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

Tuesday, October 28, 2014

Raising Awareness about MRI Imaging of the Prostate


Prostate cancer screening presents a unique challenge.  Prostate cancer is a very common, but only a minority of cases are deadly.  This creates a serious problem.  It’s good to detect high-grade disease because early treatment reduces mortality.  But PSA screening detects a lot of men with low-grade disease and these men are harmed. Why? Well-intentioned but over-enthusiastic doctors recommend treatment even though it’s truly medically unnecessary. 

Why We Over Diagnose
So what can be done?  Physician propensity for overtreatment will only change slowly.  The shortest pathway out of this dilemma is to stop diagnosing so much low-grade disease.  The crux of the problem is the random needle biopsy, a “blind” procedure that is widely considered to be the necessary first step for evaluating elevated PSA.  A million men undergo biopsy annually; 250,000 men are diagnosed; around a 100,000 have low-grade disease the can be safely monitored with “active surveillance.”

The Next Evolutionary Step
Three-Tesla multiparametric MRI (MP-MRI) scans developed by Siemens, Philips and GE can reliably detect high-grade disease without over diagnosing low-grade disease; these scanners accurately differentiate high-grade from low-grade tumors.  The availability of these new scanners makes random biopsy as currently utilized by most urologists archaic. Random biopsy involves inserting 12 needles into the rectum.  Beyond its propensity for over-diagnosis, 3% of men are hospitalized with serious infections.  Also, it is relatively inaccurate, failing to detect high grade disease over 15% of the time.

New Technology Growing Pains
Most internists and urologists are still unaware of these important technological advances.  Even those who are aware are still learning how to translate these new imaging reports into practical recommendations for their patients. Also, there is the challenge of maintaining quality control in this rapidly expanding world.  Despite these barriers the advantages of using imaging as a first step can’t be ignored.  PCRI has posted a list of centers that perform this type of imaging.  While we have some familiarity with these centers, for liability reasons we are unable to offer any official certification of their quality and accuracy.  On the other hand, new as this technology is, we feel it would be a disservice not to spread the word about its availability.


Tuesday, October 21, 2014

First Stop on the Overtreatment Express: The Unnecessary Biopsy


The first four words of the subtitle of our book, Invasion of the Prostate Snatchers are, “No More Unnecessary Biopsies.” At the appropriate time, a biopsy is an essential diagnostic tool. Unfortunately, however, far too many urologists still schedule an immediate biopsy if there is even a slight rise in PSA. And that has led to a multi-billion dollar industry bent on administering treatment to every kind of prostate cancer, whether it is life-threatening or not.

So what do you need to know before agreeing to submit to a biopsy? There are several possible reasons for an elevated PSA besides cancer:

1. A prostate infection, in which case a simple course of antibiotics may be all it takes to lower PSA into the normal range. Years ago my PSA went zooming up from an infection.

2. PSA rises after sexual activity, so abstinence is necessary a day or two prior to testing.

3. Recent bicycle riding activity can cause an elevated PSA.

4. An enlarged prostate—aka Benign Prostatic Hyperplasia, or BPH—usually results in an elevated PSA. More than half the biopsies in the U.S. are performed for evaluation of an elevated PSA coming from BPH.

