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. 

Biopsy, Not PSA, Leads to Prostate Cancer

BY MARK SCHOLZ, MD

Prostate cancer is way over treated, and the problem starts with over diagnosis.  Once men are diagnosed, the fear of cancer naturally drives them toward radical treatment. In 2011 the US Preventive Services Task Force intervened, trying to stop overtreatment, argued that PSA testing causes more harm than good.

Some have questioned the expertise of the panel because of the lack of representation by urologists, radiation therapists or medical oncologists --the types of doctors usually responsible for treating prostate cancer.  Actually, the credentials of the panel constituents appear entirely appropriate to comment on screening, because this is an area of medicine usually handled by primary care doctors.  The panel members consisted of twelve MD’s and four PhD’s trained in primary care, public health and statistics.

The Task Force agrees that PSA screening may save lives. Their judgment, however, was that too few lives are saved to justify thousands of men getting unnecessary radical treatment. One statistic indicates that a thousand men must be screened to save one life within the next 12 years.

Personally, I agree with the panel in regards to over diagnosis is a root cause of over treatment. However, simply discarding PSA is an oversimplification. PSA can detect a variety of problems infection and benign prostate enlargement. Actually, the majority of men with elevated PSA, don’t have prostate cancer.

No, the real problem is after a PSA test rises. Every year, a million men are advised to have a dozen, large-bore needles jabbed into their rectums “Just to be sure there is no cancer.”  Such behavior sounds ridiculous, but really, it is just the survival instinct in action. People will do practically anything when they fear for their lives.

So if not a biopsy to evaluate an elevated PSA, what’s next?

First, the fear must be faced. Ralph Waldo Emerson says “Knowledge is the antidote to fear.” So let’s look at some basic facts:

• One out of 38 men die of prostate cancer
• One out of seven men are diagnosed with prostate cancer
• In men who are “diagnosed”
  • Five-year survival is 100%
  • Ten-year survival is 99%
  • Fifteen-year survival is 94%
    

Considering it is cancer, survival rates are great! At least these numbers should overcome any urge to rush. Clearly there is plenty of time is to study and learn more. Confusion arises because a minority of prostate cancers can indeed be dangerous. Not as dangerous as lung or pancreas cancer which kill within months. However, demise from prostate cancer certainly qualifies as “dangerous,” even if it is rather infrequent and much postponed.

These statistics reveal something else that is quite useful. Prostate management issues are of long-range nature, like saving for college or for retirement. Just as expert financial planners are limited in the ability to make predictions about economic activity ten years in the future, doctors should be equally humble in their pronouncements about the future of prostate cancer. We don’t know for sure, but we strongly suspect there will be substantial breakthroughs in the diagnosis and treatment of prostate cancer in the next ten years.

For the short term, I think the best way to proceed is with imaging the prostate with a 3Tmulti-parametric MRI or color Doppler ultrasound. Scans are about as accurate as a random biopsy for detecting aggressive cancers and they usually fail to detect the harmless low grade types, which is a good thing. However, if there is a worrisome abnormality, a targeted biopsy with just a couple cores is needed.

Over-diagnosis and over-treatment is not due to PSA. It’s the misguided policy of rushing into an immediate random biopsy whenever there is a slight elevation.  .The random biopsy procedure should be abandoned.  PSA abnormalities should be evaluated with prostate imaging A targeted biopsy can be considered in men who have a distinct abnormality detected by imaging.    

Ah, Yes. . .Your Medical Records

BY RALPH BLUM

 

When you are diagnosed with prostate cancer, keeping a folder with all your medical records can be a challenge, especially when you are working with several doctors and addressing different health concerns. But that is also when it is most important, both for your own understanding and safety, and for the use of any specialists you might want to consult for a second opinion.

The following is a list of the variety of information you need to preserve in your medical folder (MMF):

* A Chronological Log of all your PSA tests with dates, and note in the log any general health changes that might impact your PSA.

*  A copy of your urologist's notes that give the results of your Digital Rectal Exam (DRE).

*  A copy of your urologist's Transrectal Ultrasound (TRUS) report that lists the size of your prostate.

