Treating Prostate Cancer

Screening timetables are confusing and controversial, but doctors say knowledge is critical

An estimated 6,380 Georgia men will learn this year that they have prostate cancer. For some, the diagnosis will be the first they have heard of the disease.

While most men don’t know much about prostate cancer, they should, says Durado Brooks, M.D., director of prostate and colorectal cancers for the Atlanta-based American Cancer Society. Aside from skin cancer, prostate cancer is the most common cancer among American men, affecting as many as one in six men at some point in their lives. After lung cancer, it is the most common cause of cancer death in men.

For Georgia men that risk is particularly great. According to the American Cancer Society, the state of Georgia ranks 11th in number of estimated deaths per capita from the disease, a statistic that doesn’t surprise Dr. Brooks.

“In general you will see high death rates in areas of the country where you have higher African-American populations, because African-American men are more likely to be diagnosed with the disease and, once diagnosed, are more likely to die from it,” he says.

Other factors in Georgia’s high death rate may include environmental exposures, such as certain pesticides used in largely agricultural areas, and obesity, which is a serious problem in Georgia and associated with an increased risk of death in men with prostate cancer.

“Diets that are high in fat may also increase the likelihood of developing and dying from prostate cancer, but we don’t have solid evidence like we have for some other forms of cancer,” Dr. Brooks says. “There are a lot of unexplained factors. We don’t have a real good handle on what causes it.”

But research into potential causes, better screening tools, improved treatments and even a better understanding of which cancers require treatment combine to offer hope for the thousands of Georgians with this disease.

Screening Controversies

While research has yet to confirm a cause, it has shown the disease is rarely fatal if treated early. This has prompted several organizations, including the American Urological Association (the organization of the medical specialty that treats prostate cancer) and Georgia Prostate Cancer Coalition (a nonprofit organization founded by representatives from various prostate cancer support groups to promote awareness of the disease) to recommend widespread testing, beginning by age 40 for most men and by age 35 for African Americans and men with a family history of prostate cancer.

But such practices are controversial. In its prostate cancer screening guidelines, revised in 2010, the American Cancer Society encourages men to understand their risk for the disease and the implications of testing and possible treatment – before beginning testing for the disease.

Instead of recommending a particular time for baseline testing, it recommends a timeframe in which men should start having conversations with their doctors about testing, which is age 50 for most men, 45 for African-American men and men who have a father, brother or son diagnosed with prostate cancer before age 65, and 40 for men who have multiple family members diagnosed with the disease before age 65. Men with no symptoms who are not expected to live more than 10 years (because of age or poor health) should not be offered prostate cancer screening. For them, the risks likely outweigh the benefits, researchers have concluded.

Screening for prostate cancer involves two tests – prostate specific antigen (PSA) and digital rectal exam (DRE). PSA is a protein produced in the prostate and present in the semen and bloodstream. A blood test showing elevated PSA levels could indicate prostate cancer. DRE is performed by inserting a gloved finger into the rectum to check for irregularities in the prostate, which can be felt through the rectum wall.

While the tests themselves are fairly simple, the results are not always easy to interpret – for example, blood PSA levels can rise with infection and other benign prostate conditions – and may lead to unnecessary anxiety and treatment. Treatments for prostate cancer can have adverse side effects, such as incontinence and impotence, which can affect quality of life, says Dr. Brooks.

There are limits to both methods, but the main issue is that even when these tests find cancer, they can’t tell how dangerous it is, says Brooks. “They can’t predict which cancers will be aggressive and require aggressive treatment.”

Mass screenings can be problematic because they aren’t always accompanied by the education patients need to act knowledgably on the results. Without that education, a positive result can cause fear that clouds a man’s treatment decisions. “When men hear the word cancer associated with themselves, most of them will tell you the first thing they think is ‘I am going to die,’” says Dr. Brooks.

The fact is, many prostate cancers are not deadly – with or without treatment. Some prostate cancers grow slowly and may never cause problems, he says.

Treatment Options

If prostate cancer is diagnosed, there are a number of effective treatment options available. Selecting the best treatment depends on a number of factors, including the patient’s age and other health conditions and whether the disease has spread beyond the prostate. (See “Treatment Consider-ations,” page 83).

“For localized cancer, one option has been to monitor it conservatively because it is a slow-growing cancer,” says Dr. Martha Terris, professor in the Department of Surgery at the Medical College of Georgia and a prostate cancer surgeon. Monitoring the disease would require periodic PSAs and DREs and possibly biopsies to check for progression of the cancer that would require treatment.

“For younger men [who tend to have more aggressive disease] and more aggressive cancer, we would treat with surgery or radiation,” she says.

While these basic treatment ap-proaches have not changed a lot in recent years, the techniques have improved. “In radiation therapy, there are new ways of dosing radiation or delivering it in the form of an implant that provides more concentrated and precise means of delivery,” she says.

One of the most commonly used – a treatment called brachytherapy – in-volves implanting radioactive seeds into the prostate, which allows a high dose of radiation to be delivered directly to the prostate while causing limited damage to the surrounding tissues. Traditionally doctors implanted the seeds, which would eventually become inert, and left them there indefinitely, says Dr. Terris.

