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

BY MARK SCHOLZ, MD

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. 

Making Friends with Your PSA

BY RALPH BLUM

It’s a simple enough blood test. So who’s afraid of a PSA? The straight answer? Every guy who’s ever been told his PSA was elevated for his age, and that he needs to have a biopsy. Because from that point on, things can happen fast. It’s the prostate cancer version of the old Tinker-to-Evers-to-Chance double play: PSA Test to Biopsy to Surgery.

PSA is an acronym for prostate-specific antigen, a protein produced by normal prostate cells. Cancer cells, however, produce more PSA per unit volume than benign cells. Since 1986, PSA testing, although not perfect, has served as the gold standard for early diagnosis and—the area of most controversy—screening for prostate cancer.

While with the majority of younger men, early diagnosis far too often leads to unnecessary treatment and anxiety, urologists are justifiably concerned that, without PSA testing, they will miss diagnosing the less-common high-grade form. So, when in doubt, test.

So, I’m talking primarily to those of you with low-grade tumors, conditions that qualify as “chronic” and might better not even be called “cancer.” That doesn’t mean that being newly diagnosed with prostate cancer is any less of a shock. But there are things you can do to reduce the anxiety.

Bottom line, after all the millions spent and all the years of research, we still don’t have a foolproof diagnostic test for prostate cancer. So don’t panic if you get a high PSA reading. Here are some factors that can distort PSA test results in ways that don’t necessarily indicate cancer:

BPH: Benign prostatic hyperplasia, prostate enlargement caused by age or infection, can produce elevations in PSA not indicative of cancer. Check it out.

Infection: Consider the possibility of infection. When my PSA spiked unaccountably from 5 to 17, my wife, Jeanne, who practices Traditional Oriental Medicine, put me on a course of Cipro, and my PSA plummeted back to 6.5 within two weeks.

The 48 Hour Rule: Strenuous exercise, heavy lifting, sexual activity, even bicycle riding before a PSA test are all considered to negatively effect the result. So don’t do any of it before your PSA test.

Inconsistent Lab Work: Standardization between assays and labs is still lacking, making comparisons between PSA tests from different labs are unreliable. Make certain your urologist uses the same lab every time.

Then, there are those of you for whom PSA testing is a higher priority:

Family history: If you have a family history of prostate cancer, it’s advisable to begin PSA testing at 40 and repeat the test at six-month intervals.

African Americans: All African-Americans are advised to begin tests by age 40 regardless. The death rate from undiagnosed prostate cancer for African-Americans is currently twice that of Caucasian men. Partly for genetic reasons, partly from refusal to submit to the DRE, the finger-up-the-butt trick the rest of us, so to speak, take in our stride. Trust me, it’s over before you know it. 

Men Over 75: Nowadays, men over 75 are apt to be spared testing entirely. So avoid the anxiety, and have a good time? On the other hand, you might just go for the PSA test, and take the prostate cancer alert as a wake up call to get yourself a checkup.How long since your last physical, dude?

Finally, remember that the big decisions are all yours to make. So never hesitate to go for a second opinion—or a third. And if you don’t like the test results, get another PSA test done by a different lab. Or find a different urologist.

The best clinicians do not mindlessly screen all of their male patients. They decide which men should be tested based on age, symptoms, family history, expected longevity, general medical condition, physical examination findings, and—a significant factor—the patient's own request for the test. The goal of early detection remains to identify patients who have clinically significant cancers at a time when treatment is most likely to be effective.  

And here’s the really good news: 28 out of 30 men reading this blog, who do have prostate cancer, will die with it, not of it.  Regardless of its shortcomings, the PSA is still the most useful test that is widely available.

So if you’ve been avoiding it, have a PSA test done this week. And while you wait for results, instead of fretting, call the golf pro and get yourself a tee time for Saturday.

PSA, The Human “Check Engine” Light

BY MARK SCHOLZ, MD


Why all the controversy about PSA? How can people fault a simple blood test that uncovers cancer at an early stage? The problem is that the PSA test doesn't specify what type of cancer the patient has. In addition to the presence of cancer, there are two other common causes of PSA elevation—prostate gland enlargement that comes with age, called BPH, and chronic prostate inflammation, called prostatitis.

PSA by itself doesn’t diagnose prostate cancer.  It is a nonspecific indicator, like the “check engine” light on the dashboard of your car.*  Does this eliminate the value of PSA?  Of course not.  An elevated PSA reading is a useful indicator of the need for further research into the cause.

