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.    

Confessions of a Treatment Conservative

BY RALPH BLUM

While studies demonstrate that the new gold standard for detection of clinically significant prostate cancer with a high degree of certainty is a combination of systematic and MRI targeted biopsies, the practicality of this approach still poses problems.

Mark has written many times about the growing pains involved in the common sense use of this sophisticated technology, and also its tremendous potential to finally help distinguish men with non-aggressive cancer who do not need treatment from those with aggressive disease who do.

Making this technology available to every man with prostate cancer who would benefit from it is problematic for one main reason—the process is not very available due to the relatively few centers of excellence that have access both to the technology, and to the highly skilled uro-radiologists capable of reading the MRI scans with accuracy.

Prostate cancer affects men in many different ways. Its management is complicated by extremely variable behavior patterns ranging from slow-growing and insignificant to rapidly growing and life-threatening. Sometimes an abnormal PSA suggests cancer but none is found at biopsy. Sometimes a man who is thought to be a good candidate for surgery will turn out to have cancer that cannot be effectively treated surgically. Other times a decision has to be made whether to treat what appears to be a very small amount of cancer and risk the inevitable side effects. All of these are issues where prostate MRI is of value.

The biggest challenge in prostate cancer treatment is to try to find all the cancer, but treat only that cancer which is aggressive. Multiparametric MRI scans can help identify areas in the prostate that are suspicious for aggressive cancer that can be missed by biopsy. They also happen to be safer, minimally invasive, and less uncomfortable!

The main reason that Mark and I wrote our book—Invasion of the Prostate Snatchers—was to try to prevent the exorbitant number of biopsies performed every year in the United States leading to immediate radical treatment that in many cases was totally unnecessary.

There is no doubt that advances in MRI technology could dramatically curb the number of biopsies performed and reduce unnecessary treatment of non-life-threatening cancers.  From my own experience of co-existing with prostate for over 20 years cancer, I remain conservative when it comes to invasive treatment.

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

 

 

Raising Awareness about MRI Imaging of the Prostate

BY MARK SCHOLZ, MD

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.

CHECK OUT THIS VIDEO: SO YOUR PSA IS HIGH, NOW WHAT? 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.

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

 

Abstracts from the Meeting of the American Urological Association

BY MARK SCHOLZ, MD

Each year in May the American Urology Association meeting provides a treasure-trove of new scientific information.  As noted in my reviews from earlier scientific meetings, the results of new studies are communicated in 350-word Abstracts which concisely summarize the efforts of a team of scientists working on a specific clinical question.  Several thousand abstracts are published in the proceedings of the meeting, amounting to over a million published words.  On the topic of prostate cancer there were merely hundreds. This year I selected 46 for comment. This blog briefly comments on only a few of these abstracts. Each bullet point is for a separate abstract.

Active Surveillance

·        A large registry in Michigan that tracks prostate cancer treatment reports that about 50% of men with low-risk prostate cancer who are eligible for active surveillance actually undergo active surveillance (the other half get radical therapy). As sad as this sounds, 50% is double the reported active surveillance rates from 3-4 years ago, showing progressively increasing acceptance of active surveillance by doctors and patients. 

·        Laurence Klotz, the father of active surveillance and the lead investigator of the longest study of over a thousand men on active surveillance, reports that after more than ten years of monitoring, 3.6% of patients have developed metastatic disease and 1.7% have died of prostate cancer. Dr. Klotz points out that these statistics are similar to the expected mortality in low-risk patients that get treated with initial surgery or radiation.

Can Gleason 3 + 3 = 6 Metastasize?

·        2500 surgical patients were reviewed to determine if Gleason grade 6 can spread outside the prostate into the seminal vesicle.  In this study not a single case of seminal vesicle invasion was documented when the cancer was exclusively grade 6.

·        Out of 173 men with Gleason grade 6 who had their lymph nodes removed, not a single case of lymph node spread was observed. After an average of five years of observation, no patient has developed metastases.

Metformin and Statins

A number of previous reports have suggested that metformin and statins have anticancer effects. The anticancer effects of metformin have been only studies in diabetics but there is no reason to believe that metformin would be ineffective as an anticancer agent in non-diabetic men. Four abstracts at the AUA elaborate further on this active area of interest.

·        In Denmark, men taking metformin (for diabetes) were at one-third lower risk of being diagnosed with prostate cancer compared to men who were not taking metformin.

·        Men undergoing surgery for prostate cancer who were taking both metformin plus a statin had a reduced risk of cancer relapse—from 30% down to 15%.

·       In Finland, prostate cancer survival was evaluated in 6000 men depending on whether they were taking statins. Statin use reduced prostate cancer mortality by two-thirds.

·       In a study from Europe, there was a 60% reduction in overall mortality in men with advanced prostate cancer who were taking statins compared to those who were not. Both cancer mortality and cardiovascular mortality were reduced by a similar increment.