Today there are seeds that are implanted temporarily and designed to deliver a higher dose over a shorter period of time. This technique, called high-dose rate (HDR) brachytherapy, provides advantages including treatment optimization, accurate dose delivery, and better protection of surrounding tissue from radiation damage. Some patients who are not candidates for permanent seed implants may be candidates for HDR.

In surgery, perhaps the biggest advance in recent years is the development of robotic procedures, now performed at Medical College of Georgia, Emory and several other large medical centers in Georgia.

More formally referred to as laparoscopic robotic-assisted prostatectomy, the surgical procedure involves removing the prostate using several small incisions like traditional laparoscopic surgery, but with greater precision and less blood loss, says Dr. Terris.

“In traditional [laparoscopic prostatectomy] the surgeon makes several small incisions to insert telescopes and tools,” Dr. Terris says. She likens the difficulty of the traditional laparoscopic pro-cedure to tying your shoes with chopsticks. Robotic surgery, however, is more like tying them with gloves on, she says.

“Instead of working with instruments on sticks, there is actually flexibility, magnification and 3-D visualization. The surgeon gets to sit down while they are doing it. It is a more accurate and easier surgery to perform.”

For more severe cancer that has spread beyond the prostate, treatment may consist of chemotherapy and hormone treatment (also called androgen deprivation therapy or androgen suppression therapy) to permanently or temporarily block the production of testosterone and all other male hormones on which prostate cancer can thrive.

Improving Outcomes

Increasingly, however, doctors are learning that some of the most exciting potential advances in prostate treatment are very low-tech. One of the most promising areas of prostate cancer research involves diet, says Dr. Omer Kucuk, professor of hematology and medical oncology at the Winship Cancer Institute of Emory University.

“One of the main things we focus on in our research program here is the role of nutrition and how we can bring nutrition into prostate cancer prevention and treatment,” he says.

Dr. Kucuk and his colleagues have found that certain dietary compounds are helpful additives to traditional treatments. Perhaps the most studied and most promising of these compounds is soy isoflavones, small molecules found in soybeans.

“We found that if you administer chemotherapy or radiation therapy in the presence of these soy isoflavones, chemotherapy and radiation become much more effective, can kill more cancer cells,” he says. “In addition, we found if you administer chemotherapy and radiation with this compound you can prevent the toxicity, so not only are you improving the efficacy of the treatment, you are also preventing the toxicity.”

Research by the Emory group has found that one of the mechanisms by which these compounds work is by inhibiting a molecule called NF-kappa B, which is key to cancer cell survival. “We found that when cancer cells are exposed to chemotherapy and radiation, they increase their NF-kappa B trying to survive – the NF-kappa B levels go way up,” says Dr. Kucuk. “But if you give these soy isoflavones before exposing cancer cells to chemo and radiation, NF-kappa B does not go up. Soy isoflavones disarm the cancer cells so they can’t defend themselves; they [the cancer cells] can’t survive chemo-therapy and radiation.”

Interestingly, soy isoflavones have the opposite effect on healthy cells, making them more resilient and resistant to the negative effects of cancer treatment.

Other nutrients being studied in connection with prostate cancer include:

• Curcumin: A compound found in the Indian spice turmeric that gives curry powder its yellow color, curcumin has been found by Emory researchers to kill cancer cells similarly to soy isoflavones, says Dr. Kucuk.

• Pectin: A study from the Univers-ity of Georgia found that this naturally ocurring substance found in fruits and vegetables caused cancer cells to undergo apoptosis, or programmed cell death. UGA Cancer Center re-searcher Debra Mohnen and her colleagues found that exposing prostate cells to pectin in the laboratory reduced the number of cancerous cells by as much as 40 percent.

• Resveratrol: Studies by research-ers in Georgia and elsewhere have shown that this substance, found in grapes, may work to inhibit cells without bothering healthy cells and may be useful for prostate cancer treatment and prevention.

Although studies show that such nutrients may be effective cancer treatments, further research is needed before doctors can recommend specific supplements at specific doses, says Dr. Kucuk. In the meantime, he says, following a diet high in fruits, vegetables and soy couldn’t hurt and it may well help. “I tell my patients, why don’t you drink soy milk every day, and if someone wants to eat more tofu or roasted soy nuts, by all means, do it,” he says.

What’s Ahead

Dr. Brooks says the long-term solution is not only the development of better treatments, but of better screening tests, better diagnostic tests and better ways of individualizing treatment for patients who need it.

All of those are goals of the Collaborative Cancer Genomics Center, a new partnership between Clark Atlanta University’s Center for Cancer Research and Therapeutic Development and Georgia Tech’s Integrative Cancer Research Center, which will help researchers find a biomarker to help effectively screen for prostate cancers and will focus on identifying personalized cancer treatment based on an individual’s genetic make-up.

John McDonald, Ph.D., director of the Integrative Cancer Research Center at Georgia Tech, says the group is particularly interested in developing algorithms that will allow them to use gene expression and DNA sequence data gathered from specific patients to generalize a customized prognosis and optimal therapeutic treatment program for individual cancer patients.

With such research, Dr. Brooks believes the next decade will see major advances in the way prostate cancer is diagnosed and treated.

In the meantime, however, he says the best tool is knowledge. He encourages men to learn all they can about prostate cancer and to discuss risk factors and the possible need for testing and treatment with their doctors.