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Ask Stanford Med: Answers to your questions on prostate cancer and the latest research

In recognition of Prostate Cancer Awareness Month, Eila Skinner, MD, chair of the urology department at Stanford, took questions via the @SUMedicine Twitter feed and Scope on prostate cancer and the research advancements in the screening, diagnosis and treatment of the disease. Below she responds to a selection of the submissions, which ranged from the controversy over the PSA test to the ways the field of genetics is changing prostate-cancer research.

@Prach82 and @gaisison ask: Why is the PSA test not considered to be reliable? Is the PSA test still advisable as a basic screening tool for prostate cancer? Are there updates on the recommendations?

PSA (prostate specific antigen) is a protein that was originally discovered at Stanford and can be detected in the blood. Men with prostate cancer tend to have higher levels of this protein. There is no question that prostate cancer can be detected earlier using this test combined with a prostate examination compared with an exam alone. It is estimated that the cancer can be detected on an average of 5 to 10 years earlier. It is also clear that cancers detected with PSA screening are more likely to be caught before they spread and at a stage when they are more likely to be cured with current treatments. So why the controversy?

First, men with other common prostate problems, like non-cancerous prostate enlargement (called BPH) can have an elevated PSA. Because of this only about 20-30 percent of men with elevated PSA on screening actually have cancer. They often have to undergo invasive testing like prostate biopsy in order to know that there is no cancer there. These tests are expensive and can sometimes cause side effects like infection. We are always searching for a more accurate test to use for screening, and a number of potential alternatives are being developed. Some are already available, like the urine PCA3 test. This test is still very expensive and has not yet gained widespread use as a screening tool.

Secondly, prostate cancer is usually very slow growing. It might take 10 to 30 years for an early cancer to become one that is life threatening. The risk of cancer goes up with age, so many of the men diagnosed with cancer using PSA testing at age 70 or 80 are never going to live long enough for their cancer to cause problems. Many patients are undergoing treatment today, such as surgery or radiation therapy, for cancers that are not destined to threaten their life.

Finally, we still don’t have proof that if every man got tested, even at age 50 or 60, they would end up living longer than ones who didn’t get tested. Current studies trying to test this have been difficult to complete. They suggest that there may be some benefit, but 40 or more men may have to be treated to save one life. Because the treatment can cause significant side effects, it isn’t clear if this is worth it from a public health perspective.

Still, we shouldn't give up on the PSA test. We need to be smarter about using the test and learning how to predict how a cancer is going to behave in an individual patient. In other words, use the test to find the cancer, but don’t treat everyone’s cancer the same way. Many cancers can be safely watched, thus avoiding the side effects of treatment. On the other hand, the patient with an aggressive cancer that is picked up earlier might be saved with treatment.

At this point, I'd recommend that you discuss the pros and cons of testing with your doctor.

GS asks: Previous research has found that men who eat one and a half servings of pan-fried red meat weekly have a 30 percent higher risk of being diagnosed with advanced prostate cancer. How does eating certain foods increase or decrease you prostate cancer risk?

There have been a number of dietary studies (subscription required) demonstrating a relationship between the intake of red meat and the risk of prostate cancer. Most studies have shown that processed meats, such as hamburger and grilled meats, have the highest risk. These meats seem to particularly increase the risk of more aggressive cancers. Cooking meat to high temperatures on a grill or barbecue, especially when charring occurs, may increase the production of heterocyclic amines and polycyclic aromatic hydrocarbons, both of which are known carcinogens. White meats, such as chicken, and fish can generate these compounds as well. But they tend to be cooked more quickly, have less charring and generally haven't been associated with an increase risk of prostate cancer. Marinating meat before cooking can decrease these compounds. To decrease risk of prostate cancer, eating red meat that is rare or cooked at lower temperatures or eating less red meat and opting for white meats, such as chicken, or fish may be safest.

There are still many questions about diet and prostate cancer prevention and treatment, though a few large studies have been completed. Sometimes we have seen opposite effects than we expected. For example, earlier studies suggested high selenium intake might prevent prostate cancer. But the SELECT study of over 30,000 men showed that men who took supplemental selenium did not have less prostate cancer but actually developed more diabetes! Other studies have suggested benefits of some dietary intake such as soy protein and pomegranate juice, but these have not been confirmed by larger studies.

The best advice for men is to follow a heart-healthy diet. Heart disease is still by far the greatest threat to men’s health, and evidence suggests that a heart-healthy diet, which is high in vegetables and fruits and whole grains, low in saturated fats and red meat, is also the best diet for prostate cancer prevention.

Ella asks: Findings published this month show that “stop-and-start” hormone-deprivation therapy for localized prostate cancer doesn’t shorten overall survival compared to continuous treatment.” What are your thoughts on this type of intermittent therapy approach? 

Hormone therapy works by stopping the production of testosterone and other androgens (male hormones) or by blocking their ability to act on the cancer cells. It has been known for over 50 years that removing testosterone will cause the cancer to go into remission, though most advanced cancers will eventually become resistant to this treatment (called castrate-resistant prostate cancer). This approach is still the mainstay of treatment for men with prostate cancer that has spread outside the prostate. Hormone therapy like this can cause significant side effects including hot flashes, sexual dysfunction and osteoporosis, among others.

It was theorized that hormone blockade could be utilized on an intermittent basis, which might decrease the side effects of treatment or even delay the development of castrate-resistant disease. For these protocols, the hormone therapy is stopped after 9-12 months, when the cancer has usually had the maximum expected response, and testosterone levels are allowed to return to normal. The disease is monitored using serum PSA and the therapy is restarted once the PSA rises to a predetermined level. Such an on-off cycle can be repeated many times if necessary.

