Fighting Stress: The Amygdala as Super-Hero

BY RALPH BLUM

Writing about “Stress Management” has been a Pandora’s box for me. I am convinced that, along with taking charge of my own recovery, an understanding of stress—it’s nature, how it operates, how to manage it—has served me well in facing the dragon of prostate cancer. Whether you are newly diagnosed or coping with bone metastases, I hope my exploration of stress will serve you—and give you renewed hope.

 

Stress is a poisonous compound of worry, anxiety, exhaustion, regret, fear, despair, and all the other toxic tourniquets that bind us to the wheel of suffering. In most people’s lives, these negative feelings are registering in our bodies chemically and organically much of the time. So let’s take a close look at the factor of stress in our lives, and see how it weighs down and impedes the process of recovery.

 

Really ancient, the word “stress” is a form of the Middle English destresse, which is in turn derived, through Old French, from the Latin stringere, “to draw tight.” Used first in physics to refer to strain on a material body, by the 1920s stress was being applied in medical circles to refer to mental strain, or harmful environmental “agents” that cause illness.

 

In 1926, Harvard Physiologist Walter Cannon used the term “stress” for its clinical significance, describing external factors that disrupted what he called “homeostasis,” a steady state or  equilibrium ideal for our well-being and healing. Moreover, Cannon’s book, The Wisdom of the Body, was the breakthrough in understanding that we actually have a capacity to self-correct from stress, and restore homeostasis.

 

It goes without saying that a potentially life-threatening situation, like cancer creates the kind of stress that persists over time, taking a significant toll on the body and seriously disrupting homeostasis. So what can we do to alleviate chronic stress?

 

While I was looking for fresh ways to manage stress in my life, I came across an exotic “game” created by high school teacher and psychologist, Justin Galusha.  His game asks you to create 17 “Superheroes, Villains and Sidekicks” for "17 areas of the human brain.” In order to “play,” you need a name for the character, a description of that character’s super powers and/or weaknesses, the brain area where the character is found, and what it actually controls in the brain. Among the areas (and characters) he includes Cerebellum, Thalamus, Hippocampus, Temporal Lobe and the Amygdala. Since we’re not playing the game, we don’t have to look at all seventeen,  focusing on just one—the one that coordinates all the others—the amygdala.

 

I was already aware of the power of the amygdala to process emotions and manages stress, particularly when feelings of anxiety or fear are involved. Seated at the center of an exquisitely tuned and coordinated emergency response system, the amygdala is a small almond-shaped structure, buried deep within the temporal lobe, part of the brain’s limbic system.  For his game, Galusha describes the amygdala as “governing emotions related to self-preservation . . . in particular stimuli that are threatening to the organism.” And he means life threatening, So that’s what this is all about—self-preservation.

 

In Galusha’s brain game, here is how the role of the amygdala—dubbed “Amyg’DaMan”—is described:

Blessed with a heightened amygdala thanks to a freak accident in the Vidal Sassoon mouse testing facility, Amyg’DaMan knows when he can win a fight or when he needs to take flight . . . With only his superhuman ability to read facial features and govern emotions, Amyg’DaMan never gets in over his head. He sports a caveman like costume as a shout out to his ancestors. . .  Had it not been for their amygdalas they wouldn’t have known when to run from predatory trolls with extra arms or stay and slaughter innocent docile foes. This one’s for you Amygdala guy—and the quick judgment that saves your life.

The whole idea—including a hairy caricature of his club-wielding caveman hero—made me laugh. And while the conventional fight or flight options described here are not available to a man with newly diagnosed with prostate cancer, the primitive emotions are the same. Stress is the result. Laughter is one antidote. And self-preservation is the objective.

 

I’d say laughing at the vision of Amyg’DaMan whooping those four-armed predatory trolls is good anti-stress activity.

 

In my next blog I will consider stress as three-tiered, one toxic, one tolerable, and one (I was surprised to learn) both positive and useful, capable of improving the function of the immune function.

The AZURE Shade of Blue

BY MARK SCHOLZ, MD

Patients frequently ask their physicians, “Am I stage A, B, C or D,” without realizing that the original purpose of a lettering system was simply to guide urologists in the selection of candidates for surgery. While stage matters, a combination of PSA level and the Gleason grade is a better way to assess disease status. So rather than using stage, it’s best to incorporate all three factors together—PSA, Gleason and stage—to divide prostate cancer into five broad categories or Shades of Blue.

Using standard doctor terminology, the AZURE Shade of Blue is essentially the same thing as “High-Risk” prostate cancer. “Risk” refers to a higher probability of relapse after surgery or radiation compared to men in SKY or TEAL shades. Therefore, men in AZURE are usually treated with combination therapy consisting of IMRT, a seed implant and testosterone inactivating pharmaceuticals (TIP) for 18 months.