*  A copy of your Biopsy Pathology Report. This should provide your Gleason Score, how many cores were positive for cancer, the extent of disease in the cores, and the location of the cancer in the prostate gland.

*  Copies of the radiology reports of any scans (color Doppler ultrasound, bone, CT, MRI), and if available, digital copies of the actual scans.

*  Copies of all information regarding your medical history, including any current (unrelated to the prostate cancer) health problems you may be dealing with, even if they seem minor.

*  A list of all your medications (including the dosages), and a list of any over-the-counter supplements you are taking.

It is also wise to retrieve your biopsy slides from the pathologist and send them to a world-class cancer treatment center, such as MD Anderson, Johns Hopkins, Sloan Kettering, Saint John's, for a second opinion. In fact if you live in a small town or in the country, if possible you should get yourself to a urologist or oncologist specializing in prostate cancer at one of the major centers for a consultation before making a treatment decision.

Keeping this medical record not only gives you a feeling of control, but it is extremely helpful when you consult different specialists. It is also something your partner can help you create. Giving your partner something constructive to do can help her (or him) deal with the worry they inevitably feel over your diagnosis.

I personally feel very strongly about the importance of keeping and organizing all your medical information when dealing with prostate cancer because I didn't do it. And I know how often I and my doctors have found the MMF invaluable support. Truly, we are partners with our oncologists and our urologists. Be an active partner.

 

The Premature Biopsy Blues

BY RALPH BLUM

As I have said many times I am no fan of biopsies, but to most urologists, an elevated PSA calls for an immediate biopsy. A majority of urology practices rush men into biopsy despite the risks and discomfort involved, and despite the fact that there are other, far less invasive indicators to help determine what is going on in the prostate before doing a biopsy. If these indicators point to the presence of an aggressive cancer, submitting to a biopsy to get further information is appropriate. But in most cases, it is not appropriate, and almost inevitably gets you a first class ticket on the Overtreatment Express.

Prostate cancer is different from other cancers and, in a majority of cases, far less malignant. Accumulating studies show that approximately 30% of men in their fifties, and as many as 70% of eighty-year-old men, harbor microscopic amounts of the disease. In fact, in the opinion of one well-known urologist, "If you are over seventy, and you don't have prostate cancer, chances are you're a woman."

Yet despite the fact that so many men have it, less than 3% of men in the U.S. die from it, and the mortality rate is dropping every year.

So if your PSA is elevated, take a deep breath and don't panic. Rather than triggering an immediate biopsy, an elevated PSA should set a risk assessment process in motion. More than half the biopsies in this country are done for evaluation of an elevated PSA coming from BPH—an enlarged prostate. And there are various other non-cancerous causes of an elevated PSA. So check them out and repeat the test. Still elevated? Insist on having an OPKO-4k blood test. Studies show that the OPKO-4K can not only demonstrate the presence or absence of cancer, it gives a readout on the likelihood of higher-grade cancer, the kind of cancer that should be treated rather than watched.

Some major cancer centers use 3-Tesla, multi-parametric MRI as a diagnostic tool. Also to be considered is another form of imaging—color Doppler ultrasound—that is comparable in quality to MP-MRI, is easier to perform, takes less time, can be done in the doctor's office. Color Doppler provides higher resolution images than the usual gray-scale ultrasound machines, and also shows areas of increased blood flow associated with higher-grade or more aggressive prostate cancers. If a suspicious lesion is detected a targeted rather than a random biopsy can be performed.

PSA is a remarkable tool. However PSA testing alone frequently gives an inconclusive message. So if your PSA is slightly elevated, instead of submitting immediately to a random needle biopsy that would likely lead to un-called-for radical treatment for a non-threatening cancer, ask your urologist to slow down. Now is the time to gather more information by testing with OPKO-4K and color Doppler ultrasound. Never forget that prostate cancer is the tortoise of cancers, so don’t be frightened into making a decision you might regret.  This is one situation where taking the Local may provide a better ride than the Express.    