 Benefits of Surgery

·       In Denmark, the estimated length of life gained with surgery compared to the general population was only 0.4 years after 10 years of observation.

·       In France within 60 days following surgery, the mortality rate was one in a thousand surgeries. Mortality after surgery was nearly twice as high in hospitals performing less than 10 prostate operations a year compared to more experienced centers.

Treatment of a PSA Relapse

Here I quote directly from two abstracts on the topic of a rising PSA after surgery or radiation:

·        “We found that salvage radiation was associated with decreased use of salvage hormone therapy, as well as lower risks of local recurrence, systemic progression, and death from prostate cancer.”

·        “Approximately 16% of patients with a detectable PSA after radical prostatectomy may have false biochemical failure. Repeating the serum PSA in all patients with a detectable level is paramount before making treatment recommendations, especially if the patient had Gleason score 6, negative margins, and the cancer was organ−confined.”

Accuracy of Prostate MRI

One of the problems with random biopsy is that it finds too much grade 6 disease, leading to too much unnecessary radical treatment. Previous studies have indicated that multiparametric MRI finds high-grade disease quite well, only missing small tumors.  However, multiparametric MRI “sees” low-grade tumors much less, which is a good thing. Below are two new reports on this important new technology.

·       A multiparametric prostate MRI showing no cancer in the prostate is accurate 82% of the time for grade 6 cancer and 98% of the time for grade 7 or higher using a 12-core biopsy as the reference standard.

·       A multiparametric prostate MRI showing no high-grade cancer is accurate 74% of the time when using surgical removal and pathologic dissection of the prostate as the reference standard. The types of high-grade cancers that were missed by MRI tended to be smaller, secondary tumors that were organ confined.

I was encouraged to see so many abstracts on active surveillance at this year’s meeting. Also gratifying were the numerous reports on imaging, which in my opinion is the technology of the future that will eventually supplant random biopsy. All the 46 abstracts I judged interesting have been posted here: http://goo.gl/ZzwmpB

 

Imaging is Superior to Random Biopsy

BY MARK SCHOLZ, MD

Recently, our attention has been directed at the overtreatment of low-grade prostate cancer.  While PSA screening has been fingered as the problem, overuse of random needle biopsies is the real culprit. Over a million men undergo biopsies every year to address concerns about the possibility of underlying cancer.  Few people realize, however, that random biopsy reveals low-grade prostate cancer in one out of five men in the general population—even if PSA is normal.

 

Most of these “cancers” are harmless. Even so, it’s hardly surprising that patients with “cancer” want immediate treatment.  The words “low grade” or “microscopic” can’t offset the instinctual fears generated by this venomous word.   Despite dire warnings about the risks of treatment-induced impotence and incontinence—and reassurance from experts that low-grade prostate cancer can be safely monitored—studies show that 85% of men still throw caution to the wind and get treatment anyway.

 

Imaging is “Blind” to Small Low-Grade Cancers

While latent prostate cancers are more common, aggressive prostate cancer is also a reality. After all, 30,000 men die every year of prostate cancer. Back when doctors believed that all types of prostate cancer were universally dangerous, prostate imaging, which often misses small, low-grade lesions, was deemed inadequate. However, now with a more modern perspective we know that color Doppler ultrasound or multiparametric, three-tesla MRI overlook low grade disease while still detecting high-grade disease accurately.  Imaging spares men the shock of an unnecessary cancer diagnosis and unwarranted treatment.

 

Targeted Rather than Random Biopsies

When an overtly suspicious lesion is detected by imaging, 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 can be monitored without treatment.  If high-grade disease is diagnosed, further staging followed by counseling about treatment is needed.

 

The doctor who reads the scan summarizes his 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

When to Biopsy Ambiguous Lesions
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, bulge the prostate capsule or are associated with increased blood flow or diffusion. An ambiguous lesion may require biopsy if a subsequent scans show an enlarging lesion. Expert judgment that takes individual patient characteristics into account comes into play during a discussion between the patient and doctor about whether or not a targeted biopsy is indicated.

“Cross Checking” Ambiguous Lesions
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.

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 capabilities modern imaging can achieve. And finally, even the well informed doctors may be reluctant to venture outside their comfort zone to embrace imaging as a substitute for doing a random biopsy.

Final Thoughts
Lack of awareness about how random biopsy leads to the over diagnosis of harmless, low grade cancers is resulting in a 100,000 men undergoing unnecessary surgery and radiation every year. Forgoing PSA screening altogether is both foolish and dangerous. State-of-the-art prostate imaging, not random biopsy, should be the first step in evaluating men with elevated PSA levels.

Join us in Long Beach, CA at Barnes & Noble Marina June 26, 2014 @ 7pm- Ask the Author: Mark Scholz, MD will be discussing his book, Invasion of the Prostate Snatchers and Men's Health. More June events and details here: https://groups.google.com/forum/#!topic/prostateoncology/H1AE5oeW2jc