 

Here are the specific factors that define AZURE. 

1.     No previous treatment with surgery or radiation.

2.     Bone and body scans without metastasis.

3.     One or more of the following three factors:

a.     PSA above 20 and less than 100, or

b.    Gleason score above 7, or

c.     A prostate tumor felt by digital rectal exam extending across the midline of the gland or outside the capsule.

Men with two or three of these factors are still classified as AZURE. Men with spread to pelvic nodes are classified as INDIGO.  Men with metastasis that has spread to bones or to nodes outside the pelvis are ROYAL. Radiation—rather than surgery—is the preferred treatment for AZURE because of the risk for cancer infiltration outside the prostate. Safe surgical removal is next to impossible when the disease extends into surrounding organs.  Incomplete cancer removal means radiation will be required to “mop up” the residual cancer anyway. Therefore, most experts recommend radiation because the risk of needing both surgery and radiation is so much lower.

Within the AZURE category exist subcategories of men who have a relatively more advanced type of AZURE. For example, some men have larger tumors, higher PSA levels above 40 and Gleason grade 9 or 10.  Men in this situation might want to try to further enhance their cure rates by adding a more potent form of TIP such as Xtandi or Zytiga to their therapeutic plan.  Also, a short course of Taxotere chemotherapy can be considered.

My last blog (about TEAL) reviewed potential side effects from surgery and radiation.  The side effects of TIP become more severe when treatment duration is prolonged. The three most troublesome TIP-related problems are low libido, weight gain and fatigue. However, libido recovers after TIP is stopped.  Weight gain and fatigue can be reduced with diet and exercise. Yet as we all know, maintaining a consistently good diet and getting adequate exercise over long periods of time can be very challenging.  Obtaining professional support from a trainer or a physical therapist is one way to sustain a disciplined program on an ongoing basis. 

 

Other common TIP side effects can be controlled with medications.  Hot flashes regress with a low-dose estrogen patch. Calcium loss from the bones can be prevented with an injection of Prolia every six months, a Fosamax pill weekly or with an Actonel or Boniva pill monthly. Mood swings can be reduced with low-doses of an antidepressant called Effexor.  Effexor also has salutary effects on hot flashes. Breast growth can be prevented with an estrogen-blocking pill called Femara.  When libido is chronically low, men tend not to care about getting erections, so taking daily Cialis should be considered standard for men receiving TIP.

Unfortunately, many doctors have limited knowledge about how to prevent TIP side effects. Patients, therefore, need to protect themselves by getting as much education as possible. Certain side effects, such as breast growth, erectile atrophy and osteoporosis, are preventable with appropriate intervention.  However, once they are allowed to occur, these effects can be permanent.

While side effects are an important consideration, men in the AZURE group have a relatively more dangerous type of prostate cancer compared to men with SKY or TEAL.  The appropriate treatment stance, therefore, is to be aggressive—to get cured.

The good news is that the majority of men with the AZURE stage of prostate cancer will be cured with the treatment approach outlined above.  Studies have shown that the best results come from using IMRT, radioactive seed implantation and testosterone inactivating pharmaceuticals (TIP) in combination with each other. 

So if you do find yourself in the AZURE zone, don’t despair: There is good reason for hope.

A Few Words About Prostate Biopsy by Someone Who Will Go a Long Way to Avoid Having One

BY RALPH BLUM

The large majority of men I meet are not aware that by agreeing to a prostate biopsy they are starting down a slippery slope. The biopsy is a pivotal step—not because it is painful— when expertly performed there should be minimal pain—but because, more often than not, if any of the tissue samples or “cores” taken from different sections of the prostate prove positive for cancer, the whole radical treatment process is set in motion.

Very few men understand that in most cases, prostate cancer is the more common Low-Risk type that is not life threatening and does not require immediate treatment.

So what can be done to prevent this rush to over treatment? Especially the panic to “just cut it out?”

First of all, family doctors need to refrain from recommending a biopsy at the first sign of an elevated PSA. You’d be surprised to learn how often this happens. But a slight increase in PSA does not justify an immediate biopsy. Instead, it should merely result in a risk assessment process to determine what is really going on in the prostate.

 

For instance, an enlarged prostate, the result of Benign Prostatic Hyperplasia (BPH), common in aging men, is often the cause of an artificially elevated PSA reading. Similarly, a random laboratory error, an underlying chronic prostate infection or even recent sexual activity, can cause a rise in PSA. I remember once, about ten years ago, my PSA was unaccountably elevated. Then I remembered I had helped a friend move some heavy carpets from his house to his truck the day before the test. We repeated the test a week later, and my PSA had dropped back again to its previous level. Could it have come from my vigorous exertion?