Prostate Cancer: Starting at the Very Beginning

BY MARK SCHOLZ, MD

Yesterday I sat down with a new patient, Sam, a charming man who, unfortunately, was just found to have a prostate nodule and a PSA of 50. When I asked Sam why he had not visited a doctor for over 10 years or undergone any PSA testing, he responded, “I have always enjoyed perfect health. Why see a doctor?” Sounds sort of like a stupid response, but judging by his healthy appearance, (looking more like a 70 year old than an 80 year old), one would have to say that until now his policy has been pretty successful.

However, if Sam was going to participate intelligently in further discussions about the selection of optimal treatment, his prostate cancer knowledge would need a major upgrade. Since my instruction had to begin at a very elementary level, I thought I would use this blog to share the main themes of our almost two-hour meeting together.  Focusing on the basic first steps seems an appropriate theme for this, my first blog of the New Year.

Not All Cancers Are the Same
Many patients introduced into the cancer world fail to understand that lung cancer, breast cancer, brain cancer and prostate cancer are each a distinct illness, each with more differences than similarities. These different cancers are as different as kidney stone disease is different from pneumonia. Therefore, preconceived notions coming from personal experiences with one type of cancer occurring in family members or friends are frequently misleading.

Prostate Cancers are a Mixed Bag
It’s fairly easy to see why dissimilar cancer types, such as bladder cancer and skin cancer for example, behave differently; it may be harder to understand that prostate cancer itself comes in many different and distinct subtypes. Part of this varied behavior can be explained by the disease stage: No one is surprised by the fact that cancer diagnosed at an early stage has a different outlook compared to cancer diagnosed after it has metastasized.

However, beyond the issue of variable stage, when comparing two different prostate cancers of exactly the same stage, what we call “prostate cancer” can be extremely variable. Consider the following: In 2014, 70,000 men were diagnosed with a type of prostate cancer considered to be so harmless that experts universally agree it is best managed with active surveillance only. However, at the other extreme, also in 2014, a very different type of prostate cancer led directly to 28,000 deaths.

Prostate Cancer in the Bone is Not Bone Cancer
A common misconception that needs to be rectified is that cancer that originates in the bone, i.e bone cancer, is a totally different entity than prostate cancer that has spread to the bone. Primary bone cancer grows quickly, often spreads to the lungs and does not respond to hormones. Prostate cancer that spreads to the bone tends to grow much more slowly, only rarely spreads to the lung and usually regresses radically with hormone therapy. Prostate cancer in the bone and primary bone cancer are two separate and distinct illnesses that should not be confused with each other.

Doctors and Patients, the Human Factor
The human factor further complicates the selection of optimal treatment. Doctors who treat prostate cancer come from different schools of thought. Not only are urologists, who are surgeons, trained differently from radiation specialists, the true cancer specialists, the medical oncologists, are practically never involved with early-stage prostate cancer. Differences among patients—age, fitness, prostate size for example—can also radically influence treatment selection.

Sam’s Situation
With a PSA of 50, Sam is going to need a bone scan. He may have already developed metastases. His initial color Doppler ultrasound shows a rather vascular tumor (about an inch and a half long) with some early extra-capsular spread. A targeted biopsy, a single core of the tumor, is scheduled for next week and will let us know the Gleason score.

If the scans turn out to be clear, and if Sam was ten years younger, radiation and hormone therapy would give him the best chance for cure. But in an 80-year-old, the possible side effects that can result are more problematic. Also, we don’t know anything yet about the pace of his disease. Might it be feasible for Sam monitor to the situation for a while? Alternatively, radiation alone or mild hormonal therapy alone (with Casodex) could be considered. Sam and his wife left our meeting with a copy of Invasion of the Prostate Snatchers promising to read it in preparation for our next meeting.

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.

INDIGO: Relapsed Prostate Cancer

MARK SCHOLZ, MD

Those dreaded words, “relapsed cancer,” shake you to the core. They mean that surgery or radiation has failed to “get it all.”  However, while with most cancers “relapse” is a fatal pronouncement.  However, prostate cancer has its own distinct reality. Most men who relapse don’t die from the disease.  The outlook is good because relapses are usually detected by a rising PSA when the cancer is still microscopic. Visible, scan-detected metastases may not appear for ten or more years after the PSA relapse occurs.

