The co-authors of Invasion of the Prostate Snatchers, blog alternate posts weekly. We invite you to post your comments.

Tuesday, May 27, 2014

A New Model of Treatment


Once you have been diagnosed with prostate cancer, I can’t stress too often the importance of being an active participant in your own cancer care.

All too often, the old model of care involved rushing mindlessly into whatever radical treatment your doctor recommended, often without understanding your options, and nervously hoping that the treatment the urologist chose would get rid of the cancer. The entire process was focused on the tumor; minimal attention was given to you as a person, or to the underlying factors that may have predisposed you to getting the prostate cancer in the first place. In fact you were, as we say nowadays, “disempowered”- you played no role in your own healing.

Conversely, the emerging new model of cancer care recognizes the important role you can, and should, play in your recovery. The emerging model understands that simply attacking the cancer is not enough; that when you feel empowered, when you regain a sense of control by engaging in your own recovery, it optimizes your body’s healing potential. Unfortunately, not all cancer specialists have adopted the new model.

So now that you know for sure that you’ve got prostate cancer,  what do you need to do?

First, find a cancer doctor who gives you confidence, listens to you, and who understands that you need to take the central role in your treatment choices and recovery process.  Then, do your own “due diligence” thoroughly research all your treatment options, check, and recheck with a second opinion your doctor’s recommendations, and  only then, choose the treatment program you believe in.

Equally important, your role in your recovery doesn’t stop with your choice of treatment. Cancer survivors agree that taking charge of their entire health and well-being by focusing on nutrition, exercise, support-and-attitude, enhanced their immune system and laid the foundation of the healing process.

The emphasis on lifestyle choices has been one of the most significant shifts in cancer care in the last decade. A cancer diagnosis is a heads-up to launch a nutritional makeover, and a regular, moderate exercise program. Nothing extreme is called for.  But it’s not enough to depend solely on medical treatment to fight your cancer.

When it comes to support and attitude I realize I’m getting into territory where most men are inclined to think, “B.S!”  But plenty of research demonstrates the benefits of supportive friendships, and intimate relationships that support and nurture us. And a great many cancer survivors report that they a direct link between a positive attitude and successful recovery.

The emerging model of cancer care recognizes that psychological and emotional states are as important to your healing as nutrition and exercise. A sense of optimism and hope strengthen and inspire the will to live, and actually impact the body on a physiological level. Inevitably there will be times during treatment when you feel fearful, depressed, exhausted and yes, hopeless. When that happens, instead of going into denial, allow yourself to feel the feelings, but refuse to get stuck in negativity. Surround yourself with supportive friends, believe in your treatment, and know that you are making lifestyle choices that support your healing.

It cannot be stated too often: reclaiming a sense of being in charge of your life and your health provide a vitally important foundation for the healing process— and the rest of your life.

Tuesday, May 20, 2014

Introduction to Hormone Therapy for Prostate Cancer


Testosterone is the primary male hormone. It comes mostly from the testicles and to a lesser degree, from the adrenal glands. Testosterone causes the common male characteristics such as bigger muscles, facial hair growth and increased sex drive. Testosterone is also essential for prostate cancer to grow.
Why Blocking Testosterone Kills Prostate Cancer
The prostate gland, located near the bladder, makes semen. Prior to puberty the gland is only the size of a peanut. However, when the testicles begin making testosterone, the prostate comes to life and grows to the size of a walnut. The cells of the prostate, therefore, require testosterone to proliferate. Since prostate cancer originates from the prostate gland, the cancer also depends on testosterone.
Hormonal therapy works by blocking testosterone. When prostate cancer cells are deprived of testosterone they commit suicide in a cell death process called apoptosis.  The amount of cell death in early-stage prostate cancer is usually dramatic.  Not uncommonly, when men are pretreated with potent forms of hormonal therapy, there is no residual cancer after surgery. More typically, there is a dramatic reduction in the number of cancer cells, but not total elimination of the cancer.
The mechanism for testosterone to stimulate cancer growth occurs through the activation of a multifaceted protein called the androgen receptor.  Before binding with testosterone the androgen receptor is inactive. Once the receptor comes into contact with testosterone, the activated androgen receptor is transported into the nucleus of the cell where it stimulates DNA.  As a result, a plethora of cell-growth-enhancing proteins are synthesized that stimulate cancer growth and progression.

