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.  Prostate cancer that is resistant (does not respond ) to hormonal therapy is also referred to as stage .

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.

Treatment of recurrent prostate cancer depends on many factors, including previous therapies and the overall condition of the patient. If the patient had surgery to remove the prostate and the cancer comes back only in a small area near the operation, radiation therapy may be given. If the patient already received radiation therapy to the prostate or to the area of the operation after a radical prostatectomy, radiation therapy typically cannot be administered again to the same part of the body. Systemic therapy using hormonal or chemotherapy treatment is typically given if tests show that the prostate cancer has spread to other parts of the body. Radiation therapy may be given to relieve symptoms, such as bone pain. When prostate cancer continues to grow despite hormone therapy, this condition is known as hormone-refractory prostate cancer. Patients with hormone-refractory prostate cancer have historically had few treatment options.

Recurrent Prostate Cancer After Surgery

Radiation therapy may be recommended to patients following surgical prostatectomy if they are found to have cancer involving the margins of the surgical specimen, the PSA remains persistently elevated or the PSA returns to normal and then begins rising again, assuming there is no evidence of cancer elsewhere in the body.

Patients with cancer involving the surgical margins and a persistently elevated or a rising PSA all have evidence that some cancer was not removed by surgery. For some patients, the remaining cancer will be confined to an area near the prostate gland. For many patients, the cancer will have spread to more distant locations in the body. The difficult question faced by the patients is: What is the chance persistent cancer can be eliminated with additional radiation therapy?

In general, 75% of patients treated with radiation after prostatectomy will still experience recurrence of cancer as evidenced by a rising PSA level within 5 years of radiation therapy. Patients with high Gleason scores, more advanced stages, and higher PSA levels are more likely to have cancer recurrence following radiation than those with lower Gleason scores and lower PSA levels. The high rate of failure following radiation therapy occurs because the radiation could not kill all of the cancer cells or because many undetectable cancer cells had already spread beyond the limited reach of the radiation therapy. Patients must decide whether receiving additional radiation therapy (along with its inconvenience and toxicity) is likely to be beneficial, or whether participation in clinical studies directed at treating cancer that has already spread away from the radiation field are more appealing in offering potential benefit from additional treatment.

Recurrent Prostate Cancer After Radiation Therapy

Depending on the features of the prostate cancer, some patients will experience a rise in the PSA level after radiation therapy. This occurs because cancer cells may have survived despite radiation therapy, or patients may already have small amounts of cancer that have spread outside the prostate and were not treated by the radiation. These cancer cells cannot be detected with any of the currently available tests. Undetectable areas of cancer outside the prostate gland are referred to as micrometastases. The presence of these microscopic areas of cancer or surviving cancer cells can cause the relapses that follow treatment with 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. Because the complications of surgery or cryosurgery tend to be more frequent in patients previously treated with radiation therapy, most doctors do not advise further local treatments.

Patients with recurrent prostate cancer after radiation therapy are usually treated with hormone therapy. Hormone therapy deprives a man's body of male hormones necessary for prostate cancer to grow. Hormone therapy can affect the growth of prostate cancer everywhere in the body, whether the cancer cells are in the prostate itself or elsewhere in the body. Recurrent prostate cancer usually can be controlled with hormone therapy for a period of time, often several years. Eventually, however, most prostate cancers continue growing despite the hormone therapy.

Hormone therapy may be administered surgically (orchiectomy) or with drugs. To learn more, go to Hormone Treatment of Prostate Cancer. While hormonal therapy can prevent prostate cancer growth and improve symptoms, it is not curative. Many patients may want to consider participation in clinical studies evaluating new treatment approaches for recurrent prostate cancer.

Hormone-Refractory Prostate Cancer

Prostate cancer cells need male hormones in order to grow. Hormone therapy decreases the level of male hormones in the blood, which causes prostate cancer cells to die. Prostate cancer usually can be controlled with hormone therapy for a period of time, often several years. Eventually, however, most prostate cancers are able to grow and spread despite the hormone therapy, and these cancers are called hormone-refractory. Hormone-refractory metastatic prostate cancer is incurable, with patients surviving an average of 6-9 months after developing resistance to hormone therapy. Treatment options for hormone-refractory prostate cancer include chemotherapy or local radiation therapy for the purpose of alleviating symptoms from progressive cancer or participation in clinical studies evaluating new treatments.

Chemotherapy treatment can reduce the severity and duration of pain and improve overall well-being of patients with hormone-refractory prostate cancer. In a clinical study, men with prostate cancer that no longer responded to hormonal treatment received 1 of 2 treatments: 1) chemotherapy treatment with the drugs Novantrone® and prednisone or 2) low doses of the anti-inflammatory agent, prednisone, alone. The purpose of this direct comparison was to determine whether chemotherapy treatment could improve the overall well-being and/or survival of patients with late stage hormone-refractory prostate cancer.