Multiple Treatment Options for a Rising PSA
The list of potential treatment options for INDIGO is extensive: observation, radiation, hormone therapy with Lupron and Casodex, salvage seed implant, salvage cryotherapy, Zytiga, Xtandi and Taxotere. However, combinations of these treatments are most commonly employed. Some of these combinations are listed below in order of increasing treatment intensity:  

1.     Observation

2.     Mild hormone therapy consisting of continuous or intermittent Casodex

3.     Monotherapy with fossa radiation, seed implant or cryotherapy for persistent local disease

4.     Combination hormone therapy with Lupron and Casodex given intermittently

5.     Same as #4 but with the addition of pelvic radiation and 4 months of hormone therapy

6.     Same as #5 but with hormone therapy extended for 18 months

7.     Same as #6 but with the addition of Taxotere or Zytiga or Xtandi

Defining Different Types of Relapses
Just as PSA, cancer grade, scan findings and stage were instrumental for assigning a SHADE in newly-diagnosed men; SHADES are important for putting a relapsed in perspective. Ultimately, how to treat INDIGO is guided by a combination of four factors— the SHADE before treatment, the PSA doubling time, individual patient factors such as age, sexual functionality and urinary control, and last, but not least, the cancer location.

The Original Shade before Treatment
In general, treatment should be more aggressive (combined therapy with Lupron and pelvic lymph node radiation) if the original SHADE was unfavorable (AZURE for example).  Treatment should lean toward a less aggressive approach—cryotherapy alone, seed implant alone or Casodex alone—if the original SHADE was SKY.

The PSA Doubling Time
Treatment is heavily influenced by the rate of PSA rise. For example, if the PSA is doubling in less than six months, aggressive combination treatment with Lupron and Casodex plus radiation (or cryosurgery in men previously treated with radiation) is probably required.  If the PSA doubling rate is between six and twelve months, a less aggressive treatment approach with radiation alone, cryosurgery alone or intermittent Lupron and Casodex is reasonable.  When more than a year is required for the PSA to double, observation without immediate treatment may be considered.

Patient Factors that Affect Treatment Selection
A patient’s age needs to be factored into the treatment decision-making process. Men who are more elderly can “step down” the intensity of their treatment by temporizing with milder hormone therapy such as Casodex with Avodart. Younger men, who, prior to relapse, were in the High-Risk (AZURE) category may want to consider upgrading the intensity of treatment by using prophylactic pelvic lymph node radiation plus a more intensive hormone therapy such as Zytiga or Xtandi and/or chemotherapy with Taxotere.

Searching for the Location of the Cancer
Men with rising PSA should undergo standard imaging studies (listed below) in an attempt to determine the location of the cancer. Unfortunately, these scans are often unable detect recurrent cancer unless the PSA is over 20. However, improved PET scans that utilize C11 choline or acetate have the potential to detect recurrent disease with much lower PSA levels. Unfortunately, the PET scans are so new that insurance coverage is often limited.

Sometime even the best scans can’t detect where the cancer is. When this occurs after surgery, particularly when the PSA doubling time is slow, residual cancer in prostate fossa is often suspected and radiation to the prostate fosse is often administered. Cure rates are better when radiation is initiated at a lower level of PSA. 

Standard Imaging Studies for INDIGO

• Color Doppler Ultrasound or Multiparametric 3 Tesla MRI can be used to look for residual cancer in the surgical fossa or in the prostate gland in men previously treated with radiation. 
• Pelvic MRI or CT scans are used to check for spread to pelvic lymph nodes. (Carbon 11 acetate PET scan, however, is far more accurate than CT or MRI but some centers still consider them investigational/experimental)
• Technetium bone scans are standard. New F18 PET bone scans, however, are preferable because they can detect much smaller cancers than technetium bone scans.

Apparent Locally Recurrent Disease

Scans done in a man with a rising PSA after radiation that indicate a recurrence localized inside the prostate, may be curable with cryosurgery alone or possibly with a seed implant alone.  Similarly, an isolated local relapse in the prostate fossa after surgery may be curable with radiation alone. Even though scans show no metastases outside the prostate or the fossa, microscopic metastases in the pelvic nodes may be present, especially in men who have fast PSA doubling times or whose SHADE was originally AZURE.  In these higher risk situations, the addition of prophylactic pelvic lymph node radiation with intensity modulated radiation (IMRT) combined with hormone therapy may be advisable.