5. A random laboratory error is always a possibility, and occurs more often than we realize.

So rather than triggering the scheduling of an immediate biopsy, an “abnormal” PSA should set a risk-assessment process in motion. The first step is to eliminate any of the above possible causes—checking for an infection, repeating the PSA to see if a lab error caused the elevation, performing an ultrasound scan to determine the size of the prostate to see how much BPH is present, and to determine whether the ratio between PSA and prostate size is in the expected range.
If these measures all fail to explain the elevated PSA, further testing—with an OPKO-4K blood test that is specific for high-grade cancer—should be considered before resorting to a biopsy. Other useful procedures prior to undertaking a biopsy are color Doppler ultrasound and/or multiparametric  MRI. Imaging studies provide an accurate measure of the prostate size so that the PSA “density” (PSA elevation in the context of prostate size) can be calculated.  If  the OPKO-4k,  PSA density and imaging are favorable, then surveillance with periodic PSA and  imaging, may be preferable to an immediate biopsy.
You have probably realized by now that I am not a fan of biopsies.They can be painful, can cause erectile dysfunction, and fail to spot cancer as much as 20% of the time, especially in men with large prostates. But the main reason I am against unnecessary biopsies is because of the unnecessary radical prostatectomies that usually follow—estimated at above 80,000 annually in the U.S. alone. Having a biopsy is like opening Pandora’s box.
According to Thomas Stamey, M.D., who developed the PSA blood test, prostate cancer is a disease that almost all men get if they live long enough. So the older the man, the more likely a biopsy will reveal cancer. But that doesn’t mean every man should have his prostate removed. However, only too often, that is what happens. The treatment of choice of most urologists is surgery (they are, after all, surgeons), and most men yield to the emotional appeal of “cutting it out.” This unfortunate situation is what led to Stamey’s famous quote: “When the final chapter of this disease is written, it will prove that never in the history of oncology will so many men have been so over treated for one disease.”
An unwarranted biopsy is the first stop on the Overtreatment Express.

Tuesday, October 14, 2014

Avodart & Proscar


Frequently I am asked about Proscar and Avodart, two medications that are FDA approved to reduce urinary side effects from prostate enlargement (BPH).  It turns out that these medications have a much wider spectrum of application than simply treating BPH. They function by blocking a type of testosterone called dihydrotestosterone (DHT) that occurs primarily inside the prostate. A short blog can’t summarize this vast field.  However, I think even a brief review might be helpful.  Here is a list of their potential applications:
  • Lower the risk of being diagnosed with prostate cancer
  • Improve the detection rate of high-grade prostate cancer
  • Cause Gleason 6 cancer to regress or be suppressed
  • Synergize with other hormone therapy medications (such as Casodex)
  • Help maintain men on active surveillance to avoid surgery or radiation
  • Prolong the “holiday period” in men on intermittent hormone therapy
  • Reduce male pattern baldness
  • Delay orgasm in men with premature ejaculation

The occasional side effects that can occur, such as reduced libido, impotence and breast enlargement, are manageable or preventable as long as the medication is stopped in a timely fashion when side effects occur.

In a randomized study comparing Proscar with placebo, 10,000 men underwent a prostate biopsy. The Proscar-treated men were diagnosed with cancer 25% less frequently compared to placebo. However, enthusiasm for the routine use of Proscar to prevent cancer was dampened when the same study reported a 1% increased incidence of diagnosing high-grade prostate cancer. Even though many experts hypothesized that Proscar was increasing the detection rate, not causing high-grade disease, Peter Scardino, a prominent urologist from Memorial Sloan Kettering published an opinion that Proscar could be causing high-risk cancer, raising all kinds of consternation and inciting the FDA to place a warning. Fortunately, subsequent follow up published in the August 15, 2013 issue of the New England Journal of Medicine showed that after 18 years of observation there was no increased prostate cancer mortality from Proscar.

Much of what is known about Proscar can also be said about Avodart. Both agents block 5- alpha reductase (5-AR), an enzyme that converts testosterone into DHT.  A possible advantage of Avodart is that it blocks two of the three forms of 5-AR whereas Proscar only blocks one.  No clinical trials, however, have been performed to compare clinical efficacy of the two agents.  In our in-house trials we have found that DHT blood levels are lower with Avodart than Proscar.

Since both Proscar and Avodart lower PSA by about 50%, the question arises, “Are they masking the capacity of PSA to signal cancer progression?”  Briefly, the answer is no. These medications do not stop a PSA rise in men with progressive cancer. However, after starting Proscar or Avodart the PSA baseline does reset 50% lower. On average, a man with a PSA of 6.0 before starting Proscar will drop to 3.0 within a few months. Subsequently, if the PSA rises consistently above 3.0, cancer progression should be entertained as a possible cause.

