Sir Spheres for Liver Metastases from Prostate Cancer

BY MARK SCHOLZ, MD

Cancer that spreads outside the prostate gland is what makes prostate cancer dangerous. Metastatic prostate cancer cells cause malfunction by impeding normal function. Some organs, like lymph nodes for example, continue to function quite nicely, even if the degree of cancer spread is extensive.  Lymph node spread, therefore, is the least dangerous form of prostate cancer metastases.  At the other end of the spectrum is the liver, which is far less tolerant.  The seriousness of bone metastases, the most common site of prostate cancer spread, lies about half way between that of node metastases and liver metastases.


The earliest stages of metastases are microscopic and therefore invisible even with the best available technology. To be detected with the best available PET scan technology, small tumors must measure more than 1/8 of an inch across. For detection with standard CT scans and MRI scans, more than a half-inch sized tumor is necessary. Since the presence of metastases is such a defining issue when describing a cancer’s character, men who are newly-diagnosed are labeled as low, intermediate or high-risk depending on their estimated likelihood of micro-metastatic disease. Liver metastases are extremely rare at the time of initial diagnosis of prostate cancer. When they occur it is usually after many years of ongoing treatment for known metastatic disease in the bone.


Prophylactic treatment with hormone therapy, chemotherapy or radiation to treat the possibility of micro-metastases is common for high-risk prostate cancer and occurs maybe half the time in intermediate-risk prostate cancer. The goal is to cure the micro-metastases at an early stage when they are most susceptible to eradication, thus preventing the future development of detectable metastases which is what makes cancer life threatening.


When talking about prostate cancer, even though this is a blog about metastases, it should always be remembered that many common types of prostate cancer never spread. These low grade “cancers” are genetically distinct and represent a totally different category of disease.  However, when discussing the type of prostate cancer that is capable of metastasis, the following factors impact how dangerous it is:

1. The site of spread.
2. The extent of spread
3. The tumor cell growth rate
4. The efficacy of available treatment

As noted above, the liver is far less tolerant to metastatic invasion than bone or lymph nodes.  In addition, because liver metastases tend to occur in men with advanced disease, tumor growth rates tend to be brisk. Also, the most commonly administered treatments, hormone therapies and chemotherapy, have often already been tried before liver metastases first develop. The advent of liver metastases, therefore, usually represents a very serious and life threatening issue.


Liver metastases may first be suspected when standard blood tests such as ALT, AST or ALP which are components of a hepatic panel blood test, register outside the normal range. Investigation into their cause often leads to doing a CT scan or MRI scan of the abdomen and pelvis to confirm the presence of disease in the liver. Alternatively, a scan may detect abnormal spots in the liver during routine periodic scanning that is being performed as regular surveillance.


Hormone therapy with Lupron, Zytiga and Xtandi, or chemotherapy with Taxotere, Jevtana and Carboplatin, is the standard approach to treatment for liver metastasis.  However, these treatments may have already been tried or may no longer be effective.  Since liver failure is tantamount to death, prostate cancer growth in the liver needs to be stopped immediately, regardless of how the disease is faring in the bones or nodes.


Much that has been learned about the treatment of liver metastases comes from reviewing common methods for managing metastatic colon cancer. The liver is the cancer’s preferred site of metastatic spread for colon cancer.  Treatments that have been employed include surgery, radiation and blockage of the blood supply to the liver by embolization of the arteries, all with variable success.  More recently, radioactive microspheres injected directly into the tumor, called SIR-Spheres, have shown notable efficacy with very tolerable side effects.


Prostate cancer and colon cancer are similar in that they are both adenocarcinomas which means they are derived from glands. Therefore, they are likely to have similar susceptibility to radiation.  As such, we have been administering SIR-Spheres to a limited number of prostate cancer patients with liver metastases.  Results have been encouraging with a notable improvement of survival compared to our historical experience treatment patients with liver metastases without SIR-Spheres.  Our preliminary results using SIR-Spheres in six patients is being presented at the 2016 Genitourinary Cancers Symposium - San Francisco in January 2016.

Discussing a Painful Subject: Fear of the Process of Dying

BY MARK SCHOLZ, MD

Many men tell me that they fear the process of dying—suffering and experiencing pain—more than they fear death itself.  While I am no fan of pain, as a medical oncologist I have been responsible for the treatment of hundreds of patients with terminal cancer. I have learned that with good communication and proper medical management, pain can almost always be effectively controlled.

However, when reviewing the results of a recent patient survey at a meeting sponsored by Bayer Pharmaceuticals with a number of patient advocates, healthcare experts, and other physicians, it became sadly apparent that many patients are not being managed expertly. The survey indicated that many men with advanced cancer are suffering needlessly, mostly due to a lack of good communication with their doctors.

This survey of 410 men with advanced prostate cancer reported that two-thirds of men are trying to handle their pain by ignoring it!  One-third of all the men surveyed felt that acknowledging pain made them more fearful, raising anxiety about the possibility that their cancer is progressing.  A quarter of the men said, “It was difficult to talk about their pain,” relating that such discussions made them feel weak.