Regional Spread to Lymph Nodes

When cancerous nodes are detected in the pelvis, the idea of doing node-directed IMRT is even more compelling. Since overt cancer in the lymph nodes is an indication of potentially life threatening disease, an extended course of hormone therapy, possibly with the addition of second generation hormones such as Zytiga or Xtandi, can be contemplated. Taxotere chemotherapy is an additional consideration.

Hormone Therapy Alone

When the location of the relapse is unclear, or if the risks of side effects from radiation appear too high, relapsed disease can be effectively suppressed for many years with hormone therapy alone. The side effects of hormone therapy tend to increase with longer use so intermittent therapy is very popular. A typical intermittent protocol is to begin with an initial course of treatment for six to twelve month followed by treatment holiday. After hormone therapy is stopped, testosterone starts to recover and the PSA begins to rise. Treatment is restarted when the PSA rises back to the original PSA baseline, or up to five, whichever is lower.

Putting It All Together

Treatment selection for INDIGO can be complex. Constructing a cancer “profile” using the original SHADE, the PSA doubling time, and scan finding, is the first step. Unfortunately, the location of the recurrent cancer may remain uncertain, even after doing the best scans.  When this is the case the extent of disease may require a professional “guesstimate” based on the PSA doubling time and the original SHADE.  Despite all these difficulties and uncertainties, the good news is that a wide variety of treatment options are available and treatment is usually very effective. For the majority of men the disease can be controlled on a long-term basis, and some cases it can even cured. 

CALENDAR ALERT TO THOSE WHO LIVE AROUND LONG BEACH, CA Learn more about prostate cancer treatments as Mark Scholz, MD, discusses treating PSA relapsed disease at UsTOO Long Beach Prostate Cancer Support Group July 22, 2014 - 6:30 PM to 8:30 PM, at Long Beach Memorial Medical Center. For more information follow this link: http://goo.gl/HMojNV

 

Prostate Imaging with Color Doppler Ultrasound

BY MARK SCHOLZ, MD

Prostate cancer is the most common form of cancer in men. While some types are life-threatening others are not.  Recently the media have been reporting on serious concerns that have surfaced about men with the benign forms of the disease undergoing unnecessary radical treatment.  PSA screening has been receiving most of the blame, but the real problem is over reliance on random needle biopsies performed by an aggressive medical community made up of surgeons.

Significance of an Elevated PSA
An elevated PSA can occur as a result of any physical alteration of the environment in the prostate-- recent sexual activity, infection, cancer, and gland enlargement (BPH). A modest elevation of PSA is medically nonspecific. As one man explained, “Think of the Check Engine light on the dashboard of your car. It’s significant if it is ON, but further specifics need to be determined before taking any action.”

Time for a Random Biopsy?
PSA elevation typically triggers an immediate 12-core random biopsy. Presently, over a million men are undergoing biopsy every year at a cost of billions of dollars. Unfortunately, low grade prostate cancer is so prevalent in the general male population that a random biopsy will find prostate cancer 20% of the time, even when PSA is normal. Obviously a great preponderance of all this “cancer” must be harmless. After all, historical death rates from prostate cancer before 1987, when PSA screening first became available, were only 3%.

Damn the Possible Side Effects, Treat it Anyway
Cancer is a frightening word. To many, it portends death. Therefore it’s hardly surprising that both doctors and patients swing into immediate action when the biopsy shows CANCER. Amending and tempering words such as “low grade” or “microscopic” seem to produce no soothing affect whatsoever on the instinctual fears generated by this venomous diagnosis.   Despite the universal agreement of hundreds of prostate experts at a consensus conference back in 2007 which concluded that low-grade prostate cancer can be safely monitored, 85% of all men diagnosed still throw caution to the wind and get treatment anyway.