 

So an obvious first step, when there is an unexplained shift upward, is to make certain that all the above reasons are ruled out and have your doctor repeat the PSA. If on retesting your PSA is still elevated, additional testing with PCA-3, color Doppler ultrasound or mulitparametric MRI should be considered before resorting to a biopsy and starting down that slippery slope to unnecessary radical treatment—treatment that all too often leads to incontinence and loss of sexual potency.

 

If further testing indicates that you should to go ahead with a biopsy, remember that some margin of error is always present. Biopsies fail to spot cancer about 20% of the time, especially in men with enlarged prostates. So even when an initial biopsy comes up free of cancer, you are not off the hook.  Naturally doctors are concerned about missing cancer in their patients, so chances are they will recommend a second or even a third biopsy, and one of these follow-up biopsies is likely to show something that was missed in the first go-around.

 

A better approach is to consider an image-guided, targeted biopsy with MRI or Color Doppler Ultrasound. Not only is high grade disease located more frequently, low-grade disease can be overlooked.

 

However, if this should happen, don’t panic. As Mark pointed out in our book, Low-Risk prostate cancer is so common that the likelihood of the average man harboring some degree of microscopic disease can be estimated by putting a percentage sign after his age. Low-grade disease is a normal part of aging, not something to be frightened of.

 

So if your PSA is only slightly elevated, my advice to you—depending on your age, your life expectancy, your overall health and your family history—is to think very carefully about the risks inherent in radical treatment, and don’t allow yourself to be rushed into getting a biopsy before less invasive diagnostic methods have been explored.

 

In the meantime, put that percentage sign after your age, and know you are in good company. Just remember: The odds are on your side. Time is on your side. For my part, I am doing my best to live up to the sub-title of our book: “No more unnecessary biopsies, radical treatmentor loss of sexual potency.”

The TEAL Shade of Blue

BY MARK SCHOLZ, MD

People assume that the differences in the way prostate cancer behaves—one man develops symptoms and another doesn’t—is because they are seeing different stages of the same illness.  What’s overlooked, often with disastrous consequences, is that these differences are also due to the fact that distinct varieties of prostate cancer exist.

Receiving optimal therapy depends on matching an appropriate treatment with both the correct stage and the correct type of prostate cancer.  Since blue is the color for prostate cancer, as pink is the color for breast cancer, the PCRI has subdivided prostate cancer into five major Shades of Blue. These shades incorporate both the stage and the type of disease. The five shades are SKY, TEAL, AZURE, INDIGO and ROYAL.

The first three shades, SKY, TEAL and AZURE, represent men who have had no previous surgery or radiation. TEAL is what medical professionals call “Intermediate-Risk.” Men in the TEAL shade have identical characteristics to SKY—PSA under 10, Gleason under 7 and a small nodule (or no nodule) on digital rectal examination. However, in addition, men in TEAL have one of the following: PSA between 10 and 20, or, Gleason of 7, or digital rectal exam with a “biggish” nodule confined to one side of the gland.

Since men in TEAL have a small but real chance of cancer spread, staging scans of the bone and body are needed.  In addition, a multiparametric MRI or a Color Doppler Ultrasound should be done to check for spread around the gland just outside the capsule. If extra-capsular disease is seen, the shade changes from TEAL to AZURE.

Treatment for TEAL
The list of treatment options for TEAL is long.  While occasionally men are candidates for active surveillance— particularly those who are older—one of the following treatments is usually administered: Robotic surgery, open surgery, intensity modulated radiation, temporary high-dose seed radiation, permanent seed radiation, a combination of seed radiation and IMRT, proton therapy, Cyberknife, focal therapy or testosterone inactivating pharmaceuticals (TIP).  Sometimes a short course of TIP is combined with radiation.

Focal therapy “focuses” treatment on the cancer itself rather than the whole gland.  Typical tools used for focal therapy are cryotherapy, HIFU or laser. In general, skillfully administered focal therapy is thought to be associated with a lower risk for side effects and only slightly higher risk of future cancer relapse. However, focal therapy is very new and there are relatively few studies accurately describing long-term results.

Another option is to use TIP. TIP causes the cancer to shrivel up.  Typically TIP is continued for six to twelve months after which men are placed on active surveillance.

One general principle is that treatment success depends just as much on the skill of the administering doctor as it does on the type of treatment selected.

The second general principle is that cure rates with most of the different treatments are so close that for comparison purposes, they should be considered identical. Of course, the truth of this principle is predicated on the assumption that all treatments are administered by equally skilled experts.

