Prostate cancer is not always an obvious enemy. Quiet often it grows silently for many years and, in fact, many men end up dying from other causes, never knowing they had the disease at all. Nevertheless, prostate cancer is one of the most commonly diagnosed cancers in America, and is the second-most common cause of cancer death in men: over 230,000 will be diagnosed and over 30,000 will die this year alone.
But new advances in the treatment of this disease are giving a glimmer of hope to men living with advanced-stage prostate cancer. Below, Dr. James A. Eastham, an associate attending in urology from the Memorial Sloan-Kettering Cancer Center in New York City, explains how these new therapies work.
What is advanced-stage prostate cancer?
Advanced prostate cancer really means anything that is not curable with either surgery or radiation therapy. It's cancer that has extended outside the prostate to a point where local therapy alone will not cure it.
Do most men have advanced-stage prostate cancer at diagnosis?
Men can certainly be diagnosed with advanced prostate cancer at an initial evaluation, but that's becoming more rare with the widespread use of prostate-specific antigen (PSA) testing. This test uses a blood sample to measure the amount of PSA, a protein made by the prostate. The more PSA present, the higher the likelihood of a patient having prostate cancer. If this test indicates that cancer might be present, a biopsy will be done to confirm the diagnosis.
The vast majority of men diagnosed with prostate cancer have what doctors believe to be clinically localized cancer. That means those patients are treated with either surgery or radiation because the cancer has remained mostly localized to the prostate.
If you look at patients who have been treated with surgery or radiation, about 25 to 30 percent have a cancer recurrence. Not all of those men go on to have symptoms from the disease, but many men end up being treated for the cancer that has come back after initial therapy.
What is the goal for treating advanced-stage prostate cancer?
The goal of cancer therapy, in general, is to try to cure the cancer. If a cure is not possible, then prolonging a person's life and equally, if not more importantly, maintaining quality of life becomes the goal. With advanced stage disease, many men have problems with cancer in their bones, which can lead to a significant amount of pain, and, in some instances, fractures. So the goals of therapy are to try to prevent or delay the progression of the disease and to reduce symptoms from the disease in the bones.
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What is hormonal therapy?
Traditionally, the approach to advanced disease has been hormonal therapy. Prostate cancer is driven by testosterone. By taking testosterone away, you stop one of the promoting factors of cancer growth. Originally, this was done by removing the man's testicles, the source of testosterone. Today, it's more commonly done with medications. The drugs basically trick the body to stop making testosterone, or block testosterone or the other male hormones where they act. There are two ways to do that. One is with what's called a GnRH or LHRH agonist. These are medicines that are given by injection and basically tell the testicles to not make testosterone. Other types of agents called anti-androgens don't affect the amount of hormones produced by the testicles, but they stop the hormone from promoting growth by preventing it from working in the prostate. The limitations of hormonal therapy, however, are that it is not curative and eventually the cancer can grow, despite the hormonal manipulations.
How long can hormonal therapy work?
How long a man responds to hormonal therapy depends on how advanced his cancer is. If the cancer has spread to his bones, the response to hormonal therapy lasts just a couple of years. For men who are treated with hormonal therapy because of a rising PSA after surgery or radiation therapy, the response to treatment can be a decade or more.
Cancer unfortunately is smart. Its goal is to live, and for every action that doctors do, be it hormonal therapy or chemotherapy, cancer cells adapt. In general, if a man has advanced prostate cancer and lives long enough, the tumor will eventually find a way to grow.
Also there are cancer cells in the prostate that don't need testosterone to live. They are probably present very early on in the disease, but in very low numbers. As the hormonal therapy basically takes care of the cancer cells that are dependent on the hormones, these other cells can then blossom. One of the areas of research now is to counteract how cancer acts in response to the hormones.
How do you know when the hormonal therapy may be failing?
The main way in which doctors find that hormonal therapy might no longer be working is by measuring PSA levels. Those blood levels are a good measure of cancer activity. If PSA levels are going up, that's usually a sign that the treatment isn't working as well. There are rare instances when the PSA may not go up as the cancer is growing. In those cases, doctors usually know the cancer is growing because the patient presents with new symptoms.
What do you do for someone who is no longer responding to hormonal therapy?
Once the hormonal therapy becomes ineffective, you have a small window of opportunity to manipulate hormones. Sometimes drugs that are supposed to block hormonal agents are recognized over time by the cancer cell as being a stimulant. So by taking that medicine away, you're actually treating the cancer. You're removing a little bit of the fuel from the fire, if you will. But no more than 20 to 30 percent of the men in whom doctors try to manipulate the hormones respond to it. And the responses are usually short-lived, and the cancer is then considered hormone refractory.
Can chemotherapy be used to treat advanced-stage prostate cancer?
Traditionally, chemotherapy has had a limited role in advanced prostate cancer. Fortunately, there have been some advances in men with advanced hormone-refractory prostate cancer, very late stage disease. The initial advance in chemotherapy was a drug called mitoxantrone, which, while it did not prolong survival, it did help with symptoms of pain. Men who were on the drug had greater pain relief than men who weren't. More recently another drug, Taxotere, has been shown to actually not only help with pain, but also prolonged survival in metastatic prostate cancer.
How long can the new chemotherapy drug prolong life?
The survival advantage in the large clinical trials looking at Taxotere showed a modest benefit, in the range of 2 to 3 months. And while that doesn't sound like a prolonged period of time, life expectancy in men with advanced prostate cancer is only about 14 to 16 months. So an extra 2 to 3 months is actually significant.
Even more significant is the fact that doctors had never seen a survival advantage for any type of drug, chemotherapy or not, in this stage of disease. So, while it's certainly not a home run, it gives researchers, clinicians and most importantly patients, some hope that door is starting to open. The results from the Taxotere clinical trials will allow experts to start looking at newer combinations of agents and other agents to hopefully prolong survival and get better responses.
What advice do you have for prostate cancer patients who are not responding to hormonal therapy?
For men who are failing hormonal therapy, as with any other stage of prostate cancer, the key is being aware of other alternatives and talking to your doctor about them. Certainly, most medical oncologists will be aware of Taxotere prolonging survival. But there is also the chance to participate in clinical trials. The only way to get to answers about treatment is if patients agree to participate in studies that try a new approach.