The results of this direct comparison demonstrated that men receiving chemotherapy had significant improvement in their overall well-being and the quality of their life as measured by an improvement in the duration and severity of pain associated with their cancer. Men treated with the chemotherapy had an improvement in their severity of pain that lasted 43 weeks, or just over twice as long as patients who did not receive the chemotherapy treatment. Unfortunately, patients who received Novantrone® chemotherapy did not live any longer than those who did not receive chemotherapy. However, because of the significant improvement in pain relief observed with this chemotherapy treatment, the Food and Drug Administration approved Novantrone® as the first chemotherapy drug for the treatment of prostate cancer. Because of the demonstration of an improvement in symptomatic control of prostate cancer with chemotherapy, future clinical trials evaluating other chemotherapeutic agents, alone or in combination, as well as other novel compounds, will continue to be evaluated in men with hormone-refractory and earlier stage prostate cancer.

Recently, researchers in the Cancer and Leukemia Group B performed a clinical trial evaluating a chemotherapy combination in men with hormone-refractory prostate cancer. In this study, 47 men were treated with the combination of Taxotere®, estramustine and low-dose hydrocortisone. Following the completion of treatment, anti-cancer responses were achieved in 50% of patients. Sixty-eight percent of men had a 50% or greater decrease in prostate specific antigen (PSA) levels (blood levels of proteins produced by cancer cells) and 57% had a 75% or greater decrease in PSA levels. Following treatment, the average survival duration was 20 months. The average time to cancer progression following treatment for patients in this study was 8 months.

Suramin is another chemotherapy drug and is active against prostate cancer. Suramin blocks growth factors that stimulate growth and function of cancer cells. Results from four initial clinical studies using suramin have demonstrated complete disappearances of cancer in 3-18% of patients and partial disappearance in 18-42% of patients. Fifty to seventy percent of patients experienced a reduction in PSA levels by more than 50%. Importantly, patients whose serum PSA levels declined by more than 75% also showed improvement in survival.

Several other chemotherapeutic drugs have also demonstrated ability to kill prostate cancer cells in patients with hormone-refractory disease. Developing and exploring single or multi-agent chemotherapy combinations as a treatment approach for patients with widespread prostate cancer is an area of active investigation. In particular, Taxotere®, paclitaxel, estramustine and suramin have the ability to kill prostate cancer cells and reduce PSA levels in patients with hormone-refractory disease.

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 lead to a life-threatening condition characterized by an increased amount of calcium in the blood called hypercalcemia.  Treatments for bone complications may include bisphosphonate drugs 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. Bone is constantly being “remodeled” by two types of cells: osteoclasts, which break down bone; and osteoblasts, which rebuild bone. Although the exact process by which bisphosphonates work is not completely understood, it is thought that bisphosphonates inhibit osteoclasts and induce apoptosis (cell death) in these cells, thereby reducing bone loss. There is also evidence that these drugs bind to bone, thereby blocking osteoclasts from breaking down bone.Cancer cells release various factors that stimulate osteoclastic activity, causing increased breakdown of bone. By inhibiting osteoclasts, bisphosphonate drugs effectively reduce the detrimental impact that cancer cells have on bone density.

Bisphosphonate drugs that are FDA-approved for the treatment of cancer-related skeletal complications include Zometa® (zoledronic acid) and Aredia® (pamidronate). Of these two drugs, Zometa® appears to demonstrate the strongest activity. An added benefit of Zometa® is that it is administered in a dose ten times lower than Aredia®, which considerably reduces the administration time from several hours to 15 minutes, resulting in a more convenient regimen for patients.

Zometa® has been shown to be a safe and effective treatment in prostate cancer patients with bone metastases.  Zometa® significantly reduces the proportion of patients who experience skeletal complications, extends the time to first skeletal complication, and reduces the risk of skeletal complications.

Zometa® also appears to benefit patients with prostate cancer undergoing androgen deprivation therapy, or “hormonal therapy”. Hormonal therapy in the treatment of prostate cancer has been shown to cause bone loss.

Researchers from Massachusetts General Hospital and 5 other medical institutions conducted a clinical trial evaluating Zometa® in patients with localized prostate cancer being treated with androgen deprivation therapy. This study included 106 men who were randomly selected to receive either Zometa® or a placebo for one year. Bone mineral density in the spine, hips, and legs increased among patients who were treated with Zometa® and decreased in patients who received placebo .

Radiation therapy: Pain from bone metastases may also be relieved with radiation therapy directed to the affected bones. The side effects of radiation therapy for relief of bone pain depends on the area of the body being treated. Another method for treatment of bone pain is the use of radioisotopes, such as strontium-89. Strontium-89 is given intravenously and accumulates in the bones where it kills prostate cancer cells by delivering small amounts of radiation. Clinical studies have shown that bone pain and the need for pain medications can be reduced in the majority of patients treated with strontium-89. Since strontium-89 is given by vein, it can affect all bones in the body, whereas external radiation therapy is limited to only small areas of the body. The major side effect of strontium-89 is a reduction in blood cell counts.

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. Areas of active investigation aimed at improving the treatment of recurrent prostate cancer include the following:

• Targeted Therapies
  • SERA™: atrasentan (Xinlay™)
• Other Advances in the Treatment of Recurrent Prostate Cancer
  • New Chemotherpay Regimens
  • Combination therapy
  • Cryosurgery
  • Phase I clinical trials
  • Gene therapy