In other words, these men are using a common psychological defense mechanism called “denial.” One thing I have learned from years of experience treating patients is that denial can be a wonderful approach, but only if the situation is totally hopeless. I have observed men who appear to be in denial who are quite happy even when everyone knows that they are dying.

On the other hand, denial is a serious problem if what is being denied, in this case pain, can be fixed or remedied.  If men who are in denial fail to discuss pain with their doctors, their access to a solution is blocked.

Using denial can effectively control pain for short periods of time, however, using it on an ongoing basis is psychologically exhausting. Also, while denial might work for the patient, it can’t fool their surrounding loved ones. They see the effects of pain in the patient manifesting as fatigue, depression, inactivity, impatience, insomnia and hopelessness. Ultimately, the caregivers who are not shielded by denial end up suffering even more than the patient.

Cancer patients experience pain from multiple causes, not just their cancer.  Invariably, life itself is painful.  However, most types of cancer pain can be resolved.  The first step is to acknowledge its existence. The second step is to diagnose whether the pain is cancer-related. In the prostate cancer world, cancer-related pain is usually the result of bone metastases. Of course, not all bone pain is from cancer and not all bone metastases cause pain. If a man has pain in one of his bones and a bone scan shows a metastatic lesion in the exact same area as where the pain is occurring, then the probability is high that the pain is cancer-related.

The third step, once it has been confirmed that the pain is cancer-related, is to undertake the appropriate treatment. How to treat cancer-related pain is a topic big enough for another blog all its own. In my next blog I will also elaborate further on the correct medical approach used to distinguish cancer pain from non-cancer pain.

Someone has said, “Not knowing what to do is the worst kind of suffering.”  Helping men find a workable solution for pain not only relieves their pain, but it also releases them and their caregivers from the uncertainty and anxiety that comes from not knowing what to do.   

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.

Osteoporosis Basics for Men

BY MARK SCHOLZ, MD

Osteoporosis is the medical term for “weakened bones” resulting from the slow leaching of calcium over time. Osteoporosis is incorrectly thought to happen only in females. However, one-third of hip fractures occur in men and are associated with higher mortality rates in men with prostate cancer. Calcium loss is a silent process until a fracture suddenly occurs. Common fracture sites are spine, rib, wrist, and hip. Compression fractures of the spine can be quite painful and result in loss of height with forward curvature of the spine.  

Cause of Osteoporosis
Just as there is a link between lack of estrogen and osteoporosis in women, studies show that there is also a relationship between a lack of testosterone and osteoporosis in men. Other causes of osteoporosis are thyroid or parathyroid hyperactivity, excessive alcohol, cortisone, lack of exercise, low vitamin D and low calcium intake. Osteoporotic fractures also occur more frequently in men taking testosterone inactivating pharmaceuticals (TIP).

Detecting Osteoporosis
Osteoporosis, when it is diagnosed at an early stage, is easier to treat. Unfortunately, the most common scanning technique for diagnosing osteoporosis, the DEXA scan—grossly underestimates the degree of bone mineral loss from the spine in men. Why? Because almost all men over fifty have calcium deposition in the ligaments surrounding the spine. When the DEXA is used to measure bone density, the excess calcium in the ligaments causes an incorrectly “normal” bone density reading.

Fortunately there is a better technique called QCT that measures bone mineral density in the center of the vertebral column. Awareness of the DEXA scans' limitations in men is under appreciated by many physicians even though these limitations have been well documented in a study from Massachusetts General Hospital. In this study 41 men underwent both DEXA and QCT scanning. QCT detected osteoporosis in 26 of the men (63%) but DEXA only diagnosed it in two (5%).

Preventing Osteoporosis
Osteoporosis treatment begins with an exercise program. Supplementation with calcium and vitamin D should also be considered routine. We recommend 500 mg of calcium at bedtime and a starting dose of 1,000 units of Vitamin D. Blood levels of vitamin D should be checked and oral intake of vitamin D adjusted accordingly.  Studies show that using TIP intermittently (compared to continuous TIP) results in less bone loss. Treatment with bisphosphonates or denosumab (see below) can prevent TIP-induced bone loss.

Osteoporosis Medications
Osteoporosis can be reversed with bisphosphonates or denosumab. Normal bone metabolism is a balance between the rate of bone breakdown and the formation of new bone. Osteoporosis occurs when the formation of new bone lags behind the rate of bone breakdown. Bisphosphonates and denosumab function by slowing the rate of bone breakdown, allowing the osteoblasts, the cells that form new bone, to increase the net amount of bone matrix.

Oral Medications: Boniva, Actonel and Fosamax
Bisphosphonates come in both oral and intravenous forms. Absorption into the blood of oral forms is enhanced when they are administered with an empty stomach. The most common side effect from oral bisphosphonates is stomach or esophageal irritation which can be minimized by maintaining an erect position for an hour after taking the drug.

Intravenous Bisphosphonates: Zometa (zolendric acid)
Intravenous administration of Zometa has the advantage of bypassing the stomach thus avoiding concerns about stomach irritation. Also with the intravenous approach 100% of the drug gets into the system as compared to the oral preparations that are only 1-2% absorbed. The most common side effect from Zometa is a brief flu-like muscle soreness lasting a day or so. These symptoms do not usually recur on subsequent infusions. For the treatment of osteoporosis the infusions are repeated every three to six months.