Side Effects of Treatment
The prostate gland is so close to other critical organs it becomes very difficult to target the gland without damaging surrounding structures. The most common side effects, therefore, are persistent difficulties with sexual, urinary or rectal function.  For example, after radiation in an average 65-year-old, about 75% of men will recover back to their normal pretreatment level of urinary function. About 50% will recover back to their normal pretreatment level of sexual function. After surgery, about 50% of men have urinary function that is restored but only 20% describe their sexual function as recovering back to baseline.

Predictions about the incidence of side effects after focal treatment are less than certain because this technology is so new. Overall, assuming that the treating physicians are skillful, one would expect somewhat better potency rates and somewhat lower cure rates compared to standard surgery or radiation.

Comparing TIP with others options is even more difficult.  Cure rates are certainly much lower. However, the good news is that permanent side effects are rare.  The three most troublesome side effects during therapy are low libido, weight gain and fatigue. Weight gain and fatigue are partially counteracted with diligent diet and exercise. Low libido only resolves after TIP is stopped. Other common side effects such as hot flashes, calcium loss from the bones, mood swings, breast growth and erectile dysfunction can be prevented with medication.

Final Thoughts
Men in the TEAL Shade of Blue, compared to men in the other shades, face the biggest challenge—making a therapeutic choice.  First, there are so many options. Second, none of the options are attractive.  The “best” choice is only relatively better than the others; it’s never something you want to do. Making the best choice for yourself requires good comparison shopping skills, and that requires extensive homework. There are no shortcuts. Third, the biggest differences between the options are not related to the cure rates, it’s the concern about permanent side effects that needs the most attention.

Therefore, my recommendation for selecting treatment is to create a list of all the reasonable choices and study them closely, especially in term of the potential long-term side effects.  The “worst” choices should be eliminated one by one. The last option left on the list will probably be the best treatment for you. 

Stress Management

BY RALPH BLUM

Shining a light on stress from a different angle always yields new insights. The very term “stress management” is like a suitcase you can unpack layer by layer.

There can be no doubt that emotional factors influence biology. Some studies indicate that stress plays a role in causing the occurrence and recurrence of prostate cancer. In fact, most major illnesses have been linked to chronic stress.

Receiving a diagnosis of cancer, and living with cancer, can cause an enormous burden of stress. While experiencing feelings such as depression, despair, anger and fear is totally understandable, if those feelings are not recognized and  “managed,” they put endless wear and tear on the body until eventually the immune system—our most powerful defense against cancer—is no longer capable of performing its job efficiently.

The body has its own stress inhibitors.  Consider cortisol. Known as the “stress hormone,” cortisol is synthesized from cholesterol, produced in the adrenal cortex, and secreted during a stress response. Among cortisol’s primary functions are: to aid in fat and protein metabolism, and to redistribute energy to those regions of the body that need it most; for example, to the brain and major muscles during a fight-or-flight situation. Most important, cortisol helps to regulate the body’s inflammatory response to stress, which it does by increasing blood sugar through the process known as  gluconeogenesis. However, during long periods of chronic stress, cortisol is over-produced, and when cortisol levels are too high, the result is a disruption of its anti-inflammatory function.

Led by Sheldon Cohen, professor of psychology and director of the Laboratory for the Study of Stress, Immunity and Disease at Carnegie Mellon University, a teamof researchers found that chronic psychological stress was associated with the body losing its  ability to regulate its inflammatory response and fight infection. They found that, over a prolonged period of stress, body tissue becomes desensitized to cortisol and the hormone loses its effectiveness in regulating inflammation. As a result, disease can prosper.

The links between psychological stress and metastatic growth of disease suggest that stress management should be an integral part of cancer treatment—and possibly the treatment of all inflammatory diseases.

After I completed six weeks of Intensity Modulated Radiation Therapy (IMRT) at St. John’s Health Center in Santa Monica, California, part of the post-procedural concern was monitoring levels of inflammation. For that reason I continued to take Avodart, a drug that both inhibits the transition of testosterone to the more pernicious dihydrotestosterone and acts to keep inflammation levels down. At the same time, I began consciously to monitor my own stress levels and mindfully work to diminish them.

Practically speaking, one thing we can we do is to consider the potential benefits of “mind-body medicine,” which embraces such practices as relaxation therapy techniques, yoga, meditation and tai chi, all of which have been found to be useful as de-stressing activities.

For those of you who think of meditation as an exotic eastern exercise, check out Meditation for Dummies by Stephan Bodian (Wiley Publishing). On the other hand, some people respond well to biofeedback or hypnotherapy. Moreover, it seems that just stroking your pet cat or dog for a few minutes each day has a significant calming effect.

At the very least, adding some form of stress management to whatever conventional treatment you elect to undergo will certainly improve your quality of life—and at the same time enhance your chances of recovery.