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A new trial is exploring an androgen receptor blocker in treating prostate cancer. FG Trade/Getty Images
  • A second-generation androgen receptor blocker added to other prostate cancer treatments improves five-year survival rates for people with metastasized disease.
  • The blocker, enzalutamide, improved outcomes in a range of prostate cancers even where chemotherapy is ineffective.
  • Enzalutamide works by reducing the ability of prostate cancer cells to bind to testosterone, which promotes cancer growth.

Adding a second-generation androgen receptor inhibitor when treating metastasized prostate cancer can increase survival rates at five years, according to a new study. The study reports the findings of ENZAMET, international open-label trials that took place at 83 sites in Australia, Canada, Ireland, New Zealand, the U.K., and the U.S.A.

Significantly more patients who received enzalutamide in addition to standard treatment survived after five years than those who received standard treatment alone.

The study found that enzalutamide increased survival rates when added to the standard treatment of testosterone suppression plus docetaxel chemotherapy, as well as to testosterone suppression alone.

The four-year survival rate for patients receiving standard therapy is 57%, while the five-year survival rate for those who also received enzalutamide was 67%.

The study is published in THE LANCET Oncology.

Prostate cancer is the second-most common cancer in men after skin cancer. According to the American Cancer Society, about 288,300 new cases of prostate cancer are diagnosed each year, and 34,700 men die of the disease annually.

Prostate cancer occurs when cells in the prostate gland, which is located beneath the bladder and in front of the rectum, become cancerous.

Most, though not all, prostate cancers are slow-growing, and the disease is not fatal more often than it is. The ACS estimates there are more than 3.1 million men living in the U.S. with diagnosed prostate cancer.

For men who are diagnosed with early-stage prostate cancer that has not metastasized — that is, it has not advanced beyond the prostate gland — there are several common therapeutic approaches.

The most common treatments for such cases are radical prostatectomy — in which the prostate is removed — and radiotherapy. There is also “watchful waiting,” with which the cancer is actively monitored without treatment unless the disease advances. All three have similarly high survival rates of about 97%.

An additional option is focal therapy, in which cancerous tissue on the prostate is destroyed using any of several techniques, including cryotherapy, ultrasound, laser treatment, and photodynamic therapy.

Metastasized prostate cancer

Prostate cancer cell division is commonly fueled by the hormone testosterone, the primary male sex hormone, and one of the two androgens the body produces. It is primarily produced by the testicles, and less so by the adrenal glands.

About 90% of prostate cancer is hormone-sensitive, according to urologist Dr. Mehran Movassaghi, who was not involved in the study. “All prostate cells use testosterone as their main fuel,” he said.

For men whose prostate cancer has spread to other organs or parts of the body, physicians attempt to cut off the cancerous cells’ supply of testosterone or reduce their ability to use it.

When a lab technician examines a biopsy of hormone-dependent prostate cancer tissue, androgen receptors are typically visible on the surface of cancerous cells.

The primary element of the standard treatment for patients with metastasized prostate cancer is testosterone suppression, which can be achieved in two ways.

With orchiectomy, a surgical procedure removes one or both testicles. There is also “medical castration,” in which LHRH agonists prevent the secretion of the pituitary gland’s luteinizing hormone. Without this hormone, the testicles no longer produce testosterone, typically leading them to shrink, sometimes becoming so small they can no longer be felt.

In higher-income countries, surgical castration is no longer commonly used. However, Dr. Movassaghi noted that in lower-income countries, “That’s still ‘standard of care.’”

In many cases, “the cancer learns to utilize other types of fuel, and then it becomes hormone-insensitive,” explained Dr. Movassaghi.

“The cancer has essentially outsmarted its normal pathway that the prostate uses,” he said.

When this occurs, it becomes more difficult to control the disease and androgen-receptor blockers may be added to treatment, and in some cases, docetaxel.

Enzalutamide is a second-generation androgen-receptor blocker. Urologist Dr. David Shusterman was also not involved in the study.

Dr. Shusterman explained that enzalutamide is a better drug than earlier blockers because “it is more potent, which means that it is more effective at blocking the activity of androgen receptors in the body.”

In addition, he said, “it can block androgen receptors in more areas of the body, which can help to slow down the spread of cancer cells.”

“It has fewer side effects than first-generation inhibitors, which can make it a more attractive option for patients,” he added.

The researchers found that enzalutamide was effective across different cancers, which are classified according to two characteristics:

  • The volume of metastases — With high-volume prostate cancer, four or more cancerous bone lesions exist along with one or more lesions somewhere in the body beyond the pelvis or spine, or in the body’s viscera. Low-volume prostate cancer involves fewer than four bone lesions, and may involve visceral lesions.
  • Timing of sites — Cancers are also identified as being synchronous or metachronous. Synchronous cancers develop at the same time wherever they appear. Metachronous cancers are of different ages, suggesting more prolonged development.

While docetaxel is more effective than testosterone suppression alone for most prostate cancers, it has little value with metachronous low-volume cancer. Enzalutamide, however, is effective in such cases.

“The results of this study are groundbreaking in that they suggest that enzalutamide can significantly improve survival rates for men with this type of cancer,” said Dr. Shusterman.

Dr. Movassaghi added that the study makes it easier to convince patients to try enzalutamide. It also makes it easier “for us to have insurance companies cover these newer and more expensive drugs because it solidifies the fact that they are actually extending the life expectancy of all these patients.”

In the end, concluded Dr. Shusterman, the study “emphasizes the importance of ongoing research and development in the treatment of prostate cancer. The results of this trial suggest that new treatments are on the horizon that can significantly improve outcomes for patients.”