Imaging is “Blind” to Small Low-Grade Cancers
Back when doctors regarded all types of prostate cancer as universally dangerous, prostate imaging, which is prone to miss small, low-grade lesions, was deemed inadequate. However, with our modern perspective, knowing that only larger, higher-grade lesions are clinically relevant, imaging makes perfect sense. There are two types of prostate imaging: High-resolution Color Doppler Ultrasound, which is the subject of this blog, and multiparametric 3-Tesla MRI which was the subject of my last blog.

Color Doppler Ultrasound Imaging
It’s no longer appropriate to needle the prostate multiple times with the outdated belief that it’s essential to diagnose every tiny prostate cancer.  Practically speaking, only prostate cancers large enough to be “seen” (with imaging) need to be considered. Color Doppler Ultrasound scanning of the prostate is performed by a physician in the doctor’s office. It is actually two scans in one: Standard “Grey Scale” imaging and Color Doppler imaging to detect areas of increased blood flow.  First, ultrasound enables accurate measurement of the gland size. Second, from a cancer point of view, imaging with Color Doppler has three possible outcomes:   

A)   Completely clear

B)   An overtly suspicious lesion is detected

C)   Ambiguous lesion(s) are detected

Targeted Rather than Random Biopsies
When an overtly suspicious lesion is detected, a targeted biopsy (a limited number of cores aimed directly at the lesion) is typically recommended. Lesions that are biopsy-negative or show low-grade cancer are simply monitored.  When high-grade disease is diagnosed, a process of further staging followed by pertinent counseling about the different treatment options is initiated.

When to Biopsy Ambiguous Lesions
Expert judgment, with appropriate attention to the individual patient characteristics, comes into play during a discussion between patient and doctor about whether or not to do a targeted biopsy. Color Doppler “sees” all sorts of things including scar tissue, areas of active prostatitis, and nodular areas from BPH. A follow-up scan in six months to see if a lesion shows further growth may be preferred to immediate biopsy.  Lesion characteristics that raise greatest concern tend to be located in the peripheral zone of the prostate, and include lesions over a centimeter, lesions that bulge the prostate capsule and lesions that have increased blood flow.  Targeted biopsy is advised more frequently in men who are younger, are more anxious about missing cancer, and in men with PSA levels higher than they “should be” relative to the size of their prostate. 

“Cross Checking” Ambiguous Lesions with Multiparametric MRI
Color Doppler Ultrasound and Multiparametric MRI (MP-MRI) are complementary. In our experience the imaging findings match. However in a minority of cases one imaging modality will illuminate a specific lesion substantially more clearly. Therefore, in ambiguous cases, a combination of both modalities increases confidence that high-grade cancer isn’t being overlooked. Doing a second imaging procedure with MP-MRI is often preferable to doing an immediate biopsy.  If subsequently a targeted biopsy is deemed necessary, the additional imaging information obtained from MP-MRI may further increase the accuracy of the targeted biopsy.

Color Doppler for Monitoring Low-Grade Cancer
These days’ experts advise men with low-grade prostate cancer to forgo surgery or radiation and monitor their condition with Active Surveillance. The most common protocol used presently is regular PSA testing and periodic random biopsy. However, multiple random biopsies are associated with discomfort and progressive risk of serious infections and impotence.  Sequential monitoring of small lesions with Color Doppler to determine if they are growing or stable is a far more logical approach than subjecting men to repeated biopsies.

Final Thoughts
Men with elevated PSA, who initially undergo a Color Doppler, rather than random biopsy, are often spared biopsy altogether if their scan is clear.  Men who do require biopsy will need far fewer cores taken because the biopsy is targeted to a specific lesion within the gland. Men on Active Surveillance and men who have undergone previous treatment with surgery, radiation, cryotherapy, HIFU or hormone blockade are also candidates for Color Doppler Ultrasound to determine how well they are responding to treatment. 

Multiparametric MRI Prostate Imaging

BY MARK SCHOLZ, MD

Historically, prostate imaging with CT, ultrasound or MRI has been too inaccurate for diagnosing prostate cancer.   Random needle biopsy has been the mainstay of accurate diagnosis. However, after a number of false starts, advances have brought multiparametric MRI (MP-MRI) into the winner’s circle, even surpassing the accuracy of random biopsy.

