used for men with metastatic, hormone-refractory prostate cancer that is producing few or no symptoms.
Hormonal therapy: Zytiga™ (abiraterone) is a type of hormonal therapy that blocks the production of androgens not only by the testes, but also by the adrenal glands and the tumor itself. Zytiga can prolong survival among men with metastatic, hormone-refractory prostate cancer that has previously been treated with chemotherapy.
TREATMENT OF BONE COMPLICATIONS
Patients with advanced prostate cancer can have cancer cells that have spread to their bones, called bone metastases. Bone metastases commonly cause pain, increase the risk of fractures, and can lead to a life-threatening condition characterized by an increased amount of calcium in the blood called hypercalcemia. Treatments for bone complications may include drug therapy or radiation therapy.
Bisphosphonate drugs: Bisphosphonate drugs can effectively prevent loss of bone that occurs from metastatic lesions, reduce the risk of fractures, and decrease pain. Bisphosphonate drugs work by inhibiting bone resorption, or breakdown. Zometa® (zoledronic acid) is a bisphosphonate drug that may be used to reduce the risk of complications from bone metastases or to treat cancer-related hypercalcemia.
Xgeva™ (denosumab): Xgeva targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Studies have suggested that Xgeva may be more effective than Zometa at delaying bone complications in prostate cancer patients with bone metastases.1
Radiation therapy: Pain from bone metastases may also be relieved with radiation therapy directed to the affected bones.
STRATEGIES TO IMPROVE TREATMENT
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of recurrent prostate cancer will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician.
Experimental drugs or treatments generally pass through three phases of clinical trials before they are considered for approval. Phase I clinical trials test an experimental drug or treatment for the first time in a small group of people to evaluate its safety, determine safe dosages, and identify side effects. Phase II clinical trials evaluate a new drug or treatment (or new combinations of treatments) in a larger group of people in order to assess effectiveness and further evaluate safety. Phase III clinical trials enroll a still larger number of people in order to confirm effectiveness and safety and to compare the new drug or treatment with standard treatments. If the new drug or treatment is then approved, additional studies (referred to as Phase IV or post-marketing studies) are conducted in order to monitor safety and effectiveness and refine the use of the new drug or treatment.
Areas of active investigation in clinical trials of recurrent prostate cancer include the following:
Targeted therapy: Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target,” targeted therapies may slow cancer cell growth or increase cancer cell death.
Several targeted therapies are being evaluated for the treatment of hormone-refractory prostate cancer. An investigational drug known as cabozantinib, for example, is showing promise in prostate cancer as well as several other types of cancer.2 Cabozantinib targets two proteins—MET and VEGFR2—that play a role in the development and progression of cancer.
New chemotherapy regimens: Because hormone therapy is not curative and only controls prostate cancer for a certain amount of time, efforts are underway to discover more effective systemic chemotherapies.
Cryosurgery: Cryosurgery is a newer treatment procedure that is still being investigated for prostate cancer. Cryosurgery is a technique that kills cancer cells by freezing them with sub-zero temperatures.
Phase I clinical trials: New chemotherapy drugs continue to be developed and evaluated in patients with recurrent cancers in phase I clinical trials. The purpose of phase I trials is to evaluate new drugs in order to determine the safety and tolerability of a drug and the best way of administering the drug to patients.
Gene therapy: Gene therapy is defined as the transfer of new genetic material into a cell for therapeutic benefit. This can be accomplished by replacing or inactivating a dysfunctional gene or replacing or adding a functional gene into a cell to make it function normally. Gene therapy has been directed towards the control of rapid growth of cancer cells, control of cancer death or efforts to make the immune system kill cancer cells. While there are currently no gene therapies approved for the treatment of prostate cancer, this therapeutic technique offers the hope of changing the way cells function.
1 Fizazi K, Carducci M, Smith M et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomized, double-blind study. The Lancet. 2011;377:813-22.
2 Gordon MS, Vogelzang NJ, Schoffski P et al. Cabozantinib (XL184) has activity in both soft tissue and bone: Results of a phase II randomized discontinuation trial (RDT) in patients (pts) w/ advanced solid tumors. Paper presented at: 2011 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract 3010.