The biggest fear--and the primary argument used by PSA naysayers--is that so many urologists recommend immediate random biopsy with any PSA elevation whatsoever.  A million men are biopsied annually in the US, resulting in the over-diagnosis of innocuous prostate cancers in about 100,000 men each year.  Most of these men end up undergoing unnecessary radical surgery or radiation.

So how do we eliminate the bathwater (random biopsies) without throwing out the baby (PSA)?  The first step is avoiding the trap of rushing headlong into something before learning the whole story. Since we know PSA is nonspecific, most elevations will be from prostate enlargement, not cancer.  PSA needs to be interpreted in relation to prostate size.

One might think that only ultrasound or MRI can reliably measure prostate size.  And while imaging is indeed the most accurate method, practiced doctors can roughly estimate prostate size with a simple digital prostate exam.  Also, there is a PSA blood test variant called “free” PSA that is suppressed in men with BPH.  Free PSA is reported out as a percentage of total PSA.  When free PSA percentage drops below 10%, BPH as a cause for PSA elevation is less likely.

Sequential PSA testing is the best way to diagnose inflammatory prostatitis, the other common reason for benign PSA elevation. Inflammation can increase PSA, which often oscillates up and down as the inflammation in the gland waxes and wanes.  This bouncing PSA pattern is in sharp contrast to an elevation of PSA caused by cancer.  A rise in PSA from cancer is usually unidirectional—up, up and up.

Historically, despite the drawbacks from biopsy of over-diagnosis, infections and discomfort, it has been the gold standard for diagnosing prostate cancer. Only very recently have new advances in multiparametric MRI imaging enabled men with PSA elevation to consider this imaging alternative--rather than random biopsy--as a first step. Our recommendation to use a multiparametric MRI (at a center of excellence) followed by a targeted biopsy if a suspicious lesion is detected, has been discussed in more detail in previous blogs. 

*I wish I could take credit for the check engine light idea that so nicely conveys the useful but nonspecific character of PSA.  This little pearl of knowledge was passed on to me by a patient. 

Remember: In BPH, the “B” stands for “Benign”

BY RALPH BLUM

The prostate gland is the only organ in our body that keeps growing as we get older; all our other organs shrink and atrophy over time. A healthy prostate gland weighs around half an ounce (15 grams) in young men, and an ounce (30 grams) or more in men who are 50 or older. However, the prostate can weigh over 100 grams, in some cases causing problems with urination.

Although an enlarged prostate doesn’t inevitably lead to problems, one-third of all men older than 60 have benign prostatic hyperplasia (BPH) that causes urinary symptoms. The most common urinary symptoms are:
 
— Frequent urination.             
— A slow, weak stream of urine—there may be a lot of stopping and starting.
— A feeling of urgency when you feel like voiding.
— Painful, almost total blockage (this requires immediate medical treatment).

If you are having any of these urinary symptoms, in addition to a urine test to rule out a bladder infection, you will need an ultrasound scan to measure the size of your prostate gland, and to determine the nature and seriousness of the problem.

In most cases BPH can be treated with a category of medications, known as alpha blockers, that relax the prostate and make urinating easier. The best known of these is Flomax (generic name: tamsulosin). Another standard treatment is Proscar (generic name: finasteride) that works to shrink the size of the gland and, therefore, reverse the problem of slow urination from prostate enlargement.

However, if your symptoms are severe and/or multiple, you may require treatments using microwave, laser or electrical energy. Or if total blockage occurs, your urologist will perform transurethral resection of the prostate (TURP), a surgical procedure that removes the prostate tissue that is blocking the flow of urine.  This procedure is sometimes referred to as a “rotor-rooter job.”

BPH is the most common reason for urinary problems in older men. But equally important is the fact that an enlarged prostate causes a rise in PSA. The reason for this elevation is because the level of PSA measured in the blood is not only proportionate to the number of cancer cells in the prostate gland, but also to the size of the gland. If, therefore, the PSA level is appropriate for the size of the prostate, and if ultrasound imaging fails to reveal any sign of cancer, chances are the PSA elevation originates from BPH. In which case, active surveillance with regular PSA testing and occasional prostate imaging is, without a doubt, preferable to biopsy.

 

But the overwhelming concern of most doctors is that they might miss cancer in their patients. That concern, plus our own fear of the disease, far too often makes us jump to an immediate, unnecessary biopsy. And here’s a fact to tape to your shaving mirror:

 

--More than half the prostate biopsies performed annually

in the U.S. are done for evaluation of an elevated PSA

caused by Benign Prostatic Hyperplasia.

