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

Tuesday, February 9, 2016

Sometimes Going Fishing with the Doctor Isn’t So Much Fun


When you go fishing, you can bring up all kinds of things besides fish—old rubber boots, pieces of a broken net and discarded trash. Once I caught an eel.  You never know what you will drag in when you drop your line overboard. 

The same analogy holds true for diagnostic testing in the medical world. Investigative studies can have unintended consequences. Of course the studies seem justified at the time. We presume that the doctor is being rightfully conscientious by using all the tools of modern medicine, “fishing” for the right answers.

Dr. Scholz asked me to relate the story of an extended medical fishing trip that started with my dermatologist for my annual, too-much-California-sun screening. While talking to my dermatologist, I mentioned some itching on my arms.  He gave me a few samples of lotion and referred me to my internist for further evaluation and blood testing to “make sure” the itching wasn’t a symptom of something more serious. My internist ordered some lab work (which was normal) but recommended that I have a routine chest x-ray since itching can be associated with lung cancer.  This suggestion may have occurred to him because he knew that lung cancer caused my mother’s death.  Since I hadn’t had a chest x-ray in years, I thought, “why not?”

In retrospect, the chest x-ray may have been a mistake.  Because that’s when the boat left the dock and the fishing really began in earnest.  Two days later, the chest x-ray revealed a “suspicious” spot on my lung. So, to identify what it was, a CT was ordered.  The spot was benign. “Whew!” It was only a bone artifact (the end of a rib visible due to the angle of the x-ray).  But…. the CT scan showed a suspicious spot in the liver, which shouldn’t have been there and was large enough to be of concern.  So, an MRI of the abdomen was ordered.  The MRI revealed that the liver spot was nothing but a harmless hemangioma, a collection of blood vessels that are common and mean nothing.  Another big relief. But…. guess what else the MRI found?  At the top end of the scan in my lower neck, it showed some abnormalities in my thyroid “that could not be ignored.”  So, a thyroid ultrasound was ordered.  It revealed two nodules that looked benign and would have been ignored completely if there had only been one.  But the only way to really know what types of cells the nodules consisted of was by doing a needle biopsy or an exploratory surgery. 

Yikes!  When would I get off this merry-go round?  Who could imagine that simply mentioning some itching to a dermatologist would lead me face to face with the possibility of thyroid cancer.  However, the doctor was kind enough to offer another alternative.  Because of the known, slow-growth rates of typical thyroid cancers, active surveillance and re-testing at future intervals was also an option, and the one I have selected.

So, six months later, a second thyroid ultrasound—my fifth imaging test—showed no changes from the previous test.  The fishing trip finally seems to be over.  I am back in the waiting pool anticipating next year’s medical expedition, much the same as the next round of prostate screening tests I am scheduled to undergo early in 2017.  Now, routinely surveilling my thyroid is going to be just like my prostate.  If next year’s fishing trip doesn’t run down any new tributaries and is uneventful, I expect it may even be possible to extend by a year or two the time the frequency of testing.

My medical fishing trip was not much fun.  Personally, I’d rather spend my time working, biking or walking, or doing almost anything besides waiting for the next set of results from the last odd thing that showed up unexpectedly. But life goes on and it isn’t possible to know precisely how it will end.  My recommendation—Give careful consideration to your doctor’s invitation to go fishing.  Take control over your medical destiny and ask you doctors if close surveillance is an alternative to further testing. 

Tuesday, January 26, 2016

Crila, A Solution to Old Men’s Urinary Problems?