Prostate Imaging Presents a Special Challenge
Success with prostate imaging has been a long time coming. While mammography for breast imaging and CAT scans for lung cancer have enjoyed mainstream use for decades, the technology to differentiate the high-grade prostate cancers from harmless, low-grade prostate cancers—those that experts believe are better off being left undiagnosed—has only been developed recently.

New Technology Brings Growing Pains
You might think that new technological advances would immediately revolutionize prostate cancer management. Not necessarily. Many doctors simply don’t know what’s now available. Those that are aware are often unacquainted with the full extent of its capabilities. And finally, even the fully informed doctors may be reluctant to venture outside their comfort zone and embrace MP-MRI as a substitute for doing a random biopsy.

Barriers to Change—The Status Quo has Deep Roots
Random biopsy has been the de facto standard for 25 years.  Prior to MP-MRI, biopsy was the ONLY way to confirm the diagnosis of prostate cancer and obtain accurate information about its extent. Additionally, periodic random biopsy has been fundamental to the monitoring process in men with low-grade prostate cancer on Active Surveillance. Biopsy has grown to become a very big business, performed in more than a million men annually.  It is financially lucrative, paying thousands of dollars to providers for each procedure.

Ending the Twenty-five Year Reign of Random Biopsy
Random biopsy has major drawbacks. It misses high-grade cancer 15% of the time and 3% of men end up in the hospital with uncontrolled infections.  Repeat biopsies, such as those done to men on active surveillance are uncomfortable, affect erectile function and incur an even higher risk of infection. Most importantly, random biopsy over-diagnoses 100,000 men annually, leading to rampant and excessive use of surgery or radiation.

Imaging with Multiparametric MRI 
MP-MRI detects high-grade disease accurately and, thankfully, overlooks low grade disease, thus sparing the shock of an unnecessary cancer diagnosis and, in many cases, unwarranted treatment. Any suspicious lesions that are detected can be further investigated with a targeted biopsy, a more accurate way to find high-grade disease that requires far fewer biopsy cores. Men with a clear scan can usually forgo biopsy altogether. The word “Multi-parametric” means the performance of three scans sequentially during a single visit to the imaging center: 

1)    T2-weighted imaging allows for the best assessment of the prostate morphology, size, margins and internal structures with easy differentiation between the central and peripheral zones.

2)     Diffusion-weighted imaging details the tissue microstructure and generates an “apparent diffusion coefficient” (ADC) which helps to determine the aggressiveness of a lesion if one is seen.

3)    Dynamic contrast-enhanced imaging detects areas of increased vascularity to better detail any suspect lesions.

The radiologist who reads the scans unifies the information from all three modalities to compile a report. Findings are then summarized in an overall impression which falls into one of three categories:

First: No evidence for high grade disease, no need for biopsy

Second: A suspicious lesion is detected, a targeted biopsy is probably necessary

Third: 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

Scanning in the Context of Prostate Size, PSA and Age
Men’s prostates come in many sizes and shapes.  MP-MRI accurately measures prostate size, which is essential to interpreting PSA because an enlarged prostate produces higher PSA levels. An oversized gland, therefore, provides a reassuringly benign explanation for a modestly elevated PSA. Since many forms of prostate cancer take decades to grow large enough to present a problem, a man’s age is also relevant to the interpretation process. For example, elderly men with rather small ambiguous lesions (Third) might be advised to follow up with further scans to determine if it grows rather than going to a biopsy right away.   

Scanning at a Center of Excellence
Very few imaging centers can do prostate imaging at the level of quality we are discussing. There are essentially three components required to achieve reliable results: State-of-the-art, three-Tesla hardware; technicians who are precisely trained in how to perform prostate imaging; and physicians carefully trained specifically in the interpretation of prostate imaging. Imaging technology is developing so rapidly that even some board-certified radiologists remain unaware of what the latest technology can achieve.   

Don’t Be Cheated Out of the Best Technology
Today’s MP-MRI scans, when performed at centers of excellence, generate prostate images of stunning clarity. Every effort must be made to raise general awareness among patients and doctors alike about the advantages of MP-MRI over random biopsy in men with high PSA levels and in men who have been diagnosed with low-grade cancer that are pursuing Active Surveillance.   

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.”