Hormone Therapy Comes in Many Form
Prior to the advent of modern medications, hormone blockade was accomplished by surgical castration. These days, testosterone is blocked with shots or pills. Agents that block testosterone by inhibiting the pituitary gland are Lupron, Zoladex, Firmagon, Eligard and Trelstar.  Medications that work by interposing themselves between testosterone and the androgen receptor to block its activation are Casodex, Nilutamide or Flutamide.  A third milder type of hormonal agent, the 5-alpha-reductase inhibitors, such as Avodart and Proscar, work by inhibiting the chemical conversion of testosterone into its more potent form, dihydrotestosterone (DHT).

Recently the FDA approved two new, and more potent, hormonal agents, Zytiga and Xtandi. Their increased anticancer efficacy was demonstrated through prolonged survival in men whose cancer became resistant to Lupron. Zytiga and Xtandi work by different mechanisms. Zytiga inhibits cancer cells from making their own testosterone. Xtandi works by blocking the activity of the androgen receptor.

The Nitty Gritty of Treatment Selection
The most potent anticancer action is achieved through complete blockade with agents from different functional classes administered together for a prolonged period of time. Therefore, the variables that affect the intensity of hormone blockade treatment are:  1. the type of medicine; 2. how many medicines are used; and 3. how long the medications are continued.  Of course, medical skill and experience is required to fine-tune the selection and duration of therapy.  Nevertheless, here is a brief presentation of some rough guidelines.
1.    A short course, say three to four months, to shrink the prostate or to improve cure rates in men with intermediate-risk disease (Teal Shade of Blue) undergoing radiation

2.    A short course of four months to improve cure rates with radiation in men with intermediate-risk disease (Teal Shade of Blue)

3.    An intermediate course (6-12 months) for treatment for intermediate-risk disease (Teal Shade of Blue) as a sole form of therapy

4.    A long course (18-24 months) to improve cure rates in men with high-risk (Azure Shade of Blue) prostate cancer undergoing radiation

5.    An intermediate to long course in conjunction with radiation to improve cure rates in men with a rising PSA after surgery (Indigo Shade of Blue) who are undergoing salvage radiation

6.    Intermittent use to suppress a rising PSA after surgery or radiation (Indigo Shade of Blue)

7.    Intermittent or continuous use to treat men with metastatic disease (Royal Shade of Blue)

8.    Salvage treatment with Xtandi or Zytiga to control disease in men on Lupron who have progressive disease (Royal Shade of Blue) 

Over the last ten years the medical community has been roiled by the discovery that some forms of prostate cancer are truly harmless, raising a serious concern about men receiving surgery and radiation they don’t need. However, overtreatment with hormone therapy also occurs. The overriding goal is to use a hormone therapy approach that achieves a maximum anticancer benefit while minimizing side effects as much as possible. Treatment always has to be personalized so the intensity and duration of treatment is appropriate for each individual’s specific situation.

Tuesday, May 13, 2014

How the Caveman Lived


My concern—and hence our looking backward in time— is with the beneficial impact of reduced caloric intake on retarding, and in some cases reducing, the spread of prostate cancer. Dietary restriction, as I noted in our last blog, seems to trigger an ancient strategy written into all animal genomes, that when food is scarce, resources are switched from breeding to tissue maintenance.

In recent years biologists had considerable success in identifying the mechanisms by which cells detect the level of nutrients available to the body. One goal now is to find drugs that trick these mechanisms into thinking that famine is at hand. The positive results even include evidence that the immune system benefits from reduced caloric intake, and that there is a connection between brain function and adipose tissue in relation to obesity.

A recent study in PLOS Biology discusses the relationship between LDL, hunger, leptin, the brain, and the benefits in a number of areas: there is a ubiquitous receptor in the brain, adipose, and liver called the low-density lipoprotein receptor-related protein 1 (LRP1) which regulates leptin signaling. LRP1 has some of the following properties: lipoprotein metabolism, neurotransmission, synaptic plasticity (adaptability of the neuronal junctions), clearance of beta amyloid. (note the variant epoE4 of epoE is associated with Alzheimer's Disease), and basic cell survival.

There is now a small subculture whose members seek good health through a selective return to the habits of their Paleolithic ancestors.  Or as they sometimes refer to themselves, dietary cavemen. Their interpretation of this metaphor involves fasting between meals to approximate the lean times that his distant ancestors faced between hunts. Vegetables and fruit are appropriate, but they avoid foods like bread and pasta that were unavailable before the invention of agriculture. These Dietary Cavemen are convinced that the human body evolved from a hunter-gatherer lifestyle, and that our survival in today's world depends weaning ourselves off many millenniums of bad habits.

Now imagine if you will that you are a caveman, out innocently picking berries when you suddenly come nose to nose with a saber-tooth tiger. While you were simply gathering, the tiger was actually hunting, and the sight of you makes his mouth water.