As we get older, we run into all kinds of difficulties.  Poor hearing, sexual dysfunction, memory problems and arthritic joints, just to name a few. Bladder issues in particular can be troublesome, interrupting sleep, making us dread long drives or forcing us to visit the bathroom at an inopportune time.
As a prostate oncologist taking care of many men who are in their 60s and 70s, it’s no surprise that I hear a lot about urinary difficulties. These problems are often thought to result from prostate enlargement, otherwise known as BPH. The swollen gland ends up pinching the urinary passage way (called the urethra).  Slow urination and incomplete emptying of the bladder are the result. 
Prostate gland enlargement with incomplete bladder emptying can frequently be solved with common prescription medications like Flomax, Rapaflo and Uroxatrol which relax the muscles in the wall of the urethra and help to open up the passageway.  Proscar and Avodart can shrink the prostate but they also tend to shrink your libido. The most popular treatment is a nonprescription—Saw Palmetto an herbal product that works by relaxing the muscles in the urethra.
However, after doing thousands of color Doppler ultrasound examinations, which by the way is the most precise way to measure the size of the prostate, I have learned that BPH is a less common cause of men’s urinary problems. So what is the primary reason for men’s urinary frustrations? Prostatitis—low grade inflammation of the gland with secondary irritation. What causes prostatitis?  In a minority of cases it is due to bacterial infection. When this type of prostatitis occurs it may improve with antibiotics. But for the vast majority of cases we simply don’t know the cause.  Virus or autoimmune causes have been theorized but nothing has been proven. Our ignorance, however, has nothing to do with its prevalence. It is not widely realized, but almost all men have some degree of chronic inflammation in their prostate glands.
Though we don’t know the precise etiology, anti-inflammatory medications can be quite effective at alleviating the symptoms of prostatitis. Over the counter products like Aleve and Motrin are effective. Celebrex, is a prescription anti-inflammatory agent that is billed as having less stomach irritation. However, unless the pills are used continuously, the inflammation comes back.
Recently, I have been introduced to a natural anti-inflammatory substance discovered in the flower of the Crila plant. Several of our patients tried Crila with notable improvement to their urinary symptoms. So far we have not observed any side effects.  To investigate Crila’s effectiveness further, I have petitioned the manufacturer to provide a 3-month supply of Crila to 15 of our patients at no cost. Patients who have problems with frequent urination, a strong sense of urinary urgency or have to get up frequently at night to urinate may want to consider contacting Sabrina in our office about their eligibility for participating in this clinical trial. 

Tuesday, January 12, 2016

The Amazing Gleason Score


Everyone is excited about the latest craze in medical technology—genetic analysis of tumor cells, which I’ll call GAT for short. The scientific progress that has been made with GAT in my opinion is the second most exciting area of advancement in medical technology today (see further below for more about the first most exciting area). GAT technology is already being commercialized for use in the medical marketplace in products like Prolaris and Oncotype. This technology is able to predict the aggressiveness of prostate cancers, enabling us to differentiate between the men who need immediate treatment and those who can postpone treatment safely.

The predictive power of GAT is certainly exciting, but there is already an effective form of genetic testing available that has been around for more than 40 years, the Gleason scoring system. The Gleason system relies on the visual appearance of cells under the microscope to draw conclusions about their inner genetic makeup. In the medical world, using the visual appearance of the cancer cells is called phenotypic analysis. GAT is genotypic analysis.  Drawing conclusions about underlying genetic makeup by simple visual assessment is a pervasive in human experience.  In courtship, we rely on phenotypic analysis of the underlying genetic make-up of potential spouses to form an opinion about their suitability as potential mates.  Perusal of the genetic pool of immediate family members provides further insight.

So how can Gleason score draw conclusions about the underlying genetic potential for tumor aggressiveness simply by looking at the appearance of cells under a microscope?  The answer is to do a comparison of the visual appearance of cancer cells with the appearance of normal prostate cells. Normal cells in the prostate perform varied functions but still work together as a team.  Specifically, healthy cells form into definable structures called glands.  In these glands some cells manufacture prostatic fluid, a complex liquid comprising the ejaculate for the sperm to swim in.  Other cells organize to form ducts, a piping system to drain the fluid from the outer periphery of the gland and channel it into the middle of the prostate so that a large quantity of fluid can be expelled through the urethra at just the right moment.  All of these different cells work as a team and coexist in the prostate functioning together in a structured glandular arrangement.   

When a trained pathologist looks at tumor cells under the microscope he grades them by the degree of cellular disorder.  He is asking himself the question, “How much do these cells retain the normal glandular characteristics of the prostate gland?”  If a cross section of the tumor looks like an unbroken sheet of uniform cells, the cancer is high-grade; the cells have lost their ability to cooperate with each other and form glands. The cancer cells have been honed down into little race cars with only one mission, to aggressively pursue its own replicative destiny. When tumors have this appearance they are graded as a Gleason 9 or 10.  On the other hand, if the appearance of the tumor shows residual glandular components, it is less aggressive, perhaps a Gleason 7.  Gleason 6 “cancer,” the type the one that never spreads, looks almost like normal prostate gland tissue.  
Predicting future tumor behavior is obviously very important. How fast will it grow?  Is it likely to spread? How well can it be expected to respond to treatment?  As a result of decades of experience, doctors have learned to use the Gleason scoring system to accurately predict the long-term outcome in individual patients. The new GAT tests represent an important additional refinement, further enhancing our ability to predict the future behavior of an individual cancer. GAT holds one even bigger promise.  In the future we believe GAT testing will be a powerful aid in the selection of targeted therapy, i.e., picking cancer treatments with anticancer activity tailored to individual tumor types.  This hope, however, will have to be postponed until our limited armamentarium of effective treatments is further expanded.    
Now, what is it that I consider to be the most exciting area of medical progress? Since I am an impatient type of guy, someone who is looking for quick results, I find immunotherapy more exciting than GAT. To fully exploit the potential of GAT we will need to invent new pills for each of the myriad of genetically different tumor types. Immunotherapy on the other hand comes with its own “built-in” GAT system that enables it to target the unique genetic signature of individual cancer cells. The immune system is so smart, all we have to do is “flip the switch on” and starts cranking out genetically targeted anticancer therapy. Recent developments in the field of immunology are truly mind-boggling and hold promise for a big revolution in cancer therapy within the next 5-10 years.  I’ll try to address some of these recent advances in an upcoming blog. 

