Choosing treatment for late stage prostate cancer (advanced metastatic prostate cancer) can be a difficult decision. The options of treatment for late stage prostate cancer range from a one-of-a-kind immunotherapy called Provenge (sipuleucel-T) to standard therapies such as chemotherapy, hormone therapy, and radiation therapy, as well as several new approaches. In addition, a number of new treatments are on the horizon.
Late stage prostate cancer (stage IV prostate cancer) refers to disease that has spread (metastasized) to lymph nodes near or far from the prostate gland, or cancer that has spread to other parts of the body, such as the bones (most common site of spread), liver, bladder, rectum, or lungs. Once the disease has reached stage IV, surgery (radical prostatectomy) is not considered a cure, although it is sometimes performed to help relieve symptoms such as urinary frequency and urgency. Therefore, other options for treatment for late stage prostate cancer need to be considered.
Unique immunotherapy: Provenge
Provenge is the only immunotherapy for prostate cancer approved by the Food and Drug Administration (FDA) for treatment of prostate cancer. This approach is unique among all the other treatment options for prostate cancer because it helps harness the body’s inherent ability to heal itself by using the body’s immune system cells to fight disease. Provenge is a different prostate cancer treatment for each man because it is made by modifying each patient’s immune system cells to fight prostate cancer in that patient.
Provenge enhances the immune system and promotes healing rather than attempts to destroy cancer cells or interfere with bodily functions, as other prostate cancer treatments do. In clinical trials, Provenge increased overall survival by a mean of 4.1 months in men who had metastatic hormone-resistant prostate cancer.
Currently, Provenge is available only to men as treatment for late stage prostate cancer; specifically, asymptomatic or minimally symptomatic metastatic prostate cancer that has resisted hormone therapy. This requirement may change, as the drug’s manufacturer, Dendreon, is undertaking Phase III trials to expand the use of Provenge to men who have not yet gone through hormone therapy. This may open the door for Provenge to be offered to “healthy” men who have prostate cancer.
Hormone therapy for prostate cancer is based on the concept that male hormones, such as testosterone and dihydrotestosterone, fuel prostate cancer, and that hindering hormone production will starve the prostate tumor. This treatment for late stage prostate cancer cannot cure prostate cancer, but it can slow disease progression or cause the tumor to shrink.
Candidates for hormone therapy typically are men with advanced prostate cancer who meet one of the following criteria:
- Want to shrink the tumor before trying prostatectomy or radiation to see if it will enhance the effectiveness of other therapies
- Want to combine radiation therapy and hormone therapy because their doctors have determined their cancer is likely to recur after therapy
- Have already had a prostatectomy or radiation and cancer has returned
Hormone therapy typically involves using luteinizing hormone-releasing hormone (LHRH) agonists and anti-androgens. LHRH agonists are injected under the skin and stop the body from producing testosterone. Anti-androgens block testosterone from reaching the cancer cells. The side effects of hormone therapy can be life-altering and include, in part, erectile dysfunction, cardiovascular problems, breast augmentation, hot flashes, and weight gain.
In April 2011, the FDA approved a new hormone therapy: Zytiga (abiraterone) for advanced metastatic prostate cancer that has not responded to hormone therapy or chemotherapy (docetaxel). Abiraterone inhibits the activity of an enzyme that is involved in the development of testosterone. Clinical trials show abiraterone can improve survival by a mean of 3.9 months.
On August 31, 2012, the FDA approved another hormone therapy called Xtandi (enzalutamide) which also is a treatment for late stage prostate cancer that has spread or recurred even though it was treated with hormone therapy and docetaxel. Xtandi interferes with the hormone receptors on prostate cancer cells and prevents the receptors from communicating with prostate cancer cells. These activities can stop prostate cancer from growing. Trial results showed that men who took Xtandi survived for an average of 18.4 months compared with 13.6 months among men who took a placebo, yielding an overall survival benefit of 4.8 months.
Chemotherapy is the use of drugs that kill cancer cells or prevent them from reproducing. It is usually administered via intravenous lines and/or orally and can include a combination of medications. The goal of chemotherapy for prostate cancer is to shrink the tumor or to at least relieve symptoms.
Chemotherapy is often used as treatment for late stage prostate cancer in men who have not had success with hormone therapy. In many cases, chemotherapy drugs are combined with other cancer drugs, such as corticosteroids or 5-fluorouacil.
A significant downside of chemotherapy is that it also kills healthy cells which in turn leads to substantial, distressing side effects. Some of the side effects of chemotherapy include nausea and vomiting, erectile dysfunction, chest pain, fatigue, chills, hair loss, and bruising.
Radiation therapy is usually used only for prostate cancer that is confined to the prostate and for locally advanced prostate cancer (disease that has spread to tissue around the prostate). Men who need treatment for late stage prostate cancer should seek other options. For locally advanced prostate cancer, external beam radiotherapy (EBRT) may be used alone or along with brachytherapy, which involves implanting radiation “seeds” into the prostate gland.
Side effects of EBRT can be both short-term (occurring within 90 days of treatment) and long-term. Common short-term side effects may include changes in bowel habits, skin irritation, urinary symptoms, edema, and rectal irritation. Long-term side effects may include persistent urinary symptoms, erectile dysfunction, urinary bleeding, bowel problems, and urethral stricture.
Another treatment for late stage prostate cancer is Jevtana (cabazitaxel), which was approved in June 2010 by the FDA as the first drug to extend survival among men who no longer responded to hormone therapy or to the chemotherapy drug docetaxel. Cabazitaxel prevents the formation of structures that destroy the chromosomes in prostate cancer cells. Clinical studies show that compared with men who received standard treatment, those who received Jevtana injections survived an average of 10 weeks longer. Significant side effects can occur, including nausea, vomiting, weakness, diarrhea, fever, anorexia, kidney failure, and anemia.
Future prostate cancer treatments
Here are some of the latest prostate cancer treatments potentially slated for the market in the near future for men who have advanced prostate cancer.
- Xofigo(radium-223) was developed for treatment of hormone resistant prostate cancer that has spread to the bone. It uses short-wave alpha radiation from radium-223 decay to destroy cancer cells. The FDA put alpharadin on the fast track list for approval in September 2011 after it was shown to extend survival by a mean of 2.8 months when compared with placebo, and it was approved in May 2013.
- Ipilimumab (Yervoy™) is a type of immunotherapy approved by the FDA in March 2011 for treatment of melanoma (skin cancer) that cannot be removed surgically or that has spread. However, it is also being studied to treat other cancers. Several clinical trials are currently underway using ipilimumab alone or combined with hormone therapy in the treatment of prostate cancer, including two phase III trials as treatment for late stage prostate cancer.
- Orteronel, also known as TAK-700, is a nonsteroidal drug still in the early phases of development for treatment of metastatic hormone resistant prostate cancer. Phase III trials started in early 2012 and will examine use of orteronel plus prednisone or prednisone with placebo.
Men looking for treatment for late stage prostate cancer have a number of options they can consider and discuss along with their loved ones and their healthcare providers. Patients should also ask their physicians about any clinical trials for which they might be a candidate.
Read more in our Prostate Cancer Health Center.