It is our good fortune that millions of years of evolution have endowed you with a set of responses that take over automatically in the event of an emergency. Faced with the tiger, your hypothalamus sends a message to your adrenal glands and within seconds, you can run faster, hit harder, hear more acutely, think faster, and jump higher than you could only seconds earlier.

The transformation is instantaneous. In a heartbeat, so to speak, your heart is pumping at two to three times the normal speed, sending nutrient rich blood to the major muscles in your arms and legs. The tiny blood vessels (called capillaries) under the surface of your skin close down so you can sustain a surface wound and not bleed to death. Even your eyes dilate so you can see better.

In the same instant, all functions of your body not required for the life-saving struggle about to commence are shut down. Digestion stops; ditto sexual function; even your immune system is temporarily turned off. If necessary, excess waste is eliminated to make you light on your feet.

Your suddenly supercharged body is designed to help improve the odds of survival, with the result that you narrowly escape death. Once the danger is past, you find a safe place to lie down and rest your exhausted body. Much the same situation appears to apply when your attacker is prostate cancer.

In my next blog I will consider the elements of a diet that increases the possibility of such survival.

Tuesday, May 6, 2014

Selecting Prostate Cancer Treatment


"You mean you have never heard of diffusion-weighted imaging” Exclaimed a recently-diagnosed prostate cancer patient to his doctor.  How could his doctor be unacquainted with this important aspect of modern prostate imaging? It’s shocking when a patient realizes he possesses more medical information than the “expert.” 

No One Can Be an Expert in Everything
Actually, in this modern era, this situation is being encountered more and more frequently. It’s not so surprising when considering the explosive growth rate of new medical information. It’s humanly impossible for anyone to stay abreast of every new medical development.  For example, even though urologists “specialize” in diseases of the urinary system, their area of responsibility demands expertise in a wide variety of unrelated but important areas such as urinary infections, prostate enlargement, prostate infections, sexual dysfunction and kidney stones. They also have to be expert at the surgical treatment of such problems as congenital defects, bladder cancer, testicular cancer and kidney cancer… just to name a few.

Prostate Cancer by Itself is Quite Complex
Prostate cancer alone is intricate enough to keep a specialist occupied full time. For example, simply staging prostate cancer is complicated. Prostate cancer staging uses a multimodality profiling system that estimates the likelihood of microscopic metastases outside the prostate using PSA, Gleason grade, and a percentage of cancer-containing biopsy cores.  Now, new imaging techniques are providing further information about the size and location of the cancer within the prostate gland. And even more recently molecular profiling has become commercially available.  Staging prostate cancer properly has become a continually developing art form.

Seeking Advice—Delivered from a Level Playing Field
Equally important is the need to seek out unbiased treatment advice. Unfortunately, the process of rendering advice about treatment options is usually very slanted. Urologists (who are surgeons) usually recommend surgery.  Radiation therapists usually recommend radiation. This is not to imply that these physicians have less than the best intentions.  Over time they just become convinced that what they do is the best option for their patients who are consulting them.

What You Don’t Know Can Hurt You
The number of treatments available for men with newly-diagnosed disease is rapidly expanding.  For example, what was previously known simply as “radiation” now includes IMRT, Proton therapy, Cyberknife, two types of Brachytherapy as well as various combinations of these different radiation modalities.  Hormone therapy options have now expanded beyond traditional Casodex and Lupron to include Zytiga and Xtandi. The management of the potential side effects of hormone therapy requires special training in diet physical fitness, bone integrity and sexual health to limit the risk of lingering damage after treatment is completed. These days, relapsed or advanced prostate cancer requires physicians who are conversant in genetic typing, modern PET scans, immunotherapy and injectable radiation.

Every Journey Begins with a Single Step
So newly diagnosed prostate cancer patients are faced with daunting situation. Clearly there is no simple answer to this tangle of complicated issues. However, the newly diagnosed cancer patient is far from helpless. He has two overriding responsibilities. First, he must learn as many facts as possible by getting thoroughly educated about the different treatments for his specific type of prostate cancer. Second, he must use discernment in the selection of which physicians to consult.

There is Time to Learn
With prostate cancer there is rarely a need to rush into making a treatment decision because it is usually slow growing.  There is plenty of time for the shock of diagnosis to wear off, giving you enough time to get educated about the scientific facts.  Published studies comparing outcomes are available. The PCRI in particular publishes articles that translate scientific information into a patient-friendly format.  Ultimately, all claims about treatment should be supported by references published in the scientific literature.  Selecting treatment for prostate cancer is a high stakes proposition, potentially risking sexual function, urinary function, even life itself.  I want to encourage patients to take a leadership role in the treatment-selection process.