Tuesday, December 29, 2015

Predicting Prostate Cancer’s Future Behavior


Developing an accurate prognosis, i.e., predicting how a man’s cancer is likely to behave in the future, is the first and most important step toward optimal care. Future predictions are often looked at with some suspicion. With prostate cancer, however, our power to anticipate future cancer behavior is quite accurate unless there is a lack of thoroughness in gathering information.

The Size of the Tumor

Tumor size is a universally important prognostic sign for almost all types of cancer including prostate cancer. The method for incorporating tumor size into the Anthony D’Amico’s staging system relies on the degree of PSA elevation, the tumor grade and on how the prostate "feels" with the finger of a trained practitioner. These indicators are useful but don’t incorporate information from modern imaging. Imaging provides accurate information about tumor size and the presence or absence of extracapsular extension. These are very powerful prognostic predictors and it would be foolish to disregard their importance. As things stand presently these indicators are often used to divide the low, intermediate and high risk categories into "favorable" and "unfavorable" subcategories, each with a different spectrum of recommended treatment options.

Knowing Past Treatments Tells Something about Future Prognosis
Historically, since the total number of available treatments is relatively limited, practitioners have used a sequential "trial and error" treatment methodology that administers the standard treatment options in a fairly predictable sequence. For example, it is not uncommon for men to start with surgery or radiation. When a relapse occurs, standard hormone therapy (Lupron) is often started and given intermittently or continuously. Hormone therapy usually controls the disease for an average of 10 years. When Lupron stops working, immunotherapy with Provenge is usually follows. After Provenge, more potent hormone therapy with Xtandi or Zytiga is started. If these two agents prove ineffective, chemotherapy with Taxotere or radiation with Xofigo would be considered next.

The whole point of presenting the treatment sequence described in the previous paragraph is to convey the idea that the number of previous treatments communicates important information about that patients’ future prognosis. Having "failed" Lupron, for example, bespeaks of a much more worrisome prognosis compared to the situation where Lupron continues to be effective.

Response to Lupron, The Mother of All Metrics
The quality of the "response" to Lupron is actually one of the most powerful prognostic metrics available. The degree of PSA decline after Lupron is incredibly important. How low the PSA drops after starting Lupron is called the "PSA nadir." The specific PSA threshold used to determine a "good response" is less than 0.1. Believe it or not, there is a huge difference in prognosis between a man on Lupron for six months who has a PSA of 0.1 versus a man whose PSA levels off at 1.0.

An Established History is also a Prognostic Indicator
Another somewhat obvious prognostic indicator that is often overlooked and almost never discussed in textbooks has to do with the prognosis of men who have been diagnosed years ago -- over time it is apparent that things are turning out much better than what might have been expected based on their initial indicators. For example, take the case of a man who started off with a panoply of bad indicators—tumor is in the lymph nodes and Gleason 10—but after aggressive treatment remains in remission for 5 years. The fact that things have gone well for five years counts bigtime in his favor going forward. Remember, the original prognostic predictors of a Gleason 10 were just that, predictors. No predictor is 100% accurate. Five years of established history is a stronger predictor than the original Gleason score. The fact that things have gone well for five years, strongly indicates that the future is for that individual is bright. Such individuals have "beaten the odds."

The Location of the Tumor in the Body
Another extremely important indicator of prognosis, something that even laypeople anticipate by simple common sense, is the location of the cancer in the body. Location says volumes about how things are likely to progress in the future. For example, consider the following sequence of progressively more serious cancer sites:

•Contained within the prostate
•Extended into the seminal vesicle
•Spread to the lymph nodes
•Bone metastases
•Liver metastasis

Each of these locations is very important for determining prognosis.

This short blog is just an introduction to some of the "profiling" methods utilized in generating an accurate prognosis. Space limitations preclude discussion here about other known prognostic factors such as the size of the prostate gland (discussed in a previous blog), genetic tests and PSA doubling time. The D’Amico risk categories constitute the backbone of useful prognostic information. However, the additional prognostic information beyond the D’Amico risk categories that are discussed in this blog, provide additional useful information necessary for determining an accurate prognosis. An accurate prognosis is the starting point for accurate selection of treatment.