The INDIGO Shade of Blue

BY MARK SCHOLZ, MD

Prostate cancer is a vast and complicated field. To make it more manageable, PCRI breaks it down into five separate Shades of Blue. Men with recurrent disease after surgery or radiation are in the INDIGO shade. The outlook for men with INDIGO is optimistic.  Some men can still be cured. For those who can’t, the vast majority will be able to keep their disease in check with treatment.

A rising PSA confirmed on sequential measurements is the most common sign of a relapse.

Less common signs of relapse are:

a.     A positive biopsy from the prostate fossa. The “fossa” is where the prostate gland used to be prior to surgery (also, a nodule may or may not be felt on digital rectal examination)

b.    Persistent prostate cancer detected in the gland after radiation by needle biopsy, or by scans or by digital rectal examination

c.     Prostate cancer that has been detected in the pelvic lymph nodes by a scan.

 

People need to be aware that a PSA elevation after surgery or radiation can occur for noncancerous reasons, including incomplete removal of the prostate gland after surgery, prostate tissue “left behind” in the fossa, results in low but persistent levels of detectable PSA.

After radiation, the prostate gland remains in place. Therefore, in men who have been recently treated with radiation combined with testosterone inactivating pharmaceuticals (TIP), discontinuing TIP will lead to testosterone recovery which causes PSA levels to rise. Also, radiation-induced inflammatory reactions can occur in residual prostate gland cause a PSA rise. This rather common phenomenon is called the “PSA Bump.”  It’s essential to be aware of the noncancerous causes of PSA elevation so that well-intentioned but unnecessary treatment can be avoided.  

INDIGO men will require imaging studies to determine the extent of the disease.

1.     Color Doppler or MRI is used to look for residual cancer located in the surgical fossa or in the prostate gland in men previously treated with radiation. 

2.     Pelvic MRI or CT scans are used to look for spread to pelvic lymph nodes. (Carbon 11 acetate PET scan is more accurate than CT or MRI but is still considered to be under investigation)

3.     CT or MRI of the abdomen and bone scans are used to detect the presence of more distant spread to lymph nodes outside the pelvis or to the bones. Scan-detected disease outside the pelvis or in the bones changes the shade to ROYAL. 

Treatment for INDIGO

Treatment options include observation, radiation, TIP, cryotherapy, or combinations of TIP with radiation or cryotherapy. Treatment selection is guided by four factors—the cancer location, the original Shade, the PSA doubling time and a patient’s age. By incorporating all four factors into the treatment selection process, the risk over-treating, i.e., incurring unnecessary side effects from treatment, is reduced.  Awareness of all four of the factors also helps to avoid another common mistake—under-treating—which reduces the likelihood of achieving durable remission.

An isolated “local” relapse is one that appears to be localized inside the prostate after radiation. Local relapse may be curable with cryosurgery alone.  An isolated “local” relapse in the prostate fossa after surgery may be curable with radiation alone.

When no local disease can be detected and when all the scans are clear—termed a “pure” PSA relapse—treatment selection will be influenced primarily by the rate of PSA rise. For example, if the PSA is doubling in less than six months, aggressive combination treatment with TIP plus radiation or TIP plus cryosurgery may be best.  If the PSA doubling rates is between six and twelve months, a less aggressive treatment approach with radiation alone, cryosurgery alone or intermittent TIP alone, is reasonable.  When the doubling time is greater than 12 months, observation without immediate treatment may be considered.

A patient’s age and the original shade at the time of diagnosis also need to be factored into the treatment decision-making process. Men who are more elderly can “step down” the intensity of their treatment plan by temporizing with mild forms of TIP, such as low-dose Casodex. Younger men, who prior to relapse, were in the High-Risk (AZURE) category may want to consider prophylactic pelvic lymph node radiation, a more intensive type of TIP with Zytiga or Xtandi or even chemotherapy with Taxotere.    

Side Effects of Treatment—INDIGO

The residual prostate gland after radiation is anatomically close to the rectum, urinary bladder, and the nerves that control erections. Therefore treatment with salvage radiation or cryotherapy increases the risk of additional long-term sexual, urinary or rectal dysfunction beyond what has already caused by the original surgery or radiation.

Men who are already struggling with incontinence problems from previous surgery may experience further decline in their urinary control when they undergo radiation directed at the fossa. Men who have cryosurgery for a relapse after radiation almost always become impotent. Incontinence can also occur. Surgery to remove a previously radiated prostate causes very high rates of impotence and incontinence.

Radiation to the pelvic lymph nodes can cause damage to the surrounding intestines with symptoms of cramping, diarrhea or loss of rectal control. Since the advent of intensity modulated radiation (IMRT), however, bowel damage from pelvic radiation is a much less common event.

TIP is a common component of the treatment plan for men in the INDIGO category. The severity of side effects from TIP increases when it is continued for a longer duration. As a result, intermittent TIP is very popular. The intermittent TIP protocol is to continue treatment for six to twelve month after which TIP is stopped and a treatment “holiday” is ensues—assuming the PSA drops below the 0.1/ng threshold. The next cycle of TIP is resumed when the PSA rises back to the original PSA baseline, or up to five, whichever is lower.

The most troublesome side effects from TIP are weight gain and fatigue. Maintaining a careful diet and doing regular exercise is very helpful in offsetting these problems. Low libido, however, only responds to a treatment holiday. Daily Cialis is necessary to reduce the risk of permanent erectile atrophy.

Other side effects of TIP typically respond well to the following medications:  Low-dose estrogen controls hot flashes. Osteoporosis can be prevented by Prolia, Boniva or Actonel. Mood swings stabilize with antidepressants. Breast growth is prevented with nipple radiation or Femara.  Erectile dysfunction can be counteracted with Viagra.

Finding the right type of treatment for men in INDIGO is achieved when the benefit of treatment is weighed carefully against the potential for treatment-related side effects. Fortunately, a wide variety of effective treatment is available for men with INDIGO and the majority will have their disease controlled on a long term basis.

So much for getting “the Blues” when you have prostate cancer!

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.”