Denosumab Injections: Prolia and Xgeva
Like Zometa, denosumab inhibits the osteoclasts, but by a different mechanism.  Denosumab is marketed in two strengths for injection. A half-dose shot called Prolia is administered every 6 months for osteoporosis.  A full dose shot called Xgeva is given monthly for cancer metastasis to the bone.

Medication Induced Jaw Problems: Osteonecrosis
Zometa and denosumab and to a much lesser degree, oral bisphosphonates can rarely induce damage to the jaw, a condition termed osteonecrosis.  The risk of developing osteonecrosis is much higher when a tooth is extracted. When osteonecrosis occurs, the gum tissue recedes leaving exposed bone which is susceptible to recurrent infections. The risk of osteonecrosis becomes higher as the lifelong cumulative medication dosage increases. In my experience, osteonecrosis almost always reverses, albeit slowly, after the medication is stopped.

 

Bone Metastases

Zometa and denosumab are also FDA approved to treat cancer that has metastasized to bone. Their anticancer effect is believed to occur because by inhibiting bone breakdown, cancer cell access to the growth factors and cytokines that are normally locked up in the bone matrix is blocked. So these medications that inhibit bone turnover by stopping osteoclast activity not only help osteoporosis but also help to prevent bone metastases from progressing.

Final thoughts

Eventually some degree of osteoporosis occurs in most men as they age.  Regular exercise, calcium and vitamin D help delay bone loss.  Bone density screening in men should probably begin when they are in their 60s, so the condition can be detected early.  Bone density augmentation with denosumab or bisphosphonates seems to be more effective when osteoporosis is not too severe at the start of therapy.   

 

 

Harmony & Spirituality Practice Cultivating “Wa”

BY RALPH BLUM

Many years ago, I was invited to attend a breakfast fund raising event at the Bel Air Hotel in West Los Angeles. Ted Turner was attempting to squeeze donations from a room full of Hollywood moguls. The private dining room was filled with sunlight, and I remember sitting there, bored, zoned out and forking segments of my eggs Benedict around, when Turner’s Savannah chain gang growl poked a hole in my reverie: “I tell you, it’s spiritual,” he exclaimed. “And you know how I know it’s spiritual? Because I paid cash money for it.”

To this day, I have no idea what “it” was. But Turner’s logic—his working definition of “spiritual”—made me smile and stuck with me to this day. And while I’d rather steer the long way around when it comes to spiritual matters in general, I have become a devoted fan of harmony, as in feeling at peace. What the Japanese call Wa. Bottom line: I try not to regret anything that has already happened, and not to worry about what might happen. And in a way, I think this has played a role in my coming to terms with prostate cancer.

When discord hobbles me, throws off my vital signs, fogs up my reasoning, I feel it has a definite impact on my immune system. Efforts to counter mindless anxious behavior through breathing and light meditation may help, but in my case, only minimally. Instead, whenever I encounter discord, or more to the point, when I catch myself creating or contributing to the dissonance, I retreat from that discord as fast as I can. This happens in three steps:

First, I catch myself, recognize what’s happening, mark the moment: Blum, you’re doing it!

Second, I apply the brakes, stop what I am doing as best I can. Do whatever it takes to get into reverse and back away. I think of this step as “circuit breaking.”

Third, I substitute different behavior, consciously find a better way to look at what is disturbing my peace and serenity, my wa.

Example: Despite my expectations, my PSA has risen. And I’m suddenly scared s—tless my next Gleason score will have deteriorated from 3 + 3 to 3 + 4, and that I will start feeling pressure to “act,” to begin radical treatment. As a Remedy, I hold a conversation with myself,

Me:  How many years has your cancer been in the seminal vesicle?
Myself: About six.
Me: So six years out of the capsule?
Myself: Yup.
Me:  Is the cancer in your bones?
Myself: No.
Me: Well, how about the lymph system?
Myself: Don’t think so.
Me: So And how old are you?  

Myself: I’ve been around the sun 80 times.
Me: So in 10 years you’ll be 90?
Myself: You might look at it that way.
Me: And your cancer, basically untreated, has been stable for almost a quarter of a century.

Myself: Something like that.

Myself: So given hour history, what kind  of prognosis would you expect for the years to come. . . ?

The Q and A continues until I find myself relaxing, counting my blessings. This sounds like pretty simple-minded stuff. But not getting caught in the quicksand of negative emotions or behavior that is toxic, just staying in the “here and now,” is a spiritual practice that helps maintain Wa. I do my best to stay in the present moment. But when I slip, ASAP after the fact I review what has happened. I replay what happened in my mind with different features, focus on a better way to handle it next time. And some day perhaps I’ll find out what spiritual stuff Ted Turner paid cash money for. And place an order for myself. A baseball team. An ocean going racing yacht. A date  withJane Fonda. CNN. A day at the beach. . .

To each his own kind of Wa.

More to come.