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Hormone Refractory Prostate Cancer

Most patients with advanced prostate cancer are placed on some form of hormone treatment as the primary therapy for their prostate cancer. Hormone refractory prostate cancer (also known as 'HRC') refers to patients whose cancer is progressing after or while on hormone therapy.

HRC includes:

Men who have had radical prostatectomy or radiation or implants and because of a high likelihood of recurrence of cancer are placed on hormone treatments and then develop a rising PSA without other evidence of cancer.
Men without symptoms on hormone therapy for metastatic cancer and have a rising PSA or change in bone scan or other cancer diagnostic test.
Men with increasing symptoms of cancer while on hormone therapy regardless of PSA or other blood tests.

Initial Hormone Therapy For Prostate Cancer-Review

Male hormones are usually referred to as 'androgens'. The most important and one of the most powerful androgens is testosterone. Almost all of the male's testosterone is made in the testicles. Therefore, treatment for prostate cancer is aimed at reducing the testicle's production of testosterone. This treatment can be done through injectable medications such as Lupron (leuprolide) or Zoladex (goserlin) or by surgical removal of the testicles. Another option is treatment with female hormones which also suppress the testicles production of testosterone.

In addition, many patients receive drugs which are called anti-androgens which also help by blocking the effects of any residual androgens on the prostate cancer. These drugs include flutamide (Eulexin) or bicalutamide (Casodex) or nilutamide (Nilandron).

The response rate for hormone treatment is in the range of 70 to 80%. This response is usually associated with a dramatic falling of the prostate specific antigen (PSA) level as well as improvement to any of the symptoms that might be caused by the prostate cancer at that time.

HRC

Unfortunately, hormone therapy is not effective indefinitely in most patients. Each individual's response time is different. However, the average response time to hormone therapy is around two to three years. When a patient no longer is responding to hormone treatment, he is considered to be hormone refractory or HRC.

The most common way that physicians realize that the cancer is no longer responding to the hormone treatments is by a rising prostate specific antigen (PSA) level.

In some patients, however, PSA is no longer made by the cancer and therefore PSA is not a good marker of return of cancer growth. In these patients, other tests such as the acid phosphatase or progression of symptoms may herald the hormone refractory state. Recurrence can occur any place in the body.

If the cancer recurrence is located in or near the prostate gland, one might expect difficultly urinating because of blockage of the urinary channel. Blood in the urine and even blockage of the ureters (the tubes bringing urine from the kidneys to the bladder) can occur.

The most common site of recurrence outside the prostate is bone. These types of recurrences are also called 'metastases'. Any bone in the body is at risk, but the spine, hips and pelvic bones are the ones most commonly affected. Bone recurrence can cause pain. In some patients, a fracture at the sight of involvement can occur without warning or prior symptoms. In some patients, the bone marrow can be involved. The bone marrow is responsible for the production of red and white blood cells. Extensive marrow involvment can cause serious anemia and weakness.

Any area of the body, including lung, liver, brain and lymph nodes are potential sites. Each patient's prostate cancer behaves in a unique fashion with differing growth rates and differing sites of metastases that can cause problems. As physicians we are hopeful that we can detect areas that the tumor is growing early enough so that problems can be treated with other forms of therapy, such as chemotherapy or radiation.

What Do We Do When Hormone Refractory Cancer Is Found?

To be absolutely certain that an HRC state exists, we often check the testosterone levels to make sure that they have been lowered adequately by the medications.

When a patient is first found to have evidence of hormone refractory prostate cancer we usually reassess the extent of the cancer by doing the appropriate scans. These may include a bone scan and sometimes a CAT scan or MRI scan depending on the patient's history and findings. We usually follow the PSA level closely if it remains an accurate marker for that individual's cancer. The rate of rise of the PSA level gives us some idea how aggressive or fast the tumor has been growing. In some others, the acid phosphatase blood test is a useful tumor marker.

To date, no standard treatment exists for patients with HRC. The decision about treatment may be determined by the extent of the tumor and symptoms that the tumor is causing.

Many patients who have been on anti-androgens such as Eulexin (flutamide), Casodex or Nilandron are initially withdrawn from these treatments. It has been shown that some patients actually do better for a period of time when anti-androgens are withdrawn (about 3 out of 10 men will have a decrease in their PSA by stopping their anti-androgen). The average reponse to withdrawal is 4 months. Switching anti-androgens may also be beneficial in some patients. High dose anti-androgen may also be effective (Casodex 150-200 mg/ day).

Who Treats Patients With Hormone Refractory Cancer?

When it is obvious that the cancer has become unresponsive to any of these simple medical maneuvers we consider the addition of various forms of chemotherapy. These treatments are usually given by a medical oncologist, a medical doctor or internist with a special interest in the medical treatment of all cancers. Some urologists will also give chemotherapy if they have developed an interest and experience.

Among the drugs which have shown activity against hormone refractory cancer are estramustine, cyclophosphamide, vinblastine, etoposide, cisplatin, paclitaxel, suramin, ketoconozole, ketoconozole with prednisone, doxorubicin, and anthracyclines. A new addition to this list of drugs is mitoxantrone (Novantrone@) in combination with steroids (prednisone or hydrocortisone) has been approved by the FDA specifically for the use in hormone refractory prostate cancer. Often chemotherapy drugs are used in combinations. Some of the more common combinations are: ketoconazole/doxorubicin, estramustine/vinblastine, estramustine/etoposide and estramustine and paclitaxel.

The decision as to which chemotherapy should be used is usually based on the experience of the medical oncologist and each individual's other medical problems in terms of tolerating the medications.

In some patients medical therapy is not effective against hormone refractory cancer. In these cases some form of local therapy often needs to be done to handle certain problems. Radiation therapy given to localized area of regrowth of cancer, particularly on the bones and hips is often necessary and very effective.

Bone Pain

In patients with diffuse bone involvement and bone pain, radioactive strontium89 (Metastron) or samarium153 EDTMP (Quadramet) can be given as an injection with a good chance of relief of bone pain. Symptom relief usually starts within two to three weeks after injection. The average response time is around six months and lasts longer than a year in some. Repeat treatments can be offered if the patient's blood counts are normal.

Biphosphonates, such as pamidronate, are also effective for bone pain in some patients.

Patients who have difficulty urinating because of obstruction of urinary flow by the regrowth of cancer can be treated through surgical removal of the obstructing part of the cancer with a telescopic knife. This is technically called a transurethral resection of the prostate or TURP. Blockage of the ureters can often be treated with a small plastic tube or stent that is placed through the blockage. This allows the urine to flow freely into the bladder and protects necessary kidney function.

As mentioned before, each patient's tumor behaves in a unique fashion, and each patient is handled quite differently. Please ask if you have any questions about hormone refractory cancer.

What's New?

Research is going on actively through multiple centers looking for new drugs and treatments which show activity against hormone refractory prostate cancer, including various types of vaccines, vitamin derivatives, growth factor treatments, and antibodies. You may be asked to participate in such a drug study. Preliminary reports from research on vaccines is much to early to comment on at this time.

Staging terms

Staging terms used by some physicians for patients with Stage D disease are as follows:

D0	Elevated Acid Phosphatase
D1	Positive pelvic lymph nodes
D1.5	Rising PSA after failed radiation or surgery
D2	Metastatic disease in bone and/or other organs (lung, liver, etc)
D3	Hormone refractory prostate cancer

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Content reprinted with permission from Neil Baum, MD, neilbaum.com.

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