The rationale for concluding these agents are beneficial when added to other hormonal agents is based on the known fact that no pharmaceutical drug by itself can totally eradicate or block testosterone. So logically, the addition of a nontoxic 5-AR inhibitor to further lower DHT is likely to be helpful. Studies show that these agents suppress PSA in men with relapsed disease, delaying the rise in PSA, on average, for a couple of years.  It has also been shown that these agents can double the duration of the “holiday period” in men on intermittent hormone blockade.

Proscar and Avodart—mild agents with mostly reversible side effects—almost never interact with other medications.  They can be taken anytime of the day, with or without food. Proscar is available as a generic called finasteride and is very affordable. There is certainly an important role for these well-tolerated medications though in this era of new, high-powered hormonal agents such as Zytiga and Xtandi, Proscar and Avodart often get forgotten.  

Read another Prostate Snatchers blog written on Avodart & Proscar here:

Tuesday, October 7, 2014

How to Cope with a Prostate Cancer Diagnosis


There is no easy way to receive the news that you have cancer of any kind, but—and I cannot say this too often‑—it is important to realize that prostate cancer is typically not a death sentence. The majority of men diagnosed with prostate cancer have Low-Risk disease and will live a normal life span. And even more aggressive High-Risk type is now being successfully treated with a combination of therapies.

Having said that, a diagnosis of prostate cancer is daunting, and once you join the ranks of the newly diagnosed, you enter into what Mark calls “a medical minefield.”  While you are still reeling from shock you are required to make treatment decisions that can permanently affect your quality of life, and there are no easy answers. There are, however, a few basic things to bear in mind while you navigate the prostate cancer minefield.

1)    Don’t waste energy asking yourself, “How did this happen? Did I bring this on myself?” Because regardless of your lifestyle—eating habits, exercise regime, or anything else that might contribute to getting this disease—you did not cause it. Prostate cancer is incredibly common. Like diminished sight and hearing, it comes with advancing age.  In the words of one prostate oncologist, “If you are over seventy, and you don’t have prostate cancer, chances are you’re a woman.”

2)    Stay as calm as possible. The very process of gathering the information necessary to make an informed decision can be scary. But do not be panicked by all the numerical tables, statistics and graphs. Statistics measure populations. You are not a statistic. You’re a person. And statistics and pathology reports do not take into account all the variables and intangibles that make you an individual.

3)    Be proactive. The days of the passive patient with a “Whatever-you-say-Doc” attitude are over. The single most influential decision maker when it comes to obtaining the best care and treatment is you. Do your own research, and become actively involved with your doctor in the decision-making process. Ask your doctor about all your treatment options, and make sure you understand their short-term and long-term side effects.

4)    Recognize and resist your natural desire to rush into radical treatment. Be aware that a combination of the urologist’s preference for surgery and most men’s “just get it out” attitude, leads to tens of thousands of unnecessary radical prostatectomies every year. These men would have lived just as long without surgery, without the risk of losing both potency and normal urinary function and greatly compromising their quality of life.

5)    Even if you are satisfied with your urologist, it is critically important to get a second opinion, preferably from an independent board-certified medical oncologist—a cancer specialist—and if possible, an oncologist with a specialty in prostate cancer. Obtaining a second opinion doesn’t imply that you don’t trust your doctor. On a decision this important, you owe yourself the benefit of more than one person’s thinking.  Be prepared for conflicting opinions, and remember to trust your instincts about which doctor is right for you. Finding the right doctor may require traveling to a major cancer center to talk with a leading edge specialist.
Above all remember: if you are diagnosed with Low-Risk disease you do not require any immediate radical treatment. You can be safely monitored with “Active Surveillance.” When you are watched closely, treatment can be safely delayed until there is some sign of progression.
Even then, the cancer will still be manageable. Multiple studies clearly show that survival rates of men on Active Surveillance match those of men getting immediate surgery. Also, be particularly careful if you are in your 70s or 80s.  Men in this age group are rarely at risk of disease that will be clinically significant in their lifetime, and these men have the highest incidence of overtreatment. As you start out on your prostate cancer journey, be very aware that overtreatment of this disease is rampant, and do not become a needless victim of unnecessary treatment.