There have now been several (.pdf) randomized trials comparing this approach to one using continuous hormone therapy in patients with metastatic disease, and several others that are still underway. While the findings (.pdf) have been mixed, it appears that intermittent therapy does improve quality of life and is less expensive compared to continuous therapy. While the time to castrate-resistant disease does not appear to be prolonged, it has been basically equivalent to continuous therapy, suggesting that it is safe to use hormone therapy this way. Further analysis of these studies might help us decide which patients gain the most benefit from intermittent therapy, allowing us to individualize our treatments in the future.

JBL asks: How has new research on genes linked to prostate cancer helped scientists better understand how the disease develops? 

I asked my colleague Jim Brooks, MD, an expert in genetic predictors of prostate cancer risk and progression, to answer this question. He responds:

Genetic research into the causes of prostate cancer has taken two forms. The first is the investigation of the genes we inherit from our parents that increase our risk of getting prostate cancer. The second is research into the genetic changes that turn normal prostate cells into cancerous cells. In the first, researchers have found several locations in the genome that increase a man’s risk of getting prostate cancer, but surprisingly, they only do so a very small amount. This contrasts sharply with breast cancer in which hereditary gene mutations (in BRCA1 and BRCA2) virtually guarantee that a woman will get breast cancer at some point in her life.

Furthermore, the parts of the DNA that are associated with prostate cancer risk are not found to lie within genes. This surprising finding has begun to make more sense in light of the ENCODE project, which shows that these regions of DNA are important in regulating genes. Of the few spots that lie within genes, these provide hints that inflammation in the prostate might be important in causing prostate cancer.

We have learned more about the genetic changes that distinguish prostate cancers from normal prostate tissues that presumably cause prostate cancer. For example, it appears that each individual patient’s prostate cancer is unique – i.e. has a set of mutations that make it different from another patient’s. This makes it unlikely that a single therapy will work for all prostate cancers. However, there are several common themes found in the majority of prostate cancers including particular mutations and cell regulating pathways that are activated in prostate cancer. For example, the androgen signaling pathway, which is driven by the male hormone testosterone, is active in nearly all prostate cancers.

Recently, new therapies targeting that pathway have been developed that work for men in whom traditional androgen blocking strategies have failed. We and others are working hard to identify other pathways that are turned on in more aggressive forms of prostate cancer, both for identifying men who need more aggressive therapies and for devising new treatment strategies for treatment. Large efforts are now underway to sequence the DNA in many prostate cancers. In other types of cancer, this has allowed clinicians to choose specific treatments, especially ones they might not have thought of, that are tailored to the genetic changes in an individual’s cancer. This will almost certainly be the case for prostate cancer in the near future.

Peggy P. asks: My husband was successfully treated for stage II prostate cancer. I’ve read that aspirin may aid in prostate cancer recovery. What are your thoughts on research showing that aspirin may play a beneficial role in the treatment, or potentially the prevention, of prostate cancer?

There have been a number of studies suggesting that long-term regular use of aspirin may decrease the risk of developing prostate cancer. The Health Professionals Follow-up Study found that men who took aspirin regularly experienced a 10-15 percent decrease risk of prostate cancer. The benefit was most in men who took aspirin daily over 5 years or more, and the effect seemed to be greatest in reducing the most aggressive types of cancer. However, starting aspirin after diagnosis did not seem to change the course of the disease. Similar results have been demonstrated in other studies.

Once again, the greatest risk to health for men is heart disease, and there is very strong evidence that daily aspirin can have a positive effect on cardiovascular health. The possible preventive effect on the risk of prostate cancer is a bonus.

Greg asks: I am a 55 year old male recently diagnosed with prostate cancer... My urologist recommends either DaVinci prostatectomy or brachytherapy. Which treatment option carries the lowest risk of side effects?

There are currently a number of different treatment options for localized prostate cancer, including the two mentioned above plus open surgery, external radiation, cryosurgery and others. There are many factors that need to be considered when recommending a specific therapy. These include the aggressiveness and extent of the cancer and the patient's symptoms, age, general health and preferences. There are also physician factors including the doctor’s experience with the treatment and the equipment available to him or her.

The best way to answer the question of which treatment is best would be to run a large randomized trial including several thousand men where the type of treatment was determined by a flip of a coin. These studies have been unpopular and extremely difficult to complete, so we don’t have this type of information available today. The best we have been able to do is to follow patients treated with the different types of therapy, trying to match the patients as best we can and see which is best from the standpoint of cancer cure and side effects.

From these studies it appears that the effectiveness of surgery and radiation for the average patient is similar, in other words both have a similar cure rate in the long term. Every type of treatment for prostate cancer has potential side effects, especially on urinary symptoms and sexual function. The types of side effects and their timing vary between these treatment options. For example, men who undergo a surgical prostatectomy tend to have some incontinence and impotence that are worse right after surgery and often improve over time. There are also some relatively rare complications from the operation itself. Men with brachytherapy (also called ‘seed implants’) have less incontinence but tend to have significant bladder irritation at the beginning causing urinary frequency and urgency, which also improves over time. Impotence with radiation tends to occur later, perhaps a year or more after treatment. Rectal problems are more common with radiation treatments than with surgery. As you can imagine, it is difficult to say one of these treatments is ‘best’.

I would recommend that you have a frank discussion with your doctor about the expected cure rate with each of these treatments in your particular situation, as well as the risks of the side effects mentioned above. I would highly recommend that you get a second opinion, and consult with both a surgeon and a radiation therapist before making a final decision.

Previously: Stanford Hospital to host free panel discussion about prostate cancer on SaturdayAsk Stanford Med: Urology chair taking questions on prostate cancer and the latest researchStudy calls for increased awareness for minorities and gay men following prostate cancer treatment and Making difficult choices about prostate cancer

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