Prostate Cancer –Management of Low Risk Disease*

Prostate cancer remains one of the most common cancers in men with 250,000 new cases each year and causes nearly 40,000 deaths each year. Like most other cancers there are shades of gray and not all cancers need to have treatment. This blog will discuss the use of androgen deprivation therapy and when it might used in men with advanced prostate cancer.

There’s nothing like an elevated prostate specific antigen (PSA) test result to strike fear into even the most unflappable and courageous of men. That’s because elevations in PSA in the blood can point to the presence of prostate cancer. On the other hand, elevated PSA can also indicate prostatic enlargement or inflammation of the prostate. However, an elevated PSA test result, combined with a digital rectal exam and a 12-core prostate biopsy to remove small pieces of prostate tissue from the gland, will provide a very good idea as to whether a man has cancer or not.

About 40 to 50 percent of the 241,000 men expected to be diagnosed with prostate cancer this year will have a suspicious PSA score and a Gleason score of 6 out of 10, which is based on the prostate biopsy. A Gleason score of 6 is an indicator of a very favorable or low-risk disease, a disease that is treatable and curable — if, in fact, a man chooses to treat it.

Facing treatment decisions. Once a man has a prostate cancer diagnosis, he then has to choose what type of treatment he wants, which can include surgery or radiation therapy; men with low-risk cancer can also opt for active surveillance, or close monitoring without any immediate treatment. However, these men have to have a digital rectal exam and PSA test and possibly a repeat biopsy on a regular basis.

The good news is that low-risk prostate cancer — meaning low grade and low stage with a PSA below 10 ng/mL — grows slowly, if at all. Therefore, a man should be sure to discuss with his doctor whether he really needs to undergo any therapy to treat his cancer. That’s because in the majority of cases the answer will be “not now.”

What we have learned over the years with low-grade cancer is that sometimes the best option is no treatment whatsoever. And that includes treatment with androgen deprivation therapy, or ADT.
Earlier this summer, I came across a study in JAMA Internal Medicine that reminded me that many men with low-risk prostate cancer are still being offered primary ADT to treat their cancer, something that we would not recommend at Johns Hopkins. The reason: ADT offers no survival benefit for men with low-risk cancer and it causes significant side effects, including osteoporosis, diabetes and decreased libido.

Androgen deprivation therapy (ADT)–also called hormone deprivation, or hormonal or androgen ablation–is effective at turning off the body’s supply of male hormones, which prostate cells need to grow and develop. When the supply is shut off by drugs or by removing the testes, a portion of the cancer dies, tumors generally shrink, and PSA levels drop.

It’s androgens, or male hormones, that stimulate the growth of prostate tumors. The two most common androgens are testosterone and dihydrotestosterone (DHT). Since the Nobel Prize-winning discovery by Dr. Charles Huggins of the University of Chicago that prostate tumors depend on these hormones to grow, reducing androgen levels or blocking the action of androgen (androgen suppression) has become the standard of care for men with cancer that has spread beyond the prostate (metastasized) to the bones and other organs. There has also been increasing interest in using it in men whose PSA level has begun to rise after treatment with surgery or radiation (“biochemical recurrence,” an early sign that the cancer has not been eradicated).

Most urologists typically wait until there is evidence of metastatic disease before starting with ADT. There is an exception, however, and that is when we see a rapid PSA doubling time (less than six months) — because this provides indirect evidence of micrometastic disease that will develop in the next few years.

While ADT plays a significant role in the treatment of advanced prostate cancer, it has no role in the treatment of older men with low-risk cancer. Yet primary ADT is nevertheless being prescribed for one in eight men over age 65 diagnosed with localized prostate cancer.

The JAMA article. In the JAMA Internal Medicine study conducted by Grace L. Lu-Yao, Ph.D., a cancer epidemiologist at the Rutgers Cancer Institute of New Jersey and professor of medicine at Rutgers Robert Wood Johnson Medical School, more than 66,000 older men with low-risk prostate cancer were followed for up to 15 years. Dr. Lu-Yao reported that those men who received ADT lived no longer on average when compared with men who did not receive the therapy.

Prescribing ADT for these low-risk patients may decrease the high anxiety level that a patient may have due to his cancer diagnosis, however, it is necessary to note that such treatment may carry more risk than benefit. ADT helps reduce anxiety by quickly dropping PSA levels into the undetectable range, so the doctors may feel that they are doing something positive for their patients. However, ADT may not really be in the patient’s best interest due to complex side effects. The doctor should really be talking to patients with low-risk disease about pursuing active surveillance, not ADT.

There are serious potential risks associated with ADT, including coronary heart disease, and the associated high costs of the medications, the use of primary ADT should be limited to patients in the high-risk cancer group who are not suitable for, or opt not to receive, primary therapy — surgery or radiation — that has the potential to cure.
The side effects associated with ADT. In general, hormonal therapy will cause significant side effects after several months of treatment. Long-term side effects of ADT may include one, some or all of the following:
• Anemia
• Coronary heart disease
• Decreased energy
• Decrease in mental acuity
• Depression
• Diabetes
• Erectile dysfunction
• Hot flashes
• Loss of muscle mass
• Osteopenia
• Osteoporosis

Bottom Line: Many men with prostate cancer who have low risk disease or who have recurrence after treatment with radiation or surgery. This is usually detected by a rising PSA after treatment for prostate cancer that is confined to the prostate gland. These men should have a discussion with their urologists and discuss if androgen deprivation therapy is really in their best interests and that the benefits vs. the side effects are worth the treatment with androgen deprivation therapy.

*This blog was modified from the Johns Hopkins Newsletter, July 2014

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