 

Isn’t it time we got smarter and started acting out of knowledge, instead of out of panic? And to remember what the “Benign” in BPH stands for?

 

VIDEO: Learn more about High PSA, Multiparametric MRI and random biopsies  http://youtu.be/6QgcfVBzFNs

 

 

First Stop on the Overtreatment Express: The Unnecessary Biopsy

RALPH BLUM

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.

Avodart & Proscar

BY MARK SCHOLZ, MD

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:  http://prostatesnatchers.blogspot.com/2011/05/avodart-proscar-for-men-on-active.html
 

The Unending PSA Controversy

BY MARK SCHOLZ, MD

The controversy about PSA has been reignited by new data from Lancet and recently reported in the NY Times.  Even though PSA screening reduces mortality from the aggressive type of prostate cancer, the Lancet article again confirms that far too many men routinely receive unnecessary radical treatment for a low grade type of prostate cancer that is essentially harmless, an entity that should never have been called cancer in the first place.

Grade 6 “cancers” are harmless. However, it’s hardly surprising that men (and doctors) push for immediate treatment anyway.  No amount of reasoning seems to ease the instinctual fears generated by this venomous word.  Despite warnings about impotence and incontinence—and reassurance that low-grade prostate cancer can be safely monitored— 85% of these low-risk men undergo radical treatment anyway.

Unfortunately, outrage against the genuine harms of overtreatment is routinely directed at PSA when the real culprit is the 12-core random prostate biopsy. I have previously weighed in on this matter in various blogs and videos, but the prostate cancer intelligentsia continues to be totally clueless, routinely blaming PSA rather than the ridiculous policy of randomly jabbing needles into the rectums of a million men annually.

Random biopsy could perhaps be justified if prostate scans were unreliable. In fact prostate imaging does often miss small, low-grade cancers; the very ones we now know are harmless. But for high-grade disease, color Doppler ultrasound and multiparametric, three-tesla MRI, are very accurate. Evaluating an abnormal PSA with an imaging study rather than a biopsy greatly reduces the chance of diagnosing grade 6 disease, the type that so commonly leads to unwarranted treatment.

Low grade cancers are incredibly common. However, higher-grade cancers also occur.  When imaging detects a high grade lesion, a targeted biopsy (a limited number of cores aimed directly at the lesion) should be performed. Lesions that are biopsy-negative or show low-grade cancer, can be monitored without treatment.  If high-grade cancer is confirmed, further staging followed by treatment counseling is needed.

Trained doctors using state-of-the-art technology read the scans and summarize their overall impression which falls into one of three categories:

1.        No evidence for high grade disease, no need for biopsy

2.        A suspicious lesion is detected, a targeted biopsy is necessary

3.        An ambiguous area is detected. Either a targeted biopsy can be considered or alternatively, ongoing monitoring with another scan in 6-12 months can be considered

Imaging “sees” all sorts of things besides cancer, including scar tissue, areas of active prostatitis, and nodular areas from BPH. Lesions of greater concern are located in the peripheral zone, over a centimeter in size, show bulging of the prostate capsule or are associated with increased blood flow or diffusion. An ambiguous lesion should be targeted for biopsy if it enlarges over time during observation on subsequent scanning. Expert judgment that takes each individual’s characteristics into account comes into play during a discussion between the patient and doctor about whether or not a targeted biopsy is indicated.

Color Doppler ultrasound and multiparametric MRI are complementary. In our experience, the imaging findings between these two modalities match 80% of the time. However, in a minority of cases, one imaging modality illuminates a specific lesion more clearly. Therefore, with ambiguous lesions using one modality, we usually consider additional imaging with the other modality before recommending targeted biopsy.

One would think that new advances in imaging would lead to an immediate revolution in prostate cancer management. Unfortunately many doctors are either unaware of what’s available or unacquainted with the full capabilities of the latest technology.  Finally, even well informed doctors may be reluctant to embrace imaging when they are well paid to do random biopsies.

Random biopsy continues to fly unscathed under the radar while people mistakenly blame PSA for the great misfortune of having thousands of men undergo unnecessary surgery or radiation every year. Forgoing PSA screening altogether is both foolish and dangerous. State-of-the-art prostate imaging, rather than random biopsy, should be the first step in evaluating men with elevated PSA levels.

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.”